Sex/gender differences in the brain and cognition in schizophrenia

Highlights

• Evidence of sex differences in the neurocognitive function in schizophrenia is presented.

• Two trends emerge: a) normal sex differences in the lateral frontal network b) disturbed sexual dimorphism in the corticolimbic system.

• Involvement of sex steroid hormones and gender role socialization is discussed.

Abstract

The early conceptualizations of schizophrenia have noted some sex/gender differences in epidemiology and clinical expression of the disorder. Over the past few decades, the interest in differences between male and female patients has expanded to encompass brain morphology and neurocognitive function. Despite some variability and methodological shortcomings, a few patterns emerge from the available literature. Most studies of gross neuroanatomy show more enlarged ventricles and smaller frontal lobes in men than in women with schizophrenia; finding reflecting normal sexual dimorphism. In comparison, studies of brain asymmetry and specific corticolimbic structures, suggest a disturbance in normal sexual dimorphism. The neurocognitive findings are somewhat consistent with this picture. Studies of cognitive functions mediated by the lateral frontal network tend to show sex differences in patients which are in the same direction as those observed in the general population, whereas studies of processes mediated by the corticolimbic system more frequently reveal reversal of normal sexual dimorphisms. These trends are faint and future research would need to delineate neurocognitive differences between men and women with various subtypes of schizophrenia (e.g., early versus late onset), while taking into consideration hormonal status and gender of tested participants.

Introduction

Significant sex/gender differences in schizophrenia have been noted already by Kraepelin (1919/1971) who wrote: “The male sex appears in general to suffer somewhat more frequently and to be affected more severely by the dementia praecox”. In the scientific literature we often use terms ‘sex’ and ‘gender’ interchangeably, but over the past decade several researchers suggested to be more specific and refer to ‘sex’ as a biological variable defined principally by sex chromosomes and sex steroid hormones, while using the term ‘gender’ as a psychosocial construct determined mainly by family, society and culture (Holdcroft, 2007, Mendrek, 2015). Nevertheless, it is difficult to disentangle the influence of these two sets of variables, as they continually interact with each other, especially in humans. This is why we sometimes use ‘sex/gender’ throughout this paper, to indicate that in many discussed studies it is impossible to determine if the differences we are presented with were mainly due to a biological sex or a psychosocial gender, and most likely reflected a combination of both factors. In this review we concentrate on neuroanatomical, neurofunctional and cognitive studies of differences between men and women diagnosed with schizophrenia. Some of these studies have assessed sex steroid hormones, but gender identity and socialization was almost never taken into consideration. Before delving into this literature, a brief introduction to schizophrenia is in order.