Sex Differences in Insomnia and Cognition in Schizophrenia

RESEARCH UPDATE

There is increased recognition of sex differences in the epidemiology and phenomenology of schizophrenia. For example, compared to males, females have a slightly lower incidence of the disorder, a later age of onset, and more depressive symptoms.^1,2 Such sex differences may be mediated, in part, due to neuroprotective effects of estrogen.³ By 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 sexual dimorphic effect) in schizophrenia is less clear.

Case Vignette

“Ms Smith” is a 50-year-old Caucasian female with a 20+ year history of schizoaffective disorder, bipolar type, and a remote history of a cerebellar hemorrhagic stroke. She has been on a stable dose of antipsychotic medication for the past 10 years, prior to which a clozapine trial was discontinued due to tolerability and adverse effects. She chronically sleeps 3 to 5 hours per night, with both initial and terminal insomnia. She has chronic auditory hallucinations, thought insertion, and persecutory beliefs. She also has chronic cognitive impairment, thought to be in part due to not only her chronic psychotic illness, but also a sequela of the past cerebellar infarct. She graduated with a 2-year technical degree after high school. She has completed different forms of the Digit Symbol Coding test at multiple outpatient psychiatric clinic visits over the years, with a mean (SD) score of 31±4. A trial of adjunctive electroconvulsive therapy for residual positive symptoms of psychosis was discontinued due to exacerbation of cognitive impairment.

The Current Study

Zhu and colleagues investigated sex differences in insomnia and cognition in a large sample of Chinese patients with chronic schizophrenia.⁵ They recruited 718 patients (480 males and 238 females) with chronic schizophrenia from 2 psychiatric hospitals and 397 healthy controls (169 males and 228 females) without a personal or family history of psychiatric or neurological disease. Inclusion criteria for patients were age 17 to 70, Chinese Han ethnicity, DSM-IV diagnosis of schizophrenia, and stable antipsychotic dose for > 6 months. Patients were excluded if they had a history of neurological disease, severe medical comorbidity, head injury, pregnancy or lactation, or history of drug or alcohol abuse.

Insomnia was assessed as both a categorical (yes/no) and a continuous measure with the Insomnia Severity Index (ISI). Symptoms were rated using the Positive and Negative Syndrome Scale (PANSS). Cognition was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The authors used 2 x 2 ANOVA (insomnia x sex) and Spearman correlation coefficients to investigate sex differences in clinical variables in patients with and without insomnia.

The mean subject age was 46. There was a significantly increased prevalence of (categorical) insomnia in females versus males with schizophrenia (25.6% versus 18.3%, OR=1.54). Females with schizophrenia also had significantly higher PANSS total and subscale scores. Males with schizophrenia had higher (better) RBANS total, visuospatial/constructional, and language scores than females. In both males and females with schizophrenia, patients with (categorical) insomnia had higher PANSS scores than those without insomnia. By contrast, there was no difference in RBANS scores in males with versus without insomnia. However, females with insomnia had lower RBANS total and subscale scores. As a continuous measure, ISI scores were significantly, negatively correlated with RBANS total scores, language, attention, and delayed memory scores in males (ρ=-0.14 - -0.12 for each). By contrast, ISI scores were significantly negatively correlated with RBANS total scores (ρ=-0.18) and immediate memory (ρ=-0.19) scores in females.

Study Conclusions

The authors concluded that females with schizophrenia had an increased prevalence of insomnia and greater cognitive impairment than males. They also found sex differences in correlations between insomnia and cognition in these patients. Study strengths included the large cumulative sample size. Study limitations included the cross-sectional study design and the nonstandardized antipsychotic (and other) medications in the study sample. Future studies should consider associations between insomnia and cognition using a longitudinal design and also in first-episode and antipsychotic-free patients with schizophrenia.

The Bottom Line

Findings support evidence for sex differences in insomnia and cognition in patients with schizophrenia. Given associations with more severe symptoms and greater cognitive impairment, insomnia represents an important potential treatment target in this patient population.

Dr Miller is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times^TM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

References

1. Riecher-Rossler 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. Schizophr Res Treatment. 2012;2012:916198.

3. Riecher-Rossler A. Oestrogens, prolactin, hypothalamic-pituitary-gonadal axis, and schizophrenic psychoses. Lancet Psychiatry. 2017;4(1):63-72.

4. Hou CL, Li Y, Cai MY, et al. Prevalence of insomnia and clinical and quality of life correlates in Chinese patients with schizophrenia treated in primary care. Perspect Psychiatr Care. 2017;53(2):80-86.

5. Zhu R, Wang D, Tian Y, et al. Sex difference in association between insomnia and cognitive impairment in patients with chronic schizophrenia. Schizophr Res. 2022;240:143-149.