Cerebral Blood Flow Heritability and Correlation With Schizophrenia Spectrum Disorders

Cerebral blood flow (CBF) is heritable in the frontal lobes; in the thalamus and the putamen, higher regional CBF (rCBF) is correlated with schizophrenia spectrum disorders. In the left putamen, this correlation is carried by shared genetic influences. These findings suggest that rCBF in the left putamen could serve as a potential marker of genetic susceptibility for schizophrenia, according to a recent study published in the Schizophrenia Bulletin.

The investigators of this study aimed to determine the heritability of CBF in the thalamic, frontal, and striatal areas. A second aim was to assess whether CBF associations with schizophrenia were under genetic influence. The study participants were recruited using the Danish Twin Register. The inclusion criteria included both twins being alive, living in Denmark, and without research protection. Exclusion criteria were serious physical illness, addiction to alcohol or illicit drugs, head trauma, and pregnancy. The investigators recruited monozygotic twin pairs concordant (n=2) or discordant (n=20) for schizophrenia spectrum disorders, matched on sex and age with dizygotic (n=20) and healthy control pairs (N=181).

CBF in the thalamus, frontal lobes, and putamen was measured with pseudo-continuous arterial spin labeling on a 3 T magnetic resonance scanner. Structural equation modeling was used to perform twin statistics. CBF in the frontal lobes was not correlated to disease but was heritable (h²=0.44; 95% CI 0.22-0.60). CBF correlated to schizophrenia spectrum disorders in the left thalamus (r=0.17, 0.03-0.31; P =.02), as well as in the left putamen (r=0.19; 95% CI, 0.05-0.32; P =.007) and the right putamen (r=0.18; 95% CI, 0.03-0.32; P =.02). When restricting the sample to schizophrenia only, shared genetic influences between CBF in the left putamen and schizophrenia liability (phenotypic correlation 0.44; 95% CI, 0.28-0.58; P <.001) were found.

Limitations of this study included the restriction of groups in the analysis of schizophrenia and schizophrenia spectrum which could reduce statistical power, thus increasing the risk for type II errors. Also, there was a lack of control for treatment effects with antipsychotic medication, due to lack of information about previous antipsychotic exposure and variability in patient use of antipsychotics.

The investigators of the study concluded that in this twin design composed of 181 participants, CBF in the frontal lobes was heritable and CBF in the left thalamus and bilateral putamina is correlated to liability for schizophrenia spectrum disorders. Genetic influences could explain higher rCBF in the putamen of patients with schizophrenia, and this is present in monozygotic and to a lesser extent in dizygotic unaffected co-twins of individuals with schizophrenia.

Reference

Legind CS, Broberg BV, Brouwer R, et al. Heritability of cerebral blood flow and the correlation to schizophrenia spectrum disorders: a pseudo-continuous arterial spin labeling twin study [published online February 18, 2019]. Schizophr Bull. doi: 10.1093/schbul/sbz007