Elisabeth M. Weiss

Sex differences in cognitive functions

Abstract Gender differences in neuropsychological functioning of patients with psychiatric disorders have been studied extensively in the last years. The available studies provide conflicting results, which can be attributed to the complexity of variables influencing cognitive sex differences. In the present study, we tried to evaluate the magnitude of gender differences in verbal and visual–spatial functions and to correlate the results with a self-rating of these abilities in healthy men and women. Ninety-seven college students (51 women and 46 men) were examined with a neuropsychological battery, focusing on verbal and visual–spatial abilities. In general, we found, that women tend to perform at a higher level than men on most verbal tests and men outperfom women on visual–spatial tasks. Nevertheless, it is worth mentioning, that the effect sizes were generally small, which suggests the assumption, that the overlap in the distribution of male and female scores is much greater than the difference between them. Additionally, in a self-rating scale, men rated their spatial abilities significantly superior to those of women, while women did not rate their verbal abilities superior to those of men. In this context, the relevance of socio-cultural factors, educational factors and training on the occurrence of sex differences is highlighted, as these factors add significantly to the overall explanation of neuropsychological task-performance.

Frontal white matter microstructure, aggression, and impulsivity in men with schizophrenia: A preliminary study

BACKGROUND Aggression and impulsivity may involve altered frontal white matter. METHODS Axial diffusion tensor images were acquired in 14 men with schizophrenia using a pulsed gradient, double spin echo, echo planar imaging method. White matter microstructural measures (fractional anisotropy and trace) were calculated from these data. Regions of interest were placed in frontal white matter on four slices. Impulsivity was measured using the Motor Impulsiveness factor of the Barratt Impulsiveness Scale. Aggressiveness was measured using the Assaultiveness scale of the Buss Durkee Hostility Inventory and the Aggression scale of the Life History of Aggression. RESULTS Lower fractional anisotropy in right inferior frontal white matter was associated with higher motor impulsiveness. Higher trace in these regions was associated with aggressiveness. CONCLUSIONS Inferior frontal white matter microstructure was associated with impulsivity and aggression in men with schizophrenia. These results implicate frontal lobe dysfunction in aggression and certain aspects of impulsivity.

Sex differences in brain activation pattern during a visuospatial cognitive task: a functional magnetic resonance imaging study in healthy volunteers

Sex differences in mental rotation tasks, favoring men, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. Regions of activation were detected after performance of a mental rotation task inside the scanner. In contrast to previous studies, confounding factors such as performance differences between genders or high error rates were excluded. Men showed significantly stronger parietal activation, while women showed significantly greater right frontal activation. Our results point to gender specific differences in the neuropsychological processes involved in mental rotation tasks.

Five out of 16 plasma signaling proteins are enhanced in plasma of patients with mild cognitive impairment and Alzheimer's disease☆

Alzheimers disease (AD) is a progressive neurodegenerative disorder with characteristic neuropathological changes of the brain. Great efforts have been undertaken to determine the progression of the disease and to monitor therapeutic interventions. Especially, the analysis of blood plasma had yielded incongruent results. Recently, Ray et al. (Nat. Med. 13, 2007, 1359f) identified changes of 18 signaling proteins leading to an accuracy of 90% in the diagnosis of AD. The aim of the present study was to examine 16 of these signaling proteins by quantitative Searchlight multiplex ELISA in order to determine their sensitivity and specificity in our plasma samples from AD, mild cognitive impairment (MCI), depression with and without cognitive impairment and healthy subjects. Quantitative analysis revealed an increased concentration in Biocoll isolated plasma of 5 out of these 16 proteins in MCI and AD patients compared to healthy subjects: EGF, GDNF and MIP1δ (in AD), MIP4 (in MCI) and RANTES (in MCI and AD). ROC analysis predicted a sensitivity of 65-75% and a specificity of 52-63% when comparing healthy controls versus MCI or AD. Depression without any significant cognitive deficits did not cause any significant changes. Depressed patients with significant cognitive impairment were not different from MCI patients. In conclusion, we detected a number of altered proteins that may be related to a disease specific pathophysiology. However, the overall expression pattern of plasma proteins could not be established as a biomarker to differentiate MCI from AD or from depression.

Brain activation pattern during a verbal fluency test in healthy male and female volunteers: a functional magnetic resonance imaging study

Sex differences in executive speech tasks, favoring women, have been noted in behavioral studies and functional imaging studies. In the present study ten female and ten male volunteers underwent functional magnetic resonance imaging in a conventional block design. All subjects were selected on the basis of high performance on the verbal fluency task. Regions of activation were detected after performance of a covert lexical verbal fluency task inside the scanner. Men and women who did not differ significantly in verbal fluency task performance showed a very similar pattern of brain activation. Our data argue against genuine between-sex differences in cerebral activation patterns during lexical verbal fluency activities when confounding factors like performance differences are excluded.

Sex differences in clustering and switching in verbal fluency tasks

Sex differences in executive speech tasks, favoring women, have been noted in behavioral studies and functional imaging studies. In the present study, the clustering and switching components of semantic and phonemic verbal fluency tests were examined in 40 healthy men and 40 healthy women. Possible sex differences in the influence of cognitive factors such as speed of information processing, word knowledge, and/or verbal long-term memory on these verbal fluency factors were also assessed. The results showed that women switched more often between categories in the phonemic fluency test, whereas men showed a trend toward a larger cluster size leading to a smaller total number of words generated. Additionally, higher performance on the Digit Symbol test was associated with better performance on the semantic and phonemic verbal fluency test in men, whereas in women, better memory performance was associated with better performance on these verbal fluency tests. Our data indicate that men and women are using different processing strategies for phonemic verbal fluency tests to optimize verbal fluency task performance. In the current study, women adopted a more successful strategy of balancing clustering and switching in the phonemic fluency task.

Second-generation antipsychotics : Is there evidence for sex differences in pharmacokinetic and adverse effect profiles?

Six second-generation antipsychotics (SGAs), aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone, are currently US FDA approved. The aim of this review is to investigate whether sex differences exist for efficacy and adverse effects of these drugs.Sex-related differences have been shown in the pharmacokinetics of cytochrome P450 (CYP), with a higher activity in females for CYP3A4 and CYP2D6. However, even if there are pharmacokinetic differences between females and males, significantly higher plasma concentrations in women have been demonstrated only for olanzapine and clozapine.To date, sex differences in adverse effects have not been well studied, but some adverse effects such as weight gain, hyperprolactinaemia and cardiac effects are reported to be particularly problematic for women. Most of the studies reviewed indicate that clozapine and olanzapine are associated with greater bodyweight gain than the other atypical antipsychotics, and that serious adverse effects such as metabolic syndrome, which includes increased visceral adiposity, hyperglycaemia, hypertension and dyslipidaemia induced by SGAs, are more frequent in females. According to most studies, the risk for cardiac adverse effects induced by SGAs is the same in male and female patients. Although women are at a lower risk of sudden cardiac death, they have a higher risk of induced long QT syndrome from antiarrhythmic and, probably, antipsychotic drugs. The propensity of sexual dysfunctions is higher with conventional antipsychotics than with SGAs. Additionally, there is some evidence that female sexual dysfunction is associated with high prolactin levels; however, whether the degree of prolactin level elevation is different between female and male patients remains controversial. There is no evidence for sex differences for any of the SGAs to cause a higher rate of extrapyramidal symptoms, acute dystonia or any other movement disturbance. Knowledge of the risks and benefits associated with the use of SGAs during pregnancy and lactation is limited, although the direction of dose adjustments during pregnancy depends on the drug and the enzyme that is responsible for its metabolism.In general, data on sex differences were mostly obtained by post hoc analysis and, therefore, the conclusions that can be drawn are limited. For a better understanding of the basic mechanisms of sex differences, future studies with a primary focus on this topic are required. Data that are more specific will help determine the extent to which these differences will have implications for clinical management.

Pattern of brain atrophy in elderly patients with depression revealed by voxel-based morphometry

In this study, we explored to what extent brain abnormalities can be identified in specific brain structures of patients suffering from late onset depression. We examined the structural difference in regional gray and white matter volume between 14 community-dwelling patients suffering from geriatric depression and 20 age-matched non-depressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging. All subjects also underwent an extensive neuropsychological assessment. Compared with control subjects, patients with depression were impaired in measures of verbal and visual memory, construction, executive ability, and information-processing speed. VBM of gray matter revealed a significant decrease of volume in the right rostral hippocampus, in the right amygdala and in the medial orbito-frontal cortex (gyrus rectus) bilaterally. In the correlation analysis of gray matter volume with the score of the geriatric depression scale, we observed a negative correlation with the medial orbito-frontal cortex (gyrus rectus) bilaterally. There were no differences in white matter volumes between patients with depression and healthy control subjects. The most important limitation of this study was sample size. A larger sample size may have improved detection of changes not reaching significance. Furthermore, our results may not be generalizable across depression severity or to hospitalized patients. The findings are consistent with our hypothesis that depression in the elderly is associated with local gray matter dysfunction.

Brain activation patterns during a verbal fluency test: a functional MRI study in healthy volunteers and patients with schizophrenia

FMRI was used to study cortical activation patterns in nine healthy male subjects and nine high-functioning male schizophrenia patients during a letter verbal fluency task. Both groups showed similar patterns of activation, however, in controls the activation was primarily in the left broca area, while for schizophrenia patients, it was more bilateral. These data indicate that high-functioning schizophrenia patients show a reduced language lateralization of the frontal cortex compared to healthy controls.

Language lateralization in unmedicated patients during an acute episode of schizophrenia: a functional MRI study.

In a previous fMRI study of high-functioning outpatients with remitted schizophrenia, we found that healthy subjects and schizophrenia patients showed similar patterns of activation during a verbal fluency task. However, the activation in controls was primarily in Brocas area on the left, while it was more bilateral for schizophrenia patients, implicating a reduced language lateralization in schizophrenia patients. The same fMRI procedure was used in this subsequent study to investigate unmedicated patients during an acute episode of schizophrenia. Schizophrenia patients showed reduced language lateralization in the frontal cortex, because of a more bilateral activation of Brocas area compared with a primarily left hemisphere activation in healthy controls. Furthermore decreased lateralization was correlated to the severity of hallucinations. Although patients with schizophrenia showed a significantly reduced performance on the verbal fluency task when compared with healthy subjects, we were not able to find evidence of decreased language-related activity in the left hemisphere. These results suggest that decreased language lateralization is also evident in unmedicated patients experiencing an acute episode of schizophrenia.