Nadia Lakis

Disturbed sexual dimorphism of brain activation during mental rotation in schizophrenia.

BACKGROUND Sex differences in visuo-spatial abilities have been well documented in the general population, but there are only a few inconsistent reports in schizophrenia. The purpose of the present study was to examine potential sex differences in performance and pattern of brain activations during mental rotation in schizophrenia patients relative to control participants. METHODS Thirty three schizophrenia patients (17 women and 16 men) were compared to thirty five healthy control participants (17 women and 18 men), while performing a classic mental rotation task (3-D figures). Blood oxygen level dependent (BOLD) echo-planar images were acquired on a 3-Tesla Siemens TRIO system. Random-effect analyses were performed using SPM5 (UK Wellcome Institute). RESULTS Behavioural data revealed a diagnosis-by-sex interaction with healthy men (HM) performing significantly better than schizophrenia men (SZ-M) and no significant difference between healthy women (HW) and schizophrenia women (SZ-W). fMRI results revealed an overall similar pattern of extensive cerebral activations (in the parietal and lateral prefrontal cortex) and deactivations (in the medial prefrontal cortex) in HM and SZ-W during performance of the mental rotation versus control task. In contrast, both HW and SZ-M showed much more restricted activations and no significant deactivations. CONCLUSIONS Sex differences in performance and cerebral activations during mental rotation in schizophrenia patients deviated significantly from what we observed in healthy volunteers. This finding supports and extends existing evidence of a disturbed sexual dimorphism in schizophrenia. Moreover, the results emphasize the importance of including both sexes in neurocognitive and neuroimaging studies of schizophrenia.

Associations of sex steroid hormones with cerebral activations during mental rotation in men and women with schizophrenia

Sex steroid hormones have been implicated in the visuo-spatial abilities in the general population, as well as in the pathophysiology of schizophrenia. Nevertheless, almost nothing is known about the association between levels of testosterone and/or estrogen with brain activations during visuo-spatial processing in schizophrenia. The fMRI data collected during performance of a mental rotation task in 42 schizophrenia patients (21 women) and 42 matched controls, were correlated with the levels of testosterone and estrogen. Results revealed significant relationship between sex steroid hormones and cerebral activations in healthy men and in schizophrenia women, but no correlations were detected in healthy women or in male patients. The lack of correlations and the overall diminished levels of testosterone in male patients are consistent with some existing literature. On the other hand, the findings of augmented levels of testosterone and its implication in cerebral activations in female patients are unprecedented and merit further exploration.

Neural correlates of emotional recognition memory in schizophrenia: effects of valence and arousal.

Schizophrenia patients are often impaired in their memory for emotional events compared with healthy subjects. Investigations of the neural correlates of emotional memory in schizophrenia patients are scarce in the literature. The present study aimed to compare cerebral activations in schizophrenia patients and healthy controls during memory retrieval of emotional images that varied in both valence and arousal. In a study with functional magnetic resonance imaging, 37 schizophrenia patients were compared with 37 healthy participants while performing a yes/no recognition paradigm with positive, negative (differing in arousal intensity) and neutral images. Schizophrenia patients performed worse than healthy controls in all experimental conditions. They showed less cerebral activation in limbic and prefrontal regions than controls during retrieval of negatively valenced stimuli, but had a similar pattern of brain activation compared with controls during retrieval of positively valenced stimuli (particularly in the high arousal condition) in the cerebellum, temporal lobe and prefrontal cortex. Both groups demonstrated increased brain activations in the high relative to low arousing conditions. Our results suggest atypical brain function during retrieval of negative pictures, but intact functional circuitry of positive affect during episodic memory retrieval in schizophrenia patients. The arousal data revealed that schizophrenia patients closely resemble the control group at both the behavioral and neurofunctional level.

Sex differences in memory of emotional images: A behavioral and electrophysiological investigation

Current research suggests that emotional responses differ between men and women. Sex differences regarding emotional effects on memory have been recently studied through brain imaging techniques. However, the majority of investigations have often neglected to balance the variable of emotional intensity (arousal) across pleasant and unpleasant pictures. Additionally, men and women were often mixed or studied separately. The current study aims at comparing men and womens electrophysiological responses related to emotional memory of photographic material. These responses were measured using Event Related brain Potentials (ERP) in response to a task of episodic memory of emotional images. The frontal N200, the parietal P300 and the central LPC were compared in 17 men and 17 women matched for age, social economic status, education and intelligence. Behavioral results showed that, in men, reaction times were modulated by valence, whereas for women, reaction times were mainly modulated by arousal. Accuracy was affected by both emotional valence and arousal, but only in women. ERP analyses revealed that emotional valence influenced earlier time components (frontal N200 and parietal P300), whereas arousal influenced memory in the later time component (central LPC). Moreover, sex differences, mediated by valence and arousal, were found in ERP responses at different times in the processing stream.

Progesterone and Cerebral Function during Emotion Processing in Men and Women with Schizophrenia

Schizophrenia has been associated with disturbed levels of sex-steroid hormones, including estrogen and testosterone. In the present study we have examined the implication of a less studied hormone progesterone. Forty-three patients with schizophrenia (21 women) and 43 control participants (21 women) underwent functional MRI while viewing emotionally positive, negative, and neutral images. Blood samples were taken prior to the scanning session to evaluate progesterone levels. Simple regression analyses between levels of progesterone and brain activations associated with emotion processing were performed using SPM5. A positive correlation was found between progesterone levels and brain activations during processing of emotionally charged images in both healthy and schizophrenia men, but no significant relationship was revealed in women. These preliminary results indicate that progesterone is significantly associated with brain activations during processing of positive and negative affect in healthy and schizophrenia men, but not in women. Further investigation is warranted.

Cannabis abuse is associated with better emotional memory in schizophrenia: A functional magnetic resonance imaging study

In schizophrenia cannabis abuse/dependence is associated with poor compliance and psychotic relapse. Despite this, the reasons for cannabis abuse remain elusive, but emotions may play a critical role in this comorbidity. Accordingly, we performed a functional magnetic resonance imaging study of emotional memory in schizophrenia patients with cannabis abuse (dual-diagnosis, DD). Participants comprised 14 DD patients, 14 non-abusing schizophrenia patients (SCZ), and 21 healthy controls (HC) who had to recognize positive and negative pictures while being scanned. Recognition of positive and negative emotions was prominently impaired in SCZ patients, relative to HC, while differences between DD and HC were smaller. For positive and negative stimuli, we observed significant activations in frontal, limbic, temporal and occipital regions in HC; in frontal, limbic and temporal regions in DD; and in temporal, parietal, limbic and occipital regions in the SCZ group. Our results suggest that emotional memory and prefrontal lobe functioning are preserved in DD relative to SCZ patients. These results are consistent with previous findings showing that cannabis abuse is associated with fewer negative symptoms and better cognitive functioning in schizophrenia. Longitudinal studies will need to determine whether the relative preservation of emotional memory is primary or secondary to cannabis abuse in schizophrenia.

Individuals Diagnosed with Schizophrenia Assign Emotional Importance to Neutral Stimuli: An fMRI Study

The majority of functional neuroimaging studies investigating neural correlates of emotion processing in schizophrenia report a significant deficit in limbic structures activation in patients relative to control participants. Recently it has been suggested that this apparent “deficit” could be due to an enhanced sensitivity of the neutral material in individuals diagnosed with schizophrenia, rather than due to their inefficiency in emotion processing. The purpose of the present study was to test this supposition and verify if the potential effect is present in both men and women diagnosed with schizophrenia. In order to do that we examined the pattern of cerebral activation associated with processing of neutral stimuli in schizophrenia. Thirty-seven schizophrenia patients and 37 healthy controls viewed neutral and emotional images while in a functional magnetic resonance imaging scanner. Schizophrenia patients rated the neutral images as more emotionally salient than controls. Additionally, patients showed significant activation during processing of neutral images in limbic and prefrontal regions; similar areas were underactivated in patients relative to controls during processing of emotional information. Investigation of sex differences revealed that the enhanced responsiveness to the emotionally neutral material was attributed primarily to men with schizophrenia.

Clozapine and visuospatial processing in treatment-resistant schizophrenia

Introduction. Clozapine, the most widely used option in treatment-resistant schizophrenia, has been shown to be superior to other antipsychotic medications in improving cognitive function in patients. However, the results have not been consistent and the mechanisms underlying this effect have not been elucidated. Thus, the purpose of the present study was to evaluate verbal and nonverbal cognition (using visuospatial processing tests) in patients treated with clozapine (initially treatment resistant) and those treated with other second-generation antipsychotics, relative healthy control subjects. Furthermore, we examined neural correlates of visuospatial processing in the three groups. Methods. Twenty schizophrenia patients treated with clozapine (TR-C group), 23 patients stabilised with atypical antipsychotics other than clozapine (NTR group), and 21 healthy control participants completed a battery of verbal and visuospatial cognitive tests. In addition, participants underwent functional magnetic resonance imaging (fMRI) while performing one of the visuospatial tests (the mental rotation task). The fMRI data were analysed separately in each group using Statistical Parametric Mapping software (SPM5). Results. Overall, schizophrenia patients exhibited deficit on verbal and nonverbal processing relative to the healthy controls, but we observed some interesting differences between the two groups of patients. Specifically, the NTR group performed better than the TR-C group on the Block Design and the Ravens Progressive Matrices. With respect to brain function during mental rotation, the NTR group showed significant activations in regions of the temporal and occipital cortex, whereas the TR-C patients did not. The relative deactivations associated with the task were also more robust in NTR compared to the other group of patients, despite a similar performance. Conclusion. Present results suggest better visuospatial processing in the NTR relative to the TR-C group. This difference could be attributed to the treatment resistance itself or a lack of beneficial effect of clozapine relative to other atypical antipsychotics in ameliorating nonverbal abilities. Future studies of the relationship between clozapine and cognition, as well as between treatment resistance and cognition, are warranted.

Emotion processing in women with schizophrenia is menstrual cycle phase and affective valence dependent: an FMRI study.

Despite a large number of functional neuroimaging investigations of emotion processing in schizophrenia, very few have included women. In the present study 21 schizophrenia and 23 healthy women underwent functional MRI (3T) on two occasions (during the follicular and luteal phase of their menstrual cycle) while viewing blocks of emotionally negative, positive and neutral images. During exposure to negatively charged images patients showed relatively less activations than controls during the luteal phase, but no between-group differences were observed during the follicular phase. In contrast, the exposure to positively valenced material produced no significant interaction, but the main effect of group; schizophrenia patients exhibited less activation than healthy controls during both phases of the menstrual cycle. This is the first study demonstrating that atypical neural activations associated with emotion processing in women diagnosed with schizophrenia depend on the menstrual cycle phase and on the affective valence of presented stimuli.