Heritability of specific cognitive functions and associations with schizophrenia spectrum disorders using CANTAB: a nation-wide twin study.

BACKGROUND: Many cognitive functions are under strong genetic control and twin studies have demonstrated genetic overlap between some aspects of cognition and schizophrenia. How the genetic relationship between specific cognitive functions and schizophrenia is influenced by IQ is currently unknown. METHODS: We applied selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to examine the heritability of specific cognitive functions and associations with schizophrenia liability. Verbal and performance IQ were estimated using The Wechsler Adult Intelligence Scale-III and the Danish Adult Reading Test. In total, 214 twins including monozygotic (MZ = 32) and dizygotic (DZ = 22) pairs concordant or discordant for a schizophrenia spectrum disorder, and healthy control pairs (MZ = 29, DZ = 20) were recruited through the Danish national registers. Additionally, eight twins from affected pairs participated without their sibling. RESULTS: Significant heritability was observed for planning/spatial span (h2 = 25%), self-ordered spatial working memory (h2 = 64%), sustained attention (h2 = 56%), and movement time (h2 = 47%), whereas only unique environmental factors contributed to set-shifting, reflection impulsivity, and thinking time. Schizophrenia liability was associated with planning/spatial span (rph = -0.34), self-ordered spatial working memory (rph = -0.24), sustained attention (rph = -0.23), and set-shifting (rph = -0.21). The association with planning/spatial span was not driven by either performance or verbal IQ. The remaining associations were shared with performance, but not verbal IQ. CONCLUSIONS: This study provides further evidence that some cognitive functions are heritable and associated with schizophrenia, suggesting a partially shared genetic etiology. These functions may constitute endophenotypes for the disorder and provide a basis to explore genes common to cognition and schizophrenia.

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

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.