Mental illness has a complex pattern of inheritance. Both genetic and environmental factors play important roles in determining an individual’s risk of developing mental health conditions. This article examines the evidence on how mental illnesses may be passed down through families.
Basic patterns of inheritance
In general, genetic traits are inherited in a few main patterns:
- Autosomal dominant – only one copy of the gene variant is needed to express the trait. The gene has a 50% chance of being passed down from an affected parent.
- Autosomal recessive – two copies of the gene variant are needed to express the trait. Both parents must be carriers. There is a 25% chance of the child inheriting the variants from both parents and expressing the trait.
- X-linked – the gene variant is located on the X chromosome. Males are more frequently affected since they only have one X chromosome. The gene variant has a 50% chance of being passed from an affected mother to her son.
- Mitochondrial – the gene variant is located in mitochondrial DNA, which is only passed down from mother to child.
Evidence on inheritance patterns for specific mental illnesses
Schizophrenia
Schizophrenia has a strong genetic component with heritability estimated around 80%. However, it does not follow a simple Mendelian inheritance pattern. Instead, it is a complex polygenic disorder involving variations in many different genes interacting with environmental factors.
Having a parent or sibling with schizophrenia increases an individual’s risk. However, most cases involve de novo mutations not found in the parents. The risk from an affected parent is around 13% compared to 1% in the general population. The risk is similar for affected mothers versus fathers.
Bipolar disorder
Like schizophrenia, bipolar disorder is highly heritable but involves many genetic and environmental influences. If one parent has bipolar disorder, the risk to a child is around 15-30%. The risk increases to 50-75% if both parents are affected.
Some studies have found a slightly higher risk of transmission from an affected mother compared to father. However, most analyses find similar levels of transmission from mothers versus fathers.
Major depressive disorder
Major depressive disorder (MDD) also has a heritability around 40%. First-degree relatives of an individual with MDD have a 2-4 times higher risk compared to the general population.
Results are conflicting on whether MDD risk is higher from maternal versus paternal transmission. Some studies have found a higher risk from mothers, but a recent large analysis found similar levels of transmission from mothers and fathers.
Anxiety disorders
Anxiety disorders like generalized anxiety disorder (GAD), social anxiety, and panic disorder have estimated heritabilities around 30-40%. First-degree relatives have a 2-3 times higher risk compared to the general population.
Most studies have not found significant differences in transmission rates from mothers versus fathers. However, some analyses have suggested slightly higher transmission rates from affected mothers for disorders like GAD and agoraphobia.
Autism spectrum disorder
Autism spectrum disorder (ASD) has a strong genetic component with heritability over 50%. Having one affected first-degree relative increases an individual’s risk for ASD 2-18 times.
Some earlier studies reported higher risks from maternal inheritance. However, most recent large studies find an equal risk transmission from mothers and fathers with ASD.
X-linked mental illness
While most mental illnesses involve autosomal genes, a few rare syndromes are caused by variants on the X chromosome. These X-linked conditions more severely affect males since they only have one X chromosome. Examples include:
- Fragile X syndrome – causes intellectual disability and autism symptoms
- Rett syndrome – neurodevelopmental disorder causing intellectual disability
- Fabry disease – can include psychiatric symptoms like mood disorder
Since these disorders are X-linked, they can only be passed down from mother to son. Affected fathers pass the gene to all daughters but none of their sons.
Mitochondrial mental illness
Mitochondria have their own DNA separate from the nuclear genome. Mitochondrial DNA is only inherited maternally through the egg cell. Several mitochondrial diseases can include neurological and psychiatric symptoms such as:
- MITOCHONDRIAL ENCEPHALOMYOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES (MELAS) – causes strokes and progressive dementia
- Myoclonic Epilepsy with Ragged Red Fibers (MERRF) – includes neurological regression, seizures, and cognitive impairment
- Leigh Syndrome – progressive loss of mental and movement abilities
Since mitochondrial DNA is only maternally inherited, only mothers can pass on mitochondrial genetic disorders to their children.
Imprinting effects
Genomic imprinting refers to a phenomenon where genes are expressed differently depending on whether they are inherited from the mother or father.
Imprinting effects have been observed for several neuropsychiatric disorders. This indicates that the same genetic variant may have different effects on disease risk depending on whether it is paternally or maternally inherited. Examples include:
- Prader-Willi syndrome – caused by deletion of paternal chromosome 15q11-13
- Angelman syndrome – caused by deletion of maternal chromosome 15q11-13
- Autism – some studies suggest imprinted genes affect autism risk
- Schizophrenia – evidence that imprinting influences schizophrenia risk
Imprinting provides another mechanism whereby maternal versus paternal inheritance could differentially affect mental health outcomes in offspring.
Maternal health effects
Maternal health during pregnancy may also impact the developing fetal brain and future mental health of offspring. Poor maternal nutrition, high stress levels, infections, smoking, alcohol use, and other factors are associated with increased risks for mental disorders in children.
Some examples of maternal influences on mental health outcomes include:
- Maternal folate levels linked to risk of schizophrenia and autism in offspring
- Maternal stress associated with increased risk for schizophrenia, depression, anxiety, ASD
- Maternal influenza infection increases schizophrenia, ASD, and cognitive impairment risk
Through these types of effects, the uterine environment provided by the mother can affect brain development and long-term mental health risks for her children.
Conclusion
In summary, mental illness inheritance involves complex interactions between many genetic and environmental influences. For most major mental health conditions, current evidence does not support large differences in transmission risk from affected mothers versus fathers.
However, some neuropsychiatric syndromes demonstrate definitive maternal inheritance patterns such as mitochondrial diseases and X-linked intellectual disabilities. Maternal health and prenatal environment also impact neurodevelopment and future mental health risks.
While mental illness can cluster in families, most disorders do not follow simple Mendelian inheritance. Having an affected parent increases risk, but many cases arise from de novo mutations. The interplay between genetic vulnerabilities and environmental exposures determines an individual’s actual risk of developing mental health conditions.