Cross-cultural differences through subjective cognition: illustration in translatology with the SSTIC-E in the UAE.

The development of appropriate and valid multicultural and multilingual instruments research is necessary due to a growing multicultural and multilingual society in the 21st century. We explored the use of a cognitive scale related to subjective complaints, focusing on the first step: a cross-cultural and semantic validation. This study presents the translation and cross-validation process of the "Subjective Scale to Investigate Cognition in Schizophrenia" (SSTICS) for the United Arab Emirates (UAE) region via different languages used in Dubaï/Abu Dhabi. This scale measures cognitive complaints and has been validated with psychosis and used in 20 clinical trials worldwide. It evaluates areas of the illness related to self-awareness focusing on memory dysfunction and deficits of attention, language, and praxis. We described the method of cross-cultural validation, with back-translation, semantic steps, and societal contexts. The use of the Subjective Scale to Investigate Cognition in Emirates (SSTIC-E) was explored with different samples of UAE Arabic-speaking subjects. First, a pilot sample mean SSTICS total score was 16.5 (SD:16.9); (p < 0.001). The SSTIC-E was then administered to 126 patients and 84 healthy control participants. The healthy group has a lower mean score of 22.55 (SD = 12.04) vs. 34.06 (SD = 15.19). The method was extended to nine other languages, namely, Pakistani/Urdu, Hindi, Marathi, Lithuanian, Serbian, German, Romanian, Sinhala, and Russian. The scales are provided in the article. The overall aim of the translation process should be to stay close to the original version of the instrument so that it is meaningful and easily understood by the target language population. However, for construct validity, some items must be adapted at the time of translation to ensure that the questioned cognitive domain is respected. For example, cooking, an executive function, does not have the same occurrence for an Emirati male, or remembering a prime minister's name, semantic memory, requires an electoral system to appoint the leader of a country. Translation methods and processes present many challenges but applying relevant and creative strategies to reduce errors is essential to achieve semantic validation. This study aims to measure personally experienced knowledge or attitudes; such language effects can be a thorny problem.

Sex, Age, Symptoms and Illness Duration and Their Relation with Gyrification Index in Schizophrenia.

INTRODUCTION: The Gyrification Index (GI) represents the degree of cortical folding and is of special interest in schizophrenia, since alterations in cortical folding indirectly reflect white matter development and axonal connectivity underneath. To the best of our knowledge, very few studies have investigated the effect of sex on GI in schizophrenia. Differences in the GI between patients with schizophrenia and healthy controls and the relation between sex, age symptoms and duration of illness with GI were investigated. METHODS: T1-images were acquired from schizophrenia patients (24 males [SZ-M] and 24 females [SZ-F]) and healthy volunteers (24 males [NC-M] and 24 females [NC-F]) matched for age, sex and handedness. GI analyses were performed using the fully automated CIVET pipeline. RESULTS: Significantly lower GI was found in patients relative to controls bilaterally in frontal, temporal, and parietal cortex. Sex differences were found: negative correlation was found between the duration of illness and the right parietal GI and right occipital GI in SZ-M, while SZ-F was found in the left frontal and bilateral temporal GI. Patients, regardless of sex, showed positive correlations between negative symptoms and GI in the right occipital. NC-F had greater GI values than SZ-F and both male groups. CONCLUSIONS: Since GI reflects, in part, alterations in cerebral development and connectivity, the decrease in GI observed in patients is in agreement with the neurodevelopmental model of disconnectivity in schizophrenia; in addition, we emphasize the importance of sex differences in schizophrenia.

Sex/gender differences in the brain and cognition in schizophrenia.

The early conceptualizations of schizophrenia have noted some sex/gender differences in epidemiology and clinical expression of the disorder. Over the past few decades, the interest in differences between male and female patients has expanded to encompass brain morphology and neurocognitive function. Despite some variability and methodological shortcomings, a few patterns emerge from the available literature. Most studies of gross neuroanatomy show more enlarged ventricles and smaller frontal lobes in men than in women with schizophrenia; finding reflecting normal sexual dimorphism. In comparison, studies of brain asymmetry and specific corticolimbic structures, suggest a disturbance in normal sexual dimorphism. The neurocognitive findings are somewhat consistent with this picture. Studies of cognitive functions mediated by the lateral frontal network tend to show sex differences in patients which are in the same direction as those observed in the general population, whereas studies of processes mediated by the corticolimbic system more frequently reveal reversal of normal sexual dimorphisms. These trends are faint and future research would need to delineate neurocognitive differences between men and women with various subtypes of schizophrenia (e.g., early versus late onset), while taking into consideration hormonal status and gender of tested participants.

Cognition and lobar morphology in full mutation boys with fragile X syndrome.

The aims of the present study are twofold: (1) to examine cortical morphology (CM) associated with alterations in cognition in fragile X syndrome (FXS); (2) to characterize the CM profile of FXS versus FXS with an autism diagnosis (FXS+Aut) as a preliminary attempt to further elucidate the behavioral distinctions between the two sub-groups. We used anatomical magnetic resonance imaging surface-based morphometry in 21 male children (FXS N=11 and age [2.27-13.3] matched controls [C] N=10). We found (1) increased whole hemispheric and lobar cortical volume, cortical thickness and cortical complexity bilaterally, yet insignificant changes in hemispheric surface area and gyrification index in FXS compared to C; (2) linear regression analyses revealed significant negative correlations between CM and cognition; (3) significant CM differences between FXS and FXS+Aut associated with their distinctive behavioral phenotypes. These findings are critical in understanding the neuropathophysiology of one of the most common intellectual deficiency syndromes associated with altered cognition as they provide human in vivo information about genetic control of CM and cognition.

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.

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.

Brain morphology in autism and fragile X syndrome correlates with social IQ: first report from the Canadian-Swiss-Egyptian Neurodevelopmental Study.

Fragile X syndrome shares most of the behavioral phenotypic similarities with autism. How are these similarities reflected in brain morphology? A total of 10 children with autism and 7 with fragile X underwent morphological (T1) 1.5-T magnetic resonance imaging (MRI). The authors found no significant difference in total brain volumes, regional volumes, gyrification index, sulcul depth, and cerebral cortical thickness. However, children with autism showed significant decrease in the medial prefrontal bilaterally and the left anterior cingulate cortices. Regression analysis revealed positive correlation between the medial prefrontal cortical thickness and the social IQ. The authors suggest that the difference between the 2 groups in the medial prefrontal and anterior cingulate cortices thickness may entail an altered social cognitive style. Functional MRI studies directly differentiating between social indifference (autism) and social avoidance (fragile X) are needed to further characterize the spectrum of social abnormalities between these 2 groups.

Prenatal maternal stress from a natural disaster predicts dermatoglyphic asymmetry in humans.

Dermatoglyphic asymmetry of fingertip ridge counts is more frequent in schizophrenia patients than normal controls, and may reflect disruptions in fetal development during Weeks 14-22 when fingerprints develop. However, there are no data in humans linking specific adverse events at specific times to dermatoglyphic asymmetries. Our objective was to determine whether prenatal exposure to a natural disaster (1998 Quebec ice storm) during Weeks 14-22 would result in increased dermatoglyphic asymmetry in children, and to determine the roles of maternal objective stress exposure, subjective stress reaction, and postdisaster cortisol. Ridge counts for homologous fingers were scored for 77 children (20 target exposed [Weeks 14-22] and 57 nontarget exposed [exposed during other gestation weeks]). Children in the target group had more than 0.50 SD greater asymmetry than the nontarget group. Within the target group, children whose mothers had high subjective ice storm stress had significantly greater asymmetry than those with lower stress mothers, and maternal postdisaster cortisol had a significant negative correlation with the children's dermatoglyphic asymmetry (r = -.56). Prenatal maternal stress during the period of fingerprint development results in greater dermatoglyphic asymmetry in their children, especially in the face of greater maternal distress.

Increased grey matter densities in schizophrenia patients with negative symptoms after treatment with quetiapine: a voxel-based morphometry study.

Among new-generation antipsychotics, quetiapine was found to be associated with a partial 'normalization' of reduced functional activation in prefrontal and temporal areas and studies conducted by our group found a clinical improvement in negative symptoms in addition to restoration of frontal activation in schizophrenia patients with blunted affect after treatment with quetiapine. Here we investigated the parallelism between improved clinical symptoms and grey mater density (GMD) changes in the frontal region after quetiapine treatment in 15 schizophrenia patients. We hypothesize that improvement in clinical symptoms will be associated with change in GMD in prefrontal regions of interest. By using voxel-based morphometry, paired t-test random-effect analysis showed a significant increase in GMD bilaterally in the inferior frontal cortex/orbitofrontal gyrus and anterior cingulate cortex after 5.5 months of treatment with quetiapine. This GMD increase was associated with a significant improvement in negative symptoms. When GMD was correlated with psychiatric assessment scores, there was a negative correlation between GMD in the anterior cingulate cortex and the Rating Scale for Emotional Blunting score (r=-665, P=0.008) and between the orbitofrontal gyrus and the total Positive and Negative Syndrome Scale negative score (r=-764, P=0.001). Results suggest that increased GMD in some frontal regions are associated with an improvement of negative symptoms. Although not unique to quetiapine, it would be reasonable to attribute the GMD changes in the study to treatment.

Orbitofrontal dysfunction in a monozygotic twin discordant for postpartum affective psychosis: a functional magnetic resonance imaging study.

BACKGROUND: Incomplete concordance for psychosis in monozygotic (MZ) twins has been interpreted as indicative of non-genetic cofactors in transmission of the illness. In this case study, we consider childbirth a landmark in the onset of psychotic symptoms, leading to the diagnosis of puerperal psychosis and then to bipolar/schizoaffective disorder. At the end of the third trimester, there is a sudden drop in estrogen, which exerts prominent effects on the serotonergic system in the orbitofrontal cortex (OFC). OBJECTIVES: The purpose of the present study was to investigate OFC activation during emotional processing in MZ twins discordant for affective psychosis. METHODS: Blood-oxygen-level-dependent activation using functional magnetic resonance imaging was measured during the passive viewing of emotional film excerpts. RESULTS: Consistent with our hypothesis, a significant locus of activation was found in the left OFC in the normal MZ twin, but not in the psychosis MZ twin. CONCLUSIONS: The personality changes noted in the psychosis MZ twin (postpartum psychosis) may be related to dysfunctional OFC. Ms J's childbirth may have triggered the onset of psychotic symptoms, leading to the diagnosis of bipolar or schizoaffective disorder.

Sex differences in the cerebral function associated with processing of aversive stimuli by schizophrenia patients.

OBJECTIVE: Impaired processing of various emotions is considered one of the fundamental features of schizophrenia. In the recent study intriguing sex differences were observed in the cerebral function associated with the experience of sadness in schizophrenia patients. The aim of the present study was to explore this phenomenon during exposure to aversive stimuli. METHOD: Fifteen men and 10 women with the DSM-IV diagnosis of schizophrenia underwent functional magnetic resonance imaging (fMRI) while viewing alternating blocks of negative and neutral pictures. Data were analysed using random-effects model within statistical parametric mapping (SPM99) software. RESULTS: Processing of negative stimuli evoked significantly greater activations in men in the thalamus, cerebellum, temporal, occipital and posterior cingulate cortex, while women exhibited greater activations in the left middle frontal gyrus. CONCLUSIONS: The sex differences in the cerebral activations in schizophrenia patients deviate from what has been observed in the general population during exposure and experience of negative affect. As such the present study supports and extends the authors' preliminary observation of the anomalous sexual dimorphism in schizophrenia at the functional neuroanatomical level, suggesting potential masculinization of female subjects and feminization of male subjects with schizophrenia.

Individual variation in neural correlates of sadness in children: a twin fMRI study.

Functional neuroimaging studies show substantial individual variation in brain activation accompanying the experience of emotion, including sadness. Here we used functional magnetic resonance imaging (fMRI) in 104 pairs of 8-year-old twins (47 MZ, 57 DZ) to assess genetic-environmental contributions to individual differences in neural activation in two prefrontal cortex (PFC) areas previously shown to be involved in sadness. No genetic effects were found for any area, individual environmental factors entirely accounting for individual variation in brain activation related to sadness. Sadness being the prevailing mood in depression, these findings may be of relevance to the etiology of childhood depressive disorders.

Increased striatal gray matter densities in patients with schizophrenia and substance use disorder: a voxel-based morphometry study.

We sought to investigate the link between substance abuse and increased striatal gray matter densities (GMD) in schizophrenia, using voxel-based morphometry (VBM). Increased striatal GMD were found in patients with schizophrenia and substance use disorder (n=12), but not schizophrenia only patients (n=11), compared to healthy volunteers (n=15).

Processing of social emotion in patients with schizophrenia and substance use disorder: an fMRI study.

The lifetime prevalence of substance use disorders among schizophrenia patients is close to 50%. The negative consequences of substance abuse in schizophrenia are well documented, but the aetiology of this comorbid condition remains unknown. Mounting evidence suggests that dual-diagnosis patients have fewer negative symptoms and better social skills, compared to non-abusing patients. We hypothesized that schizophrenia patients with substance use disorder (SCZ-SUD) would display increased cerebral activations in response to socioemotional stimuli, relative to patients with no SUD (SCZ). Schizophrenia patients (DSM-IV criteria) were divided into two groups: patients with (n=12) and without (n=11) substance use (alcohol and/or cannabis). Using functional magnetic resonance imaging (fMRI), patients were scanned during passive viewing of an emotional film excerpt with social content. Loci of activation were identified in the right mPFC (BA 10) and the right supramarginal gyrus (BA 40) in SCZ-SUD patients, and in the left pons in SCZ patients. Relative to SCZ patients, increased loci of activation were found in the right superior parietal cortex (BA 7) and the left medial prefrontal cortex (BA 10) in SCZ-SUD patients, who reported higher subjective emotional experience on a self-report scale. To our knowledge, this is the first fMRI study to assess social emotions in dual-diagnosis schizophrenia. Our results suggest that socioemotional processing may be less impaired in dual diagnosis, which recruited brain regions seemingly involved in "social cognition." Further studies on the topic are warranted.

Fatal agranulocytosis: the use of olanzapine in a patient with schizophrenia and myelodysplasia.

Neutropenia and agranulocytosis are risks known to occur with phenothiazines and clozapine. The mechanisms responsible for these conditions currently remain unclear. To our knowledge, no case of fatal agranulocytosis as a result of olanzapine treatment was reported in the literature. Thus any case of severe neutropenia occurring in a patient receiving olanzapine is alarming to clinicians. First, a review of the literature produced 41 anecdotic cases of neutropenia or agranulocytosis during treatment with olanzapine (Zyprexa) reported in a total of 24 publications. Second, we report a case of neutropenia, which proved to be fatal in a schizophrenia patient receiving olanzapine and thiazide. The cause of the death was Myelodysplastic syndrome. There is not enough evidence to prove the involvement of either olanzapine or hydrochlorothiazide or the interaction between them in this patient's myelodysplasia. Bone marrow cytogenetic study confirmed the deletion of the long arm of chromosome 11, as reported in myeloid leukemia. If this patient would have died suddenly without the laboratory investigations that lead to the diagnosis of myeloblastic leukemia, the cause would have been probably and wrongfully allotted to treatment with olanzapine.

Quetiapine in patients with comorbid schizophrenia-spectrum and substance use disorders: an open-label trial.

BACKGROUND: Preliminary evidence suggests that clozapine relieves the craving for psychoactive substances in schizophrenia patients. Quetiapine shares crucial pharmacological properties with clozapine. Promising results have been described with quetiapine therapy in patients with psychosis and substance use disorder. METHODS: Based on Diagnostic and Statistical Manual of Mental Disorders - fourth edition (DSM-IV) criteria, patients were diagnosed with comorbid schizophrenia-spectrum and substance use disorders. Patients were switched to quetiapine for a 12-week open-label trial. Craving, quantities used, days of consumption, and severity of substance abuse were assessed every 3 weeks. Alcohol and Drug Use Scales were administered on baseline and end-point. Psychiatric symptoms, depressive symptoms, extrapyramidal symptoms, and cognition were also assessed at baseline, week 6 and week 12. RESULTS: Twenty-four schizophrenia-spectrum patients were included in the last observation carried forward (LOCF) analyses, responding to one or more of the following substance use disorders: cannabis (15 patients), alcohol (10 patients), and other psychoactive substances (nine patients). Overall, severity of substance abuse improved during the study. Less weekly days were spent on drugs of abuse. A decrease in the weekly Canadian dollars spent on psychoactive substances was also observed. Cognition, psychiatric, depressive, and extrapyramidal symptoms also significantly improved (p < 0.05). CONCLUSIONS: In this open-label, uncontrolled trial, significant improvements were noted in substance abuse, psychiatric symptoms, extrapyramidal symptoms, and cognition during quetiapine therapy. The study suffered from three main limitations: (1) the open-label design of the study; (2) the patients' poor compliance; and (3) the small sample size involved. Controlled studies on the use of quetiapine in dual diagnosis schizophrenia are warranted to confirm that the effects are drug-related.

Neural correlates of the affect regulation model in schizophrenia patients with substance use history: a functional magnetic resonance imaging study.

BACKGROUND: The lifetime prevalence of substance use disorders among schizophrenia patients is close to 50%. The negative consequences of substance abuse in schizophrenia are well documented, but the etiology of this comorbid condition remains unknown. According to the affect regulation model, schizophrenia patients abuse drugs in order to cope with their negative affects. Supporting the model, clinical studies have shown that dual-diagnosis patients have less blunting of affect and that they experience more negative affect. We hypothesized that patients with a history of substance use would have increased cerebral activations in response to aversive stimuli when compared to abstinent patients. METHOD: Schizophrenia patients were divided into 2 groups: patients with (SCZ-SU group; N = 12) and without (SCZ group; N = 11) a current or past substance use disorder (alcohol, cannabis, and/or LSD). Diagnoses were made according to DSM-IV criteria. Using functional magnetic resonance imaging (fMRI), patients were scanned during passive viewing of emotionally negative pictures (International Affective Picture System). Data were gathered from September 2001 to December 2003. RESULTS: Subjectively, the emotional experience induced by viewing the negative pictures was rated significantly higher in the SCZ-SU group than in the SCZ group (p = .008). Neurally, in the SCZ-SU group, significant loci of activation were identified in the right medial prefrontal cortex (Brodmann's area [BA] 10), left medial prefrontal cortex (BA 10), right orbitofrontal cortex (BA 47), and left amygdala. No significant loci of activation were observed in the SCZ group. CONCLUSIONS: These results suggest that the functioning of the medial prefrontal cortex, thought to be impaired in patients with prominent negative symptoms, is more preserved in dual-diagnosis schizophrenia. This relative preservation could be primary or secondary to substance use.