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• Published: 20 July 2022

The serotonin theory of depression: a systematic umbrella review of the evidence

• Joanna Moncrieff 1 , 2 ,
• Ruth E. Cooper 3 ,
• Tom Stockmann 4 ,
• Simone Amendola 5 ,
• Michael P. Hengartner 6 &
• Mark A. Horowitz 1 , 2  

Molecular Psychiatry volume  28 ,  pages 3243–3256 ( 2023 ) Cite this article

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A Correspondence to this article was published on 16 June 2023

A Comment to this article was published on 16 June 2023

The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT 1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n  = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use ( n  = 1869). Two meta-analyses of overlapping studies examining the 5-HT 1A receptor (largest n  = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n  = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers ( n  = 566), but weak evidence of an effect in those with a family history of depression ( n  = 75). Another systematic review ( n  = 342) and a sample of ten subsequent studies ( n  = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study ( n  = 115,257) and one collaborative meta-analysis ( n  = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.

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Introduction.

The idea that depression is the result of abnormalities in brain chemicals, particularly serotonin (5-hydroxytryptamine or 5-HT), has been influential for decades, and provides an important justification for the use of antidepressants. A link between lowered serotonin and depression was first suggested in the 1960s [ 1 ], and widely publicised from the 1990s with the advent of the Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants [ 2 , 3 , 4 ]. Although it has been questioned more recently [ 5 , 6 ], the serotonin theory of depression remains influential, with principal English language textbooks still giving it qualified support [ 7 , 8 ], leading researchers endorsing it [ 9 , 10 , 11 ], and much empirical research based on it [ 11 , 12 , 13 , 14 ]. Surveys suggest that 80% or more of the general public now believe it is established that depression is caused by a ‘chemical imbalance’ [ 15 , 16 ]. Many general practitioners also subscribe to this view [ 17 ] and popular websites commonly cite the theory [ 18 ].

It is often assumed that the effects of antidepressants demonstrate that depression must be at least partially caused by a brain-based chemical abnormality, and that the apparent efficacy of SSRIs shows that serotonin is implicated. Other explanations for the effects of antidepressants have been put forward, however, including the idea that they work via an amplified placebo effect or through their ability to restrict or blunt emotions in general [ 19 , 20 ].

Despite the fact that the serotonin theory of depression has been so influential, no comprehensive review has yet synthesised the relevant evidence. We conducted an ‘umbrella’ review of the principal areas of relevant research, following the model of a similar review examining prospective biomarkers of major depressive disorder [ 21 ]. We sought to establish whether the current evidence supports a role for serotonin in the aetiology of depression, and specifically whether depression is associated with indications of lowered serotonin concentrations or activity.

Search strategy and selection criteria

The present umbrella review was reported in accordance with the 2009 PRISMA statement [ 22 ]. The protocol was registered with PROSPERO in December 2020 (registration number CRD42020207203) ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=207203 ). This was subsequently updated to reflect our decision to modify the quality rating system for some studies to more appropriately appraise their quality, and to include a modified GRADE to assess the overall certainty of the findings in each category of the umbrella review.

In order to cover the different areas and to manage the large volume of research that has been conducted on the serotonin system, we conducted an ‘umbrella’ review. Umbrella reviews survey existing systematic reviews and meta-analyses relevant to a research question and represent one of the highest levels of evidence synthesis available [ 23 ]. Although they are traditionally restricted to systematic reviews and meta-analyses, we aimed to identify the best evidence available. Therefore, we also included some large studies that combined data from individual studies but did not employ conventional systematic review methods, and one large genetic study. The latter used nationwide databases to capture more individuals than entire meta-analyses, so is likely to provide even more reliable evidence than syntheses of individual studies.

We first conducted a scoping review to identify areas of research consistently held to provide support for the serotonin hypothesis of depression. Six areas were identified, addressing the following questions: (1) Serotonin and the serotonin metabolite 5-HIAA–whether there are lower levels of serotonin and 5-HIAA in body fluids in depression; (2) Receptors - whether serotonin receptor levels are altered in people with depression; (3) The serotonin transporter (SERT) - whether there are higher levels of the serotonin transporter in people with depression (which would lower synaptic levels of serotonin); (4) Depletion studies - whether tryptophan depletion (which lowers available serotonin) can induce depression; (5) SERT gene – whether there are higher levels of the serotonin transporter gene in people with depression; (6) Whether there is an interaction between the SERT gene and stress in depression.

We searched for systematic reviews, meta-analyses, and large database studies in these six areas in PubMed, EMBASE and PsycINFO using the Healthcare Databases Advanced Search tool provided by Health Education England and NICE (National Institute for Health and Care Excellence). Searches were conducted until December 2020.

We used the following terms in all searches: (depress* OR affective OR mood) AND (systematic OR meta-analysis), and limited searches to title and abstract, since not doing so produced numerous irrelevant hits. In addition, we used terms specific to each area of research (full details are provided in Table  S1 , Supplement). We also searched citations and consulted with experts.

Inclusion criteria were designed to identify the best available evidence in each research area and consisted of:

Research synthesis including systematic reviews, meta-analysis, umbrella reviews, individual patient meta-analysis and large dataset analysis.

Studies that involve people with depressive disorders or, for experimental studies (tryptophan depletion), those in which mood symptoms are measured as an outcome.

Studies of experimental procedures (tryptophan depletion) involving a sham or control condition.

Studies published in full in peer reviewed literature.

Where more than five systematic reviews or large analyses exist, the most recent five are included.

Exclusion criteria consisted of:

Animal studies.

Studies exclusively concerned with depression in physical conditions (e.g. post stroke or Parkinson’s disease) or exclusively focusing on specific subtypes of depression such as postpartum depression, depression in children, or depression in bipolar disorder.

No language or date restrictions were applied. In areas in which no systematic review or meta-analysis had been done within the last 10 years, we also selected the ten most recent studies at the time of searching (December 2020) for illustration of more recent findings. We performed this search using the same search string for this domain, without restricting it to systematic reviews and meta-analyses.

Data analysis

Each member of the team was allocated one to three domains of serotonin research to search and screen for eligible studies using abstract and full text review. In case of uncertainty, the entire team discussed eligibility to reach consensus.

For included studies, data were extracted by two reviewers working independently, and disagreement was resolved by consensus. Authors of papers were contacted for clarification when data was missing or unclear.

We extracted summary effects, confidence intervals and measures of statistical significance where these were reported, and, where relevant, we extracted data on heterogeneity. For summary effects in the non-genetic studies, preference was given to the extraction and reporting of effect sizes. Mean differences were converted to effect sizes where appropriate data were available.

We did not perform a meta-analysis of the individual meta-analyses in each area because they included overlapping studies [ 24 ]. All extracted data is presented in Table  1 . Sensitivity analyses were reported where they had substantial bearing on interpretation of findings.

The quality rating of systematic reviews and meta-analyses was assessed using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews) [ 25 ]. For two studies that did not employ conventional systematic review methods [ 26 , 27 ] we used a modified version of the AMSTAR-2 (see Table  S3 ). For the genetic association study based on a large database analysis we used the STREGA assessment (STrengthening the REporting of Genetic Association Studies) (Table  S4 ) [ 28 ]. Each study was rated independently by at least two authors. We report ratings of individual items on the relevant measure, and the percentage of items that were adequately addressed by each study (Table  1 , with further detail in Tables  S3 and S4 ).

Alongside quality ratings, two team members (JM, MAH) rated the certainty of the results of each study using a modified version of the GRADE guidelines [ 29 ]. Following the approach of Kennis et al. [ 21 ], we devised six criteria relevant to the included studies: whether a unified analysis was conducted on original data; whether confounding by antidepressant use was adequately addressed; whether outcomes were pre-specified; whether results were consistent or heterogeneity was adequately addressed if present; whether there was a likelihood of publication bias; and sample size. The importance of confounding by effects of current or past antidepressant use has been highlighted in several studies [ 30 , 31 ]. The results of each study were scored 1 or 0 according to whether they fulfilled each criteria, and based on these ratings an overall judgement was made about the certainty of evidence across studies in each of the six areas of research examined. The certainty of each study was based on an algorithm that prioritised sample size and uniform analysis using original data (explained more fully in the supplementary material), following suggestions that these are the key aspects of reliability [ 27 , 32 ]. An assessment of the overall certainty of each domain of research examining the role of serotonin was determined by consensus of at least two authors and a direction of effect indicated.

Search results and quality rating

Searching identified 361 publications across the 6 different areas of research, among which seventeen studies fulfilled inclusion criteria (see Fig.  1 and Table  S1 for details of the selection process). Included studies, their characteristics and results are shown in Table  1 . As no systematic review or meta-analysis had been performed within the last 10 years on serotonin depletion, we also identified the 10 latest studies for illustration of more recent research findings (Table  2 ).

Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flow diagramme.

Quality ratings are summarised in Table  1 and reported in detail in Tables  S2 – S3 . The majority (11/17) of systematic reviews and meta-analyses satisfied less than 50% of criteria. Only 31% adequately assessed risk of bias in individual studies (a further 44% partially assessed this), and only 50% adequately accounted for risk of bias when interpreting the results of the review. One collaborative meta-analysis of genetic studies was considered to be of high quality due to the inclusion of several measures to ensure consistency and reliability [ 27 ]. The large genetic analysis of the effect of SERT polymorphisms on depression, satisfied 88% of the STREGA quality criteria [ 32 ].

Serotonin and 5-HIAA

Serotonin can be measured in blood, plasma, urine and CSF, but it is rapidly metabolised to 5-hydroxyindoleacetic acid (5-HIAA). CSF is thought to be the ideal resource for the study of biomarkers of putative brain diseases, since it is in contact with brain interstitial fluid [ 33 ]. However, collecting CSF samples is invasive and carries some risk, hence large-scale studies are scarce.

Three studies fulfilled inclusion criteria (Table  1 ). One meta-analysis of three large observational cohort studies of post-menopausal women, revealed lower levels of plasma 5-HT in women with depression, which did not, however, reach statistical significance of p  < 0.05 after adjusting for multiple comparisons. Sensitivity analyses revealed that antidepressants were strongly associated with lower serotonin levels independently of depression.

Two meta-analyses of a total of 19 studies of 5-HIAA in CSF (seven studies were included in both) found no evidence of an association between 5-HIAA concentrations and depression.

Fourteen different serotonin receptors have been identified, with most research on depression focusing on the 5-HT 1A receptor [ 11 , 34 ]. Since the functions of other 5-HT receptors and their relationship to depression have not been well characterised, we restricted our analysis to data on 5-HT 1A receptors [ 11 , 34 ]. 5-HT 1A receptors, known as auto-receptors, inhibit the release of serotonin pre-synaptically [ 35 ], therefore, if depression is the result of reduced serotonin activity caused by abnormalities in the 5-HT 1A receptor, people with depression would be expected to show increased activity of 5-HT 1A receptors compared to those without [ 36 ].

Two meta-analyses satisfied inclusion criteria, involving five of the same studies [ 37 , 38 ] (see Table  1 ). The majority of results across the two analyses suggested either no difference in 5-HT 1A receptors between people with depression and controls, or a lower level of these inhibitory receptors, which would imply higher concentrations or activity of serotonin in people with depression. Both meta-analyses were based on studies that predominantly involved patients who were taking or had recently taken (within 1–3 weeks of scanning) antidepressants or other types of psychiatric medication, and both sets of authors commented on the possible influence of prior or current medication on findings. In addition, one analysis was of very low quality [ 37 ], including not reporting on the numbers involved in each analysis and using one-sided p-values, and one was strongly influenced by three studies and publication bias was present [ 38 ].

The serotonin transporter (SERT)

The serotonin transporter protein (SERT) transports serotonin out of the synapse, thereby lowering the availability of serotonin in the synapse [ 39 , 40 ]. Animals with an inactivated gene for SERT have higher levels of extra-cellular serotonin in the brain than normal [ 41 , 42 , 43 ] and SSRIs are thought to work by inhibiting the action of SERT, and thus increasing levels of serotonin in the synaptic cleft [ 44 ]. Although changes in SERT may be a marker for other abnormalities, if depression is caused by low serotonin availability or activity, and if SERT is the origin of that deficit, then the amount or activity of SERT would be expected to be higher in people with depression compared to those without [ 40 ]. SERT binding potential is an index of the concentration of the serotonin transporter protein and SERT concentrations can also be measured post-mortem.

Three overlapping meta-analyses based on a total of 40 individual studies fulfilled inclusion criteria (See Table  1 ) [ 37 , 39 , 45 ]. Overall, the data indicated possible reductions in SERT binding in some brain areas, although areas in which effects were detected were not consistent across the reviews. In addition, effects of antidepressants and other medication cannot be ruled out, since most included studies mainly or exclusively involved people who had a history of taking antidepressants or other psychiatric medications. Only one meta-analysis tested effects of antidepressants, and although results were not influenced by the percentage of drug-naïve patients in each study, numbers were small so it is unlikely that medication-related effects would have been reliably detected [ 45 ]. All three reviews cited evidence from animal studies that antidepressant treatment reduces SERT [ 46 , 47 , 48 ]. None of the analyses corrected for multiple testing, and one review was of very low quality [ 37 ]. If the results do represent a positive finding that is independent of medication, they would suggest that depression is associated with higher concentrations or activity of serotonin.

Depletion studies

Tryptophan depletion using dietary means or chemicals, such as parachlorophenylalanine (PCPA), is thought to reduce serotonin levels. Since PCPA is potentially toxic, reversible tryptophan depletion using an amino acid drink that lacks tryptophan is the most commonly used method and is thought to affect serotonin within 5–7 h of ingestion. Questions remain, however, about whether either method reliably reduces brain serotonin, and about other effects including changes in brain nitrous oxide, cerebrovascular changes, reduced BDNF and amino acid imbalances that may be produced by the manipulations and might explain observed effects independent of possible changes in serotonin activity [ 49 ].

One meta-analysis and one systematic review fulfilled inclusion criteria (see Table  1 ). Data from studies involving volunteers mostly showed no effect, including a meta-analysis of parallel group studies [ 50 ]. In a small meta-analysis of within-subject studies involving 75 people with a positive family history, a minor effect was found, with people given the active depletion showing a larger decrease in mood than those who had a sham procedure [ 50 ]. Across both reviews, studies involving people diagnosed with depression showed slightly greater mood reduction following tryptophan depletion than sham treatment overall, but most participants had taken or were taking antidepressants and participant numbers were small [ 50 , 51 ].

Since these research syntheses were conducted more than 10 years ago, we searched for a systematic sample of ten recently published studies (Table  2 ). Eight studies conducted with healthy volunteers showed no effects of tryptophan depletion on mood, including the only two parallel group studies. One study presented effects in people with and without a family history of depression, and no differences were apparent in either group [ 52 ]. Two cross-over studies involving people with depression and current or recent use of antidepressants showed no convincing effects of a depletion drink [ 53 , 54 ], although one study is reported as positive mainly due to finding an improvement in mood in the group given the sham drink [ 54 ].

SERT gene and gene-stress interactions

A possible link between depression and the repeat length polymorphism in the promoter region of the SERT gene (5-HTTLPR), specifically the presence of the short repeats version, which causes lower SERT mRNA expression, has been proposed [ 55 ]. Interestingly, lower levels of SERT would produce higher levels of synaptic serotonin. However, more recently, this hypothesis has been superseded by a focus on the interaction effect between this polymorphism, depression and stress, with the idea that the short version of the polymorphism may only give rise to depression in the presence of stressful life events [ 55 , 56 ]. Unlike other areas of serotonin research, numerous systematic reviews and meta-analyses of genetic studies have been conducted, and most recently a very large analysis based on a sample from two genetic databanks. Details of the five most recent studies that have addressed the association between the SERT gene and depression, and the interaction effect are detailed in Table  1 .

Although some earlier meta-analyses of case-control studies showed a statistically significant association between the 5-HTTLPR and depression in some ethnic groups [ 57 , 58 ], two recent large, high quality studies did not find an association between the SERT gene polymorphism and depression [ 27 , 32 ]. These two studies consist of  by far the largest and most comprehensive study to date [ 32 ] and a high-quality meta-analysis that involved a consistent re-analysis of primary data across all conducted studies, including previously unpublished data, and other comprehensive quality checks [ 27 , 59 ] (see Table  1 ).

Similarly, early studies based on tens of thousands of participants suggested a statistically significant interaction between the SERT gene, forms of stress or maltreatment and depression [ 60 , 61 , 62 ], with a small odds ratio in the only study that reported this (1.18, 95% CI 1.09 to 1.28) [ 62 ]. However, the two recent large, high-quality studies did not find an interaction between the SERT gene and stress in depression (Border et al [ 32 ] and Culverhouse et al.) [ 27 ] (see Table  1 ).

Overall results

Table  3 presents the modified GRADE ratings for each study and the overall rating of the strength of evidence in each area. Areas of research that provided moderate or high certainty of evidence such as the studies of plasma serotonin and metabolites and the genetic and gene-stress interaction studies all showed no association between markers of serotonin activity and depression. Some other areas suggested findings consistent with increased serotonin activity, but evidence was of very low certainty, mainly due to small sample sizes and possible residual confounding by current or past antidepressant use. One area - the tryptophan depletion studies - showed very low certainty evidence of lowered serotonin activity or availability in a subgroup of volunteers with a family history of depression. This evidence was considered very low certainty as it derived from a subgroup of within-subject studies, numbers were small, and there was no information on medication use, which may have influenced results. Subsequent research has not confirmed an effect with numerous negative studies in volunteers.

Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress. Weak evidence from some studies of serotonin 5-HT 1A receptors and levels of SERT points towards a possible association between increased serotonin activity and depression. However, these results are likely to be influenced by prior use of antidepressants and its effects on the serotonin system [ 30 , 31 ]. The effects of tryptophan depletion in some cross-over studies involving people with depression may also be mediated by antidepressants, although these are not consistently found [ 63 ].

The chemical imbalance theory of depression is still put forward by professionals [ 17 ], and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades [ 14 ]. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities [ 15 , 16 ], and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood [ 64 , 65 , 66 ]. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue antidepressant medication and may discourage people from discontinuing treatment, potentially leading to lifelong dependence on these drugs [ 67 , 68 ].

As with all research synthesis, the findings of this umbrella review are dependent on the quality of the included studies, and susceptible to their limitations. Most of the included studies were rated as low quality on the AMSTAR-2, but the GRADE approach suggested some findings were reasonably robust. Most of the non-genetic studies did not reliably exclude the potential effects of previous antidepressant use and were based on relatively small numbers of participants. The genetic studies, in particular, illustrate the importance of methodological rigour and sample size. Whereas some earlier, lower quality, mostly smaller studies produced marginally positive findings, these were not confirmed in better-conducted, larger and more recent studies [ 27 , 32 ]. The identification of depression and assessment of confounders and interaction effects were limited by the data available in the original studies on which the included reviews and meta-analyses were based. Common methods such as the categorisation of continuous measures and application of linear models to non-linear data may have led to over-estimation or under-estimation of effects [ 69 , 70 ], including the interaction between stress and the SERT gene. The latest systematic review of tryptophan depletion studies was conducted in 2007, and there has been considerable research produced since then. Hence, we provided a snapshot of the most recent evidence at the time of writing, but this area requires an up to date, comprehensive data synthesis. However, the recent studies were consistent with the earlier meta-analysis with little evidence for an effect of tryptophan depletion on mood.

Although umbrella reviews typically restrict themselves to systematic reviews and meta-analyses, we aimed to provide the most comprehensive possible overview. Therefore, we chose to include meta-analyses that did not involve a systematic review and a large genetic association study on the premise that these studies contribute important data on the question of whether the serotonin hypothesis of depression is supported. As a result, the AMSTAR-2 quality rating scale, designed to evaluate the quality of conventional systematic reviews, was not easily applicable to all studies and had to be modified or replaced in some cases.

One study in this review found that antidepressant use was associated with a reduction of plasma serotonin [ 26 ], and it is possible that the evidence for reductions in SERT density and 5-HT 1A receptors in some of the included imaging study reviews may reflect compensatory adaptations to serotonin-lowering effects of prior antidepressant use. Authors of one meta-analysis also highlighted evidence of 5-HIAA levels being reduced after long-term antidepressant treatment [ 71 ]. These findings suggest that in the long-term antidepressants might produce compensatory changes [ 72 ] that are opposite to their acute effects [ 73 , 74 ]. Lowered serotonin availability has also been demonstrated in animal studies following prolonged antidepressant administration [ 75 ]. Further research is required to clarify the effects of different drugs on neurochemical systems, including the serotonin system, especially during and after long-term use, as well as the physical and psychological consequences of such effects.

This review suggests that the huge research effort based on the serotonin hypothesis has not produced convincing evidence of a biochemical basis to depression. This is consistent with research on many other biological markers [ 21 ]. We suggest it is time to acknowledge that the serotonin theory of depression is not empirically substantiated.

Data availability

All extracted data is available in the paper and supplementary materials. Further information about the decision-making for each rating for categories of the AMSTAR-2 and STREGA are available on request.

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JM conceived the idea for the study. JM, MAH, MPH, TS and SA designed the study. JM, MAH, MPH, TS, and SA screened articles and abstracted data. JM drafted the first version of the manuscript. JM, MAH, MPH, TS, SA, and REC contributed to the manuscript’s revision and interpretation of findings. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry 28 , 3243–3256 (2023). https://doi.org/10.1038/s41380-022-01661-0

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Summary of the clinical practice guideline for the treatment of depression across three age cohorts

• PMID: 34843274
• DOI: 10.1037/amp0000904

The American Psychological Association (APA) developed this clinical practice guideline to provide recommendations for the treatment of depressive disorders, including major depression, subsyndromal depression, and persistent depressive disorder. It addresses three developmental cohorts: adolescents, general adults, and older adults (ages 60 and over). Ten systematic reviews and meta-analyses, along with other literature and observations from practitioners and patients, served as the basis for the guideline. The guideline development panel consisted of health professionals from psychology, psychiatry, and family medicine as well as community members who self-identified as having had depression. The panel examined the efficacy of psychological treatments and of complementary and alternative medicine treatments. It also examined comparative effectiveness among psychological treatments, by themselves and in combination with pharmacotherapy, and comparative effectiveness of psychological treatments in relation to pharmacotherapy and to complementary and alternative treatments. The panel made recommendations for treatment of depression in adolescents, adults, and older adults but did not make treatment recommendations specific to children. These recommendations, presented in detail in the guideline, are summarized here. The target audience for the guideline includes clinicians, researchers, patients, family members, and policymakers. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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• Depression* / therapy
• Depressive Disorder*
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An Exploratory Study of Students with Depression in Undergraduate Research Experiences

• Katelyn M. Cooper
• Logan E. Gin
• M. Elizabeth Barnes
• Sara E. Brownell

*Address correspondence to: Katelyn M. Cooper ( E-mail Address: [email protected] ).

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Biology Education Research Lab, Research for Inclusive STEM Education Center, School of Life Sciences, Arizona State University, Tempe, AZ 85281

Depression is a top mental health concern among undergraduates and has been shown to disproportionately affect individuals who are underserved and underrepresented in science. As we aim to create a more inclusive scientific community, we argue that we need to examine the relationship between depression and scientific research. While studies have identified aspects of research that affect graduate student depression, we know of no studies that have explored the relationship between depression and undergraduate research. In this study, we sought to understand how undergraduates’ symptoms of depression affect their research experiences and how research affects undergraduates’ feelings of depression. We interviewed 35 undergraduate researchers majoring in the life sciences from 12 research-intensive public universities across the United States who identify with having depression. Using inductive and deductive coding, we identified that students’ depression affected their motivation and productivity, creativity and risk-taking, engagement and concentration, and self-perception and socializing in undergraduate research experiences. We found that students’ social connections, experiencing failure in research, getting help, receiving feedback, and the demands of research affected students’ depression. Based on this work, we articulate an initial set of evidence-based recommendations for research mentors to consider in promoting an inclusive research experience for students with depression.

INTRODUCTION

Depression is described as a common and serious mood disorder that results in persistent feelings of sadness and hopelessness, as well as a loss of interest in activities that one once enjoyed ( American Psychiatric Association [APA], 2013 ). Additional symptoms of depression include weight changes, difficulty sleeping, loss of energy, difficulty thinking or concentrating, feelings of worthlessness or excessive guilt, and suicidality ( APA, 2013 ). While depression results from a complex interaction of psychological, social, and biological factors ( World Health Organization, 2018 ), studies have shown that increased stress caused by college can be a significant contributor to student depression ( Dyson and Renk, 2006 ).

Depression is one of the top undergraduate mental health concerns, and the rate of depression among undergraduates continues to rise ( Center for Collegiate Mental Health, 2017 ). While we cannot discern whether these increasing rates of depression are due to increased awareness or increased incidence, it is clear that is a serious problem on college campuses. The percent of U.S. college students who self-reported a diagnosis with depression was recently estimated to be about 25% ( American College Health Association, 2019 ). However, higher rates have been reported, with one study estimating that up to 84% of undergraduates experience some level of depression ( Garlow et al. , 2008 ). Depression rates are typically higher among university students compared with the general population, despite being a more socially privileged group ( Ibrahim et al. , 2013 ). Prior studies have found that depression is negatively correlated with overall undergraduate academic performance ( Hysenbegasi et al. , 2005 ; Deroma et al. , 2009 ; American College Health Association, 2019 ). Specifically, diagnosed depression is associated with half a letter grade decrease in students’ grade point average ( Hysenbegasi et al. , 2005 ), and 21.6% of undergraduates reported that depression negatively affected their academic performance within the last year ( American College Health Association, 2019 ). Provided with a list of academic factors that may be affected by depression, students reported that depression contributed to lower exam grades, lower course grades, and not completing or dropping a course.

Students in the natural sciences may be particularly at risk for depression, given that such majors are noted to be particularly stressful due to their competitive nature and course work that is often perceived to “weed students out”( Everson et al. , 1993 ; Strenta et al. , 1994 ; American College Health Association, 2019 ; Seymour and Hunter, 2019 ). Science course instruction has also been described to be boring, repetitive, difficult, and math-intensive; these factors can create an environment that can trigger depression ( Seymour and Hewitt, 1997 ; Osborne and Collins, 2001 ; Armbruster et al ., 2009 ; Ceci and Williams, 2010 ). What also distinguishes science degree programs from other degree programs is that, increasingly, undergraduate research experiences are being proposed as an essential element of a science degree ( American Association for the Advancement of Science, 2011 ; President’s Council of Advisors on Science and Technology, 2012 ; National Academies of Sciences, Engineering, and Medicine [NASEM], 2017 ). However, there is some evidence that undergraduate research experiences can add to the stress of college for some students ( Cooper et al. , 2019c ). Students can garner multiple benefits from undergraduate research, including enhanced abilities to think critically ( Ishiyama, 2002 ; Bauer and Bennett, 2003 ; Brownell et al. , 2015 ), improved student learning ( Rauckhorst et al. , 2001 ; Brownell et al. , 2015 ), and increased student persistence in undergraduate science degree programs ( Jones et al. , 2010 ; Hernandez et al. , 2018 ). Notably, undergraduate research experiences are increasingly becoming a prerequisite for entry into medical and graduate programs in science, particularly elite programs ( Cooper et al. , 2019d ). Although some research experiences are embedded into formal lab courses as course-based undergraduate research experiences (CUREs; Auchincloss et al. , 2014 ; Brownell and Kloser, 2015 ), the majority likely entail working with faculty in their research labs. These undergraduate research experiences in faculty labs are often added on top of a student’s normal course work, so they essentially become an extracurricular activity that they have to juggle with course work, working, and/or personal obligations ( Cooper et al. , 2019c ). While the majority of the literature surrounding undergraduate research highlights undergraduate research as a positive experience ( NASEM, 2017 ), studies have demonstrated that undergraduate research experiences can be academically and emotionally challenging for students ( Mabrouk and Peters, 2000 ; Seymour et al. , 2004 ; Cooper et al. , 2019c ; Limeri et al. , 2019 ). In fact, 50% of students sampled nationally from public R1 institutions consider leaving their undergraduate research experience prematurely, and about half of those students, or 25% of all students, ultimately leave their undergraduate research experience ( Cooper et al. , 2019c ). Notably, 33.8% of these individuals cited a negative lab environment and 33.3% cited negative relationships with their mentors as factors that influenced their decision about whether to leave ( Cooper et al. , 2019c ). Therefore, students’ depression may be exacerbated in challenging undergraduate research experiences, because studies have shown that depression is positively correlated with student stress ( Hish et al. , 2019 ).

While depression has not been explored in the context of undergraduate research experiences, depression has become a prominent concern surrounding graduate students conducting scientific research. A recent study that examined the “graduate student mental health crisis” ( Flaherty, 2018 ) found that work–life balance and graduate students’ relationships with their research advisors may be contributing to their depression ( Evans et al. , 2018 ). Specifically, this survey of 2279 PhD and master’s students from diverse fields of study, including the biological/physical sciences, showed that 39% of graduate students have experienced moderate to severe depression. Fifty-five percent of the graduate students with depression who were surveyed disagreed with the statement “I have good work life balance,” compared to only 21% of students with depression who agreed. Additionally, the study highlighted that more students with depression disagreed than agreed with the following statements: their advisors provided “real” mentorship, their advisors provided ample support, their advisors positively impacted their emotional or mental well-being, their advisors were assets to their careers, and they felt valued by their mentors. Another recent study identified that depression severity in biomedical doctoral students was significantly associated with graduate program climate, a perceived lack of employment opportunities, and the quality of students’ research training environment ( Nagy et al. , 2019 ). Environmental stress, academic stress, and family and monetary stress have also been shown to be predictive of depression severity in biomedical doctoral students ( Hish et al. , 2019 ). Further, one study found that self-esteem is negatively correlated and stress is positively correlated with graduate student depression; presumably research environments that challenge students’ self-esteem and induce stress are likely contributing to depressive symptoms among graduate students ( Kreger, 1995 ). While these studies have focused on graduate students, and there are certainly notable distinctions between graduate and undergraduate research, the research-related factors that affect graduate student depression, including work–life balance, relationships with mentors, research environment, stress, and self-esteem, may also be relevant to depression among undergraduates conducting research. Importantly, undergraduates in the United States have reported identical levels of depression as graduate students but are often less likely to seek mental health care services ( Wyatt and Oswalt, 2013 ), which is concerning if undergraduate research experiences exacerbate depression.

Based on the literature on the stressors of undergraduate research experiences and the literature identifying some potential causes of graduate student depression, we identified three aspects of undergraduate research that may exacerbate undergraduates’ depression. Mentoring: Mentors can be an integral part of a students’ research experience, bolstering their connections with others in the science community, scholarly productivity, and science identity, as well as providing many other benefits ( Thiry and Laursen, 2011 ; Prunuske et al. , 2013 ; Byars-Winston et al. , 2015 ; Aikens et al. , 2016 , 2017 ; Thompson et al. , 2016 ; Estrada et al. , 2018 ). However, recent literature has highlighted that poor mentoring can negatively affect undergraduate researchers ( Cooper et al. , 2019c ; Limeri et al. , 2019 ). Specifically, one study of 33 undergraduate researchers who had conducted research at 10 institutions identified seven major ways that they experienced negative mentoring, which included absenteeism, abuse of power, interpersonal mismatch, lack of career support, lack of psychosocial support, misaligned expectations, and unequal treatment ( Limeri et al. , 2019 ). We hypothesize negative mentoring experiences may be particularly harmful for students with depression, because support, particularly social support, has been shown to be important for helping individuals with depression cope with difficult circumstances ( Aneshensel and Stone, 1982 ; Grav et al. , 2012 ). Failure: Experiencing failure has been hypothesized to be an important aspect of undergraduate research experiences that may help students develop some the most distinguishing abilities of outstanding scientists, such as coping with failure, navigating challenges, and persevering ( Laursen et al. , 2010 ; Gin et al. , 2018 ; Henry et al. , 2019 ). However, experiencing failure and the stress and fatigue that often accompany it may be particularly tough for students with depression ( Aldwin and Greenberger, 1987 ; Mongrain and Blackburn, 2005 ). Lab environment: Fairness, inclusion/exclusion, and social support within one’s organizational environment have been shown to be key factors that cause people to either want to remain in the work place and be productive or to want to leave ( Barak et al. , 2006 ; Cooper et al. , 2019c ). We hypothesize that dealing with exclusion or a lack of social support may exacerbate depression for some students; patients with clinical depression react to social exclusion with more pronounced negative emotions than do individuals without clinical depression ( Jobst et al. , 2015 ). While there are likely other aspects of undergraduate research that affect student depression, we hypothesize that these factors have the potential to exacerbate negative research experiences for students with depression.

Depression has been shown to disproportionately affect many populations that are underrepresented or underserved within the scientific community, including females ( American College Health Association, 2018 ; Evans et al. , 2018 ), first-generation college students ( Jenkins et al. , 2013 ), individuals from low socioeconomic backgrounds ( Eisenberg et al. , 2007 ), members of the LGBTQ+ community ( Eisenberg et al. , 2007 ; Evans et al. , 2018 ), and people with disabilities ( Turner and Noh, 1988 ). Therefore, as the science community strives to be more diverse and inclusive ( Intemann, 2009 ), it is important that we understand more about the relationship between depression and scientific research, because negative experiences with depression in scientific research may be contributing to the underrepresentation of these groups. Specifically, more information is needed about how the research process and environment of research experiences may affect depression.

Given the high rate of depression among undergraduates, the links between depression and graduate research, the potentially challenging environment of undergraduate research, and how depression could disproportionately impact students from underserved communities, it is imperative to begin to explore the relationship between scientific research and depression among undergraduates to create research experiences that could maximize student success. In this exploratory interview study, we aimed to 1) describe how undergraduates’ symptoms of depression affect their research experiences, 2) understand how undergraduate research affects students’ feelings of depression, and 3) identify recommendations based on the literature and undergraduates’ reported experiences to promote a positive research experience for students with depression.

This study was done with an approved Arizona State University Institutional Review Board protocol #7247.

In Fall 2018, we surveyed undergraduate researchers majoring in the life sciences across 25 research-intensive (R1) public institutions across the United States (specific details about the recruitment of the students who completed the survey can be found in Cooper et al. (2019c) ). The survey asked students for their opinions about their undergraduate research experiences and their demographic information and whether they would be interested in participating in a follow-up interview related to their research experiences. For the purpose of this study, we exclusively interviewed students about their undergraduate research experiences in faculty member labs; we did not consider students’ experiences in CUREs. Of the 768 undergraduate researchers who completed the survey, 65% ( n = 496) indicated that they would be interested in participating in a follow-up interview. In Spring 2019, we emailed the 496 students, explaining that we were interested in interviewing students with depression about their experiences in undergraduate research. Our specific prompt was: “If you identify as having depression, we would be interested in hearing about your experience in undergraduate research in a 30–60 minute online interview.” We did not define depression in our email recruitment because we conducted think-aloud interviews with four undergraduates who all correctly interpreted what we meant by depression ( APA, 2013 ). We had 35 students agree to participate in the interview study. The interview participants represented 12 of the 25 R1 public institutions that were represented in the initial survey.

Student Interviews

We developed an interview script to explore our research questions. Specifically, we were interested in how students’ symptoms of depression affect their research experiences, how undergraduate research negatively affects student depression, and how undergraduate research positively affects student depression.

We recognized that mental health, and specifically depression, can be a sensitive topic to discuss with undergraduates, and therefore we tried to minimize any discomfort that the interviewees might experience during the interview. Specifically, we conducted think-aloud interviews with three graduate students who self-identified with having depression at the time of the interview. We asked them to note whether any interview questions made them uncomfortable. We also sought their feedback on questions given their experiences as persons with depression who had once engaged in undergraduate research. We revised the interview protocol after each think-aloud interview. Next, we conducted four additional think-aloud interviews with undergraduates conducting basic science or biology education research who identified with having depression to establish cognitive validity of the questions and to elicit additional feedback about any questions that might make someone uncomfortable. The questions were revised after each think-aloud interview until no question was unclear or misinterpreted by the students and we were confident that the questions minimized students’ potential discomfort ( Trenor et al. , 2011 ). A copy of the final interview script can be found in the Supplemental Material.

All interviews were individually conducted by one of two researchers (K.M.C. and L.E.G.) who conducted the think-aloud interviews together to ensure that their interviewing practices were as similar as possible. The interviews were approximately an hour long, and students received a $15 gift card for their participation.

Personal, Research, and Depression Demographics

All student demographics and information about students’ research experiences were collected using the survey distributed to students in Fall 2018. We collected personal demographics, including the participants’ gender, race/ethnicity, college generation status, transfer status, financial stability, year in college, major, and age. We also collected information about the students’ research experiences, including the length of their first research experiences, the average number of hours they spend in research per week, how they were compensated for research, who their primary mentors were, and the focus areas of their research.

In the United States, mental healthcare is disproportionately unavailable to Black and Latinx individuals, as well as those who come from low socioeconomic backgrounds ( Kataoka et al. , 2002 ; Howell and McFeeters, 2008 ; Santiago et al. , 2013 ). Therefore, to minimize a biased sample, we invited anyone who identified with having depression to participate in our study; we did not require students to be diagnosed with depression or to be treated for depression in order to participate. However, we did collect information about whether students had been formally diagnosed with depression and whether they had been treated for depression. After the interview, all participants were sent a link to a short survey that asked them if they had ever been diagnosed with depression and how, if at all, they had ever been treated for depression. A copy of these survey questions can be found in the Supplemental Material. The combined demographic information of the participants is in Table 1 . The demographics for each individual student can be found in the Supplemental Material.

a Students reported the time they had spent in research 6 months before being interviewed and only reported on the length of time of their first research experiences.

b Students were invited to report multiple ways in which they were treated for their depression; other treatments included lifestyle changes and meditation.

c Students were invited to report multiple means of compensation for their research if they had been compensated for their time in different ways.

d Students were asked whether they felt financially stable, particularly during the undergraduate research experience.

e Students reported who they work/worked with most closely during their research experiences.

f Staff members included lab coordinators or lab managers.

g Other focus areas of research included sociology, linguistics, psychology, and public health.

Interview Analysis

The initial interview analysis aimed to explore each idea that a participant expressed ( Charmaz, 2006 ) and to identify reoccurring ideas throughout the interviews. First, three authors (K.M.C., L.E.G., and S.E.B.) individually reviewed a different set of 10 interviews and took detailed analytic notes ( Birks and Mills, 2015 ). Afterward, the authors compared their notes and identified reoccurring themes throughout the interviews using open coding methods ( Saldaña, 2015 ).

Once an initial set of themes was established, two researchers (K.M.C. and L.E.G.) individually reviewed the same set of 15 randomly selected interviews to validate the themes identified in the initial analysis and to screen for any additional themes that the initial analysis may have missed. Each researcher took detailed analytic notes throughout the review of an interview, which they discussed after reviewing each interview. The researchers compared what quotes from each interview they categorized into each theme. Using constant comparison methods, they assigned quotes to each theme and constantly compared the quotes to ensure that each quote fit within the description of the theme ( Glesne and Peshkin, 1992 ). In cases in which quotes were too different from other quotes, a new theme was created. This approach allowed for multiple revisions of the themes and allowed the authors to define a final set of codes; the researchers created a final codebook with refined definitions of emergent themes (the final coding rubric can be found in the Supplemental Material). Once the final codebook was established, the researchers (K.M.C. and L.E.G.) individually coded seven additional interviews (20% of all interviews) using the coding rubric. The researchers compared their codes, and their Cohen’s κ interrater score for these seven interviews was at an acceptable level (κ  =  0.88; Landis and Koch, 1977 ). One researcher (L.E.G.) coded the remaining 28 out of 35 interviews. The researchers determined that data saturation had been reached with the current sample and no further recruitment was needed ( Guest et al. , 2006 ). We report on themes that were mentioned by at least 20% of students in the interview study. In the Supplemental Material, we provide the final coding rubric with the number of participants whose interview reflected each theme ( Hannah and Lautsch, 2011 ). Reporting the number of individuals who reported themes within qualitative data can lead to inaccurate conclusions about the generalizability of the results to a broader population. These qualitative data are meant to characterize a landscape of experiences that students with depression have in undergraduate research rather than to make claims about the prevalence of these experiences ( Glesne and Peshkin, 1992 ). Because inferences about the importance of these themes cannot be drawn from these counts, they are not included in the results of the paper ( Maxwell, 2010 ). Further, the limited number of interviewees made it not possible to examine whether there were trends based on students’ demographics or characteristics of their research experiences (e.g., their specific area of study). Quotes were lightly edited for clarity by inserting clarification brackets and using ellipses to indicate excluded text. Pseudonyms were given to all students to protect their privacy.

The Effect of Depressive Symptoms on Undergraduate Research

We asked students to describe the symptoms associated with their depression. Students described experiencing anxiety that is associated with their depression; this could be anxiety that precedes their depression or anxiety that results from a depressive episode or a period of time when an individual has depression symptoms. Further, students described difficulty getting out of bed or leaving the house, feeling tired, a lack of motivation, being overly self-critical, feeling apathetic, and having difficulty concentrating. We were particularly interested in how students’ symptoms of depression affected their experiences in undergraduate research. During the think-aloud interviews that were conducted before the interview study, graduate and undergraduate students consistently described that their depression affected their motivation in research, their creativity in research, and their productivity in research. Therefore, we explicitly asked undergraduate researchers how, if at all, their depression affected these three factors. We also asked students to describe any additional ways in which their depression affected their research experiences. Undergraduate researchers commonly described five additional ways in which their depression affected their research; for a detailed description of each way students’ research was affected and for example quotes, see Table 2 . Students described that their depression negatively affected their productivity in the lab. Commonly, students described that their productivity was directly affected by a lack of motivation or because they felt less creative, which hindered the research process. Additionally, students highlighted that they were sometimes less productive because their depression sometimes caused them to struggle to engage intellectually with their research or caused them to have difficulty remembering or concentrating; students described that they could do mundane or routine tasks when they felt depressed, but that they had difficulty with more complex and intellectually demanding tasks. However, students sometimes described that even mundane tasks could be difficult when they were required to remember specific steps; for example, some students struggled recalling a protocol from memory when their depression was particularly severe. Additionally, students noted that their depression made them more self-conscious, which sometimes held them back from sharing research ideas with their mentors or from taking risks such as applying to competitive programs. In addition to being self-conscious, students highlighted that their depression caused them to be overly self-critical, and some described experiencing imposter phenomenon ( Clance and Imes, 1978 ) or feeling like they were not talented enough to be in research and were accepted into a lab by a fluke or through luck. Finally, students described that depression often made them feel less social, and they struggled to socially engage with other members of the lab when they were feeling down.

The Effect of Undergraduate Research Experiences on Student Depression

We also wanted to explore how research impacted students’ feelings of depression. Undergraduates described how research both positively and negatively affected their depression. In the following sections, we present aspects of undergraduate research and examine how each positively and/or negatively affected students’ depression using embedded student quotes to highlight the relationships between related ideas.

Lab Environment: Relationships with Others in the Lab.

Some aspects of the lab environment, which we define as students’ physical, social, or psychological research space, could be particularly beneficial for students with depression.

Specifically, undergraduate researchers perceived that comfortable and positive social interactions with others in the lab helped their depression. Students acknowledged how beneficial their relationships with graduate students and postdocs could be.

Marta: “I think always checking in on undergrads is important. It’s really easy [for us] to go a whole day without talking to anybody in the lab. But our grad students are like ‘Hey, what’s up? How’s school? What’s going on?’ (…) What helps me the most is having that strong support system. Sometimes just talking makes you feel better, but also having people that believe in you can really help you get out of that negative spiral. I think that can really help with depression.”

Kelley: “I know that anytime I need to talk to [my postdoc mentors] about something they’re always there for me. Over time we’ve developed a relationship where I know that outside of work and outside of the lab if I did want to talk to them about something I could talk to them. Even just talking to someone about hobbies and having that relationship alone is really helpful [for depression].”

In addition to highlighting the importance of developing relationships with graduate students or postdocs in the lab, students described that forming relationships with other undergraduates in the lab also helped their depression. Particularly, students described that other undergraduate researchers often validated their feelings about research, which in turn helped them realize that what they are thinking or feeling is normal, which tended to alleviate their negative thoughts. Interestingly, other undergraduates experiencing the same issues could sometimes help buffer them from perceiving that a mentor did not like them or that they were uniquely bad at research. In this article, we use the term “mentor” to refer to anyone who students referred to in the interviews as being their mentors or managing their research experiences; this includes graduate students, postdoctoral scholars, lab managers, and primary investigators (PIs).

Abby: “One of my best friends is in the lab with me.  A lot of that friendship just comes from complaining about our stress with the lab and our annoyance with people in the lab. Like when we both agree like, ‘Yeah, the grad students were really off today, it wasn’t us,’ that helps. ‘It wasn’t me, it wasn’t my fault that we were having a rough day in lab; it was the grad students.’ Just being able to realize, ‘Hey, this isn’t all caused by us,’ you know? (…) We understand the stresses in the lab. We understand the details of what each other are doing in the lab, so when something doesn’t work out, we understand that it took them like eight hours to do that and it didn’t work. We provide empathy on a different level.”

Meleana: “It’s great to have solidarity in being confused about something, and it’s just that is a form of validation for me too. When we leave a lab meeting and I look at [another undergrad] I’m like, ‘Did you understand anything that they were just saying?’ And they’re like, ‘Oh, no.’ (…) It’s just really validating to hear from the other undergrads that we all seem to be struggling with the same things.”

Developing positive relationships with faculty mentors or PIs also helped alleviate some students’ depressive feelings, particularly when PIs shared their own struggles with students. This also seemed to normalize students’ concerns about their own experiences.

Alexandra: “[Talking with my PI] is helpful because he would talk about his struggles, and what he faced. A lot of it was very similar to my struggles.  For example, he would say, ‘Oh, yeah, I failed this exam that I studied so hard for. I failed the GRE and I paid so much money to prepare for it.’ It just makes [my depression] better, like okay, this is normal for students to go through this. It’s not an out of this world thing where if you fail, you’re a failure and you can’t move on from it.”

Students’ relationships with others in the lab did not always positively impact their depression. Students described instances when the negative moods of the graduate students and PIs would often set the tone of the lab, which in turn worsened the mood of the undergraduate researchers.

Abby: “Sometimes [the grad students] are not in a good mood. The entire vibe of the lab is just off, and if you make a joke and it hits somebody wrong, they get all mad. It really depends on the grad students and the leadership and the mood that they’re in.”

Interviewer: “How does it affect your depression when the grad students are in a bad mood?”

Abby: “It definitely makes me feel worse. It feels like, again, that I really shouldn’t go ask them for help because they’re just not in the mood to help out. It makes me have more pressure on myself, and I have deadlines I need to meet, but I have a question for them, but they’re in a bad mood so I can’t ask. That’s another day wasted for me and it just puts more stress, which just adds to the depression.”

Additionally, some students described even more concerning behavior from research mentors, which negatively affected their depression.

Julie: “I had a primary investigator who is notorious in the department for screaming at people, being emotionally abusive, unreasonable, et cetera. (…) [He was] kind of harassing people, demeaning them, lying to them, et cetera, et cetera. (…) Being yelled at and constantly demeaned and harassed at all hours of the day and night, that was probably pretty bad for me.”

While the relationships between undergraduates and graduate, postdoc, and faculty mentors seemed to either alleviate or worsen students’ depressive symptoms, depending on the quality of the relationship, students in this study exclusively described their relationships with other undergraduates as positive for their depression. However, students did note that undergraduate research puts some of the best and brightest undergraduates in the same environment, which can result in students comparing themselves with their peers. Students described that this comparison would often lead them to feel badly about themselves, even though they would describe their personal relationship with a person to be good.

Meleana: “In just the research field in general, just feeling like I don’t really measure up to the people around me [can affect my depression]. A lot of the times it’s the beginning of a little spiral, mental spiral. There are some past undergrads that are talked about as they’re on this pedestal of being the ideal undergrads and that they were just so smart and contributed so much to the lab. I can never stop myself from wondering like, ‘Oh, I wonder if I’m having a contribution to the lab that’s similar or if I’m just another one of the undergrads that does the bare minimum and passes through and is just there.’”

Natasha: “But, on the other hand, [having another undergrad in the lab] also reminded me constantly that some people are invested in this and meant to do this and it’s not me. And that some people know a lot more than I do and will go further in this than I will.”

While students primarily expressed that their relationships with others in the lab affected their depression, some students explained that they struggled most with depression when the lab was empty; they described that they did not like being alone in the lab, because a lack of stimulation allowed their minds to be filled with negative thoughts.

Mia: “Those late nights definitely didn’t help [my depression]. I am alone, in the entire building.  I’m left alone to think about my thoughts more, so not distracted by talking to people or interacting with people. I think more about how I’m feeling and the lack of progress I’m making, and the hopelessness I’m feeling. That kind of dragged things on, and I guess deepened my depression.”

Freddy: “Often times when I go to my office in the evening, that is when I would [ sic ] be prone to be more depressed. It’s being alone. I think about myself or mistakes or trying to correct mistakes or whatever’s going on in my life at the time. I become very introspective. I think I’m way too self-evaluating, way too self-deprecating and it’s when I’m alone when those things are really, really triggered. When I’m talking with somebody else, I forget about those things.”

In sum, students with depression highlighted that a lab environment full of positive and encouraging individuals was helpful for their depression, whereas isolating or competitive environments and negative interactions with others often resulted in more depressive feelings.

Doing Science: Experiencing Failure in Research, Getting Help, Receiving Feedback, Time Demands, and Important Contributions.

In addition to the lab environment, students also described that the process of doing science could affect their depression. Specifically, students explained that a large contributor to their depression was experiencing failure in research.

Interviewer: “Considering your experience in undergraduate research, what tends to trigger your feelings of depression?”

Heather: “Probably just not getting things right. Having to do an experiment over and over again. You don’t get the results you want. (…) The work is pretty meticulous and it’s frustrating when I do all this work, I do a whole experiment, and then I don’t get any results that I can use. That can be really frustrating. It adds to the stress. (…) It’s hard because you did all this other stuff before so you can plan for the research, and then something happens and all the stuff you did was worthless basically.”

Julie: “I felt very negatively about myself [when a project failed] and pretty panicked whenever something didn’t work because I felt like it was a direct reflection on my effort and/or intelligence, and then it was a big glaring personal failure.”

Students explained that their depression related to failing in research was exacerbated if they felt as though they could not seek help from their research mentors. Perceived insufficient mentor guidance has been shown to be a factor influencing student intention to leave undergraduate research ( Cooper et al. , 2019c ). Sometimes students talked about their research mentors being unavailable or unapproachable.

Michelle: “It just feels like [the graduate students] are not approachable. I feel like I can’t approach them to ask for their understanding in a certain situation. It makes [my depression] worse because I feel like I’m stuck, and that I’m being limited, and like there’s nothing I can do. So then I kind of feel like it’s my fault that I can’t do anything.”

Other times, students described that they did not seek help in fear that they would be negatively evaluated in research, which is a fear of being judged by others ( Watson and Friend, 1969 ; Weeks et al. , 2005 ; Cooper et al. , 2018 ). That is, students fear that their mentor would think negatively about them or judge them if they were to ask questions that their mentor thought they should know the answer to.

Meleana: “I would say [my depression] tends to come out more in being more reserved in asking questions because I think that comes more like a fear-based thing where I’m like, ‘Oh, I don’t feel like I’m good enough and so I don’t want to ask these questions because then my mentors will, I don’t know, think that I’m dumb or something.’”

Conversely, students described that mentors who were willing to help them alleviated their depressive feelings.

Crystal: “Yeah [my grad student] is always like, ‘Hey, I can check in on things in the lab because you’re allowed to ask me for that, you’re not totally alone in this,’ because he knows that I tend to take on all this responsibility and I don’t always know how to ask for help. He’s like, ‘You know, this is my lab too and I am here to help you as well,’ and just reminds me that I’m not shouldering this burden by myself.”

Ashlyn: “The graduate student who I work with is very kind and has a lot of patience and he really understands a lot of things and provides simple explanations. He does remind me about things and he will keep on me about certain tasks that I need to do in an understanding way, and it’s just because he’s patient and he listens.”

In addition to experiencing failure in science, students described that making mistakes when doing science also negatively affected their depression.

Abby: “I guess not making mistakes on experiments [is important in avoiding my depression]. Not necessarily that your experiment didn’t turn out to produce the data that you wanted, but just adding the wrong enzyme or messing something up like that. It’s like, ‘Oh, man,’ you know? You can get really down on yourself about that because it can be embarrassing.”

Commonly, students described that the potential for making mistakes increased their stress and anxiety regarding research; however, they explained that how other people responded to a potential mistake was what ultimately affected their depression.

Briana: “Sometimes if I made a mistake in correctly identifying an eye color [of a fly], [my PI] would just ridicule me in front of the other students. He corrected me but his method of correcting was very discouraging because it was a ridicule. It made the others laugh and I didn’t like that.”

Julie: “[My PI] explicitly [asked] if I had the dedication for science. A lot of times he said I had terrible judgment. A lot of times he said I couldn’t be trusted. Once I went to a conference with him, and, unfortunately, in front of another professor, he called me a klutz several times and there was another comment about how I never learn from my mistakes.”

When students did do things correctly, they described how important it could be for them to receive praise from their mentors. They explained that hearing praise and validation can be particularly helpful for students with depression, because their thoughts are often very negative and/or because they have low self-esteem.

Crystal: “[Something that helps my depression is] I have text messages from [my graduate student mentor] thanking me [and another undergraduate researcher] for all of the work that we’ve put in, that he would not be able to be as on track to finish as he is if he didn’t have our help.”

Interviewer: “Why is hearing praise from your mentor helpful?”

Crystal: “Because a lot of my depression focuses on everybody secretly hates you, nobody likes you, you’re going to die alone. So having that validation [from my graduate mentor] is important, because it flies in the face of what my depression tells me.”

Brian: “It reminds you that you exist outside of this negative world that you’ve created for yourself, and people don’t see you how you see yourself sometimes.”

Students also highlighted how research could be overwhelming, which negatively affected their depression. Particularly, students described that research demanded a lot of their time and that their mentors did not always seem to be aware that they were juggling school and other commitments in addition to their research. This stress exacerbated their depression.

Rose: “I feel like sometimes [my grad mentors] are not very understanding because grad students don’t take as many classes as [undergrads] do. I think sometimes they don’t understand when I say I can’t come in at all this week because I have finals and they’re like, ‘Why though?’”

Abby: “I just think being more understanding of student life would be great. We have classes as well as the lab, and classes are the priority. They forget what it’s like to be a student. You feel like they don’t understand and they could never understand when you say like, ‘I have three exams this week,’ and they’re like, ‘I don’t care. You need to finish this.’”

Conversely, some students reported that their research labs were very understanding of students’ schedules. Interestingly, these students talked most about how helpful it was to be able to take a mental health day and not do research on days when they felt down or depressed.

Marta: “My lab tech is very open, so she’ll tell us, ‘I can’t come in today. I have to take a mental health day.’ So she’s a really big advocate for that. And I think I won’t personally tell her that I’m taking a mental health day, but I’ll say, ‘I can’t come in today, but I’ll come in Friday and do those extra hours.’ And she’s like, ‘OK great, I’ll see you then.’  And it makes me feel good, because it helps me take care of myself first and then I can take care of everything else I need to do, which is amazing.”

Meleana: “Knowing that [my mentors] would be flexible if I told them that I’m crazy busy and can’t come into work nearly as much this week [helps my depression]. There is flexibility in allowing me to then care for myself.”

Interviewer: “Why is the flexibility helpful given the depression?”

Meleana: “Because sometimes for me things just take a little bit longer when I’m feeling down. I’m just less efficient to be honest, and so it’s helpful if I feel like I can only go into work for 10 hours in a week. It declutters my brain a little bit to not have to worry about all the things I have to do in work in addition the things that I need to do for school or clubs, or family or whatever.”

Despite the demanding nature of research, a subset of students highlighted that their research and research lab provided a sense of stability or familiarity that distracted them from their depression.

Freddy: “I’ll [do research] to run away from those [depressive] feelings or whatever. (…) I find sadly, I hate to admit it, but I do kind of run to [my lab]. I throw myself into work to distract myself from the feelings of depression and sadness.”

Rose: “When you’re sad or when you’re stressed you want to go to things you’re familiar with. So because lab has always been in my life, it’s this thing where it’s going to be there for me I guess. It’s like a good book that you always go back to and it’s familiar and it makes you feel good. So that’s how lab is. It’s not like the greatest thing in the world but it’s something that I’m used to, which is what I feel like a lot of people need when they’re sad and life is not going well.”

Many students also explained that research positively affects their depression because they perceive their research contribution to be important.

Ashlyn: “I feel like I’m dedicating myself to something that’s worthy and something that I believe in. It’s really important because it contextualizes those times when I am feeling depressed. It’s like, no, I do have these better things that I’m working on. Even when I don’t like myself and I don’t like who I am, which is again, depression brain, I can at least say, ‘Well, I have all these other people relying on me in research and in this area and that’s super important.’”

Jessica: “I mean, it just felt like the work that I was doing had meaning and when I feel like what I’m doing is actually going to contribute to the world, that usually really helps with [depression] because it’s like not every day you can feel like you’re doing something impactful.”

In sum, students highlighted that experiencing failure in research and making mistakes negatively contributed to depression, especially when help was unavailable or research mentors had a negative reaction. Additionally, students acknowledged that the research could be time-consuming, but that research mentors who were flexible helped assuage depressive feelings that were associated with feeling overwhelmed. Finally, research helped some students’ depression, because it felt familiar, provided a distraction from depression, and reminded students that they were contributing to a greater cause.

We believe that creating more inclusive research environments for students with depression is an important step toward broadening participation in science, not only to ensure that we are not discouraging students with depression from persisting in science, but also because depression has been shown to disproportionately affect underserved and underrepresented groups in science ( Turner and Noh, 1988 ; Eisenberg et al. , 2007 ; Jenkins et al. , 2013 ; American College Health Association, 2018 ). We initially hypothesized that three features of undergraduate research—research mentors, the lab environment, and failure—may have the potential to exacerbate student depression. We found this to be true; students highlighted that their relationships with their mentors as well as the overall lab environment could negatively affect their depression, but could also positively affect their research experiences. Students also noted that they struggled with failure, which is likely true of most students, but is known to be particularly difficult for students with depression ( Elliott et al. , 1997 ). We expand upon our findings by integrating literature on depression with the information that students provided in the interviews about how research mentors can best support students. We provide a set of evidence-based recommendations focused on mentoring, the lab environment, and failure for research mentors wanting to create more inclusive research environments for students with depression. Notably, only the first recommendation is specific to students with depression; the others reflect recommendations that have previously been described as “best practices” for research mentors ( NASEM, 2017 , 2019 ; Sorkness et al. , 2017 ) and likely would benefit most students. However, we examine how these recommendations may be particularly important for students with depression. As we hypothesized, these recommendations directly address three aspects of research: mentors, lab environment, and failure. A caveat of these recommendations is that more research needs to be done to explore the experiences of students with depression and how these practices actually impact students with depression, but our national sample of undergraduate researchers with depression can provide an initial starting point for a discussion about how to improve research experiences for these students.

Recommendations to Make Undergraduate Research Experiences More Inclusive for Students with Depression

Recognize student depression as a valid illness..

Allow students with depression to take time off of research by simply saying that they are sick and provide appropriate time for students to recover from depressive episodes. Also, make an effort to destigmatize mental health issues.

Undergraduate researchers described both psychological and physical symptoms that manifested as a result of their depression and highlighted how such symptoms prevented them from performing to their full potential in undergraduate research. For example, students described how their depression would cause them to feel unmotivated, which would often negatively affect their research productivity. In cases in which students were motivated enough to come in and do their research, they described having difficulty concentrating or engaging in the work. Further, when doing research, students felt less creative and less willing to take risks, which may alter the quality of their work. Students also sometimes struggled to socialize in the lab. They described feeling less social and feeling overly self-critical. In sum, students described that, when they experienced a depressive episode, they were not able to perform to the best of their ability, and it sometimes took a toll on them to try to act like nothing was wrong, when they were internally struggling with depression. We recommend that research mentors treat depression like any other physical illness; allowing students the chance to recover when they are experiencing a depressive episode can be extremely important to students and can allow them to maximize their productivity upon returning to research ( Judd et al. , 2000 ). Students explained that if they are not able to take the time to focus on recovering during a depressive episode, then they typically continue to struggle with depression, which negatively affects their research. This sentiment is echoed by researchers in psychiatry who have found that patients who do not fully recover from a depressive episode are more likely to relapse and to experience chronic depression ( Judd et al. , 2000 ). Students described not doing tasks or not showing up to research because of their depression but struggling with how to share that information with their research mentors. Often, students would not say anything, which caused them anxiety because they were worried about what others in the lab would say to them when they returned. Admittedly, many students understood why this behavior would cause their research mentors to be angry or frustrated, but they weighed the consequences of their research mentors’ displeasure against the consequences of revealing their depression and decided it was not worth admitting to being depressed. This aligns with literature that suggests that when individuals have concealable stigmatized identities, or identities that can be hidden and that carry negative stereotypes, such as depression, they will often keep them concealed to avoid negative judgment or criticism ( Link and Phelan, 2001 ; Quinn and Earnshaw, 2011 ; Jones and King, 2014 ; Cooper and Brownell, 2016 ; Cooper et al. , 2019b ; Cooper et al ., unpublished data ). Therefore, it is important for research mentors to be explicit with students that 1) they recognize mental illness as a valid sickness and 2) that students with mental illness can simply explain that they are sick if they need to take time off. This may be useful to overtly state on a research website or in a research syllabus, contract, or agreement if mentors use such documents when mentoring undergraduates in their lab. Further, research mentors can purposefully work to destigmatize mental health issues by explicitly stating that struggling with mental health issues, such as depression and anxiety, is common. While we do not recommend that mentors ask students directly about depression, because this can force students to share when they are not comfortable sharing, we do recommend providing opportunities for students to reveal their depression ( Chaudoir and Fisher, 2010 ). Mentors can regularly check in with students about how they’re doing, and talk openly about the importance of mental health, which may increase the chance that students may feel comfortable revealing their depression ( Chaudoir and Quinn, 2010 ; Cooper et al ., unpublished data ).

Foster a Positive Lab Environment.

Encourage positivity in the research lab, promote working in shared spaces to enhance social support among lab members, and alleviate competition among undergraduates.

Students in this study highlighted that the “leadership” of the lab, meaning graduate students, postdocs, lab managers, and PIs, were often responsible for establishing the tone of the lab; that is, if they were in a bad mood it would trickle down and negatively affect the moods of the undergraduates. Explicitly reminding lab leadership that their moods can both positively and negatively affect undergraduates may be important in establishing a positive lab environment. Further, students highlighted how they were most likely to experience negative thoughts when they were alone in the lab. Therefore, it may be helpful to encourage all lab members to work in a shared space to enhance social interactions among students and to maximize the likelihood that undergraduates have access to help when needed. A review of 51 studies in psychiatry supported our undergraduate researchers’ perceptions that social relationships positively impacted their depression; the study found that perceived emotional support (e.g., someone available to listen or give advice), perceived instrumental support (e.g., someone available to help with tasks), and large diverse social networks (e.g., being socially connected to a large number of people) were significantly protective against depression ( Santini et al. , 2015 ). Additionally, despite forming positive relationships with other undergraduates in the lab, many undergraduate researchers admitted to constantly comparing themselves with other undergraduates, which led them to feel inferior, negatively affecting their depression. Some students talked about mentors favoring current undergraduates or talking positively about past undergraduates, which further exacerbated their feelings of inferiority. A recent study of students in undergraduate research experiences highlighted that inequitable distribution of praise to undergraduates can create negative perceptions of lab environments for students (Cooper et al. , 2019). Further, the psychology literature has demonstrated that when people feel insecure in their social environments, it can cause them to focus on a hierarchical view of themselves and others, which can foster feelings of inferiority and increase their vulnerability to depression ( Gilbert et al. , 2009 ). Thus, we recommend that mentors be conscious of their behaviors so that they do not unintentionally promote competition among undergraduates or express favoritism toward current or past undergraduates. Praise is likely best used without comparison with others and not done in a public way, although more research on the impact of praise on undergraduate researchers needs to be done. While significant research has been done on mentoring and mentoring relationships in the context of undergraduate research ( Byars-Winston et al. , 2015 ; Aikens et al. , 2017 ; Estrada et al. , 2018 ; Limeri et al. , 2019 ; NASEM, 2019 ), much less has been done on the influence of the lab environment broadly and how people in nonmentoring roles can influence one another. Yet, this study indicates the potential influence of many different members of the lab, not only their mentors, on students with depression.

Develop More Personal Relationships with Undergraduate Researchers and Provide Sufficient Guidance.

Make an effort to establish more personal relationships with undergraduates and ensure that they perceive that they have access to sufficient help and guidance with regard to their research.

When we asked students explicitly how research mentors could help create more inclusive environments for undergraduate researchers with depression, students overwhelmingly said that building mentor–student relationships would be extremely helpful. Students suggested that mentors could get to know students on a more personal level by asking about their career interests or interests outside of academia. Students also remarked that establishing a more personal relationship could help build the trust needed in order for undergraduates to confide in their research mentors about their depression, which they perceived would strengthen their relationships further because they could be honest about when they were not feeling well or their mentors might even “check in” with them in times where they were acting differently than normal. This aligns with studies showing that undergraduates are most likely to reveal a stigmatized identity, such as depression, when they form a close relationship with someone ( Chaudoir and Quinn, 2010 ). Many were intimidated to ask for research-related help from their mentors and expressed that they wished they had established a better relationship so that they would feel more comfortable. Therefore, we recommend that research mentors try to establish relationships with their undergraduates and explicitly invite them to ask questions or seek help when needed. These recommendations are supported by national recommendations for mentoring ( NASEM, 2019 ) and by literature that demonstrates that both social support (listening and talking with students) and instrumental support (providing students with help) have been shown to be protective against depression ( Santini et al. , 2015 ).

Treat Undergraduates with Respect and Remember to Praise Them.

Avoid providing harsh criticism and remember to praise undergraduates. Students with depression often have low self-esteem and are especially self-critical. Therefore, praise can help calibrate their overly negative self-perceptions.

Students in this study described that receiving criticism from others, especially harsh criticism, was particularly difficult for them given their depression. Multiple studies have demonstrated that people with depression can have an abnormal or maladaptive response to negative feedback; scientists hypothesize that perceived failure on a particular task can trigger failure-related thoughts that interfere with subsequent performance ( Eshel and Roiser, 2010 ). Thus, it is important for research mentors to remember to make sure to avoid unnecessarily harsh criticisms that make students feel like they have failed (more about failure is described in the next recommendation). Further, students with depression often have low self-esteem or low “personal judgment of the worthiness that is expressed in the attitudes the individual holds towards oneself” ( Heatherton et al. , 2003 , p. 220; Sowislo and Orth, 2013 ). Specifically, a meta-analysis of longitudinal studies found that low self-esteem is predictive of depression ( Sowislo and Orth, 2013 ), and depression has also been shown to be highly related to self-criticism ( Luyten et al. , 2007 ). Indeed, nearly all of the students in our study described thinking that they are “not good enough,” “worthless,” or “inadequate,” which is consistent with literature showing that people with depression are self-critical ( Blatt et al. , 1982 ; Gilbert et al. , 2006 ) and can be less optimistic of their performance on future tasks and rate their overall performance on tasks less favorably than their peers without depression ( Cane and Gotlib, 1985 ). When we asked students what aspects of undergraduate research helped their depression, students described that praise from their mentors was especially impactful, because they thought so poorly of themselves and they needed to hear something positive from someone else in order to believe it could be true. Praise has been highlighted as an important aspect of mentoring in research for many years ( Ashford, 1996 ; Gelso and Lent, 2000 ; Brown et al. , 2009 ) and may be particularly important for students with depression. In fact, praise has been shown to enhance individuals’ motivation and subsequent productivity ( Hancock, 2002 ; Henderlong and Lepper, 2002 ), factors highlighted by students as negatively affecting their depression. However, something to keep in mind is that a student with depression and a student without depression may process praise differently. For a student with depression, a small comment that praises the student’s work may not be sufficient for the student to process that comment as praise. People with depression are hyposensitive to reward or have reward-processing deficits ( Eshel and Roiser, 2010 ); therefore, praise may affect students without depression more positively than it would affect students with depression. Research mentors should be mindful that students with depression often have a negative view of themselves, and while students report that praise is extremely important, they may have trouble processing such positive feedback.

Normalize Failure and Be Explicit about the Importance of Research Contributions.

Explicitly remind students that experiencing failure is expected in research. Also explain to students how their individual work relates to the overall project so that they can understand how their contributions are important. It can also be helpful to explain to students why the research project as a whole is important in the context of the greater scientific community.

Experiencing failure has been thought to be a potentially important aspect of undergraduate research, because it may provide students with the potential to develop integral scientific skills such as the ability to navigate challenges and persevere ( Laursen et al. , 2010 ; Gin et al. , 2018 ; Henry et al. , 2019 ). However, in the interviews, students described that when their science experiments failed, it was particularly tough for their depression. Students’ negative reaction to experiencing failure in research is unsurprising, given recent literature that has predicted that students may be inadequately prepared to approach failure in science ( Henry et al. , 2019 ). However, the literature suggests that students with depression may find experiencing failure in research to be especially difficult ( Elliott et al. , 1997 ; Mongrain and Blackburn, 2005 ; Jones et al. , 2009 ). One potential hypothesis is that students with depression may be more likely to have fixed mindsets or more likely to believe that their intelligence and capacity for specific abilities are unchangeable traits ( Schleider and Weisz, 2018 ); students with a fixed mindset have been hypothesized to have particularly negative responses to experiencing failure in research, because they are prone to quitting easily in the face of challenges and becoming defensive when criticized ( Forsythe and Johnson, 2017 ; Dweck, 2008 ). A study of life sciences undergraduates enrolled in CUREs identified three strategies of students who adopted adaptive coping mechanisms, or mechanisms that help an individual maintain well-being and/or move beyond the stressor when faced with failure in undergraduate research: 1) problem solving or engaging in strategic planning and decision making, 2) support seeking or finding comfort and help with research, and 3) cognitive restructuring or reframing a problem from negative to positive and engaging in self encouragement ( Gin et al. , 2018 ). We recommend that, when undergraduates experience failure in science, their mentors be proactive in helping them problem solve, providing help and support, and encouraging them. Students also explained that mentors sharing their own struggles as undergraduate and graduate students was helpful, because it normalized failure. Sharing personal failures in research has been recommended as an important way to provide students with psychosocial support during research ( NASEM, 2019 ). We also suggest that research mentors take time to explain to students why their tasks in the lab, no matter how small, contribute to the greater research project ( Cooper et al. , 2019a ). Additionally, it is important to make sure that students can explain how the research project as a whole is contributing to the scientific community ( Gin et al. , 2018 ). Students highlighted that contributing to something important was really helpful for their depression, which is unsurprising, given that studies have shown that meaning in life or people’s comprehension of their life experiences along with a sense of overarching purpose one is working toward has been shown to be inversely related to depression ( Steger, 2013 ).

Limitations and Future Directions

This work was a qualitative interview study intended to document a previously unstudied phenomenon: depression in the context of undergraduate research experiences. We chose to conduct semistructured interviews rather than a survey because of the need for initial exploration of this area, given the paucity of prior research. A strength of this study is the sampling approach. We recruited a national sample of 35 undergraduates engaged in undergraduate research at 12 different public R1 institutions. Despite our representative sample from R1 institutions, these findings may not be generalizable to students at other types of institutions; lab environments, mentoring structures, and interactions between faculty and undergraduate researchers may be different at other institution types (e.g., private R1 institutions, R2 institutions, master’s-granting institutions, primarily undergraduate institutions, and community colleges), so we caution against making generalizations about this work to all undergraduate research experiences. Future work could assess whether students with depression at other types of institutions have similar experiences to students at research-intensive institutions. Additionally, we intentionally did not explore the experiences of students with specific identities owing to our sample size and the small number of students in any particular group (e.g., students of a particular race, students with a graduate mentor as the primary mentor). We intend to conduct future quantitative studies to further explore how students’ identities and aspects of their research affect their experiences with depression in undergraduate research.

The students who participated in the study volunteered to be interviewed about their depression; therefore, it is possible that depression is a more salient part of these students’ identities and/or that they are more comfortable talking about their depression than the average population of students with depression. It is also important to acknowledge the personal nature of the topic and that some students may not have fully shared their experiences ( Krumpal, 2013 ), particularly those experiences that may be emotional or traumatizing ( Kahn and Garrison, 2009 ). Additionally, our sample was skewed toward females (77%). While females do make up approximately 60% of students in biology programs on average ( Eddy et al. , 2014 ), they are also more likely to report experiencing depression ( American College Health Association, 2018 ; Evans et al. , 2018 ). However, this could be because women have higher rates of depression or because males are less likely to report having depression; clinical bias, or practitioners’ subconscious tendencies to overlook male distress, may underestimate depression rates in men ( Smith et al. , 2018 ). Further, females are also more likely to volunteer to participate in studies ( Porter and Whitcomb, 2005 ); therefore, many interview studies have disproportionately more females in the data set (e.g., Cooper et al. , 2017 ). If we had been able to interview more male students, we might have identified different findings. Additionally, we limited our sample to life sciences students engaged in undergraduate research at public R1 institutions. It is possible that students in other majors may have different challenges and opportunities for students with depression, as well as different disciplinary stigmas associated with mental health.

In this exploratory interview study, we identified a variety of ways in which depression in undergraduates negatively affected their undergraduate research experiences. Specifically, we found that depression interfered with students’ motivation and productivity, creativity and risk-taking, engagement and concentration, and self-perception and socializing. We also identified that research can negatively affect depression in undergraduates. Experiencing failure in research can exacerbate student depression, especially when students do not have access to adequate guidance. Additionally, being alone or having negative interactions with others in the lab worsened students’ depression. However, we also found that undergraduate research can positively affect students’ depression. Research can provide a familiar space where students can feel as though they are contributing to something meaningful. Additionally, students reported that having access to adequate guidance and a social support network within the research lab also positively affected their depression. We hope that this work can spark conversations about how to make undergraduate research experiences more inclusive of students with depression and that it can stimulate additional research that more broadly explores the experiences of undergraduate researchers with depression.

Important note

If you or a student experience symptoms of depression and want help, there are resources available to you. Many campuses provide counseling centers equipped to provide students, staff, and faculty with treatment for depression, as well as university-dedicated crisis hotlines. Additionally, there are free 24/7 services such as Crisis Text Line, which allows you to text a trained live crisis counselor (Text “CONNECT” to 741741; Text Depression Hotline , 2019 ), and phone hotlines such as the National Suicide Prevention Lifeline at 1-800-273-8255 (TALK). You can also learn more about depression and where to find help near you through the Anxiety and Depression Association of American website: https://adaa.org ( Anxiety and Depression Association of America, 2019 ) and the Depression and Biopolar Support Alliance: http://dbsalliance.org ( Depression and Biopolar Support Alliance, 2019 ).

ACKNOWLEDGMENTS

We are extremely grateful to the undergraduate researchers who shared their thoughts and experiences about depression with us. We acknowledge the ASU LEAP Scholars for helping us create the original survey and Rachel Scott for her helpful feedback on earlier drafts of this article. L.E.G. was supported by a National Science Foundation (NSF) Graduate Fellowship (DGE-1311230) and K.M.C. was partially supported by a Howard Hughes Medical Institute (HHMI) Inclusive Excellence grant (no. 11046) and an NSF grant (no. 1644236). Any opinions, findings, conclusions, or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the NSF or HHMI.

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Submitted: 4 November 2019 Revised: 24 February 2020 Accepted: 6 March 2020

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• Acta Biomed
• v.92(3); 2021

A breakthrough in research on depression screening: from validation to efficacy studies

Luigi costantini.

1 Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

Alessandra Costanza

2 Department of Psychiatry, Faculty of Medicine, University of Geneva (UNIGE), Geneva, Switzerland

3 Department of Psychiatry, ASO Santi Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, Italy

4 Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy

Andrea Aguglia

5 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, Genoa, Italy

6 IRCCS Ospedale Policlinico San Martino, Genoa, Italy

Andrea Escelsior

Gianluca serafini, mario amore, andrea amerio.

In the last two decades the awareness of depression as a public health issue has increased and the literature has flourished towards its primary and secondary prevention. Whereas timely targeting of depression risk factors is a frontier towards reducing the incidence of the disorder, nowadays the early diagnosis is of primary importance. Screening depressive disorders is paramount, since there are several types of depression. Besides, early diagnosis would improve the outcome of treatment, reduce the frequency of relapses and generally lead to higher levels of quality of life. We highlight the feasibility of depression screening in primary care and the need of a comprehensive public health approach. ( www.actabiomedica.it )

Introduction

Depression affects more than two hundred sixty million people across the world and is a leading cause of disability ( 1 ). The estimated prevalence of depressive disorders in 2016 was 3,627 per 100,000 and in the last decade the number of all-age years lived with disability (YLDs) increased of 14% ( 2 , 3 ). Resulting from a complex interaction of social, psychological and biological factors, depressive symptoms first appear during the late teens to mid-20s, they are often overlooked and untreated and they are accompanied by poor functioning. At its worst, depression can lead to suicide, the second leading cause of death in 15-29-year-olds ( 4 , 5 ).

Depressive disorders are independent risk factors for chronic diseases, such as cardiovascular diseases and diabetes, and are associated with elevated risk of early death ( 6 , 7 ). In 2016, depressive disorders caused the loss of an overall age-adjusted rate of 526 per 100,000 disability-adjusted life years (DALYs), being the most contributor to DALYs loss among mental and behavioural disorders ( 2 ). Encouraging self-care and positive lifestyle changes especially in vulnerable segments of population can help improve, resolve or prevent depression ( 8 , 9 ).

Reduced educational achievements, poor financial success and role performance, higher amount of days out of role, and increased risk of job loss represent the social costs of depression ( 10 ). Depressive disorders bring about direct and indirect costs ( 11 ). The overall costs of depression in Europe lay around €92 billion a year, much of which caused by loss of productivity ( 12 ).

In the last two decades the awareness of depression as a public health issue has increased and the literature has flourished towards its primary and secondary prevention ( 13 ). Whereas timely targeting of depression risk factors is a frontier towards reducing the incidence of the disorder, nowadays the early diagnosis is of primary importance ( 14 ).

Screening depressive disorders is paramount, as there are several types of depression that can affect the most vulnerable individuals ( 15 , 16 ).

For example, bipolar disorder usually presents with depressive symptoms and it is common to misidentify it with major depressive disorder, a diagnosis that can negatively influence the pharmacological treatment worsening the course of illness ( 17 ) and promoting mood instability especially in presence of comorbidities ( 18 - 20 ).

Therefore, early diagnosis would improve the outcome of treatment, reduce the frequency of relapses and generally lead to higher levels of quality of life.

The present paper would like to highlight the feasibility of depression screening in primary care and the need of a comprehensive public health approach in order to develop an in-field knowledge of the real outcomes of depression screening.

Is depression screening feasible?

In the last two decades, different screening tools have been validated in primary care settings. Recent systematic reviews and meta-analyses provided an overview to the psychometric properties of widely applied depression screening tools defining the Patient Health Questionnaire 9 (PHQ-9) as the most valid one in terms of sensitivity and specificity ( 21 , 22 ). Short Likert-scale questionnaire, like PHQ-9 and PHQ-8, have been successfully used ( 23 ), while scarce evidence accounts for the widespread primary care use of ultra-short screening tools (i.e. PHQ-2) ( 21 ).

Screening tools are rather easy to use, since they consist in structured questionnaires charted either by health care professionals, caregivers, or patients themselves. PHQ-9 is being used in higher income countries as well as in the lower ones ( 21 ). Depression screening fits the need of low-resource settings by promoting the task sharing ( 24 ).

Theoretically speaking, depression screening implies very low costs, since the process could be easily performed in the context of the routine activity of general practices. Nevertheless, few studies analysed the cost-effectiveness of the screening process.

Some researchers rose concerns on the lack of evidence of screening harmlessness: the psychological consequences of a false positive, as well as the risks and costs of over-diagnosis, require careful in-field analysis ( 25 ).

Standardising the diagnostic approach to psychiatric disorders is challenging. The more common screening tools have been developed for adult patients use in Western, high-income countries. Discrepancies have therefore come to light between rigid symptom definitions and different framework of illness depending on the social and cultural background as well as the age of the patients ( 26 , 27 ). Screening tools are flexible enough to be adapted to specific situations.

However, homogeneity must be a priority in order to produce high quality evidence.

The answer to the issues above, and many others, go along with two assumptions. First, screening is useless without in-depth diagnostic confirmation. The results of screening should never be proposed as a diagnosis. On the contrary, the screening process should always include the referral to a Mental Health Professional. Second, our knowledge of screening functioning is limited by the lack of longitudinal studies. Cross-sectional studies have been able to widely validate the screening tools in different countries. From now on, research should be directed toward a better comprehension of the impact of the screening on the efficacy of treatment and the quality of health services.

Screening: a first step against stigma and toward curing

Depression is a pathology largely still affected by stigma in many cultures ( 2 ). The administration of a questionnaire might help primary care practitioners to break the wall of stigma.

Screening tools, as the PHQ-9, offer a clear description of the main features of depressive disorders. Patients charting the questionnaire might discover aspects of the illness they have never known. Thus, patients would be able to recognize depressive symptoms in themselves and others and act as caregivers. PHQ-9 administration to adolescents highlighted the increased self-awareness of depressive symptoms ( 27 ). Therefore, depression screening might become a direct way towards therapeutic education, health literacy and patients’ empowerment.

Directions for future research

The accuracy of screening tools has been already widely investigated ( 21 ). Actual research questions are represented by the efficacy of screening protocols, the impact of screening on patients’ life and the cost-effectiveness of a widespread screening program.

It is clear that cross-sectional studies are not adequate to answer those questions and longitudinal protocols must be implemented. Screening protocols should be standardised in order to increase homogeneity across different studies ( 20 ). Some lessons can be learned from the literature to be applied in future studies.

The available literature suggests the use of PHQ-8 as a standard screening tool for depression in primary care ( 23 ). PHQ-8 is widely used, straightforward and highly consistent with the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders. A two-stage screening model has been implemented by several studies and should be adopted. Semi-structured diagnostic interview, i.e., the SCID and the SCAN, performed the most accurate diagnoses ( 28 ).

The questionnaire can be charted either by the patients themselves or by general practitioners, health care professionals, and lay health workers. The demographic questionnaire should include the past medical history with special stress on mental disorders, known depression risk factors as housing, instruction, employment, and health insurance coverage. Questionnaires should be adapted to be easily understood by all the patients, according to their age, culture and educational level.

Longitudinal protocols should include the most appropriate treatment for each case. Patients should be followed up and outcomes as reduction of morbidity and mortality, reduced DALYs, and increased social functioning, should be measured. The general practitioners would have a key role in explaining the process, revising the screening results, deepening the clinical investigation and reassuring about the possibility of false positives.

Digital technologies have been effectively implemented in only few studies ( 29 ). Technology could streamline procedures and make screening sustainable to the organizational needs of primary care practices and speed up data processing ( 30 ). Organizational factors, cost-effectiveness and compliance predictors should be properly included in research protocols.

Conclusions

The gap in evidence of primary care depression screening concerns its efficacy rather than its validity or safety. Different skills are necessary to produce high quality scientific evidence. We encourage epidemiologists, psychiatrists, and general practitioners to team up, in accordance with the translational research approach, to address the research questions about depression prevention.

Acknowledgements:

This work was developed within the framework of the DINOGMI Department of Excellence of MIUR 2018-2022 (Law 232/2016).

Conflicts of interest:

Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article.

Author contributions:

Authors LC, AC, AO, AAg, AE, and AAm wrote the first draft of the manuscript. GS and MA carefully revised the final version of the manuscript. Our manuscript has been approved by all authors.

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