Exploring the sex and gender correlates of cognitive sex differences.

The correlates of cognitive sex differences are yet to be fully understood. Many biological and psychosocial factors modulate these cognitive abilities leading to mixed results in the scientific literature. The current study aims to explore the different parameters potentially influencing cognitive abilities acting in synergy. Sex and gender correlates of cognitive functioning were assessed in a sample of individuals ages 18 to 45 years (N = 87) from diverse sexual orientations. Sex hormones were assessed via saliva samples at four timepoints throughout the testing. Gender roles, sexual orientation and socio-demographics were measured via self-report questionnaires. Participants completed mental rotation and verbal fluency tasks. Men performed better than women at mental rotation, while no significant difference was found for verbal fluency. Significant positive associations were observed between estradiol and word fluency for the naturally cycling women compared to the women using oral contraception. While controlling for sex hormones, a significant interaction effect of sex by gender roles was identified for mental rotation among masculine women. These exploratory results suggest an effect principally driven by sex and sex hormones on cognitive performance that will need to be furthered with larger studies.

The regional effect of serum hormone levels on cerebral blood flow in healthy nonpregnant women.

Sex hormones estrogen (EST) and progesterone (PROG) have received increased attention for their important physiological action outside of reproduction. While studies have shown that EST and PROG have significant impacts on brain function, their impact on the cerebrovascular system in humans remains largely unknown. To address this, we used a multi-modal magnetic resonance imaging (MRI) approach to investigate the link between serum hormones in the follicular phase and luteal phase of the menstrual cycle (MC) with measures of cerebrovascular function (cerebral blood flow [CBF]) and structure (intracranial artery diameter). Fourteen naturally cycling women were recruited and assessed at two-time points of their MC. CBF was derived from pseudo-continuous arterial spin labeling while diameters of the internal carotid and basilar artery was assessed using time of flight magnetic resonance angiography, blood samples were performed after the MRI. Results show that PROG and EST had opposing and spatially distinct effects on CBF: PROG correlated negatively with CBF in anterior brain regions (r = -.86, p < .01), while EST correlations were positive, yet weak and most prominent in posterior areas (r = .78, p < .01). No significant correlations between either hormone or intracranial artery diameter were observed. These results show that EST and PROG have opposing and regionally distinct effects on CBF and that this relationship is likely not due to interactions with large intracranial arteries. Considering that CBF in healthy women appears tightly linked to their current hormonal state, future studies should consider assessing MC-related hormone fluctuations in the design of functional MRI studies in this population.

Functional Connectivity During Visuospatial Processing in Schizophrenia: A Classification Study Using Lasso Regression.

BACKGROUND: Robust evidence shows that schizophrenia is associated with significant cognitive impairments, including deficits in visuospatial abilities. While other cognitive domains have sparked several functional neuroimaging studies in schizophrenia, only a few brain activation studies have examined the neural correlates of visuospatial abilities in schizophrenia. PURPOSE: Here, we propose to perform a functional connectivity study on visuospatial processing in schizophrenia, and to determine the classification accuracy of the observed alterations. METHODS: Thirty-nine schizophrenia patients and 42 healthy controls were scanned using functional magnetic resonance imaging while performing a mental rotation task. Task-based functional connectivity was examined using a region-of-interest (ROI) to ROI approach, as implemented in the CONN Toolbox. ROIs were selected from a previous meta-analysis on mental rotation. Logistic regression with Lasso regularization was performed, using train-test cross-validation. RESULTS: Schizophrenia was associated with a complex pattern of dysconnectivity between the superior, middle and inferior frontal gyrus, the precentral gyrus, the superior parietal lobule (SPL) and the inferior lateral occipital cortex. The classification accuracy was 86.1%. Mental rotation performance was predicted by the dysconnectivity between the right and left superior frontal gyrus (SFG), as well as between the left SFG and left SPL. CONCLUSION: The results of the current study highlight that visuospatial processing is useful for examining the widespread dysconnectivity between executive, motor and visual brain regions in schizophrenia. We also demonstrate that very good classification accuracy can be achieved using visuospatial-related functional connectivity data.

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia.

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.

Violent Behavior Is Associated With Emotion Salience Network Dysconnectivity in Schizophrenia.

Background: Despite individuals with schizophrenia being at an elevated risk of violence compared to the general population, limited efforts have been invested in investigating the neurobiological etiology explaining the increase. Among the few studies examining functional disruptions pertaining to violent schizophrenia patients using fMRI, only one study has considered functional connectivity. The current state of knowledge does not allow to infer deficits in functional connectivity specific to distinct cognitive/emotional states that have been associated with the emergence of violence in schizophrenia, such as negative emotion processing. This study sought to identify disrupted connectivity among men with schizophrenia and a history of violence (SCZ+V), compared to men with schizophrenia without a history of violence (SCZ-V) and healthy controls, during negative emotion processing using fMRI. Methods: Twenty SCZ+V, 19 SCZ-V, and 21 healthy men were scanned while viewing negative images. Results: Negative images elicited an increased connectivity between the dorsal anterior cingulate cortex (dACC) and the bilateral rostral prefrontal cortex (rPFC), as well as a decreased functional connectivity between the frontal regions (bilateral rPFC and dACC) and the putamen and hippocampus in SCZ+V men as compared to SCZ-V men and healthy controls. Concurrently, the centrality of the dACC within the network was reduced in SCV+V subjects. Conclusions: These results suggest an inefficient integration of the information by the dACC between frontal and limbic regions in SCZ+V men during negative emotion processing and highlight the importance of the ACC in the neurobiological bases of violent behavior in schizophrenia.

Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with Attention-Deficit Hyperactivity Disorder: A Systematic Review.

Mindfulness-based interventions (MBIs) are becoming increasingly popular as treatments for physical and psychological problems. Recently, several studies have suggested that MBIs may also be effective in reducing symptoms of attention-deficit hyperactivity disorder (ADHD). Most studies have examined the effectiveness in children, but there are now a sufficient number of individual treatment trials to consider a systematic review in adults. Majority of existing systematic reviews and meta-analyses only consider ADHD symptoms as an outcome, and most of them do not fully report potential biases of included studies, thus limiting considerably their conclusions. This is an important facet because some studies could be found ineligible to be included in future analysis due to their low quality. In this systematic review, we followed the PRISMA/PICO criteria and we thoroughly assessed the risks of bias for each of the selected studies according to Cochrane guidelines. We searched the available literature concerning MBIs in adult participants with ADHD using PsycINFO, PubMed, Scopus, and ERIC databases. In total, 13 studies conducted with 753 adults (mean age of 35.1 years) were identified as eligible. Potential moderators such as participants' age, ADHD subtypes, medication status, comorbidity, intervention length, mindfulness techniques, homework amount, and training of therapists were carefully described. Aside from measuring the symptoms of ADHD, outcome measures were categorized into executive/cognitive functioning, emotional disturbances, quality of life, mindfulness, and grade point average at school. According to presented descriptive results, all the studies (100%) showed improvement of ADHD symptoms. In addition, mindfulness meditation training improves some aspects of executive function and emotion dysregulation. Although these are promising findings to support treatment efficacy of MBIs for ADHD, various biases such as absence of randomization and lack of a control group may affect the actual clinical value and implications of the studies. Moreover, the relatively low quality of selection and performance criteria in several studies, as well as relatively high attrition bias across studies, call for caution before considering conducting further analysis.

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.

Multisite generalizability of schizophrenia diagnosis classification based on functional brain connectivity.

Our objective was to assess the generalizability, across sites and cognitive contexts, of schizophrenia classification based on functional brain connectivity. We tested different training-test scenarios combining fMRI data from 191 schizophrenia patients and 191 matched healthy controls obtained at 6 scanning sites and under different task conditions. Diagnosis classification accuracy generalized well to a novel site and cognitive context provided data from multiple sites were used for classifier training. By contrast, lower classification accuracy was achieved when data from a single distinct site was used for training. These findings indicate that it is beneficial to use multisite data to train fMRI-based classifiers intended for large-scale use in the clinical realm.

Impaired Coupling between the Dorsomedial Prefrontal Cortex and the Amygdala in Schizophrenia Smokers Viewing Anti-smoking Images.

BACKGROUND: Cigarette smoking is highly prevalent in schizophrenia and is one of the main factors contributing to the significantly decreased life expectancy in this population. Schizophrenia smokers, compared to their counterparts with no comorbid psychiatric disorder, are largely unaware and indifferent to the long-term negative consequences of cigarette smoking. The objective of this study was to determine, for the first time, if these meta-cognitive deficits are associated with neuro-functional alterations in schizophrenia smokers. METHODS: Twenty-four smokers with no psychiatric disorder and 21 smokers with schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging and exposed to anti-smoking images. Granger causality analyses were used to examine the effective connectivity between brain regions found to be significantly activated. RESULTS: Across groups, potent activations were observed in the left ventro-lateral prefrontal cortex, the left amygdala (AMG), and the dorsomedial prefrontal cortex (dmPFC). Using the dmPFC as a seed region, we found an abnormal negative connectivity from the dmPFC to the AMG in schizophrenia smokers during the viewing of anti-smoking stimuli. This abnormal connectivity was not present during the viewing of aversive stimuli unrelated to tobacco. DISCUSSION: Given the well-established roles of the dmPFC in social cognition and of the AMG in emotional processing, our results suggest that the relative indifference of schizophrenia smokers regarding the negative consequences of tobacco smoking could be explained by a cognitive-affective dissonance.

Altered brain connectivity in patients with schizophrenia is consistent across cognitive contexts.

BACKGROUND: Schizophrenia has been defined as a dysconnection syndrome characterized by aberrant functional brain connectivity. Using task-based fMRI, we assessed to what extent the nature of the cognitive context may further modulate abnormal functional brain connectivity. METHODS: We analyzed data matched for motion in patients with schizophrenia and healthy controls who performed 3 different tasks. Tasks 1 and 2 both involved emotional processing and only slighlty differed (incidental encoding v. memory recognition), whereas task 3 was a much different mental rotation task. We conducted a connectome-wide general linear model analysis aimed at identifying context-dependent and independent functional brain connectivity alterations in patients with schizophrenia. RESULTS: After matching for motion, we included 30 patients with schizophrenia and 30 healthy controls in our study. Abnormal connectivity in patients with schizophrenia followed similar patterns regardless of the degree of similarity between cognitive tasks. Decreased connectivity was most notable in the medial prefrontal cortex, the anterior and posterior cingulate, the temporal lobe, the lobule IX of the cerebellum and the premotor cortex. LIMITATIONS: A more circumscribed yet significant context-dependent effect might be detected with larger sample sizes or cognitive domains other than emotional and visuomotor processing. CONCLUSION: The context-independence of functional brain dysconnectivity in patients with schizophrenia provides a good justification for pooling data from multiple experiments in order to identify connectivity biomarkers of this mental illness.

Abnormal effective fronto-limbic connectivity during emotion processing in schizophrenia.

BACKGROUND: Schizophrenia is associated with core emotional dysfunctions. At the neural level, functional neuro-imaging studies have highlighted fronto-limbic alterations during emotion processing in schizophrenia, as well as impaired connectivity between the amygdala and the prefrontal cortex. However, the direction of the impaired fronto-limbic connections remains largely unknown. To clarify this issue, we performed an effective connectivity study on emotion processing in schizophrenia. METHODS: Forty-one healthy individuals and 39 schizophrenia patients (DSM-IV criteria) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. RESULTS: Subjective ratings of emotionally neutral images were higher in schizophrenia patients than in controls. Across groups, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the bilateral amygdala. The Granger connectivity from the right amygdala to the dmPFC was significantly reduced in schizophrenia patients, relative to controls, during the negative and neutral conditions. The Granger connectivity from the left amygdala to the dmPFC was significantly reduced in schizophrenia patients, relative to controls, during the positive condition. DISCUSSION: The finding of a reduced lagged connectivity from the bilateral amygdala to the dmPFC in schizophrenia suggests that the bottom-up mechanisms involved in the processing of highly arousing emotional stimuli are impaired in this disorder. The finding of an impaired lagged connectivity from the right amygdala to the dmPFC during the processing of emotionally neutral stimuli in schizophrenia is novel and may explain why these patients tend to confer emotional significance to irrelevant stimuli.

Atypical Activations of Fronto-Cerebellar Regions During Forethought in Parents of Children With ADHD.

OBJECTIVE: Although several studies suggest heritability of ADHD, only a few investigations of possible associations between people at risk and neural abnormalities in ADHD exist. In this study, we tested whether parents of children with ADHD would show atypical patterns of cerebral activations during forethought, a feature of working memory. METHOD: Using Functional Magnetic Resonance Imaging (fMRI), we compared 12 parents of children with ADHD and 9 parents of control children during a forethought task. RESULTS: Parents of children with ADHD exhibited significantly increased neural activations in the posterior lobes of the cerebellum and in the left inferior frontal gyrus, relative to parents of control children. CONCLUSION: These findings are consistent with previous reports in children and suggest the fronto-cerebellar circuit's abnormalities during forethought in parents of children with ADHD. Future studies of people at risk of ADHD are needed to fully understand the extent of the fronto-cerebellar heritability.

[Emotional Memory and Electrocortical Activity in Schizophrenia]. / Mémoire émotionnelle et activités électrocorticales en schizophrénie.

Context Abnormal emotion processing is frequent in schizophrenia and affects social and functional outcome. Past event-related potential (ERP) research investigating processing of affective stimuli in schizophrenia was done mainly with facial expressions and revealed impaired facial emotion recognition in patients relative to control subjects. Experimentations involving fMRI with this group of patients, showed alteration of limbic and frontal regions in response to emotional unpleasant images, compared to neutral stimuli during a memory task. Other studies have also noted an increase in brain activity when the activation of the stimuli was high compared to low arousal stimuli. This may indicate a different sensitivity threshold to emotional arousal and emotional valence involving frontal pathways in these patients. But very few studies attempted to separate the contributions of emotional valence and arousal within an episodic memory protocol with ERP, in that population.Goal The aim of the current research is to investigate brain electro-cortical activity in schizophrenia in response to emotional images during an episodic memory task.Method ERP components were analyzed in 16 schizophrenic and 17 control participants matched for age, sex and intelligence. ERPs were obtained from 56 EEG electrodes. The tasks consisted in a classical episodic memory task that presented 100 repeated old and 100 new photographic images divided into four categories (unpleasant-high arousal, unpleasant-low arousal, pleasant-high arousal and pleasant-low arousal) selected from the International Affective Picture System. The N200, P300 and late positive component (LPC) mean amplitude, were analyzed using repeated-measure analyses of variance (MANOVA).Results Patients with schizophrenia and control subjects gave comparable subjective evaluations of arousal and valence. However, the frontal N200 and the P300 both showed an interaction of the group x memory x valence x hemisphere (F [1.32]=8.36; p <.01). Thus, this complex interaction denotes an increase of the episodic memory effect in the right hemisphere in response to unpleasant stimuli, with schizophrenic patients. With respect to the control group, there is also an increase of this memory effect in the right hemisphere, but in response to pleasant stimuli. The schizophrenic patients presented a smaller LPC memory effect, especially at the frontal region. More specifically, the frontal LPC was reduced, and the clinical group was less reactive to the emotional arousal content, compared to the control group.Discussion Altogether, our results revealed that while the subjective evaluation of emotional pictures is equivalent across groups, cerebral differences are present in schizophrenic patients during emotional recognition. N200 and P300 results in the frontal region suggest impaired selective attention and episodic memory to unpleasant stimuli in patients, while later processes related to conscious recollection (parietal LPC) are not affected with patients affected with schizophrenia.Conclusion This finding provides further support for the notion of a possible discrepancy between the subjective experience and the physiological expression of emotions in schizophrenia patients. Those results could open the door to new clinical research investigations in psychiatry, particularly in the comprehension of a relationship between frontal cortex vulnerability and episodic memory often present in psychosis.

Anterior cingulate hyperactivations during negative emotion processing among men with schizophrenia and a history of violent behavior.

BACKGROUND: Evidence suggests a 2.1-4.6 times increase in the risk of violent behavior in schizophrenia compared to the general population. Current theories propose that the processing of negative emotions is defective in violent individuals and that dysfunctions within the neural circuits involved in emotion processing are implicated in violence. Although schizophrenia patients show enhanced sensitivity to negative stimuli, there are only few functional neuroimaging studies that have examined emotion processing among men with schizophrenia and a history of violence. OBJECTIVE: The present study aimed to identify the brain regions with greater neurofunctional alterations, as detected by functional magnetic resonance imaging during an emotion processing task, of men with schizophrenia who had engaged in violent behavior compared with those who had not. METHODS: Sixty men were studied; 20 with schizophrenia and a history of violence, 19 with schizophrenia and no violence, and 21 healthy men were scanned while viewing positive, negative, and neutral images. RESULTS: Negative images elicited hyperactivations in the anterior cingulate cortex (ACC), left and right lingual gyrus, and the left precentral gyrus in violent men with schizophrenia, compared to nonviolent men with schizophrenia and healthy men. Neutral images elicited hyperactivations in the right and left middle occipital gyrus, left lingual gyrus, and the left fusiform gyrus in violent men with schizophrenia, compared to the other two groups. DISCUSSION: Violent men with schizophrenia displayed specific increases in ACC in response to negative images. Given the role of the ACC in information integration, these results indicate a specific dysfunction in the processing of negative emotions that may trigger violent behavior in men with schizophrenia.

Gonads and strife: Sex hormones vary according to sexual orientation for women and stress indices for both sexes.

This study assessed sexual orientation and psychobiological stress indices in relation to salivary sex hormones as part of a well-validated laboratory-based stress paradigm. Participants included 87 healthy adults that were on average 25 years old who self-identified as lesbian/bisexual women (n=20), heterosexual women (n=21), gay/bisexual men (n=26), and heterosexual men (n=20). Two saliva samples were collected fifteen minutes before and fifteen minutes after exposure to a modified Trier Social Stress Test to determine testosterone, estradiol, and progesterone concentrations via enzyme-immune assaying. Mean sex hormones were further tested in association to stress indices related to cortisol systemic output (area under the curve with respect to ground) based on ten measures throughout the two-hour visit, allostatic load indexed using 21 biomarkers, and perceived stress assessed using a well-validated questionnaire. Results revealed that lesbian/bisexual women had higher overall testosterone and progesterone concentrations than heterosexual women, while no differences were found among gay/bisexual men in comparison to heterosexual men. Lesbian/bisexual women and heterosexual men showed positive associations between mean estradiol concentrations and allostatic load, while gay/bisexual men and heterosexual women showed positive associations between mean testosterone and cortisol systemic output. In summary, sex hormone variations appear to vary according to sexual orientation among women, but also as a function of cortisol systemic output, allostatic load, and perceived stress for both sexes.

Emotionally Neutral Stimuli Are Not Neutral in Schizophrenia: A Mini Review of Functional Neuroimaging Studies.

Reliable evidence shows that schizophrenia patients tend to experience negative emotions when presented with emotionally neutral stimuli. Similarly, several functional neuroimaging studies show that schizophrenia patients have increased activations in response to neutral material. However, results are heterogeneous. Here, we review the functional neuroimaging studies that have addressed this research question. Based on the 36 functional neuroimaging studies that we retrieved, it seems that the increased brain reactivity to neutral stimuli is fairly common in schizophrenia, but that the regions involved vary considerably, apart from the amygdala. Prefrontal and cingulate sub-regions and the hippocampus may also be involved. By contrasts, results in individuals at risk for psychosis are less consistent. In schizophrenia patients, results are less consistent in the case of studies using non-facial stimuli, explicit processing paradigms, and/or event-related designs. This means that human faces may convey subtle information (e.g., trustworthiness) other than basic emotional expressions. It also means that the aberrant brain reactivity to neutral stimuli is less likely to occur when experimental paradigms are too cognitively demanding as well as in studies lacking statistical power. The main hypothesis proposed to account for this increased brain reactivity to neutral stimuli is the aberrant salience hypothesis of psychosis. Other investigators propose that the aberrant brain reactivity to neutral stimuli in schizophrenia results from abnormal associative learning, untrustworthiness judgments, priming effects, and/or reduced habituation to neutral stimuli. In the future, the effects of antipsychotics on this aberrant brain reactivity will need to be determined, as well as the potential implication of sex/gender.

Increased ventro-medial prefrontal activations in schizophrenia smokers during cigarette cravings.

BACKGROUND: Highly prevalent in schizophrenia, tobacco smoking substantially increases the risk of cardiac-related death. Compared to the general population, tobacco smoking cessation rates are lower in schizophrenia. Unfortunately, the reasons for these low cessation rates remain poorly understood. Recently, it has been shown that tobacco cravings are increased in schizophrenia smokers compared to smokers with no comorbid psychiatric disorder. In view of these results, we sought to examine - for the first time - the neurophysiologic responses elicited by cigarette cues in schizophrenia smokers. We hypothesized that cigarettes cues would elicit increased activations in brain regions involved in drug cravings in schizophrenia smokers relative to control smokers. METHODS: Smokers with (n=18) and without (n=24) schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging (fMRI) while viewing appetitive cigarette images. RESULTS: Schizophrenia smokers and smokers with no psychiatric comorbidity did not differ in subjective cravings in response to appetitive smoking cues. However, in schizophrenia smokers relative to control smokers, we found that appetitive cigarette cues triggered increased activations of the bilateral ventro-medial prefrontal cortex, a core region of the brain reward system. Moreover, a negative correlation was observed between cigarette cravings and activations of the right ventro-medial prefrontal cortex in schizophrenia smokers. DISCUSSION: The current results highlight a key role of the brain reward system in cigarette craving in schizophrenia, and suggest that the neurophysiologic mechanisms involved in the regulation of cue-induced cigarette craving are impaired in this population.

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.

Cigarette Cravings, Impulsivity, and the Brain.

Craving is a core feature of tobacco use disorder as well as a significant predictor of smoking relapse. Studies have shown that appetitive smoking-related stimuli (e.g., someone smoking) trigger significant cravings in smokers impede their self-control capacities and promote drug seeking behavior. In this review, we begin by an overview of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of smokers to appetitive smoking cues. The literature reveals a complex and vastly distributed neuronal network underlying smokers' craving response that recruits regions involved in self-referential processing, planning/regulatory processes, emotional responding, attentional biases, and automatic conducts. We then selectively review important factors contributing to the heterogeneity of results that significantly limit the implications of these findings, namely between- (abstinence, smoking expectancies, and self-regulation) and within-studies factors (severity of smoking dependence, sex-differences, motivation to quit, and genetic factors). Remarkably, we found that little to no attention has been devoted to examine the influence of personality traits on the neural correlates of cigarette cravings in fMRI studies. Impulsivity has been linked with craving and relapse in substance and tobacco use, which prompted our research team to examine the influence of impulsivity on cigarette cravings in an fMRI study. We found that the influence of impulsivity on cigarette cravings was mediated by fronto-cingulate mechanisms. Given the high prevalence of cigarette smoking in several psychiatric disorders that are characterized by significant levels of impulsivity, we conclude by identifying psychiatric patients as a target population whose tobacco-smoking habits deserve further behavioral and neuro-imaging investigation.

Emotion processing in treatment-resistant schizophrenia patients treated with clozapine: An fMRI study.

OBJECTIVES: To examine the neural correlates of emotion processing in treatment-resistant patients with schizophrenia (SCZ-TR). METHODS: Twenty-two SCZ-TR patients on clozapine, 24 schizophrenia patients on antipsychotics other than clozapine, and 39 healthy controls were scanned using functional neuroimaging while viewing positive, negative and neutral images. RESULTS: Emotionally-laden images (positive and negative) elicited hyper-activations in the dorso-medial prefrontal cortex and left cerebellum in SCZ-TR patients, compared to the two other groups. Similarly, neutral images prompted hyper-activations in the cingulate gyrus in SCZ-TR patients, relative to the two other groups. CONCLUSIONS: Treatment resistance is associated with neuro-functional hyper-activations in schizophrenia patients during emotion processing.