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

Effect of twist level and twist direction of core (double) yarn on dref-3 spun yarn

In this study, an attempt has been made to understand the behaviour of friction spun yarn by introducing doubled yarns as core with diversity in twist level and direction. ‘Z’ twisted 15tex (40s Ne) parent yarn has been used for doubling purposes. To examine the effect of doubling, three twist levels are chosen, viz. 50, 60 and 70 % of the parent yarn twist for both the directions viz. S and Z. Thus, six samples of doubled yarns are prepared. These samples are tested for the count, twist, breaking force and elongation. These yarns are introduced as core into DREF-3 friction spinning system; keeping the sheath fibre constant viz. combed cotton sliver of 0.15 hank for all the samples. The twist direction of the doubled yarn used as core is found to be the influential factor for the breaking force and elongation of the friction spun yar

The functional anatomy of semantic retrieval is influenced by gender, menstrual cycle, and sex hormones

This study examines the neurobiology of semantic retrieval and describes the influence of gender, menstrual cycle, and sex hormones on semantic networks. Healthy right-handed subjects (12 men, 12 women) were investigated with 3T-fMRI during synonym generation. Behavioral performance and sex hormone levels were assessed. Women were examined during the early follicular and midluteal cycle phase. The activation pattern in all groups involved left frontal and temporal as well as bilateral medial frontal, cingulate, occipital, basal ganglia, and cerebellar regions. Men showed greater left frontal activation than women in both menstrual cycle phases. Women yielded high correlations of left prefrontal activation with estradiol in the midluteal phase and with progesterone in both phases. Testosterone levels correlated highly with left prefrontal activation in all three groups. In all, we describe a cerebral network involved in semantic processing and demonstrate that it is significantly affected by gender and sex steroid hormones

Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study

<p>Abstract</p> <p>Background</p> <p>A common treatment option for men with prostate cancer is androgen deprivation therapy (ADT). However, men undergoing ADT may experience physical side effects, changes in quality of life and sometimes psychiatric and cognitive side effects.</p> <p>Methods</p> <p>In this study, hormone naïve patients without evidence of metastases with a rising PSA were treated with nine months of ADT. Functional magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks was performed at baseline prior to treatment and after nine months of ADT in five subjects. Seven healthy control patients, underwent neuroimaging at the same time intervals.</p> <p>Results</p> <p>ADT patients showed reduced, task-related BOLD-fMRI activation during treatment that was not observed in control subjects. Reduction in activation in right parietal-occipital regions from baseline was observed during recall of the spatial location of objects and mental rotation.</p> <p>Conclusions</p> <p>Findings, while preliminary, suggest that ADT reduces task-related neural activation in brain regions that are involved in mental rotation and accurate recall of spatial information.</p

Methylphenidate Normalizes Fronto-Striatal Underactivation During Interference Inhibition in Medication-Naïve Boys with Attention-Deficit Hyperactivity Disorder

Youth with attention deficit hyperactivity disorder (ADHD) have deficits in interference inhibition, which can be improved with the indirect catecholamine agonist methylphenidate (MPH). Functional magnetic resonance imaging was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naïve ADHD boys. Medication-naïve boys with ADHD were scanned twice, in a randomized, double-blind design, under either a single clinical dose of MPH or placebo, while performing a Simon task that measures interference inhibition and controls for the oddball effect of low-frequency appearance of incongruent trials. Brain activation was compared within patients under either drug condition. To test for potential normalization effects of MPH, brain activation in ADHD patients under either drug condition was compared with that of healthy age-matched comparison boys. During incongruent trials compared with congruent–oddball trials, boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition, including right inferior prefrontal cortex, left striatum and thalamus, mid-cingulate/supplementary motor area, and left superior temporal lobe. MPH relative to placebo upregulated brain activation in right inferior prefrontal and premotor cortices. Under the MPH condition, patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions. Effect size comparison, furthermore, showed that these normalization effects were significant. MPH significantly normalized the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition, but did not affect medial frontal or temporal dysfunction. MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation

Sex Differences and Autism: Brain Function during Verbal Fluency and Mental Rotation

Autism spectrum conditions (ASC) affect more males than females. This suggests that the neurobiology of autism: 1) may overlap with mechanisms underlying typical sex-differentiation or 2) alternately reflect sex-specificity in how autism is expressed in males and females. Here we used functional magnetic resonance imaging (fMRI) to test these alternate hypotheses. Fifteen men and fourteen women with Asperger syndrome (AS), and sixteen typically developing men and sixteen typically developing women underwent fMRI during performance of mental rotation and verbal fluency tasks. All groups performed the tasks equally well. On the verbal fluency task, despite equivalent task-performance, both males and females with AS showed enhanced activation of left occipitoparietal and inferior prefrontal activity compared to controls. During mental rotation, there was a significant diagnosis-by-sex interaction across occipital, temporal, parietal, middle frontal regions, with greater activation in AS males and typical females compared to AS females and typical males. These findings suggest a complex relationship between autism and sex that is differentially expressed in verbal and visuospatial domains

Prenatal testosterone does not explain sex differences in spatial ability

The most consistent sex differences in cognition are found for spatial ability, in which males, on average, outperform females. Utilizing a twin design, two studies have shown that females with male co-twins perform better than females with female co-twins on a mental rotation task. According to the Twin Testosterone Transfer hypothesis (TTT) this advantage is due to in-uterine transmission of testosterone from males to females. The present study tested the TTT across 14 different spatial ability measures, including mental rotation tasks, in a large sample of 19–21-year-old twins. Males performed significantly better than females on all spatial tasks, with effect sizes ranging from η2 = 0.02 to η2 = 0.16. Females with a male co-twin outperformed females with a female co-twin in two of the tasks. The effect sizes for both differences were negligible (η2 < 0.02). Contrary to the previous studies, our results gave no indication that prenatally transferred testosterone, from a male to a female twin, influences sex differences in spatial ability