Diathesis–Stress Model

The term “diathesis” comes from the Greek word for disposition (“diathesis”).

In the diathesis-stress model, this disposition is called a diathesis. It is a factor that makes a disorder more likely to develop after a stressful life event.

A diathesis can be a biological factor, like abnormal variations in one or more genes.

Other factors can also count as diatheses, even if they are not genetically hard-wired. They simply need to form early and stay stable across a person’s life.

For example, traumatic early life experiences, such as the loss of a parent, can act as longstanding predispositions to a psychological disorder. In addition, personality traits like high neuroticism are sometimes also referred to as diatheses.

Finally, diatheses can be situational, such as living in a low-income household or having a parent with mental illness (Theodore, 2020).

Some factors matter more for certain disorders than others. A genetic variation might raise the risk of depression, for example, but not schizophrenia.

Not all diatheses are equal. Some genetic variations only slightly raise the risk of a mental disorder. Others raise that risk substantially.

As a result, in the diathesis-stress model, different diatheses give rise to different responses to stress.

To conceptualize this, consider the “cup analogy.” Imagine several cups filled with different amounts of marbles; when water is poured into those cups, the cups with more marbles will overflow more easily.

Diatheses are like marbles, and stress is like water. The greater the diathesis, the less stress is needed to cause “overflow”, or mental illness (Theodore, 2020).

Diathesis-Stress Model

The diathesis-stress model is a concept in psychiatry and psychopathology that offers a theory of how psychological disorders emerge.

It intervenes in the debate about “nature vs. nurture” in psychopathology. This debate asks whether disorders are predominantly caused by innate biological factors (“nature”) or by social and situational factors (“nurture”). The diathesis-stress model provides an account of how both might coincide to cause a disorder.

According to the diathesis-stress model, a psychological disorder requires two things. First, a diathesis: an innate predisposition to that disorder. Second, stress: a set of challenging life circumstances that triggers its development.

Furthermore, individuals with greater innate predispositions to a disorder may require less stress to trigger that disorder, and vice versa.

In this way, the diathesis-stress model explains how psychological disorders might be related to both nature and nurture and how those two components might interact with one another (Broerman, 2017).

The diathesis-stress model is a modern development of a longstanding debate about the causes of mental illness. This debate began as early as ancient Greece and Rome when theories included imbalances in bodily fluids and interactions with the devil.

Later, this evolved into the “nature vs. nurture” debate. By the late 20th century, it became clear that nature interacts with nurture to produce disorder. The diathesis-stress model then came to the forefront (Theodore, 2020).

Two mid-twentieth-century theorists gave the model its modern shape.

Meehl (1962) proposed that schizophrenia itself is not inherited. Instead, people inherit “schizotaxia,” a subtle neural defect that develops into a vulnerable personality style called “schizotypy.” Only some people with schizotypy go on to develop schizophrenia, typically after unfavorable environments and added stress.

Zubin and Spring (1977) then reframed the disorder as one of enduring vulnerability rather than continuous illness. On their view, vulnerability is a stable trait, while a disorder episode is a temporary state that stress can trigger.

The model has been useful in explaining why some individuals with biological dispositions to mental illness do not develop a disorder. It also explains why some individuals living through stressful life circumstances nonetheless remain psychologically healthy.

It has also opened the door to research into protective factors: positive elements that counteract the effects of diathesis and stress to prevent the onset of a disorder.

Finally, it has proven particularly useful in the context of specific disorders, such as schizophrenia and depression.

Diathesis and Stress Interactions

According to the diathesis-stress model, diatheses interact with stress to bring about mental illness. Here, “stress” is an umbrella term for any life event that disrupts a person’s psychological equilibrium: their normal, healthy regulation of thoughts and emotions.

In the diathesis-stress model, these challenging life events are thought to interact with individuals’ innate dispositions to bring psychological disorders to the surface.

Stress comes in many different forms.

It may be a single traumatic event, like the death of a close relative or friend. But stress can also be an ongoing, sustained challenge in one’s life, like a chronic illness or an abusive relationship.

It can even be as mundane as everyday work or school pressures, the sort of thing we usually mean by “stress” (Theodore, 2020).

The role of stress in the diathesis-stress model is nuanced. For one, some life circumstances may constitute both a diathesis and stress.

For instance, a child of a parent with mental illness may inherit a genetic predisposition to that illness. The child may also face ongoing stress because of her parent’s condition (Theodore, 2020).

Second, the timing of stress within a person’s lifespan matters. Certain disorders have “windows of vulnerability”: developmental periods when the same stressful events carry far greater risk (Lokuge, 2011).

Moreover, positive life circumstances, called protective factors, can counteract stress. They decrease the likelihood that a disorder will emerge.

Finally, different stresses are thought to play different roles across mental disorders. A particular stressful event, for example, may matter more for depression than for schizophrenia. The sections below explore both points in more detail.

Protective Factors

Negative elements in a person’s life can make a psychological disorder more likely. Positive elements work the other way, making a disorder less likely.

These positive elements are called protective factors.

Protective factors help explain why some people with both significant diatheses and stresses nonetheless remain healthy. In these cases, the protective factor keeps a disorder from surfacing (Theodore, 2020).

Protective factors can be conditions, meaning beneficial life circumstances that protect against mental illness. They can also be attributes: traits or behaviors of an individual that make them more resilient against psychological disorders (“Protective Factors”).

Conditions that act as protective factors include strong parental and social support and assistance from psychotherapists or counselors.

Attributes that act as protective factors include social and emotional competence and the use of healthy coping strategies and stress management techniques (Theodore, 2020).

By itself, the diathesis-stress model does not necessarily include protective factors in its assessment of the causes of psychological disorders.

As a result, the model has been updated in recent years to accommodate protective factors. This updated model is sometimes called the stress-vulnerability-protective factors model (Theodore, 2020).

Examples

The diathesis-stress model has proven useful in illuminating the causes of specific psychological disorders. One area where the model has had considerable success is schizophrenia, a disease with both genetic and environmental causes.

Schizophrenia

While schizophrenia has a strong genetic component, some individuals with genetic susceptibilities to the disorder nonetheless remain healthy.

As a result, many psychiatrists hold that schizophrenia requires a genetic predisposition combined with stress later in life, which then triggers the disorder.

The Finnish Adoptive Family Study gives the clearest real-world test of this gene-environment interaction in schizophrenia.

Aim: to test whether a disturbed adoptive family environment triggers schizophrenia-spectrum disorder in adoptees who already carry a genetic risk.

Method: Tienari et al. (2004) followed adoptees whose biological mothers had schizophrenia (high genetic risk) alongside low-risk adoptees, then rated each adoptive family’s psychological health.

Results: high-risk adoptees developed a schizophrenia-spectrum disorder far more often in a disturbed adoptive family (36.8%) than a healthy one (5.8%). Family environment made little difference for low-risk adoptees (5.3% versus 4.8%).

Conclusion: genetic vulnerability and family stress were each necessary but neither alone sufficient, exactly as the diathesis-stress model predicts.

Walker and Diforio (1997) proposed an influential neural diathesis-stress model in which stress-driven activation of the HPA axis increases dopamine dysregulation in vulnerable individuals. Jones and Fernyhough (2007) refined this model by emphasizing the primacy of social-evaluative and uncontrollable stressors.

Thus, the diathesis-stress model does well to explain the origins of schizophrenia and has even been supported by evidence from neuroscience.

Depression

The diathesis-stress model has also been used to explain the origins of depression. Similarly to schizophrenia, genetic risk factors for depression have been identified, but not all people with those risk factors go on to develop the disorder.

According to the diathesis-stress model of depression, stressful life events interact with genetic predispositions to bring about depressive symptoms.

The Camberwell study supplied an early, purely social demonstration of this interaction, decades before the molecular evidence below.

Aim: to test whether enduring social vulnerability factors combine with acute or chronic “provoking” stressors to trigger depression in women.

Method: Brown and Harris (1978) surveyed 458 women in Camberwell, London, using semi-structured interviews to record stressful life events, chronic difficulties, and depressive episodes.

Results: depression followed mainly when a vulnerability factor, such as lacking a confiding relationship or losing a mother before age 11, combined with a provoking stressor. Neither alone was enough.

Conclusion: social circumstances, not only biology, can act as the diathesis, an early and explicitly interactionist test of the model.

Modern research supports this model of depression. Colodro-Conde et al. (2018) tested a polygenic risk score against an inventory of stressful life events. This score sums the small effects of thousands of genetic variants. The study found the predicted gene-by-stress interaction.

The model has also proven useful in explaining suicidal behavior. Early models focused exclusively on stress. This approach failed to explain why some people exposed to extreme stress never engage in suicidal behavior.

Suicidal behavior likely also depends on an interaction between genetic and early-childhood dispositions and later stress. Because of this, van Heeringen (2012) argued that suicide prevention and treatment should adopt a diathesis-stress model.

Different psychological disorders have different causes. Some may rely more strongly on hard-wired predispositions, while others may respond more to stressful events later in life.

Nevertheless, the diathesis-stress model has been shown to have wide applicability across many areas of psychiatry.

It offers a powerful explanation of how nature and nurture combine to cause mental illness. This marks a real advance over earlier theories that treated one cause as fully determinative.

Critical Evaluation

The diathesis-stress model offers a powerful account of mental illness, but its evidence base is mixed. Its founding molecular demonstration failed to replicate, yet its core interactionist logic keeps finding support at a larger scale.

Contemporary Research

The clearest molecular test of the model comes from research on depression and a single gene.

Aim: to test whether life stress predicts depression only in people with a specific genetic vulnerability.

Method: Caspi et al. (2003) followed the Dunedin birth cohort and genotyped a promoter polymorphism in the serotonin-transporter gene (5-HTTLPR), which comes in a short and a long form.

Results: carriers of one or two short alleles who faced stressful life events showed markedly more depression and suicidality than long-allele carriers facing the same events.

Conclusion: life stress predicted depression conditional on genotype, a classic gene-by-environment interaction that launched a decade of further research.

These findings did not hold up cleanly. Three large replications tested the same 5-HTTLPR interaction and reached a very different verdict.

The Decisive Test: Culverhouse et al. (2018)

Aim: to settle, once and for all, whether the 5-HTTLPR-by-stress interaction that Caspi and colleagues reported actually holds up.

Method: a collaborative meta-analysis pooled 31 data sets totaling 38,802 participants, including previously unpublished data, and ran every group’s data through one identical, pre-registered analysis script.

Results: no subgroup and no definition of stress produced a significant gene-by-stress interaction. Stressful life events remained a strong risk factor for depression, but 5-HTTLPR genotype itself carried no risk.

Conclusion: the data do not support the 5-HTTLPR-by-stress interaction hypothesis for depression.

Border et al. (2019) reached the same verdict. Testing the eighteen most-studied depression candidate genes, including 5-HTTLPR, they found none more linked to depression than genes picked at random.

These failures do not disprove the diathesis-stress principle itself; they show that one common gene variant is too small a diathesis to detect reliably. The field has since moved to aggregate, polygenic measures of genetic risk (see Depression above).

Criticisms

Several persistent criticisms temper this otherwise powerful framework:

• Vagueness: “diathesis” and “stress” are broad umbrella terms, and the model rarely fixes the threshold between them in advance, making it hard to falsify.
• Measuring Stress Independently: stress is often assessed retrospectively by self-report, which invites recall bias, and a person’s own diathesis can shape the stressors they encounter (Monroe & Simons, 1991).
• Replication Problems: the field’s most famous single-gene finding did not hold up in later meta-analyses, a caution about underpowered candidate-gene studies (see Contemporary Research above).
• The Differential-Susceptibility Challenge: Belsky and Pluess (2009) argue some people are more susceptible to all environments, faring worse under stress but better under support, a crossover pattern the classic model misses.
• Reductionism: the model’s biological versions can over-emphasize genes over environment, and the original version omitted protective factors entirely, before later versions added them back in.

References

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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.

Broerman, R. (2017). Diathesis-stress model. In V. Zeigler-Hill & T. K. Shackelford (Eds.), Encyclopedia of personality and individual differences (pp. 1–3). Springer International Publishing. https://doi.org/10.1007/978-3-319-28099-8_891-1

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Culverhouse, R. C., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., … Bierut, L. J. (2018). Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Molecular Psychiatry, 23(1), 133–142. https://doi.org/10.1038/mp.2017.44

Jones, S. R., & Fernyhough, C. (2007). A new look at the neural diathesis–stress model of schizophrenia: The primacy of social-evaluative and uncontrollable situations. Schizophrenia Bulletin, 33(5), 1171–1177. https://doi.org/10.1093/schbul/sbl058

Lokuge, S., Frey, B. N., Foster, J. A., Soares, C. N., & Steiner, M. (2011). Depression in women: Windows of vulnerability and new insights into the link between estrogen and serotonin. The Journal of Clinical Psychiatry, 72(11), e1563-1569. https://doi.org/10.4088/JCP.11com07089

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Monroe, S. M., & Simons, A. D. (1991). Diathesis-stress theories in the context of life stress research: Implications for the depressive disorders. Psychological Bulletin, 110(3), 406–425.

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Theodore. (2020, April). Diathesis-Stress Model (Definition + Examples). Retrieved from https://practicalpie.com/diathesis-stress-model/.

Tienari, P., Wynne, L. C., Sorri, A., Lahti, I., Läksy, K., Moring, J., . . . Wahlberg, K.-E. (2004). Genotype–environment interaction in schizophrenia-spectrum disorder: Long-term follow-up study of Finnish adoptees. British Journal of Psychiatry, 184, 216–222.

van Heeringen, K. (2012). Stress–diathesis model of suicidal behavior. In Y. Dwivedi (Ed.), The neurobiological basis of suicide. CRC Press/Taylor & Francis. http://www.ncbi.nlm.nih.gov/books/NBK107203/

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