Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls

Abstract

Schizophrenia (SZ) and bipolar disorder (BD) share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7–19 years, comprising offspring of patients with SZ (N = 27), offspring of patients with BD (N = 39) and offspring of community control parents (N = 40). We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.

Aberrant structural covariance networks in youth at high familial risk for mood disorder

“…We found no significant differences in unaffected individuals at familial risk of mood disorder compared to controls. This is in contrast to a number of potential trait markers that have so far been identified for BD, eg widespread white matter reductions, thinning of temporal brain regions, and functional activation increases in the amygdala during task performance, but consistent with other recent studies that found no differences in functional resting‐state connectivity in individuals at familial risk for mood disorder, suggesting that these differences in connectivity may not be the most sensitive biomarkers of familial risk.…”

Functional dysconnectivity of the limbic loop of frontostriatal circuits in first‐episode, treatment‐naive schizophrenia

“…According to the tripartite model of frontostriatal circuits which are defined by their cortical inputs, the sensorimotor loop connects the somatosensory and motor‐related cortices with the dorsal caudal putamen and dorsal rostral putamen, associative loop connects the dlPFC with the dorsal caudate and ventral rostral putamen, and the limbic loop connects the ACC, OFC, and ventromedial PFC with the VS (including the nucleus accumbens and ventral parts of the caudate and putamen). Among the above loops, limbic and associative loop dysfunction have been reported frequently in patients with SZ or individuals at a high risk for SZ (Juckel et al, ; Lancaster et al, ; Rausch et al, ; Sarpal et al, ; Sole‐Padulles et al, ).…”

Adolescent brain development and depression: A case for the importance of connectivity of the anterior cingulate cortex

“…Within the DMN, regions display only limited connectivity in childhood and become strongly functional connected by adulthood (Fair et al, 2008). In particular, anterior DMN connectivity of the rACC was shown to increase significantly between age 7 and 18 (Sole-Padulles et al, 2016). Similarly, looking at connectivity of the SN across development, significantly stronger functional connectivity between the dACC and anterior insula has been observed among adults relative to children (Uddin et al, 2011), with dACC connectivity increasing significantly between age 7–18 (Sole-Padulles et al, 2016).…”

“…In particular, anterior DMN connectivity of the rACC was shown to increase significantly between age 7 and 18 (Sole-Padulles et al, 2016). Similarly, looking at connectivity of the SN across development, significantly stronger functional connectivity between the dACC and anterior insula has been observed among adults relative to children (Uddin et al, 2011), with dACC connectivity increasing significantly between age 7–18 (Sole-Padulles et al, 2016). Furthermore, a direct comparison of structural and functional connectivity of the DMN across development identified the cingulum to be the most immature link in this network in childhood, and demonstrated that cingulum FA was positively correlated with DMN functional connectivity in adulthood (Supekar et al, 2010).…”