A glimpse of gender differences in schizophrenia

Li, Xin; Zhou, Wanyan; Yi, Zhenghui

doi:10.1136/gpsych-2022-100823

Cited by 46 publications

(20 citation statements)

References 22 publications

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“…In humans, there is a marked divergence in the incidence, cast of symptoms, and age of onset of SCZ in men compared to women. This sex-dependent imbalance is most obvious in the prevalence of SCZ between sexes, impacting men vs. women at a rate of roughly 1.4:1 (132,133) but is further supported by an earlier onset of symptoms and poorer functional outcome in males (134–137). The SCZ odds ratio associated with the four most common C4 alleles are all higher in men than in women (138) and protein levels of C4 and downstream effector, C3, are also higher in the cerebrospinal fluid of men compared to women (138).…”

Section: Discussionmentioning

confidence: 97%

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction

Fournier,

Phadke,

Salgado

et al. 2024

Preprint

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Fast-spiking parvalbumin (PV)-positive cells are key players in orchestrating pyramidal neuron activity and thus serve an indispensable role in cognitive function and emotional regulation. Feed-forward excitatory inputs, essential for the function of PV cells, are disrupted in various neurological conditions, including schizophrenia (SCZ). However, it is not clear how disease-associated stressors such as immune dysregulation contribute to defects in particular cell types or neuronal circuits. We have developed a novel transgenic mouse line that permits conditional, cell-type specific overexpression (OE) of the immune complement component 4 (C4) gene, which is highly associated with SCZ. Using this genetic approach, we demonstrate that specific global OE of mouse C4 (mC4) in PV cells causes pathological anxiety-like behavior in male, but not female mice. In the male medial prefrontal cortex (mPFC), this sexually dimorphic behavioral alteration was accompanied by a reduction in excitatory inputs to fast-spiking cells and an enhancement of their inhibitory connections. Additionally, in PV cells, elevated levels of mC4 led to contrasting effects on the excitability of cortical cells. In males, PV cells and pyramidal neurons exhibited reduced excitability, whereas in females, PV cells displayed heightened excitability. Contrary to the behavioral changes seen with elevated mC4 levels in PV cells, pan-neuronal overexpression did not increase anxiety-like behaviors. This indicates that mC4 dysfunction, particularly in fast-spiking cells, has a more significant negative impact on anxiety-like behavior than widespread alterations in the neuronal complement. Consequently, by employing a novel mouse model, we have demonstrated a causal relationship between the conditional overexpression of the schizophrenia risk gene C4 in fast-spiking neurons and the susceptibility of cortical circuits in male mice, resulting in changes in behaviors associated with prefrontal cortex function.

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Section: Discussionmentioning

confidence: 97%

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction

Fournier,

Phadke,

Salgado

et al. 2024

Preprint

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“…Sex differences in the neurobiological underpinnings of PLEs, and psychosis more broadly, have been largely understudied to date. In schizophrenia, men and males have a greater risk of developing negative symptoms (e.g., avolition, anhedonia, alogia), while women and females tend to display more affective symptoms (e.g., depression, impulsivity, emotional instability) [9,36]. Women and females also exhibit stronger cognitive functioning along executive, verbal, and processing domains, while men and males outperform females along memory and attention domains [36].…”

Section: Discussionmentioning

confidence: 99%

“…In schizophrenia, men and males have a greater risk of developing negative symptoms (e.g., avolition, anhedonia, alogia), while women and females tend to display more affective symptoms (e.g., depression, impulsivity, emotional instability) [9,36]. Women and females also exhibit stronger cognitive functioning along executive, verbal, and processing domains, while men and males outperform females along memory and attention domains [36]. Women and females are at a particularly elevated risk of developing psychosis during critical hormonal transition periods (e.g., pregnancy, post-partum, menopause) [37], and earlier menarche is associated with a later onset of schizophrenia [38].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the functional network underpinnings of psychotic-like experiences in children

Dhamala,

Chopra,

Ooi

et al. 2024

Preprint

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Psychotic-like experiences (PLEs) include a range of sub-threshold symptoms that resemble aspects of psychosis but do not necessarily indicate the presence of psychiatric illness. These experiences are highly prevalent in youth and are associated with developmental disruptions across social, academic, and emotional domains. While not all youth who report PLEs develop psychosis, many develop other psychiatric illnesses during adolescence and adulthood. As such, PLEs are theorized to represent early markers of poor mental health. Here, we characterized the similarities and differences in the neurobiological underpinnings of childhood PLEs across the sexes using a large sample from the ABCD Study (n=5,260), revealing sex-specific associations between functional networks connectivity and PLEs. We find that although the networks associated with PLEs overlap to some extent across the sexes, there are also crucial differences. In females, PLEs are associated with dispersed cortical and non-cortical connections, whereas in males, they are primarily associated with functional connections within limbic, temporal parietal, somato/motor, and visual networks. These results suggest that early transdiagnostic markers of psychopathology may be distinct across the sexes, further emphasizing the need to consider sex in psychiatric research as well as clinical practice.

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“…After this peak, there is a gradual decline in onset, although there is indication of a second peak around age 40, which may have some relation to the menopause, although this requires further investigation. Studies have shown that men are more likely to be assigned a diagnosis of schizophrenia, whereas women are more likely to be assigned a diagnosis of bipolar disorder (Dell'Osso et al, 2021; Li et al, 2022).…”

Section: Developmental Coursementioning

confidence: 99%

Schizophrenia and other primary psychotic disorders.

Lincoln,

French

2024

A Psychological Approach to Diagnosis: Using the ICD-11 as a Framework.

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Schizophrenia and other primary psychotic disorders are characterized by the presence of one or more psychotic experiences, such as aberrations in per ception (hallucinations), beliefs (delusions), or visible behavior (disorganized speech, bizarre behavior; World Health Organization [WHO], 2024). A central feature is referred to as loss of touch with reality, in which the person perceives things that others do not (e.g., hearing voices), holds on to extreme beliefs that deviate from the cultural norm without convincing proof (e.g., beliefs about being persecuted), or has difficulties making themself understood. However, it is important to recognize that loss of touch with reality typically only relates to the individual's symptoms and not to a broader or complete breakdown of under standing and orientation.The grouping of schizophrenia and other primary psychotic disorders in the 11th revision of the International Classification of Diseases (ICD-11; WHO, 2023) includes six categories: schizophrenia, schizoaffective dis order, schizotypal disorder, acute and transient psychotic disorder, delusional disorder, and other primary psychotic disorder. These categories differ in regard to the intensity of the symptoms (e.g., symptoms in schizotypal disorder are less pronounced than in the other categories), their duration (e.g., symptoms are of shorter duration in acute and transient psychotic disorder), the range of the experiences included (e.g., delusional disorder does not typically involve other psychotic symptoms),

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A glimpse of gender differences in schizophrenia

Cited by 46 publications

References 22 publications

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction

Sex differences in the functional network underpinnings of psychotic-like experiences in children

Schizophrenia and other primary psychotic disorders.

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