Genetics, Cognition, and Neurobiology of Schizotypal Personality: A Review of the Overlap with Schizophrenia

Abstract

Schizotypy refers to a set of temporally stable traits that are observed in the general population and that resemble the signs and symptoms of schizophrenia. Here, we review evidence from studies on genetics, cognition, perception, motor and oculomotor control, brain structure, brain function, and psychopharmacology in schizotypy. We specifically focused on identifying areas of overlap between schizotypy and schizophrenia. Evidence was corroborated that significant overlap exists between the two, covering the behavioral brain structural and functional as well molecular levels. In particular, several studies showed that individuals with high levels of schizotypal traits exhibit alterations in neurocognitive task performance and underlying brain function similar to the deficits seen in patients with schizophrenia. Studies of brain structure have shown both volume reductions and increase in schizotypy, pointing to schizophrenia-like deficits as well as possible protective or compensatory mechanisms. Experimental pharmacological studies have shown that high levels of schizotypy are associated with (i) enhanced dopaminergic response in striatum following administration of amphetamine and (ii) improvement of cognitive performance following administration of antipsychotic compounds. Together, this body of work suggests that schizotypy shows overlap with schizophrenia across multiple behavioral and neurobiological domains, suggesting that the study of schizotypal traits may be useful in improving our understanding of the etiology of schizophrenia.

Evidence From Structural and Diffusion Tensor Imaging for Frontotemporal Deficits in Psychometric Schizotypy

“…21 Several studies have examined the neurobiological basis of schizotypal personality disorder (SPD), a disorder characterized by severe schizotypal traits including asocial tendencies, difficulties with language, paranoia, odd behavior, and magical thinking. Recent reviews [22][23][24] suggest that at the structural level, SPD is associated with temporal lobe abnormalities comparable to those observed in SZ while frontal lobe regions may be more spared. Moreover, the aforementioned reviews also suggest that low fractional anisotropy (FA), a measure broadly associated with white matter integrity, in the uncinate fasciculus (UF) and temporal lobe is present in SPD; a finding generally consistent with those observed in SZ.…”

Increased resting perfusion of the hippocampus in high positive schizotypy: A pseudocontinuous arterial spin labeling study

“…HS individuals can be identified using psychometrically validated self‐report instruments such as the Oxford and Liverpool Inventory of Feelings and Experiences (O‐LIFE) (Mason, Linney, & Claridge, 2005). With a large body of evidence supporting shared genetic, environmental, neurobiological, and cognitive‐emotional factors between HS and psychotic disorders (Barrantes‐Vidal, Grant, & Kwapil, 2015; Ettinger, Meyhofer, Steffens, Wagner, & Koutsouleris, 2014; Kwapil & Barrantes‐Vidal, 2015; Nelson et al, 2013), the continuum model would predict that resting hippocampal perfusion is also elevated in individuals with subclinical psychotic‐like experiences. Although neuroimaging studies are yet to test this hypothesis, HS individuals show elevated hippocampal responses to a range of cognitive and emotional tasks (Bourque et al, 2017; Modinos et al, 2017b; Mohanty et al, 2005).…”

Autistic and schizotypal traits and global functioning in bipolar I disorder

“…Indeed, BD has a number of genetic, symptomatological and epidemiological overlaps with SSD (Laursen, Agerbo, & Pedersen, 2009;Lichtenstein et al, 2009;Murray et al, 2004), and psychosis has been recognised as an important dimension in the psychopathology of BD (van Os & Kapur, 2009). In addition, schizotypy, which encompasses a set of personality traits that reflect subclinical expression of schizophrenia (Ettinger et al, 2015), is recognised as genetically related to SSD and is considered an endophenotype common to both SSD and BD (Ettinger, Meyhofer, Steffens, Wagner, & Koutsouleris, 2014;Mahon, Perez-Rodriguez, Gunawardane, & Burdick, 2013;Schurhoff, Laguerre, Szoke, Meary, & Leboyer, 2005). Schizotypy has been reported at elevated rates in individuals with BD compared to healthy controls, although this was conducted in a relatively small BD sample (N=92) (Heron et al, 2003).…”