PSY 3740 Module 6 Emotions and Psychological Disorders Paper: Candidate Genes, Replication and the Dopamine Hypothesis Example

A Gene for Depression? Biology, Replication and the Dopamine Hypothesis

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Bachelor of Arts in Psychology, Thomas Edison State University

PSY-3740: Physiological Psychology

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Month Day, Year

A Gene for Depression? Biology, Replication and the Dopamine Hypothesis

Introduction

A relative of mine has struggled with depression for years. A friend told her that a genetic test showed she had "the depression gene," a short version of the serotonin transporter gene, and that this explained everything. My relative felt both relieved and hopeless: relieved that it was not her fault, hopeless because genes cannot be changed. This final module of physiological psychology examines the biology of emotion and psychological disorders, and this paper asks what the evidence actually shows.

The Biology of Emotion

Earlier modules described the amygdala's role in detecting threat, the hypothalamus's control of bodily responses and the stress hormone system. Emotional disorders involve these systems: anxiety disorders are associated with heightened amygdala responses, and depression with changes in stress hormone regulation, reward systems and the prefrontal cortex's control of emotion. But identifying associations is different from identifying causes.

A Famous Gene-by-Environment Finding

Caspi et al. (2003) followed a birth cohort of more than 1,000 people in Dunedin, New Zealand, from childhood into adulthood. They examined a variation in the promoter region of the serotonin transporter gene, which comes in short and long forms. People with one or two short forms who experienced several stressful life events between ages 21 and 26 were more likely to develop depression and suicidal thoughts than people with two long forms who experienced the same stress. Among people with few stressful events, the gene made little difference. The study was celebrated as evidence that genes and environment interact, and it inspired hundreds of follow-up studies.

The Replication Problem

Border et al. (2019) tested 18 candidate genes that had been most studied in depression research, including the serotonin transporter variation, using data from very large samples, up to several hundred thousand people. They found no support for the candidate genes' effects on depression, either alone or in interaction with environmental factors such as childhood trauma or recent stress, beyond what would be expected by chance. The authors concluded that the early candidate gene studies, including the serotonin transporter findings, were likely false positives produced by small samples and flexible analyses, and that depression is influenced by thousands of genetic variants, each with a tiny effect.

What This Means for My Relative

The genetic test result that my relative heard about does not, according to the best current evidence, explain her depression. Depression is moderately heritable, as twin studies discussed earlier show, but this heritability is spread across a very large number of genes, none of which acts like "the depression gene." Her experiences, her current stress, her relationships and her biology all play roles, and none of them makes recovery impossible.

The Dopamine Hypothesis of Schizophrenia

Biological explanations have fared better in some disorders. Howes and Kapur (2009) proposed a third version of the dopamine hypothesis of schizophrenia. Earlier versions focused on dopamine receptors and on too much or too little dopamine in different brain regions. Drawing on brain imaging studies, they argued that the best-supported abnormality is increased dopamine synthesis and release in the striatum, measured before the dopamine reaches receptors. Many genetic and environmental risks, such as early life adversity, migration and cannabis use, may converge on this final common pathway. Excess dopamine, they proposed, causes people to attach unusual importance to ordinary experiences, a process called aberrant salience, from which delusions may develop as explanations. Antipsychotic medications block dopamine receptors and reduce this salience, though they do not correct the underlying overproduction.

The Chemical Imbalance Story

The popular claim that depression is caused by a simple "chemical imbalance" of serotonin is also not well supported. Antidepressants affect serotonin quickly, yet improvement takes weeks, and research points to more complex changes in brain networks, stress systems and neural plasticity. Biological treatments can help without the disorder being a simple deficiency.

Talking About Biology Accurately

How biological explanations are framed matters. Some research suggests that telling people their depression is purely biological can reduce self-blame but may also increase pessimism about recovery. A more accurate message is that biology, experience and environment interact, and that therapy, medication, exercise and social support can all change the brain.

Anxiety and the Amygdala

Anxiety disorders offer another example of biological research. Brain imaging studies often find heightened amygdala responses to threatening cues in people with anxiety disorders and weaker regulation from the prefrontal cortex. Effective therapies, such as exposure therapy, appear to strengthen the prefrontal regulation of fear, showing that psychological treatment changes brain function.

Polygenic Scores

Researchers now combine the effects of thousands of genetic variants into polygenic scores. For depression, these scores predict only a small share of risk and cannot diagnose anyone, which is why commercial tests claiming to identify a person's depression gene should be treated with skepticism.

Hope and Treatment

Understanding that the brain is changeable helps convey realistic hope. Therapy, medication, exercise and social connection all produce measurable changes in brain function, and most people with depression improve with treatment.

Stigma

How disorders are explained also affects stigma, and accurate, balanced explanations can reduce it.

Limits

Border and colleagues' samples relied partly on self-reported depression, though their conclusions held across measures. The dopamine hypothesis explains psychotic symptoms better than the cognitive and motivational problems of schizophrenia.

Conclusion

Caspi and colleagues' gene-by-environment finding inspired a field, Border and colleagues' large analysis showed that it and other candidate gene findings do not hold up and Howes and Kapur's dopamine hypothesis shows that some biological models are well supported. Biology matters in psychological disorders, but not as single genes or simple imbalances, and understanding that complexity is both more accurate and more hopeful for people like my relative.

References

Border, R., Johnson, E. C., Evans, L. M., Smolen, A., Berley, N., Sullivan, P. F., & Keller, M. C. (2019). No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples. American Journal of Psychiatry, 176(5), 376-387. https://doi.org/10.1176/appi.ajp.2018.18070881

Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., & Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301(5631), 386-389. https://doi.org/10.1126/science.1083968

Howes, O. D., & Kapur, S. (2009). The dopamine hypothesis of schizophrenia: Version III, the final common pathway. Schizophrenia Bulletin, 35(3), 549-562. https://doi.org/10.1093/schbul/sbp006