Specificity of associations between parental psychopathology and offspring brain structure

Abstract

Multiple forms of parental psychopathology have been associated with differences in subcortical brain volume. However, few studies have considered the role of comorbidity. Here, we examine if alterations in child subcortical brain structure are specific to parental depression, anxiety, mania, or alcohol/substance use parental psychopathology, common across these disorders, or altered by a history of multiple disorders. We examined 6581 children aged 9 to 10 years old from the ABCD study with no history of mental disorders. We found several significant interactions such that the effects of a parental history of depression, anxiety, and substance use problems on amygdala and striatal volumes were moderated by comorbid parental history of another disorder. Interactions tended to suggest smaller volumes in the presence of a comorbid disorder. However, effect sizes were small, and no associations remained significant after correcting for multiple comparisons. Results suggest that associations between familial risk for psychopathology and offspring brain structure in 9-10-year-olds are modest, and relationships that do exist tend to implicate the amygdala and striatal regions and are moderated by a comorbid parental psychopathology history. Several methodological factors, including controlling for intracranial volume and other forms of parental psychopathology and excluding child psychopathology, likely contribute to inconsistencies in the literature.

Keywords: Adolescent; Brain structure; Depression; Parental risk; Psychopathology; Striatum.

Figure 1.

Interaction Effects Between Comorbid Parental Psychopathology on Subcortical Brain Volume Each disorder represents either parent having a history of that disorder. R = right, L = left; Alc/SU = Alcohol or Substance use Problems. Panel A: The effect of parental mania on left amygdala volume was greater with a parental history of anxiety. Panel B: The negative of parental anxiety on right amygdala volume was greater without a comorbid parental history of depression. Panels C and D: The effects of parental history of alcohol/substance use problems was associated with larger left and right caudate volume without a parental history of depression, but smaller volume with a comorbid history of depression. Panel E: A parental history of alcohol/substance use problems was associated with larger left putamen volume without a parental history of depression, but smaller volume with a comorbid history of depression.