Psychiatric disorders and comorbidity in women with Turner Syndrome: a retrospective national cohort study

Turner syndrome (TS), the most common chromosomal aneuploidy in females (affecting 1:2,500 live births), results from complete or partial absence of an X chromosome. While TS is not associated with a specific psychiatric syndrome, existing literature suggests a potential link between the genetic factors of TS and an increased risk of neuropsychiatric disorders, particularly anxiety and depression. Previous studies, often small and heterogeneous, have reported a higher lifetime prevalence of depression in women with TS (36–65%) compared to the general population (21%). However, the prevalence of other psychiatric disorders, including bipolar disorder, remains largely unknown. This study aimed to determine the presence and frequency of psychiatric diagnoses in a large, long-term followed Swedish cohort of women with TS to address this knowledge gap and clarify the relationship between TS and psychiatric morbidity.

The literature on psychiatric disorders in women with TS is sparse and inconsistent. While some studies have reported increased rates of depression and anxiety, others have found no significant differences compared to the general population. The association between TS and schizophrenia has also been explored in several case reports and studies, with varying conclusions. The heterogeneity in findings highlights the need for a larger-scale, longitudinal study to provide more robust evidence on the prevalence and correlates of psychiatric disorders in this population. The existing research suggests a potential interplay between genetic factors, hormonal imbalances, and psychosocial challenges specific to TS that may contribute to increased psychiatric vulnerability. The lack of a comprehensive understanding emphasizes the need for further investigation.

This retrospective cohort study included 487 women with TS recruited from Swedish Turner centers. The diagnosis of TS was cytogenetically verified. Data on psychiatric diagnoses between 1994 and 2021 were obtained from the Swedish National Inpatient and Outpatient Register and the National Board of Health and Welfare. The International Classification of Diseases (ICD) codes (ICD-9 and ICD-10) were used to categorize psychiatric diagnoses. The study compared the prevalence of psychiatric diagnoses in the TS cohort with data from the general female population of Sweden. Statistical analyses, including Student's t-test and Chi-squared test, were used to compare continuous and dichotomous variables, respectively. The analyses were conducted using SPSS version 24.0 and SAS version 9.4.

Of the 487 women with TS, 71 (14.6%) had at least one psychiatric diagnosis. The most common diagnoses were mood disorders (9.9%) and anxiety disorders (7.4%). The prevalence of these disorders was significantly lower in the TS group compared to age-matched women in the general population (mood disorders: 36% in the general population vs 9.9% in TS group; anxiety disorders: 11–41% in the general population vs 7.4% in the TS group). Schizophrenia was the only psychiatric diagnosis more prevalent in the TS group (0.6%) compared to the general population (0.4%). There were no significant differences between women with and without psychiatric diagnoses in terms of age, age at TS diagnosis, karyotype, spontaneous puberty, cardiovascular disease, endocrine conditions, partnership status, or childbirth. However, women with TS and psychiatric diagnoses had a higher rate of alcohol dependence (8.5% vs 1.2% in the overall TS group). Comorbidity of psychiatric diagnoses was common, with 65% of women with TS and a psychiatric diagnosis having more than one diagnosis. One woman in the TS group without a psychiatric diagnosis committed suicide.

This study provides valuable insights into the prevalence of psychiatric disorders in a large cohort of women with TS. The finding of lower prevalence of most psychiatric diagnoses compared to the general population suggests that TS itself is not a major risk factor for these conditions. While the increased prevalence of alcohol abuse in the subgroup of women with TS and psychiatric diagnoses warrants attention, the lower prevalence of other common psychiatric disorders challenges previous findings. This could be due to factors such as improved access to healthcare and psychosocial support for women with TS in Sweden, the rigorous clinical monitoring and comprehensive examinations received by the study participants, or other unmeasured factors. The lower than expected prevalence of depression may also be partially explained by the possible confounding impact of ongoing hormone replacement therapy.

This large, long-term follow-up study of women with TS found no overall increase in psychiatric diagnoses compared to the general female population. In fact, the prevalence of most common psychiatric disorders was lower in the TS group. These findings suggest that while certain psychiatric conditions may be more prevalent among specific subgroups of women with TS, particularly those with substance use disorders, TS alone is not a major determinant of psychiatric morbidity. Further research is needed to understand the complex interplay between genetic, hormonal, psychosocial, and environmental factors that influence mental health in women with TS. This research should consider the role of factors such as infertility, hormone levels, and psychosocial support in contributing to mental well-being among women with TS.

This study's limitations include the lack of data on family history of psychiatric disorders in the TS cohort and the absence of clinical data on the general population comparison group. The retrospective nature of the study may also introduce recall bias. The study did not include standardized measures of fatigue and other aspects of neuropsychological functioning, even though those are frequent complaints of individuals with TS. Future studies should utilize prospective designs and incorporate comprehensive assessments to further elucidate the relationship between TS and mental health outcomes.