The relationship between gonadal hormones and neurocognitive functioning in healthy men and women and patients with schizophrenia

The primary aim of this thesis was to examine differences between healthy men and women and men and women with schizophrenia in relation to neurocognitive functioning. The thesis also examined the role of organisational influences of gonadal hormones and gonadotropins to cognitive performance. This was investigated in three studies. Study 1 examined the differences between healthy men and women on a sexually dimorphic cognitive battery (comprising mental rotation, modified judgement of line orientation, computerized Benton judgement of line orientation, cognitive inhibition, letter and category fluency tasks, and a working memory task) in a group of healthy men (n= 42) and women (n = 42). The study also looked at the relationship of organisational influences of gonadal hormones (estrogen, testosterone, progesterone), gonadotropins (lutenizing hormone; LH, follicle stimulating hormones; FSH) and sex hormone binding globulin; SHBG to these cognitive tasks. Study 2 investigated the role of gonadal hormones and the stress hormone cortisol to neurocognitive functioning (comprising domains of attention, verbal abilities, language, memory, executive functioning, motor and speed of information processing) and symptomatology (using the Positive and Negative Syndrome Scale; PANSS) in patients (N = 37) with schizophrenia. Study 3 examined the neural correlates of sex differences in performance on a block design mental rotation task and an overt verbal fluency paradigm using compressed sequence design in a group of healthy men (n = 9) and women (n = 10), controlling for the role of estrogen. Study I showed significant sex differences favouring men on all the spatial tasks and on a cognitive inhibition task, and differences favouring women on the category fluency task. Significant relationships were found between specific conditions of the spatial and inhibition tasks and progesterone, LH, FSH and SHBG. Study 2 found no sex differences in neurocognitive performance in patients with schizophrenia but found that high levels of estrogen were related to low positive symptom scores. Within gender, cortisol levels related to poor performance on the information-processing domain. Study 3 showed sex differences favouring men on the mental rotation and favouring women on the verbal (phonological) fluency task. Analysing the sexes separately revealed activation in the right superior parietal lobe in men and women during mental rotation performance. In general, women activated a greater number of voxels compared to men on the mental rotation and verbal fluency tasks. No sex differences (comparing the groups) in neural activation were found on any of the cognitive tasks. These findings confirmed the previously cited sex differences in cognitive performance and show that with similar activation patterns, men and women showed differential behavioural performance, thus suggesting that women may need more resources to perform better. Overall, this thesis adds to a critical body of literature showing that the relationship between gonadal hormones and cognition is more unsettled than previously thought. The findings also show that hormones other than estrogen and testosterone may also moderate hormone cognition relationships in men and women