PCOS May Predispose Women to Higher Risk of Psychosis, Study Suggests

New research from Finland highlights a potential link between polycystic ovary syndrome (PCOS) and receiving a diagnosis of a severe mental, or psychotic, disorder, according to the study published in Archives of Women’s Mental Health.

Although much is known regarding the risk for certain psychological comorbidities among women with PCOS—chiefly, depression, anxiety, bipolar disorder, and disordered eating—less is known about the risk of more severe psychiatric diseases, such as schizophrenia, among this group.

“Against this background, the objective of the present work was to investigate whether women with PCOS are at higher risk for psychotic disorders,” the authors wrote.

The Northern Finland Birth Cohort 1966 provided the authors their study population (124 women with PCOS vs 2145 controls), with the PCOS cohort identified via questions on their oligo-amenorrhea and hirsutism status. The data was collected from participants at age 31

National register data on psychiatric diagnoses were also provided, and the Social Anhedonia Scale (SAS), Physical Anhedonia Scale (PHAS), Perceptual Aberration Scale (PAS), Hypomanic Personality Scale (HPS), Bipolar II scale (BIP2), and Schizoidia Scale (SCHD) helped to identify psychopathological symptoms.

More women in the PCOS group had a body mass index (BMI) of at least 25 or 30 kg/m2 (53.7% vs 29.8%), their testosterone levels were higher (1.39 [range, 1.17-1.79] vs 0.98 [range, 0.75-1.16] nmol/L; P < .001), and their free androgen index (FAI) more often fell in the upper quartile (67.1% vs 20.1%; P < .001). Incidence of parental psychosis was almost equal between the PCOS and control groups, respectively: 6.5% vs 6.2%.

Using an age cutoff of 50 years, this investigation found an almost 3-fold higher lifetime prevalence up to age 50 of any psychoses in the PCOS cohort compared with the control group: 8.1% vs 2.8%. In addition, the lifetime prevalence of psychoses other than schizophrenia was 3.5 times greater, at 5.6% vs 1.6% (P = .006), respectively.

An analysis of women aged 31 to 50 showed similar results. Women with PCOS had a greater incidence of psychosis compared with controls (5.8% vs 2.2%; P = .023). In particular, while no difference was seen in schizophrenia incidence between the groups (0.8% and 0.9%, respectively; P = .96), the overall incidence of other psychoses was almost 4-fold higher in the women with PCOS (5.7% vs 1.5%; P = .004).

When looking at risks of lifetime diagnoses of psychosis, analyses up until age 50 years and women ages 31 to 50 years continued the trend of elevated findings in women with PCOS. A Cox regression model and adjusting for parental psychoses both showed close to a 200% higher risk of any psychosis:

• Cox regression model: HR, 2.99 (95% CI, 1.53-5.83)
• Parental psychoses: HR, 2.98 (95% CI, 1.52-5.82)

The finding of schizophrenia risk until age 50 was not considered statistically significant, while risk of other psychoses alone and from parental psychoses again were higher:

• Other psychoses: HR, 3.66 (95% CI, 1.62-8.26)
• Parental psychoses: HR, 3.62 (95% CI, 1.61-6.10)

For women aged 31 to 50 with PCOS, elevated risks of psychoses continued to be seen following a Cox regression model and after adjusting for parental history of psychoses, at HRs of 2.69 (95% CI, 1.21-5.94) and 2.68 (95% CI, 1.21-5.92), respectively.

Additionally, for women who agreed to a clinical examination and blood tests at age 31 and were shown to have hirsutism, the incidence of a psychosis diagnosis between ages 31 and 50 was more than 3 times higher (9.5% vs 2.8%). Adjusting for testosterone level (HR, 3.03; 95% CI, 1.26-7.31) and FAI (HR, 2.85; 95% CI, 1.09-7.49) showed elevated risks, too, for women with PCOS.

The psychopathology scales showed mixed results. While the scales for PAS and HPS were significantly higher among the women with PCOS compared with the controls, similar results were not seen for SAS, PHAS, or BIP2.

When explaining why their findings are significant, the authors noted that their community-based findings are the first to show elevated psychoses risk among women with PCOS vs a control population to age 50. In particular, that parental history of psychosis did not influence this risk nor did isolated PCOS symptoms, BMI, or biochemical hyperandrogenism in adulthood.

Underestimation of the prevalence of severe psychiatric comorbidity in women with PCOS was a principal limitation on these study findings and the results of self-reported PCOS diagnoses, low attendance to data collection, and the low totals of schizophrenia and psychosis cases among the women with PCOS.

“Future research should focus on investigating the mechanisms behind this association, thus enabling prevention and new treatment strategies,” the authors concluded. “The fact that women with PCOS seem to have a high risk of psychiatric comorbidities warrants devoting more resources and greater efforts to improve awareness, treatment modalities, and quality of life.”

Reference

Karjula S, Arffman RK, Morin-Papunen L, et al. A population-based follow-up study shows high psychosis risk in women with PCOS. Arch Womens Ment Health. Published online November 29, 2021. doi:10.1007/s00737-021-01195-4