“In the general population, insomnia is associated with greater cognitive impairment, but its association (and potential sex-dimorphic effect) in schizophrenia is less clear.”
There is increased recognition of gender differences in the epidemiology and phenomenology of schizophrenia. For example, compared to men, women have a slightly lower incidence of the disease, a later age of onset, and more depressive symptoms.1.2 Such gender differences may be mediated, in part, by the neuroprotective effects of estrogen.3 In contrast, findings regarding sex differences in cognition in schizophrenia are inconsistent.2 Insomnia is also common in the clinical course of schizophrenia.4 In the general population, insomnia is associated with greater cognitive impairment, but its association (and potential effect of sexual dimorphism) in schizophrenia is less clear.
“Mrs. Smith” is a 50-year-old white woman with a 20+ year history of schizoaffective disorder, bipolar type, and a distant history of cerebellar hemorrhagic stroke. She has been on a stable dose of antipsychotic medication for the past 10 years, before which a trial of clozapine was halted due to its tolerability and adverse effects. She sleeps chronically 3 to 5 hours a night, with initial and terminal insomnia. She has chronic auditory hallucinations, thought insertion, and persecutory beliefs. She also suffers from chronic cognitive impairment, which is thought to be partly due not only to her chronic psychotic illness, but to a sequel of an old cerebellar infarction. She got a technical diploma in 2 years after high school. She has completed various forms of the Numerical Symbol Coding Test on several outpatient psychiatric clinic visits over the years, with a mean (SD) score of 31 ± 4. A Trial of Adjuvant Electroconvulsive Therapy for Residual Positive Symptoms of Psychosis was discontinued due to exacerbation of cognitive impairment.
Zhu and colleagues studied gender differences in insomnia and cognition in a large sample of Chinese patients with chronic schizophrenia.5 They recruited 718 patients (480 men and 238 women) with chronic schizophrenia from 2 psychiatric hospitals, as well as 397 healthy controls (169 men and 228 women) with no personal or family history of psychiatric or neurological disease. Patient inclusion criteria were 17 to 70 years old; Han Chinese ethnicity; DSM-IV diagnosis of schizophrenia; and stable antipsychotic dose for > 6 months. Patients were excluded if they had any of the following: a history of neurological disease or drug or alcohol abuse; current serious medical comorbidity; head injury; or current pregnancy or breastfeeding.
Insomnia was assessed both as a categorical (yes/no) and continuous measure with the Insomnia Severity Index (ISI). Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed with the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). The authors used 2 x 2 ANOVA (insomnia x gender) and Spearman’s correlation coefficients to investigate gender differences in clinical variables in patients with and without insomnia.
The average age of the subjects was 46 years. There was a significant increase in the prevalence of (categorical) insomnia in women compared to men with schizophrenia (25.6% vs 18.3%; OR, 1.54). Women with schizophrenia also had significantly higher total scores and PANSS subscales. Men with schizophrenia had higher (better) total, visuospatial/constructional, and linguistic RBANS scores than women. In both men and women with schizophrenia, patients with (categorical) insomnia had higher PANSS scores than those without insomnia. In contrast, there was no difference in RBANS scores in men with vs without insomnia. However, women with insomnia had lower total scores and RBANS subscales. As a continuous measure, ISI scores were significantly and negatively correlated with RBANS total scores, language, attention, and delayed memory scores in men (P = -0.14 to -0.12 for each) . In contrast, ISI scores were significantly negatively correlated with RBANS total scores (P = –.18) and immediate memory scores (P = –.19) in women.
Conclusions of the study
The authors concluded that women with schizophrenia had an increased prevalence of insomnia and greater cognitive impairment than men. They also found gender differences in the correlations between insomnia and cognition in these patients. Strengths of the study included the large cumulative sample size. Study limitations included cross-sectional study design and non-standardized antipsychotic (and other) medications in the study sample. Future studies should examine associations between insomnia and cognition using a longitudinal design and also in patients with first-episode schizophrenia and without antipsychotics.
The results support evidence for gender differences in insomnia and cognition in patients with schizophrenia. Given its association with more severe symptoms and greater cognitive impairment, insomnia represents an important potential therapeutic target in this patient population.
Dr. Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the editorial board and is chief of the schizophrenia section for Psychiatric timeMT. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.
1. Riecher-Rössler A. Sex and gender differences in schizophrenic psychoses. Eur Psychiatry. 2016;33(S1):S46.
2. Ochoa S, Usall J, Cobo J, et al. Gender differences in schizophrenia and first episode psychosis: a comprehensive literature review. Treatment of schizophrenia. 2012;2012:916198.
3. Riecher-Rössler A. Estrogens, prolactin, hypothalamic-pituitary-gonadal axis and schizophrenic psychoses. Lancet Psychiatry. 2017;4(1):63-72.
4. Hou CL, Li Y, Cai MY, et al. The prevalence of insomnia and clinical and quality-of-life correlations in Chinese patients with schizophrenia treated in primary care. Perspect Psychiatric Care. 2017;53(2):80-86.
5. Zhu R, Wang D, Tian Y, et al. Gender difference in the association between insomnia and cognitive impairment in patients with chronic schizophrenia. Schizophrenia. 2022;240:143-149. ❒