Background: Schizophrenia and bipolar disorder are severe mental illnesses emerging in late adolescence and early adulthood. Individuals with affected relatives have an increased risk of developing a severe mental illness. Neurodevelopmental markers can provide insight into illness development of familial high-risk offspring, such as intracranial volume (ICV). Reduced ICV is associated with increased prodromal psychotic symptoms, and poor cognitive control, a known risk factor for psychosis. 

Objectives: The aim of the current study is to investigate whether the association between ICV and prodromal psychotic symptoms in familial high-risk offspring is partially mediated by poor cognitive control, compared to control subjects. An exploratory aim is to investigate whether the mediating effect of cognitive control differs between high-risk subjects with relatives with bipolar disorder and high-risk subjects with relatives with schizophrenia.

Methods: In the current study 110 participants were included; 29 control subjects, 52 high-risk subjects with relatives with bipolar disorder, 29 high-risk subjects with relatives with schizophrenia. In the current study cognitive control was measured using Shifting Attentional Set Visual subtask part of the Amsterdamse Neuropsychologische Taken (ANT). Prodromal psychotic symptoms were operationalized through the Comprehensive Assessment of At Risk Mental State (CAARMS). ICV was measured with a three-dimensional T1-weighted fast-field echo MRI scans acquired with a Philips 3-Tesla Achieva scanner, using an eight-channel head coil.

Results: The overall mediation model of cognitive control in the relationship between ICV and prodromal psychotic symptoms was not significant (indirect effect: p=.947). The mediation effect did not significantly differ between control- and high-risk subjects (moderated mediation index: -0.543, 95% CI [-2.386, 1.421]), nor between bipolar disorder and schizophrenia (moderated mediation index: 1.876 with a 95% CI [-0.297, 4.185]).

Conclusion: The current findings suggest that cognitive control does not mediate the relationship between a reduced ICV and increased prodromal psychotic symptoms in familial high-risk offspring, nor in control subjects.