Depression is one of the most common mental health disorders. In 2017, over 19% of the UK population showed symptoms of either depression or anxiety. Globally, 280 million are reported to have depression.¹ Depression can be debilitating. Due to its prevalence in society, identifying the causes of depression has been of interest to psychologists for decades. We will discuss the two leading theories of depression that guide contemporary treatment approaches.
Depression is one of the most common mental health disorders, freepik.com
What is depression?
How can we tell when the low mood becomes clinical depression? To diagnose depression, clinicians use diagnostic manuals like the International Classification of Diseases 10 (ICD 10) and the Diagnostic and Statistical Manual of Mental Disorders (DSM). Let’s examine the criteria outlined for a depression diagnosis.
The characteristics of clinical depression
The International Classification of Diseases lists ten symptoms of depression based on which an individual is diagnosed. If a patient has experienced at least four of these symptoms in the past two weeks, they can be diagnosed with mild depression; experience of five to six suggests moderate depression and more than seven symptoms point to severe depression.
The frequency of symptoms is also essential for making diagnoses. Here is an overview of depressive symptoms from the ICD.
- Depressed mood for most of the day and almost every day
- Decreased energy and fatigue
- Loss of interest or pleasure in activities that are usually enjoyable
- Changes in appetite and weight
- Changes in sleep patterns or sleep disturbance (e.g. sleeping more or less than usual)
- Decrease in confidence and self-esteem
- Feelings of guilt, excessive self-criticism
- Thoughts of death and suicide
- Decreased ability to concentrate or think
- Excessive agitation or retardation (slower movements)
We can distinguish between bipolar and unipolar depression. Bipolar depression includes experiences of both depressive episodes and episodes of mania or hypomania (emotional highs), while unipolar depression only involves experiences of depressive episodes without manic episodes.
Key statistics on depression
- The reported prevalence of depression varies. It is estimated that 4.5% of the adult population in the UK suffers from depression.
- However, this number is likely larger. In 2017, 17% of the adult population was prescribed antidepressants.
- Statistics also show differences in prevalence depending on gender (higher rates of depression tend to be reported for women) and age (higher rates of depression have been reported in groups of older adults).
- Differences have also been reported based on ethnicity. Black women are more at risk of experiencing depression than White women.
Recovery from depression is common. According to NHS 2017-18 statistics, over 50% of treatments for depression end with the patient’s recovery.
What are the psychological theories of depression?
Traditionally, the biological theory of depression argues that biological dysfunction in the body causes depression. Often you can hear that mental illness results from a ‘chemical imbalance’ in the brain.
However, there’s little evidence that biological factors cause depression. The psychological theory of depression looks beyond biological correlates and focuses on cognitive and behavioural processes in depression.
Both approaches have informed treatment approaches, the biological theory has led to the development of antidepressant medications, and the psychological theory has informed therapeutic treatment approaches like cognitive behavioural therapy.
Psychological theories of depression
Psychological theories of depression focus on cognition and behaviour in regulating mood. This approach stresses the influence of our past experiences (nurture) in shaping our thought patterns that can result in depressive symptoms.
Past experiences can cause people to develop negative schemas – biased patterns of thinking about ourselves, others and the world around us, maintaining psychological distress. The psychological theories of depression are supported by the effectiveness of therapies like CBT, which aim to challenge negative schemas in treating depressive symptoms.
Negative schemas maintain depressive symptoms, freepik.com
Biological theories of depression
Biological theories of depression identify biological factors like genes, brain structure, and the function of neurotransmitters and hormones as the cause of depression. Biological theories stress the influence of nature in causing depression.
Biological theories focus on physical factors that correlate with depression, flaticon.com
Depletion of neurotransmitters: the monoamine theory of depression
The monoamine theory of depression predicts that depression results from reduced levels of monoamines like serotonin. Serotonin is a neurotransmitter. It functions as a messenger in the brain and is associated with regulating functions that are affected in depressed individuals, like mood and sleep.
Based on this theory, antidepressants (SSRIs) have been developed and shown to reduce depressive symptoms in some patients. A significant criticism of antidepressants is that their effectiveness is not much higher than a placebo, and they can cause serious side effects in some patients. However, antidepressant treatment can be more accessible than therapy for many patients.
Relying only on biological treatments for depression can be considered reductionist, as antidepressants focus only on changing the levels of neurotransmitters but don’t necessarily address the underlying psychological causes of depression.
Behavioural theory of depression
Behavioural theory of depression proposes that depressive symptoms are perpetuated by avoidance behaviour. Depressed individuals will often avoid potentially rewarding activities and become withdrawn, making their symptoms worse. One way this approach influences treatment is by informing behavioural interventions like Behavioural Activation, which encourages clients to schedule pleasant activities. Rather than focusing on changing one’s thoughts and feelings, this approach attempts to increase the amount of positive experiences in one’s daily life, which can in turn influence one’s mental state.
Ann was experiencing low mood and has become socially withdrawn. During Behavioural Activation, she was encouraged to schedule a meeting with a friend. The meeting turned out to be a very pleasant experience for her, and now she is considering meeting with friends more often. This experience positively reinforced engagement in social activities, which can be an important step for Ann in her recovery from depression.
The social rank theory of depression
Stevens and Price developed the social rank theory of depression. They proposed depression is an evolutionary adaptation; it allows individuals that fell to lower social ranks to accept their position.
Depressive symptoms prevent weaker individuals from engaging in conflicts that threaten their survival. Accepting one’s lower position allows people to save resources instead of spending energy on conflicts and trying to regain a lost social rank, which could result in greater losses upon defeat.
While some literature findings align with this theory, it has been criticised for reductionism. In this case, depression is reduced to only evolutionary influences and situations when one loses social status. Still, we know depression is not limited to these situations and can result from a variety of life events.
Tandoc et al. (2015) survey study of 736 college students found that Facebook use was negatively correlated with depression unless accompanied by envy.
The level of envy predicted depressive symptoms among Facebook users. As the social rank theory predicted, feelings of envy (perceiving yourself as a lower rank) predicted depressive symptoms.
Cognitive theory of depression
The ABC Model of clinical depression proposed by Ellis (1957) argues that distorted irrational beliefs (B) cause distress, forming as a response to an activating event (A). According to this model, depression is the consequence (C) of irrational beliefs.
Irrational beliefs can form automatically, and we may not even realise that we hold them. Irrational beliefs can include catastrophising, ‘black and white’ thinking and personalising.
Catastrophising occurs when we interpret a difficult event as worse than it is.
For example, if you didn’t have time to prepare for a test, a catastrophising belief in that situation could be that you will fail it and all your exams as well, and you’ll never be able to achieve anything in life.
Therapy helps individuals identify their irrational beliefs and challenges them so they can replace them with more adaptive ones.
Since our cognition and behaviour can be influenced by outside events or our own physiology, the ABC model supports the idea that we don’t always have free will when we make decisions about our behaviour. This puts into question how responsible, people experiencing cognitive distortions are for their behaviour.
Beck’s negative cognitive triad
Aaron Beck (1967) proposed three main types of beliefs that maintain depressive symptoms. These include negative thoughts and beliefs about the self, the world, and the future. The three types of negative beliefs can be mutually reinforcing; for example, a negative belief about the world can strengthen a negative belief about the future.
Negative belief about oneself: ‘I am a failure’ or ‘I am a bad person’
Negative beliefs about the world: ‘Others hate me’ or ‘Others want to see me fail’
Negative beliefs about the future: ‘I will never find a partner’ or ‘I will never succeed’
Beck proposed different types of cognitive distortions commonly present in depressed individuals.
- Beck’s cognitive distortions include minimisation of positive events, overgeneralising a single event, magnification of negative events, personalisation (feeling guilty for things you shouldn’t), arbitrary inference (making conclusions that fit with negative beliefs without sufficient evidence) and selective abstraction (focusing only on negative elements of a situation and making conclusions based on that).
Seligman’s negative attributions
According to Seligman, depression is an outcome of learned helplessness. Depressed individuals feel like no matter what they do, they cannot control the negative events in their life.
Learned helplessness is maintained by believing that we are the cause of the failure; we cannot change the cause, it’s stable, and the failure is global. We will always fail in every situation. By challenging these thoughts, individuals can learn to feel more in control of their life and reduce the sense of learnt helplessness associated with depressive symptoms.
Theories of depression – Key takeaways
- Clinicians use diagnostic manuals like the
International Classification of Diseases 10 (ICD) and
Diagnostic and Statistical Manual of Mental Disorders (DSM)
to diagnose depression.
- Unipolar depression involves only depressive episodes, while bipolar depression involves both manic and depressive episodes.
- Depression is one of the most common mental health disorders. The prevalence of depression in UK adults is around 4.5%. The prevalence varies across ages, genders and ethnicities. Most people recover from depressive episodes following treatment.
- Biological theories of depression focus on physical correlates of depression, like genes, brain structure or neurotransmitters.
he monoamine theory of depression stresses the role of
he monoamine theory of depression stresses the role of neurotransmitters , and the social rank theory of depression emphasises the influence of evolutionary factors.
- Psychological theories of depression focus on irrational beliefs and negative thoughts that maintain depressive symptoms. The ABC model proposes that depression is the consequence of irrational beliefs.
- Beck’s negative cognitive triad highlights the three types of negative beliefs in depression: negative beliefs about oneself, the world and the future. Seligman identified negative attributions that maintain feelings of learnt helplessness associated with depression.
1. World Health Organization, Depression, 13 September 2021
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.
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Table 2 Recent depletion studies comparing acute tryptophan depletion drink with amino acid balance drink (sham drink) – characteristics and results.
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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 . The large genetic analysis of the effect of SERT polymorphisms on depression, satisfied 88% of the STREGA quality criteria .
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 . 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-HT1A 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-HT1A receptors [11, 34]. 5-HT1A receptors, known as auto-receptors, inhibit the release of serotonin pre-synaptically , therefore, if depression is the result of reduced serotonin activity caused by abnormalities in the 5-HT1A receptor, people with depression would be expected to show increased activity of 5-HT1A receptors compared to those without .
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-HT1A 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 , 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 .
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 . 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 . 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 . 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 . 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.
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 .
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 . 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 . 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 . 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 .
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 . 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  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) . However, the two recent large, high-quality studies did not find an interaction between the SERT gene and stress in depression (Border et al  and Culverhouse et al.)  (see Table 1).
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.
Table 3 Modified GRADE ratings for each study and the overall rating of strength of evidence.
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