Regional prefrontal cortex gray matter volumes in youth at familial risk for schizophrenia from the Harvard Adolescent High Risk Study

Abstract

Background Regional prefrontal cortex gray matter reductions have been identified in schizophrenia, likely reflecting a combination of genetic vulnerability and disease effects. Few morphometric studies to date have examined regional prefrontal abnormalities in non-psychotic biological relatives who have not passed through the age range of peak risk for onset of psychosis. We conducted a region-of-interest morphometric study of prefrontal subregions in adolescent and young adult relatives of schizophrenia patients. Methods Twenty-seven familial high-risk (FHR) first-degree relatives of schizophrenia patients and forty-eight control subjects without a family history of psychosis (ages 13–28) underwent high-resolution magnetic resonance imaging at 1.5 Tesla. The prefrontal cortex was parcellated into polar, dorsolateral, ventrolateral, ventromedial and orbital subregions. The Chapman scales measured subpsychotic symptoms. General linear models examined associations of prefrontal subregion volumes with familial risk and subpsychotic symptoms. Results FHR subjects had significantly reduced bilateral ventromedial prefrontal and frontal pole gray matter volumes compared with controls. Ventromedial volume was significantly negatively correlated with magical ideation and anhedonia scores in FHR subjects. Conclusions Selective, regional prefrontal gray matter reductions may differentially mark genetic vulnerability and early symptom processes among non-psychotic young adults at familial risk for schizophrenia.

Familial and environmental influences on brain volumes in twins with schizophrenia

“…15 A pooled sample of 4 European twin cohorts rejected a significant phenotypic correlation between total grey matter volume and schizophrenia. 18 Notwithstanding these findings, subtle grey matter volume reductions have been frequently described in individuals unaffected by schizophrenia but at familial risk for the disorder; [31][32][33] this finding has also been supported by a meta-analysis. 20 More recently, unaffected sibling data sets have confirmed significant deficits in the patients' grey matter volume, but have either failed to detect significant deficits in their unaffected siblings, or detected only marginal effects.…”

Gray Matter Volume Decrease Distinguishes Schizophrenia From Bipolar Offspring During Childhood and Adolescence

“…Neuroimaging studies have revealed that, relative to controls, offspring of patients with schizophrenia (SzO) exhibit volumetric reductions in total brain volumes 10,11 , the amygdala-hippocampal complex 10,[12][13][14] and basal ganglia, 11,14 as well as grey matter volume decrease in frontal 13,15 , temporal, 16 and parietal cortices 13 . Grey matter volume reductions in these cortical regions have also been related to prodromal symptomatology 13,15 . Conversely, studies in child and adolescent offspring of patients with BD (BdO), have yielded largely negative findings 17,18 , with a single exception concerning increased grey matter volume in the left hippocampal-parahippocampal gyrus 19 .…”

“…The neuroimaging data so far has been limited by small sample sizes, especially in BdO [17][18][19] , ages centred M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 3 in late, rather than early adolescence in SzO 13,15 , and an approach driven by predefined regions of interest (ROI) in the majority of the above studies. In addition, a number of samples have also included other first-and second-degree relatives [13][14][15] , limiting extrapolation of findings.…”

“…In addition, a number of samples have also included other first-and second-degree relatives [13][14][15] , limiting extrapolation of findings. An additional shortcoming is that despite reports of increased rates of non-psychotic mental health disorders in these populations 20 , this has not been accounted for in many structural neuroimaging studies [10][11][12][13]15,18 so far. Furthermore, no study to date has directly compared child and adolescent offspring of patients with schizophrenia or BD using neuroimaging data.…”

Auditory Vigilance and Working Memory in Youth at Familial Risk for Schizophrenia or Affective Psychosis in the Harvard Adolescent Family High Risk Study

“…The Magical Ideation Scale (MIS) (Eckblad & Chapman, 1983) enquires about ideas of reference and odd beliefs (e.g., "Good luck charms don't work", keyed "false"). In previous work using the FHR-SCZ sample compared to healthy controls Rosso et al, 2010), we demonstrated that FHR-SZ were significantly impaired on revised physical anhedonia but not on PAS or MIS. The results of the FHR-AFF group were not reported in those papers.…”