Risk of Mental Illness in Offspring of Mentally Ill Parents
Risk of Mental Illness in Offspring of Mentally Ill Parents
Objective: Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Method: Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. Results: We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%–42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08–3.06, P < .001). High-risk offspring had a significantly increased rate of the disorder present in the parent (RR = 3.59; 95% CI: 2.57–5.02, P < .001) and of other types of SMI (RR = 1.92; 95% CI: 1.48–2.49, P < .001). The risk of mood disorders was significantly increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02–2.58; P = .042). The risk of schizophrenia was significantly increased in offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20–18.78, P < .001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19–15.16, P = .631). Conclusions: Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.
Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) have an increased risk of developing a mental illness themselves. Individuals with SMI want to know the probability that their offspring will develop SMI. Accurate quantification of risk is an important element in communication with patients and their families. Knowing the probability of illness in offspring is also crucial for the planning of early interventions.
Family high-risk (FHR) studies investigate psychopathology in individuals who have a biological relative, most commonly a parent, with SMI. These studies have provided a wealth of information about risk of mental disorders in offspring. However, the rates of mental disorders in offspring vary across studies, and a robust overall estimate is not available.
Most FHR studies have primarily focused on the risk of developing the same disorder as the parent suffered from; eg, schizophrenia among offspring of parents with schizophrenia. Several FHR studies have reported that familial risk was diagnosis specific, eg, children of parents with schizophrenia were at increased risk for nonaffective psychosis but not for mood disorders. However, evidence emerging from population registry studies suggests that familial risk might be broader, with children of parents with SMI also having increased risk for mental disorders other than the disorder diagnosed in the parent. Such nonspecific risks are supported by twin and molecular genetic studies showing that genetic dispositions to mood disorders and schizophrenia overlap. If these results are confirmed, the overall risk of psychopathology in offspring of parents with SMI may be higher than previously thought.
There are 2 alternative explanations for the discrepant findings of population registry and FHR studies. It may be that the familial risk is diagnosis specific, but the findings of population registry studies are distorted by misclassification due to lack of valid diagnostic instruments. Alternatively, it may be that familial risk cuts across diagnoses, but individual FHR studies might have been underpowered to detect the cross-diagnostic risks. To distinguish between these alternative explanations we conducted a meta-analysis of FHR studies. This retains the advantage of valid diagnostic interviews in FHR studies while the statistical power is increased through pooling of data across studies. We aimed to quantify the risk of a range of mental disorders among the offspring of individuals with schizophrenia, bipolar disorder, and major depressive disorder.
Abstract and Introduction
Abstract
Objective: Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Method: Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. Results: We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%–42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08–3.06, P < .001). High-risk offspring had a significantly increased rate of the disorder present in the parent (RR = 3.59; 95% CI: 2.57–5.02, P < .001) and of other types of SMI (RR = 1.92; 95% CI: 1.48–2.49, P < .001). The risk of mood disorders was significantly increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02–2.58; P = .042). The risk of schizophrenia was significantly increased in offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20–18.78, P < .001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19–15.16, P = .631). Conclusions: Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.
Introduction
Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) have an increased risk of developing a mental illness themselves. Individuals with SMI want to know the probability that their offspring will develop SMI. Accurate quantification of risk is an important element in communication with patients and their families. Knowing the probability of illness in offspring is also crucial for the planning of early interventions.
Family high-risk (FHR) studies investigate psychopathology in individuals who have a biological relative, most commonly a parent, with SMI. These studies have provided a wealth of information about risk of mental disorders in offspring. However, the rates of mental disorders in offspring vary across studies, and a robust overall estimate is not available.
Most FHR studies have primarily focused on the risk of developing the same disorder as the parent suffered from; eg, schizophrenia among offspring of parents with schizophrenia. Several FHR studies have reported that familial risk was diagnosis specific, eg, children of parents with schizophrenia were at increased risk for nonaffective psychosis but not for mood disorders. However, evidence emerging from population registry studies suggests that familial risk might be broader, with children of parents with SMI also having increased risk for mental disorders other than the disorder diagnosed in the parent. Such nonspecific risks are supported by twin and molecular genetic studies showing that genetic dispositions to mood disorders and schizophrenia overlap. If these results are confirmed, the overall risk of psychopathology in offspring of parents with SMI may be higher than previously thought.
There are 2 alternative explanations for the discrepant findings of population registry and FHR studies. It may be that the familial risk is diagnosis specific, but the findings of population registry studies are distorted by misclassification due to lack of valid diagnostic instruments. Alternatively, it may be that familial risk cuts across diagnoses, but individual FHR studies might have been underpowered to detect the cross-diagnostic risks. To distinguish between these alternative explanations we conducted a meta-analysis of FHR studies. This retains the advantage of valid diagnostic interviews in FHR studies while the statistical power is increased through pooling of data across studies. We aimed to quantify the risk of a range of mental disorders among the offspring of individuals with schizophrenia, bipolar disorder, and major depressive disorder.
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