Schizophrenia: Clinical Considerations in Men Versus Women

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RESEARCH UPDATE

The most consistently reported gender difference in schizophrenia is higher age of onset in women, though many domains may be affected.¹ Symptomatology and the course of illness may also vary between gender, but the extant literature is inconsistent, with less consistent data on a possibly better clinical course and lower mortality in women.^2,3 These differences raise the possibility for gender-specific guidelines for early diagnosis and treatment.

Summer and colleagues⁴ aimed to describe the clinical course of schizophrenia in both genders. They included all persons hospitalized for schizophrenia or schizoaffective disorder in Finland between 1972 and 2014 ages 16 to 65 years (between 2000 and 2014). Data were also retrieved from the Hospital Discharge Register, the national Prescription Register, and the National Death Register. The authors included 16,148 patients (n = 7142 women and n = 9006 men). Schizoaffective disorder was diagnosed for 31% of women and 18% of men.

5 years before schizophrenia diagnosis

Over 70% of participants had been hospitalized for another psychiatric disorder and had used antipsychotic medication before the first hospitalization for schizophrenia. Women were more likely to have mood, anxiety, eating, dissociative, and personality disorders, as well self-harm and suicide attempts during this period. Men were more likely to have substance use and autism spectrum disorders.

Age at diagnosis

Men received a diagnosis of schizophrenia earlier than women (mean age 34.4 versus 38.2). Men showed a peak around aged 22 years, with a right-skewed distribution, and women showed a more plateau-like distribution with higher values between the ages of 18 and 35 years and only slowly decreasing incidence through aged 65 years.

Re-hospitalizations after schizophrenia diagnosis

During a mean 8-year follow-up, 70% of both men and women had a psychiatric re-hospitalization, although women had a nominally higher rate of psychiatric re-hospitalization. The mean duration of hospitalizations were similar for both genders. Hospitalization for suicide attempts and self-harm was significantly more prevalent in women (8.2%) than men (5.9%).

Pharmacotherapy

During the first 5 years after the first hospitalization for schizophrenia, 97% of women and 94% of men were prescribed antipsychotic medication. Men more often than women used clozapine, olanzapine, and long-acting antipsychotics, while women more often used quetiapine and aripiprazole. Women were also more likely to use antidepressants, mood stabilizers, benzodiazepines, and zopiclon/zolpidem.

Mortality

During the follow-up (up to 17 years), 15.4% of men and 10.7% of women died, corresponding to an adjusted hazard ratio for women of 0.54 (95% CI = 0.50-0.60). Men were more likely to die by suicide and cardiovascular disease, and women had a higher cancer mortality rate.

The authors concluded that this was the largest cohort describing gender-specific differences in course of illness in schizophrenia before and after diagnosis.They found a higher gender-specific incidence in men, which may reflect effects of higher genetic vulnerability and substance use in men, and protective effects of estrogens in women.An important finding is the later mean age at diagnosis in women, which raises the possibility of diagnostic delay in women.Another important finding is that rates of psychiatric rehospitalizations were the same in both genders, which does not support a milder course of illness in women. Major strengths of the study are the large sample size and the use of Finnish registers, which eliminate selection bias and minimize loss to follow-up.

The bottom line

Gender differences in schizophrenia are extensive for comorbidity, age at diagnosis and mortality, but not for mean number of hospitalizations and re-hospitalization risk (a warning not to undertreat women).Findings support a diagnostic delay in women and the use of gendered approaches in early detection.

Dr Miller is Professor, Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is the Schizophrenia Section Chief for Psychiatric Times. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.

References

1. Cotton SM, et al. Gender differences in premorbid, entry, treatment, and outcome characteristics in a treated epidemiological sample of 661 patients with first episode psychosis. Schizophr Res. 2009;114:17–24.

2. Seeman MV. Does gender influence outcome in schizophrenia? Psychiatr Q. 2019;90:173-184.

3. Hjorthøj C, Stürup AE, McGrath JJ, et al. Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry. 2017;4:285–301.

4. Sommer IE, Tiihonen J, van Mourik A, et al. The clinical course of schizophrenia in women and men: A nation-wide cohort study. NPJ Schizophrenia. 2020;6:12.