ReviewSex/gender differences in the brain and cognition in schizophrenia
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.
Section snippets
Schizophrenia overview
Schizophrenia is one of the most complex and least understood psychiatric disorders. It is typically referred to as a ‘chronic and debilitating’ condition because it may lead to a progressive functional decline impacting cognitive, affective and social domains (Tandon et al., 2009). However, some individuals diagnosed with the disorder function relatively well, maintain their employment, and have families and friends. In addition to the varied course of the illness, the clinical presentation of
Birth complications & premorbid function
Obstetric complications have been linked to an overall increased risk to develop schizophrenia, an earlier age of illness onset, a poorer course of the illness and a ventricular enlargement (Kelly et al., 2004, Allen et al., 2013). Several studies have examined sex differences in these effects and found that the risk of developing schizophrenia following obstetric complications was higher in males than in females (Dalman et al., 1999, Kirov et al., 1996, Lewis, 1992, Lewis and Murray, 1987,
Gross neuroanatomy
One of the most robust neuroanatomical findings in schizophrenia is the enlargement of ventricles and related decreases in the total brain volume and in cortical and subcortical tissue, which appear to be particularly pronounced in the prefrontal cortex (PFC), superior temporal cortex and the hippocampal formation (Meisenzahl et al., 2008, Sun et al., 2009, Steen et al., 2006, Lang et al., 2006, Harrison and Weinberger, 2005). This increased ventricular-brain ratio (VBR) has been observed in
Sex/gender differences in cognitive function of schizophrenia patients
Given the reports of more severe gross neuroanatomical abnormalities and more negative symptoms in men relative to women with schizophrenia, one would also expect to observe more neurocognitive deficits in male patients, but the available evidence is less straightforward. Thus, some studies have reported superior cognitive function in women relative to men patients, others found the opposite effect or no sex/gender difference, while some observed a reversal of normal sexual dimorphism. These
Sex/gender differences in brain function of schizophrenia patients
Numerous studies of sex differences in brain structure and cognitive function in schizophrenia have been published, while the functional neuroimaging literature remains very modest in comparison. We have carried out several studies of sex and gender differences in the neural function associated with cognitive (Jimenez et al., 2010, Guillem et al., 2009) and emotion processing (Mendrek et al., 2007, Lakis et al., 2011) and found some alterations of a normal sexual dimorphism. Thus, in one of the
Sex steroid hormones and neurocognitive function in schizophrenia
Sex steroid hormones have been shown to influence cognitive capacities in the general population. For example, performance and cerebral function associated with visuo-spatial abilities have been related to levels of testosterone in men, with an overall positive correlation or an inverted-U shape function (Mendrek et al., 2011, Hines, 2010, Schoning et al., 2007), while performance and cerebral activations associated with language and verbal memory tasks have been positively correlated with
Gender and neurocognitive function in schizophrenia
The question of gender role socialization, gender role adherence and gender identity in schizophrenia, remains largely unexamined despite the fact that gender identity problems have been proposed to play a significant role in the diathesis-stress theory of the disorder almost 40 years ago (LaTorre, 1976). As mentioned already in the opening paragraph, several authors identify sex and gender as two independent realms with ‘sex’ referring to the biological and physical characteristics, while
Conclusions
Although variable and not free from limitations, the presented literature on neuroanatomical and neurocognitive sex/gender differences in schizophrenia has led us to discern a few emerging patterns of results. First, in terms of neuroanatomical differences we see that many studies of gross morphology show greater reductions in the total brain volume, VBR, frontal and temporal lobe, in men than in women with schizophrenia (Andreasen et al., 1990b, Bryant et al., 1999). These findings appear to
References (240)
- et al.
Covariance modeling of MRI brain volumes in memory circuitry in schizophrenia: sex differences are critical
NeuroImage
(2011) - et al.
Superior mentalizing abilities of female patients with schizophrenia
Psychiatry Res.
(2013) - et al.
Are there gender differences in neuropsychological performance in patients with first-episode schizophrenia?
Schizophr. Res.
(1997) - et al.
Differences in developmental changes in academic and social premorbid adjustment between males and females with schizophrenia
Schizophr. Res.
(2013) - et al.
Digit length pattern in schizophrenia suggests disturbed prenatal hemispheric lateralization
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2004) The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues
Horm. Behav.
(2009)- et al.
No sex differences in neuropsychological performance in first episode psychosis patients
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2014) - et al.
Testosterone and gonadotropins but not estrogen associated with spatial ability in women suffering from schizophrenia: a double-blind, placebo-controlled study
Psychoneuroendocrinology
(2008) - et al.
Genetic modifiers and subtypes in schizophrenia: investigations of age at onset, severity, sex and family history
Schizophr. Res.
(2014) - et al.
The etiology of schizophrenia and the origin of language: overview of a theory
Compr. Psychiatry
(2003)
Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia
Psychiatry Res.
Cognitive correlates of verbal memory and verbal fluency in schizophrenia, and differential effects of various clinical symptoms between male and female patients
Schizophr. Res.
The influence of sex versus sex-related traits on long-term memory for gist and detail from an emotional story
Conscious Cogn.
Persistent negative symptoms in first-episode schizophrenia: a prospective three-year follow-up study
Schizophr. Res.
Increased ratio of 2nd to 4th digit (2D:4D) in schizophrenia
Psychiatry Res.
Schizophrenia as the price that homo sapiens pays for language: a resolution of the central paradox in the origin of the species
Brain Res. Brain Res. Rev.
Indicators of developmental deviance in individuals at risk for schizophrenia
Schizophr. Res.
Insular volumes in first-episode schizophrenia: gender effect
Schizophr. Res.
Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders
J. Psychiatr. Res.
Gender and the expression of schizophrenia
J. Psychiatr. Res.
Gender and schizophrenia: implications for understanding the heterogeneity of the illness
Psychiatry Res.
Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability
Biol. Psychiatry
Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS
Schizophr. Res.
Sex differences in memory processing in schizophrenia: an event-related potential (ERP) study
Prog. Neuropsychopharmacol. Biol. Psychiatry
Schizophrenia throughout life: sex differences in severity and profile of symptoms
Schizophr. Res.
Brain region and sex differences in age association with brain volume: a quantitative MRI study of healthy young adults
Am. J. Geriatr. Psychiatry
A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia
Biol. Psychiatry
Gender differences in schizophrenia
Psychoneuroendocrinology
Cognitive impairment but preservation of sexual dimorphism in cognitive abilities in chronic schizophrenia
Psychiatry Res.
Gender differences in cognitive function of patients with chronic schizophrenia
Prog. Neuropsychopharmacol. Biol. Psychiatry
Interactive effects of sex hormones and gender stereotypes on cognitive sex differences—a psychobiosocial approach
Psychoneuroendocrinology
Sex-related variation in human behavior and the brain
Trends Cogn. Sci.
Sex differences in visuo-spatial processing: an fMRI study of mental rotation
Neuropsychologia
Hippocampal size in women but not men with schizophrenia relates to disorder duration
Psychiatry Res.
Sex differences in cognitive functioning in at-risk mental state for psychosis, first episode psychosis and healthy control subjects
Eur. Psychiatry
The case for not combining men and women in neurocognitive studies for schizophrenia
Schizophr. Res.
Disturbed sexual dimorphism of brain activation during mental rotation in schizophrenia
Schizophr. Res.
Sex differences in schizophrenia
Int. Rev. Psychiatry
Premorbid functioning, cognitive functioning, symptoms and outcome in schizophrenia
J. Psychiatry Neurosci.
Gender and affect in schizophrenia
Can. J. Psychiatry
The impact of familial loading on gender differences in age at onset of schizophrenia
Acta Psychiatr. Scand.
Gender differences in schizophrenia
J. Nerv. Ment. Dis.
Diagnosis and classification of schizophrenia
Schizophr. Bull.
Positive and negative symptoms in schizophrenia. A critical reappraisal
Arch. Gen. Psychiatry
Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities
Arch. Gen. Psychiatry
Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging
JAMA
Gender differences in age at onset of schizophrenia. An overview
Eur. Arch. Psychiatry Neurol. Sci.
Premorbid adjustment as predictor of outcome in schizophrenia: results of a prospective study
Acta Psychiatr. Scand.
Suicidal behaviour and mortality in first-episode psychosis: the OPUS trial
Br. J. Psychiatry
Sex differences in neuropsychological functioning among schizophrenia patients
Aust. N.Z. J. Psychiatry
Cited by (190)
Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia
2024, Journal of Psychiatric ResearchAnti-SFT2D2 autoantibodies alter dendrite spine and cause psychotic behavior in mice
2024, Journal of Psychiatric ResearchThe relationship between negative symptoms and MATRICS neurocognitive domains: A meta-analysis and systematic review
2023, Progress in Neuro-Psychopharmacology and Biological PsychiatryComparison of social cognition and neurocognition in schizophrenia and autism spectrum disorder: A systematic review and meta-analysis
2023, Neuroscience and Biobehavioral ReviewsPrenatal risk factors and postnatal cannabis exposure: Assessing dual models of schizophrenia-like rodents
2023, Neuroscience and Biobehavioral Reviews