What mental illnesses can skip a generation?

From the Guidelines

Mental illnesses such as bipolar disorder, schizophrenia, depression, anxiety disorders, and attention deficit hyperactivity disorder (ADHD) can skip generations due to their complex genetic inheritance patterns and environmental influences. This phenomenon is supported by studies that show a strong genetic component in these disorders, with a four- to sixfold increased risk of disorder in first-degree relatives of affected individuals 1. The concept of genetic "loading" explains how someone might carry genetic risk factors without developing the condition themselves, yet can pass these genes to their children or grandchildren.

Some key points to consider include:

• Bipolar disorder has a strong genetic component, with studies showing that offspring of parents with bipolar disorder display more symptoms suggestive of risk for the disorder than those of normal controls, including mood lability, anxiety, attention difficulties, hyperarousal, depression, somatic complaints, and school problems 1.
• The phenomenon of skipping generations is also observed in other genetic diseases, such as X-linked disorders like Fabry disease, which can skip a generation especially if there are no surviving males 1.
• Environmental factors and personal resilience also play significant roles in mental health outcomes, and having a family history increases risk but doesn't guarantee development of the condition.
• Epigenetic factors—changes in gene expression rather than the DNA sequence itself—can affect how these genes are expressed across generations, contributing to the complexity of mental illness inheritance.

In terms of specific mental illnesses, bipolar disorder is a notable example that can skip generations, with studies showing that approximately 20% of youths with major depression go on to experience manic episodes by adulthood 1. Similarly, schizophrenia and depression can also exhibit complex inheritance patterns, with genetic and environmental factors contributing to their development. Anxiety disorders and ADHD can also be influenced by genetic factors, with family history playing a role in their development.

From the Research

Mental Illnesses that can Skip a Generation

• Bipolar disorder is a mental illness that can be inherited, with a high heritability of approximately 70% 2.
• The genetics of bipolar disorder are complex, and while individual genetic markers may confer little risk, common variants together account for about 25% of the heritability of the disorder 3.
• Research has shown that offspring of parents with severe mental illness, including schizophrenia, bipolar disorder, and major depressive disorder, have a one-in-three risk of developing severe mental illness themselves, suggesting that these conditions can skip a generation 4.
• However, the exact mechanisms of inheritance are not fully understood, and more research is needed to understand the transdiagnostic nature of familial risk 4.

Factors Involved in the Familial Transmission of Mental Illness

• Psychopathology, neurocognitive, neuroanatomical, and environmental factors are all involved in the familial transmission of severe mental illness 4.
• Molecular genetic tools are becoming increasingly informative in understanding the genetics of mental illness, but family history remains the single strongest predictor of illness 4.
• The use of lithium for the treatment of bipolar disorder is a complex issue, and clinicians are advised to refer to recommendations outlined in clinical practice guidelines (CPGs) 5.

Implications for Treatment and Prevention

• Early risk identification and prevention are crucial in reducing the risk of developing severe mental illness, and a transdiagnostic approach may be necessary to facilitate this 4.
• Lithium is an effective mood stabilizer for the management of bipolar disorder, but its administration requires sophisticated management and assiduous monitoring 5.
• Further research is needed on many aspects of lithium therapy, including clear guidance on the cessation of lithium therapy, to inform CPGs and improve treatment outcomes 5.