The Diathesis-Stress Model Of Schizophrenia

Schizophrenia is typically known to scientists as a highly heritable mental health disorder, meaning one that tends to run strongly in families. Yet many people with a high genetic risk for this illness never develop the condition. Many researchers believe this apparent disconnect can be explained by a theory of schizophrenia development known as the diathesis-stress model, which suggests that psychological disorders develop in response to external stress — but some people may be more vulnerable to stress than others. 

Certain genetic variations may create an underlying susceptibility to schizophrenia. However, even people with many high-risk genes may only develop psychotic symptoms if stressful life events disrupt their mental stability. Over the past few decades, researchers have found numerous potential candidates for both the genetic and environmental risk factors behind schizophrenia. For help managing stress or schizophrenia symptoms, consider reaching out to a licensed mental health professional. 

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Is schizophrenia genetic?

In general, there’s a long-running debate within the medical community over whether schizophrenia should be considered a genetic disorder. A family history of this condition tends to be one of the strongest known risk factors, and some studies have estimated that schizophrenia’s heritability may be close to 90%. Many researchers have argued on this basis that schizophrenia should primarily be considered a disease of brain development. In this view, the disorder results from improper genetic coding that leads to structural problems in the way neurons grow and connect. 

On the other hand, the developmental biology of schizophrenia tends to be quite complicated compared to that of many other strongly genetic disorders. Huntington's disease, for example, can be explained by a single mutated gene. In contrast, the most up to date research on schizophrenia has identified more than 280 genes that appear to modify an individual’s risk profile. 

At the same time, most people with high numbers of these “schizophrenia risk genes” live their whole lives without developing this mental illness. This suggests that while genes can significantly increase a person’s odds of developing this condition, they likely don’t tell the whole story. 

Development of the diathesis-stress model

Subsequent research cast doubt on this concept, and a 1982 research review found that there was little evidence that mothers with the “schizophrenogenic” personality type were more likely than others to have children with schizophrenia. Still, the basic notion that psychosis arose in people with genetic vulnerability following stress exposure persisted. Mental health professionals began to look for other adverse life experiences that could potentially trigger schizophrenia.

The diathesis-stress model of schizophrenia applications

At the same time, the diathesis-stress concept began to be applied to other kinds of psychiatric illness. Today, most mental disorders tend to be seen as resulting from a combination of genetic risk factors and stress, and researchers have found evidence for this phenomenon in common conditions like depression. 

The neural diathesis-stress model

Investigations into the specific brain mechanisms involved in schizophrenia led to the creation of a more specific version of the theory described above: the neural diathesis-stress model. Proposed in 1997 by Elaine Walker and Donald Diforio, this theory identified the hypothalamic-pituitary-adrenal axis (HPA axis) as the likely site within the brain where disruption due to stressful events could trigger schizophrenia. 

The HPA axis appears to regulate many bodily processes, including immune system activity, metabolism, mood, emotional response, and sexual maturation. The HPA axis also seems to be a significant driver of the human response to psychosocial stress. In individuals experiencing prolonged mental distress, heightened HPA activity may lead to an overproduction of stress hormones, which can, in turn, damage brain cells.

According to the neural diathesis-stress paradigm, this process may explain how schizophrenia emerges. People with this condition tend to show higher baseline levels of cortisol, and elevated cortisol activity seems to be a warning sign for the first emergence of psychotic symptoms. Researchers have also found evidence of damage to the hippocampus — a common result of prolonged HPA dysfunction — in individuals with schizophrenia.

Inflammation and the diathesis-stress theory

Emerging research suggests that the HPA’s role in schizophrenia development may be linked to the human immune system. Many studies have noted that people with this disease often show altered activity in their microglia. These immune cells within the brain and spine generally control inflammatory activity in response to stress, damage, and disease. They can also trigger synaptic pruning, a process that breaks down the connections between nerve cells. While this can be beneficial in the right circumstances, excessive pruning might damage the brain’s cognitive abilities. This could be why many people with psychotic disorders show reduced regional brain volumes. 

Under the updated version of the diathesis-stress model, the genes responsible for schizophrenia risk might make an individual's brain more prone to dysfunctional immune responses. For example, one of the genes most strongly associated with schizophrenia risk, the C4 gene, seems to promote increased levels of synaptic pruning. However, these harmful reactions might not kick in unless the person experiences significant physiological or psychological stress. 

While many researchers consider this hypothesis promising, they also note that there are still gaps in our understanding of this process and how it might affect schizophrenia development. Future research will likely be needed to confirm or refute the idea of immune response and synaptic pruning as causes of schizophrenia.

What kinds of stress could trigger schizophrenia?

When neuroscientists talk about stress affecting gene expression and brain development, they aren’t necessarily referring to day-to-day worries and psychological pressure. “Stress” in this context can mean anything that causes the body to activate its natural defenses. This can encompass factors like illness, physical damage, and severe negative emotions.

Researchers have identified a variety of stressors that might predispose people to schizophrenia, trigger the first occurrence of psychosis, or worsen existing symptoms. Examples include the following:

• Prenatal infection: Exposure to inflammation or germs while in the womb due to the mother’s illness during pregnancy may increase an individual’s risk of schizophrenia.
• Obstetric complications: Various pregnancy complications, such as preeclampsia, could place stress on the fetus and increase psychosis risk. 
• Abuse, neglect, or other trauma in childhood: Severe traumatic experiences during childhood seem to be significant risk factors for developing schizophrenia symptoms.

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• Adolescent cannabis use: Frequent use of high-THC cannabis as a teen or young adult might increase the risk of psychosis.
• Unstable early environment: Experiencing a disruptive or chaotic environment in childhood, such as experiencing migration or living in a war zone or a high-crime area, may raise one’s chances of developing schizophrenia.

The factors listed above may not encompass all of the various kinds of life challenges that could trigger schizophrenia in high-risk individuals. There’s evidence that prolonged psychological stress of any kind might increase the likelihood of developing psychosis in those with genetic vulnerabilities.

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Managing stress and schizophrenia risk

Some of the environmental stressors associated with psychotic disorders may occur before birth or in early childhood. However, later-life stress could still play a notable role in triggering psychosis or making existing symptoms more severe. Finding healthy ways to cope with negative emotions might protect against schizophrenia. 

Effective strategies could include practices that lower your baseline stress, such as exercise, healthy sleep habits, meditation, and relaxation techniques. Working with a mental health professional might also be helpful. Psychiatric research suggests that techniques like cognitive-behavioral therapy (CBT) can protect against schizophrenia onset, even in individuals considered “ultra-high risk.” 

Online therapy

If your life is already stressful, attending therapy regularly might sound like a challenge. You might find it more convenient to meet with a care provider online. Internet-based therapy can make scheduling more convenient since you can attend from anywhere with a connection to the web. 

Online interventions have been found helpful for psychotic disorders in clinical trials. For instance, a 2017 paper reported that internet-based CBT usually decreased the severity of a variety of schizophrenia symptoms, including hallucinations and difficulty with social functioning. However, in-person care may be needed in cases of acute psychosis.