Psychological aspects in differences / disorders of sex development

Abstract: Background: Sex differentiation depends on a complex set of molecular events. These are at one point initiated by SRY gene expression and involve gene transcription, which in turn can be affected by the prescence or absence of different co-factors, availability of and exposure to sex hormones, presence and sensitivity of steroid receptors that directs growth and development. DSD conditions represent variations in typical sex differentiation with discordance between sex chromosomes, gonads, hormones or genital appearance. Both mechanisms underlying sex differentiation of body, brain, behavior and psychological outcome in many DSD conditions remain understudied. Aim: To increase knowledge of outcome in DSD patient groups regarding psychosocial and psychological parameters and contribute to the knowledge on biological factors with impact on sex differences in cognition and gender role behavior. Study I. Methods: Psychosocial outcome in men and women with congenital adrenal hyperplasia (CAH) (n=588) was assessed through registry studies with regards to education, income and participation in work life, dependency on social welfare, marriage and fertility. Patients were compared to controls from the general population matched for age, sex and place of living. Results: Individuals with CAH had less often completed primary education (OR=0.5), had more periods on sick leave (OR=1.7) and had children less often than controls (OR=0.3). Women with CAH were married less often (OR=0.2) and men were married more often than controls (OR=0.4). Women with SW had income in the top 20% more often (OR=2.0) and both men and women with SW had disability pension more often (OR=2.8). Study II. Methods: Psychiatric morbidity in women with complete androgen insensitivity (CAIS) (n=20), gonadal dysgenesis (GD) (n=13) and premature ovarian insufficiency (POI) (n=21) was assessed through a structured diagnostic interview (MINI-V) and self-report questions, and compared to age matched controls from the population. Results: Psychiatric morbidity was increased for women with CAIS and GD compared with controls from the general population (p=.003) but not in comparison to women with POI. Depression (p=.03) and anxiety disorder diagnoses (p=.003) were increased with an overrepresentation of obsessive compulsive disorder diagnoses (p<.001). Study III and IV. Methods: Cognitive abilities in women with CAIS (n=18), XYGD (n=6) and XXGD (n=7) and men with hypospadias (n=89) were assessed using a battery of cognitive tasks that typically yield sex differences and were compared to age matched controls. Results: The cognitive test battery revealed sex differences in the expected directions. Women with CAIS or XYGD performed more similar to female than male controls except on the test of emotion recognition and word fluency where they had lower performance. Women with XXGD outperformed all other groups on the emotion recognition task. There were no differences between men with hypospadias and male controls neither on the cognitive test battery nor the retrospective gender role behavior questions. Men with proximal hypospadias performed slightly lower overall than men with distal hypospadias. Conclusions: Psychosocial and psychiatric outcome is impaired in women with DSD and in some aspects for men with CAH. Results from the cognitive study in women with DSD support theories of androgen influence on cognitive abilities but factors related to karyotype may influence emotion recognition. Further studies are warranted particularly regarding mechanisms behind superior performance of women with XXGD on emotion recognition and general cognitive abilities in men with proximal hypospadias.

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