A family history of severe mental illness (SMI) is a known risk factor for the development of SMI in an individual; up to 50% of children who have a parent with an SMI will go on to develop SMI during their own lifetime. At SIRS 2023, researchers from different labs in Europe and Canada shared research findings delving into elucidating mechanisms of intergenerational transmission of risk of SMI.
The VIA Project
Up to 50% of children of parents with a mental illness will go on to develop mental illness during their own lifetime
50% of patients with SMI experience their first contact with mental health services before the age of 18, and the incidence of schizophrenia peaks at age 22. For these reasons, it is important to examine factors during childhood to late adolescence which may provide insights into the development of SMI.1
Prof. Merete Nordentoft (Mental Health Centre, Copenhagen) described the longitudinal Danish High Risk and Resilience Study (VIA) that was begun between 2013 and 2016.1,2 The Danish study cohort consists of 522 7-year-old children, 322 of whom have one or more parents with SMI, and 200 of whom do not (controls).1 Baseline assessment at the age of 7 included neurocognition, motor functioning, psychopathology, home environment, sociodemographic data, and genetic information.2 Subsequent assessments at age 11 (ongoing, occurring between 2021 and 2024) included magnetic resonance imaging (MRI) and electroencephalograms (EEG) of the children’s brains,2 and at age 15, researchers also added risk behavior, magnetoencephalography, sleep and a white noise paradigm.3
50% of patients with severe mental illness experience their first contact with mental health services before the age of 18
VIA study results to date have documented that children of parents with schizophrenia were more likely to have childhood psychiatric disorders, psychotic experiences, lower cognitive function, poorer language understanding and motor function, more traumatic life events, and a low level of physical activity.1 In addition, these children were more likely to live in home environments deemed inadequate, and imaging has demonstrated structural brain changes in these children.1
Children of parents with schizophrenia are more likely to have childhood psychiatric disorders, poorer language understanding and low levels of physical activity
The next wave of assessments is planned for when the adolescents turn 19 (2025–2028). Researchers hope to use these data to identify the influence of genetic, epigenetic and environmental exposures, and to develop a prediction model for mental illness.1
The Lausanne-Geneva Cohort
Prof. Caroline Vandeleur (Lausanne University Hospital and University of Lausanne, Switzerland) further discussed factors that can contribute to the risk of mood and psychotic disorders in offspring of parents with mood disorders (major depressive disorder [MDD], and bipolar disorder [BPD]).4
There is a strong association between early-onset BPD in parents and the risk of BPD in their offspring.4 Children of parents with MDD have a moderately increased risk of future development of MDD.4 Observational studies have shown that offspring with a familial risk of psychosis are at increased risk of developing motor development and language problems, difficulties in executive cognition, or problems with social adaptation.4 Children of parents with schizophrenia have an increased risk of experiencing trauma.4 Other studies have suggested that trauma including physical and/or sexual abuse or other stressful life events can contribute to the development of mood and psychotic disorders.4 Childhood adversity tends to happen more commonly in families of patients with both BPD and MDD than in control families.4
Physical and sexual abuse can contribute to the development of mood and psychotic disorders
Poor parental-rearing attitudes and early life stressors are also risk factors for the development of mood disorders in children of parents with BPD.4
Prof. Vandeleur emphasized the importance of the identification of risk factors and early clinical manifestations of disorders in patients with a family risk of developing a mood or psychotic disorder; the identification of these risk factors can help to inform the development of early intervention strategies that may reduce morbidity and mortality, and improve outcomes.4
The identification of risk factors for mental illness can help to inform early intervention strategies
Neurodevelopmental Trajectories
Prof. Neeltje van Haren (Erasmus Medical Centre, Netherlands) and her team sought to build on previous work which suggested a disruption of both brain structure and neural network connectivity in children whose parents had either BPD or schizophrenia.5 They measured brain volume, cortical thickness and cortical surface area in the brains of 185 patients. Of these 185 patients, 79 had at least one parent diagnosed with BPD, 52 had at least one parent diagnosed with schizophrenia, and 54 were controls.5
T1 weighted scans revealed deviations in developmental trajectories of the brain between offspring of patients with and without mental illness. Specifically, intracranial volume was decreased in the brains of patients with schizophrenia. Decreases in cortical thickness and cortical surface area with age were less pronounced in BPD than in schizophrenia. During adolescence, cortical surface area increased in patients with BPD, while it decreased in patients with schizophrenia.5
Children of parents with mental illness may experience different brain development than controls
They conclude that having a parent with an SMI may have an impact on brain development well before onset of illness, and these changes are more pronounced in schizophrenia than in BPD.5 Next steps will involve further investigation of the disease specificity of these findings in larger groups.
Epigenetic Clocks
Patients with SMI are known to have a shorter lifespan than people without SMI.6,7 Researchers have found age-related biomarkers and physiological conditions in patients with SMI, leading to a hypothesis that these patients may suffer from accelerated aging.7 Alex Segura (PhD candidate, University of Barcelona) and his team investigated epigenetic modifications in the offspring of patients with schizophrenia and BPD in the Bipolar and Schizophrenia Young Offspring Study (BASYS) to look for evidence of premature aging processes.6,7
Patients with mental illness have shorter lifespans than controls
BASYS included 117 children and adolescents between the ages of 6 and 17, 53 of whom were at familial high risk (FHR) for schizophrenia or BPD, while the remaining 64 were controls. Using blood and saliva samples, they calculated participants’ epigenetic age using six different epigenetic clock algorithms, and compared them to their biological age.6,7 They hypothesized that there would be greater asynchronicities between biological age and epigenetic age in the FHR group; however, they found the opposite: FHR individuals actually showed deacceleration in two of the epigenetic clocks, and no differences in the other four epigenetic clock algorithms.6 In cases of first episode psychosis, there was deceleration prior to the psychotic episode, and acceleration thereafter.6 Investigators could find no effect of environmental risk factors including obstetric complications, socioeconomic status or recent stressful life events on the epigenetic age.6,7
Segura et al.’s data suggest that the offspring of parents with SMI follow a slower pace of biological aging than the control group.7
Further research is needed to investigate the impact of environmental stressors prior to the onset of SMI.7
