Heritability of Cerebral Blood Flow and the Correlation to Schizophrenia Spectrum Disorders: A Pseudo-continuous Arterial Spin Labeling Twin Study

Abstract

Whether aberrant cerebral blood flow (CBF) in schizophrenia is affected by genetic influences, and consequently a potential marker for genetic susceptibility, is unknown. Our aims were to determine the heritability of CBF in thalamic, frontal, and striatal areas, and to ascertain if associations with disease were under genetic influence. Monozygotic (MZ) twin pairs concordant (n = 2) or discordant (n = 20) for schizophrenia spectrum disorders (ICD-10 F2x.x), matched on sex and age with dizygotic (DZ; n = 20) and healthy control pairs (MZ: n = 27; DZ: n = 18; total: n = 181 individuals), were recruited via the National Danish Twin Register. CBF in thalamus, frontal lobes, and putamen was measured with pseudo-continuous arterial spin labeling on a 3 T magnetic resonance scanner. Twin statistics were performed with structural equation modeling. CBF in the frontal lobes was heritable (h2 = 0.44, 95% CI [0.22–0.60]) but not correlated to disease. CBF correlated to schizophrenia spectrum disorders in the left thalamus (r = 0.17, [0.03–0.31]; P = 0.02), as well as in the left putamen (r = 0.19, [0.05–0.32]; P = 0.007) and the right putamen (r = 0.18, [0.03–0.32]; P = 0.02). When restricting the sample to schizophrenia (F20.x) only, shared genetic influences between CBF in the left putamen and schizophrenia liability (phenotypic correlation = 0.44, [0.28–0.58], P < 0.001) were found. Our results provide heritability estimates of CBF in the frontal lobes, and we find CBF in thalamus and putamen to be altered in schizophrenia spectrum disorders. Furthermore, shared genetic factors influence schizophrenia liability and striatal perfusion. Specifically, higher perfusion in the left putamen may constitute a marker of genetic susceptibility for schizophrenia.

The relative and interactive impact of multiple risk factors in schizophrenia spectrum disorders: a combined register-based and clinical twin study

“…05787). Previous results from this cohort are presented in Legind et al (2019aLegind et al ( , 2019b, Lemvigh et al (2020a, 2020b), and Rasmussen et al (2016.…”

Increased Hippocampal Blood Flow in People at Clinical High Risk for Psychosis and Effects of Cannabidiol

“…Effects in these regions do, however, also correspond with results of previous ROI-based studies, which include increased putamen rCBF in CHR patients (Kindler et al ., 2018) which was correlated with positive symptom severity. Greater perfusion in the putamen and thalamus has also been identified as a potential marker of genetic susceptibility for schizophrenia spectrum disorders in a neuroimaging twin study (Legind et al ., 2019). Conversely, although both increased (Allen et al ., 2016) and decreased (Kindler et al ., 2018) prefrontal perfusion has been observed in CHR and established psychosis groups (Schobel et al ., 2009), we did not find differences here in the present exploratory analyses.…”

Reward Processing as an Indicator of Vulnerability or Compensatory Resilience in Psychoses? Results From a Twin Study

“…All participants provided written informed consent. Data on other measures from the twin cohort have previously been published ( 18 , 19 , 20 , 21 ).…”