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

Abstract

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.

Gene-Environment Pathways to Cognitive Intelligence and Psychotic-Like Experiences in Children

“…Although some studies report the mediating role of cognitive abilities between the GPS and psychopathology in children 16,25 , such approaches have failed to address the potential environmental mechanisms behind this relationship [26][27][28] . Thus, the comprehensive causal trajectories between genes, the environment, intelligence, and psychotic disorders remain unknown.…”

“…Nonetheless, it was not until recently that researchers have drawn systematic research into the relationship between cognition and psychotic disorders in early childhood. Although some studies report the mediating role of cognitive abilities between the GPS and psychopathology in children 16, 25 , such approaches have failed to address the potential environmental mechanisms behind this relationship 26–28 . Thus, the comprehensive causal trajectories between genes, the environment, intelligence, and psychotic disorders remain unknown.…”

Flexible versus Fixed Spatial Self-Ordered Response Sequencing: Effects of Inactivation and Neurochemical Modulation of Ventrolateral Prefrontal Cortex

“…For OCD patients, planning deficits involving flexible self-ordered spatial sequencing are correlated with decreased resting state and functional connectivity between the lPFC and putamen ( Vaghi et al, 2017a,b ). For schizophrenia, similar dysconnectivity between lPFC and basal ganglia has been shown ( Zhou et al, 2007 ) as well as impairments in planning and sequencing tasks with heritable components apparently independent of IQ ( Lemvigh et al, 2020 ).…”

A nation-wide twin study of social cognition in schizophrenia spectrum disorders

“…More twin studies of social cognition are needed, including examinations of other domains of social cognition 7 . Previous twin studies of cognition have suggested that the basic genetic architecture of schizophrenia shows overlap with cognition [10][11][12] , and therefore future studies should examine potential genetic associations between social cognition and schizophrenia liability and how this cognitive domain relates to IQ to further understand the genetic underpinnings of social cognitive deficits in schizophrenia. A better understanding of the pathophysiological processes underlying cognitive impairments in schizophrenia spectrum disorders may increase our understanding of the aetiology of the illness leading from genes to psychopathology.…”

“…Social cognition is also impaired in first-degree relatives of patients with schizophrenia, suggesting that these deficits may be related to the genetic vulnerability of the disorder 8 . Previous twin studies have established that most cognitive functions are strongly influenced by genetics 9 and show genetic overlap with schizophrenia liability, indicating that shared genetic factors influence cognition and schizophrenia risk [10][11][12] . However, twin studies of social cognition in schizophrenia are lacking 9,13 .…”