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Dans cette vidéo expliquative, Madame Lina Awilé, Master en psychologie, nous fait voyager avec élégance au fin fond du cerveau afin d'explorer les méandres de l'apprentissage et la mémoire. Cette vidéo fait partie d'une série de trois vidéos expliquatives. In this explanatory video, Mrs. Lina Awilé, Master in Psychology, takes us elegantly to the depths of the brain to explore the intricacies of learning and memory. This video is part of a series of three explanatory videos.

Objective: Compared to the general population, tobacco smoking cessation rates are lower in populations with schizophrenia. Unfortunately, the potential neurophysiologic mechanisms underlying these...

Several studies have examined associations between peripheral DNA methylation patterns of the serotonin transporter gene (SLC6A4) promoter and symptoms of depression and anxiety. The SLC6A4 promoter methylation has also been associated with frontal-limbic brain responses to negative stimuli. However, it is unclear how much of this association is confounded by DNA sequence variations. We utilized a monozygotic-twin within-pair discordance design, to test whether DNA methylation at specific CpG sites in the SLC6A4 promoter of peripheral cells is associated with greater frontal-limbic brain responses to negative stimuli (sadness and fear), independently of DNA sequence effects. In total 48 pairs of healthy 15-year-old monozygotic twins from the Quebec Newborn Twin Study, followed regularly since birth, underwent functional magnetic resonance imaging while conducting an emotion-processing task. The SLC6A4 promoter methylation level was assessed in saliva samples using pyrosequencing. Relative to the co-twins with lower SLC6A4 promoter methylation levels, twins with higher peripheral SLC6A4 methylation levels showed greater orbitofrontal cortical (OFC) activity and left amygdala-anterior cingulate cortex (ACC) and left amygdala-right OFC connectivity in response to sadness as well as greater ACC-left amygdala and ACC-left insula connectivity in response to fearful stimuli. By utilising a monozygotic-twin design, we provided evidence that associations between peripheral SLC6A4 promoter methylation and frontal-limbic brain responses to negative stimuli are, in part, independent of DNA sequence variations. Although causality cannot be determined here, SLC6A4 promoter methylation may be one of the mechanisms underlying how environmental factors influence the serotonin system, potentially affecting emotional processing through frontal-limbic areas.

Objectives: The verbal abilities of autistic children differ from those of typically developing ones and they also differ among autistic children themselves. Neuroanatomical changes and an abnormal organization of functional networks are expected to accompany such a neurodevelopmental disorder. The aim of this study was to delineate the brain neuroanatomical changes in Egyptian children with autism and to compare them with previous studies in order to add more insight into the global brain imaging deviations linked to autism. Patients and Methods: Twenty-five autistic children and 25 typically developing children underwent MRI. Further analysis was performed using surface-based morphometry to obtain cortical thickness, brain volume, and cortical complexity. Results: MRI analysis results revealed significantly greater cortical thickness, cortical complexity, and gray matter volume in the autistic as compared to the control group. On the other hand, the white matter volume was significantly smaller. Conclusion: These findings generally align with findings in previous studies, except for occasional differences.

Prenatal and early postnatal adversities have been shown to be associated with brain development. However, we do not know how much of this association is confounded by genetics, nor whether the postnatal environment can moderate the impact of in utero adversity. This study used a monozygotic (MZ) twin design to assess (1) the association between birth weight (BW) and brain volume in adolescence, (2) the association between within-twin-pair BW discordance and brain volume discordance in adolescence, and (3) whether the association between BW and brain volume in adolescence is mediated or moderated by early negative maternal parenting behaviours. These associations were assessed in a sample of 108 MZ twins followed longitudinally since birth and scanned at age 15. The total grey matter (GM) and white matter (WM) volumes were obtained using the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) toolbox in the Statistical Parametric Mapping version 8 (SPM8). We found that the BW was significantly associated with the total GM and WM volumes, particularly in the superior frontal gyrus and thalamus. Within-twin-pair discordance in BW was also significantly associated with within-pair discordance in both the GM and the WM volumes, supporting the hypothesis that the specific in utero environment is associated with brain development independently of genetics. Early maternal hostile parenting behaviours and depressive symptoms were associated with total GM volume but not WM volume. Finally, greater early maternal hostility may moderate the association between the BW and GM volume in adolescence, since the positive association between the BW and total GM volume appeared stronger at higher levels of maternal hostility (trend). Together, these findings support the importance of the in utero and early environments for brain development.

The autism phenotype is associated with an excess of brain volume due in part to decreased pruning during development. Here we aimed at assessing brain volume early in development to further elucidate previous findings in autism and determine whether this pattern is restricted to idiopathic autism or shared within the autistic phenotype (fragile X syndrome [FXS]). We investigated brain volume in 37 participants, using the fully automated Civet pipeline anatomical magnetic resonance imaging. 3 groups with intellectual deficiency: autism (AUT); its most associated FXS; and its most opposite Williams syndrome (WS) were compared with each other and with normal controls (NC). We report increased total and regional gray and white matter brain volume in AUT and FXS relative to WS and NC. These findings are discussed in light of the possibilities leading for the enlarged brain volume in children with the AUT phenotype. We speculate that this excess suggests reduced regression of neuronal processes “pruning” in cortical and subcortical regions in AUT/FXS, which may be due to a mutation in specific genes involved in pruning and/or a lack of socio-emotional environmental experience during a critical developmental period.

The goal of this study is twofold: (1) to assess brain anatomical differences between children meeting diagnostic criteria for oppositional defiant disorder (ODD) and healthy controls, and (2) to investigate whether morphological brain characteristics associated with ODD differ in boys and girls. Eight-year-old participants (N = 38) were scanned using magnetic resonance imaging. ODD symptoms were assessed using the Dominic-R interactive. In ODD participants, we observed a significant reduction of gray matter density in the left orbitofrontal cortex—a prefrontal region that plays a pivotal role in emotional self-regulation and impulse control—and, conversely, an increase in the left temporal area—an area that has been associated with aggressive, impulsive, and antisocial personality. Furthermore, ODD boys showed a reduction of both gray matter density in the left orbitofrontal cortex and of white matter density in the left superior frontal area. The structural abnormalities found in the present study, in particular, the correlation between ODD symptoms and reduction of gray matter density in the left orbitofrontal cortex, may present some evidence for the existence of neuropathology associated with ODD symptoms during childhood. Furthermore, our findings indicate morphometric differences between boys and girls with ODD, which may be associated with gender differences in social behavior in children showing ODD symptoms.

Background Genetically Williams syndrome (WS) promises to provide essential insight into the pathophysiology of cortical development because its ∼28 deleted genes are crucial for cortical neuronal migration and maturation. Phenotypically, WS is one of the most puzzling childhood neurodevelopmental disorders affecting most intellectual deficiencies (i.e. low-moderate intelligence quotient, visuospatial deficits) yet relatively preserving what is uniquely human (i.e. language and social-emotional cognition). Therefore, WS provides a privileged setting for investigating the relationship between genes, brain and the consequent complex human behaviour. Methods We used in vivo anatomical magnetic resonance imaging analysing cortical surface-based morphometry, (i.e. surface area , cortical volume , cortical thickness , gyrification index ) and cortical complexity , which is of particular relevance to the WS genotype–phenotype relationship in 22 children (2.27–14.6 years) to compare whole hemisphere and lobar surface-based morphometry between WS (n = 10) and gender/age matched normal controls healthy controls (n = 12). Results Compared to healthy controls, WS children had a (1) relatively preserved Cth; (2) significantly reduced SA and CV; (3) significantly increased GI mostly in the parietal lobe; and (4) decreased CC specifically in the frontal and parietal lobes. Conclusion Our findings are then discussed with reference to the Rakic radial-unit hypothesis of cortical development, arguing that WS gene deletions may spare Cth yet affecting the number of founder cells/columns/radial units, hence decreasing the SA and CV. In essence, cortical brain structure in WS may be shaped by gene-dosage abnormalities.

Our aims were to (1) examine possible neuroanatomical abnormalities associated with the Disruptive Behavior Disorders (DBDs) as a group and (2) assess neuroanatomical anomalies specific to each DBD (i.e., conduct disorder [CD] and oppositional defiant disorder). Cortical thickness analysis and voxel-based morphometry were analyzed in 47 8-year-old boys (22 DBDs with and without CD and/or ODD and 25 healthy controls) from Magnetic Resonance Imaging brain scans. DBD symptoms were assessed using the Dominic-R. In DBD subjects relative to controls, we found (1) a decreased overall mean cortical thickness; (2) thinning of the cingulate, prefrontal and insular cortices; and (3) decreased gray matter density (GMd) in the same brain regions. We also found that scores on the Dominic-R were negatively correlated with GMd in the prefrontal and precuneus/superior temporal regions. There was a subdiagnostic main effect for CD, related to thinning of the middle/medial frontal, and for ODD in the left rectal/orbitofrontal. Findings suggest that thinning and decreased GMd of the insula disorganizes prefrontal circuits, diminishing the inhibitory influence of the prefrontal cortex on anger, aggression, cruelty, and impulsivity, and increasing a person's likelihood of aggressive behavior. These findings have implications for pathophysiologic models of the DBDs, their diagnostic classification system, and for designing more effective intervention programs.

Tourette syndrome (TS) implicates the disinhibition of the cortico-striatal-thalamic-cortical circuitry (CSTC). Previous studies used a volumetric approach to investigate this circuitry with inconsistent findings. Cortical thickness may represent a more reliable measure than volume due to the low variability in the cytoarchitectural structure of the grey matter.66 magnetic resonance imaging scans were acquired from 34 TS subjects (age range 10-25, mean 17.19+/-4.1) and 32 normal controls (NC) (age range 10-20, mean 16.33+/-3.56). Brain morphology was assessed using the fully automated CIVET pipeline at the Montreal Neurological Institute.We report (1) significant cortical thinning in the fronto-parietal and somatosensory-motor cortices in TS relative to NC (p.05); (2) TS boys showed thinner cortex relative to TS girls in the fronto-parietal cortical regions (p.05); (3) significant decrease in the fronto-parietal mean cortical thickness in TS subjects with age relative to NC and in the pre-central cortex in TS boys relative to TS girls; (4) significant negative correlations between tic severity and the somatosensory-motor cortical thickness.TS revealed important thinning in brain regions particularly involved in the somatosensory/motor bodily representations which may play an important role in tics. Our findings are in agreement with Leckman et al. (1991) hypothesis stating that facial tics would be associated with dysfunction in an orofacial subset of the motor circuit, eye blinking with the occulo-motor circuit, whereas lack of inhibition to a dysfunction in the prefrontal cortex. Gender and age differences may reflect differential etiological factors, which have significant clinical relevance in TS and should be considered in developing and using diagnostic and therapeutic interventions.

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.

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.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.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.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.

Objective:There have been reports that patients with schizophrenia have decreased activity in the prefrontal cortex during emotion processing. However, findings have been confounded by sample nonspecificity and explicit cognitive task interference with emotion processing. We aimed to further investigate this by examining the ventrolateral prefrontal cortex (VLPFC) activation in response to the passive viewing of sad film excerpts.Methods:We presented film excerpts depicting sad and neutral social situations to 25 schizophrenia patients (14 with blunted affect [BA+] and 11 without blunted affect [BA-]) in an implicit perception task to evoke prefronto-limbic activity illustrated by blood oxygenation level–dependent functional magnetic resonance imaging.Results:A random-effects analysis (2-sample t test) using statistical parametric mapping indicated that BA+ patients differed from BA–patients at a 0.05 level ( P corrected for multiple comparisons). Consistent with our a priori hypothesis, BA–patients (relative to BA+ patients) showed significant activation in the right VLPFC. An exploratory analysis revealed the following loci of activation: caudate nucleus, VLPFC, middle prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, and anterior temporal pole in the BA–group; and hippocampus, cerebellum, anterior temporal pole, and midbrain in the BA+ group.Conclusions:We observed not only hypofrontality in the BA+ group but also dysfunctional circuitry distributed throughout the brain. The temporal and midbrain activation seen in the BA+ group may indicate that these brain regions were working harder to compensate for inactivation in other regions. These distributed dysfunctional circuits may form the neural basis of blunted affect through impairment of emotion processing in the brain that prevents it from processing input efficiently and producing output effectively, thereby leading to symptoms such as blunted affect.

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.

Blood-oxygenation-level-dependent (BOLD) brain changes underlying response to quetiapine were examined using passive viewing of emotionally negative stimuli. Twelve DSM-IV schizophrenia patients with blunted affect (BA+) were scanned before and after 22 weeks of quetiapine treatment. Whole-brain, voxel-based methods were used to assess the differential hemodynamic response to quetiapine. In addition, a post hoc comparison to an independent group of 11 schizophrenia patients without blunted affect (BA-) was performed to compare them with BA+ (postquetiapine) in response to emotion processing. A 22-week treatment with quetiapine resulted in significant clinical improvement in the 12 study completers (mean +/- SD posttreatment PANSS blunted affect score of 5.50 +/- 0.76 at baseline to 2.08 +/- 1.00 at end point; t = 7.78, df = 11, P < 0.0001). Treatment response was associated with significant BOLD changes: increases in prefrontal cortex activation particularly in the right dorsolateral prefrontal cortex (DLPFC, BA 46) and the right anterior cingulate cortex (ACC, BA 32); and in the left putamen, right anterior temporal pole (ATP), and right amygdala. Conversely, before treatment with quetiapine, the same subjects activated the midbrain bilaterally and the right pons. The post hoc conjunctional analyses demonstrated that BA- subjects activated the left ACC, left insula, left ATP (BA 21), left ATP (BA 38), left amygdala, and right medial prefrontal cortex. Quetiapine seems to affect clinical recovery by modulating the functioning of specific brain regions. Unique BOLD changes in the putamen and DLPFC with quetiapine, in the BA+ postquetiapine, may reflect modality-specific effects. Controlled studies are needed to further assess these preliminary findings.

Schizophrenia is an etiologically heterogeneous syndrome. It has a strong genetic component and exists in clinically indistinguishable familial and nonfamilial (sporadic) forms. A significant role for de novo genetic mutations in genetic schizophrenia vulnerability is suggested by a strong monotonic increase in schizophrenia risk with advancing paternal age. However, an alternative explanation for the paternal age effect in schizophrenia is that childbearing is delayed in fathers who themselves have genetic schizophrenia vulnerability. In this study, we compared paternal birth ages between patient groups with familial (n = 35) and sporadic (n = 68) patients with DSM-IV schizophrenia from an inpatient schizophrenia research unit. If later age of fathering children is related to having some genetic schizophrenia vulnerability, then paternal birth age should be later in familial schizophrenia cases than in sporadic cases, and any association of father's age and schizophrenia risk in offspring would be a spurious finding, unrelated to etiology. However, if de novo mutations cause sporadic schizophrenia, then patients without a family history of schizophrenia would have older fathers than familial patients. We found that patients without a family history of schizophrenia had significantly older fathers (4.7 years) than familial patients; so later childbirth was not attributable to parental psychiatric illness. These findings support the hypothesis that de novo mutations contribute to the risk for sporadic schizophrenia.

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.

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.

BackgroundThe functional neuroimaging studies of emotion processing in schizophrenia have revealed variable results attributed partly to differential symptomatology and sex of tested patients. The aim of the present study was to investigate the relationship between cerebral activations during exposure to emotional material and schizophrenia symptoms in men versus women.MethodFifteen men and 10 women with schizophrenia, equivalent in terms of age, medication and experienced symptomatology, underwent functional MRI during viewing sad and neutral film excerpts. Data were analyzed using Statistical Parametric Mapping Software (SPM2).ResultsAcross all the patients there was a significant inverse relationship between negative symptoms and activations in the right prefrontal cortex during processing of sad versus neutral stimuli. In men, activations during sad versus neutral stimuli in the prefrontal, temporal and anterior cingulate cortex, as well as the caudate and cerebellum, were positively correlated with negative symptoms. In women, there were inverse correlations between positive symptoms and activations in the hippocampus, parietal and occipital cortex during the same condition.ConclusionPresent results confirmed association of prefrontal hypofunction with negative symptoms in schizophrenia. More interestingly, the results revealed a diametrically different pattern of symptom-correlated brain activity in men and women with schizophrenia, suggesting that the processing of sadness is mediated via neurophysiological mechanism related to negative symptoms in men and the mechanism related to positive symptoms in women.

It has been increasing rapidly interest in understanding genetic effects on brain structure and function in recent years. In this study, we examined the genetic and environmental influences on the variation in cortical thickness and specific tissue volumes in a large cohort of 8-year-old healthy twins. The present study can provide a better estimation of the genetic and environmental effects by virtue of the homogeneously-aged pediatric twin pairs with a similar growing environment. We found that common environmental factors contributed significantly to the variations of the right lateral ventricle (36%) and corpus callosum (36%) volumes while genetic factors accounted for most of the phenotypic variance in other brain tissue volumes. In the case of cortical thickness, several regions in the left hemisphere showed statistically significant additive genetic factors, including the middle and inferior frontal gyri, lateral fronto-orbital and occipitotemporal gyri, pars opercularis, planum temporale, precentral and parahippocampal gyri, and the medial region of the primary somatosensory cortex. Relatively high common environmental influence (> 50%) was observed in the right anterior cingulate cortex and insula. Our findings indicate that the genetic and common environmental influences on individual human brain structural differences are lateralized, with the language-dominant left cerebral cortex under stronger genetic control than the right.

Fraternal twin studies on normal subjects have demonstrated low heritability (intra-class correlation coefficient) estimates for frontal brain regions (r = 0.43). Here we aimed to investigate the relatedness/similarity estimates of the frontal brain regions in fraternal subjects concordant for Tourette syndrome (TS). We sought to identify regional brain similarities between siblings concordant for TS as an exploratory step towards the identification of potential brain structures involved in the TS phenotype. The identified brain structures may then serve in subsequent molecular genetic and linkage studies. In addition, we regressed cortical thickness and TS clinical severity scores to assess the relation between TS clinical symptoms and cortical structures. Sixteen sibling pairs concordant for TS were scanned using a 1.5 T magnetic resonance imaging scanner (age range 10-25, mean 17.19 +/- 4.1). Brain morphology was assessed using the fully automated Civet pipeline at the Montreal Neurological Institute. TS was assessed using the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS) and the Goetz Tic Scale. We report high relatedness/similarity estimates for fraternal siblings concordant for TS (r = 0.86-0.60) in the middle frontal-motor/cingulate/insular cortices. Regression analysis revealed significant negative correlations in the right insula with the YGTSS (r = -0.41, F = 6.09, P < 0.02) and the left cingulated cortex with the (CY-BOCS) (r = -0.35, F = 4.30, P < 0.05). Since previous findings have concluded that normal fraternal siblings are less alike in frontal cortices, the present findings may be attributed to TS. We speculate that the high ICC between siblings and the negative correlation between TS symptoms severity and cortical thickness measurements are related to the disturbances in the maturation of the motor-cingulate-insular cortical neural system that mediate self-regulatory processes. Such delayed maturation may consequently contribute to the development of TS by releasing motor and vocal tics from regulatory control. These findings may have important genetic implications.

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.

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.

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.

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).

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.

This study investigated changes in cerebral activation related to emotion processing in schizophrenia patients with blunted or flat affect (FA+) during treatment with quetiapine. Using functional magnetic resonance imaging (fMRI), brain activation in 12 FA+ schizophrenia patients during passive viewing of sad film excerpts was studied before and after a median of 5.5-months treatment with quetiapine. Random-effects 'paired sample t-test' analyses of brain activation before quetiapine (contrast=sad-neutral, before-after) revealed significant activation in the brainstem (pons, medulla). After quetiapine, the same contrast showed significant prefrontal activation (BA 9, 10 and 11). Activation of key prefrontal areas involved in emotion processing and significant symptoms improvement as measured by the subjective rating scale and PANSS suggests the potential effect of quetiapine in improving blunted affect related symptoms (i.e., passive withdrawal, emotional withdrawal, social avoidance) in schizophrenia.

Brain morphology and physiological measures in schizophrenia have yielded inconsistent results. This may be due in part to difficulties in ascertaining precisely to what degree each measure deviates from its genetically and environmentally determined potential level. We attempted to surmount this problem in a paradigm involving monozygotic twin pair discordant for schizophrenia. In this paradigm, the difference score and reaction time between the unaffected member and affected member of a twin pair should represent the degree of pathologic involvement irrespective of actual level.We investigated, using fMRI, the neural substrate underlying encoding and retrieval of aversive and neutral IAPS pictures.An ANOVA on reaction time (RT) between schizophrenia patient (J) and normal sister (D) significant difference, (F = 5.2, por = .02) for J had less RT than D. Conversely, the ANOVA for the correct pictures retrieved was insignificant (F = 1.8, por = .2). When the brain activity associated with the encoding and retrieval of the aversive pictures was subtracted (J-D and D-J) from that associated with the neutral ones, significant loci of activation were found. During encoding: for J-D the right fusiform gyrus was significantly activated (p.0001) and for D-J the orbitofrontal cortex was significantly activated (p.05). During retrieval: for J-D the right anterior cingulate (p.0001) was activated and the dorsolateral prefrontal cortex (p.002). For D-J only the cerebellum showed activation (p.0001).Results indicated subtle attenuations in some aspects of memory, thus providing another evidence for cognitive markers of a genetic component in schizophrenia. New approaches in neuropsychiatry-based on genetic methodologies should further define the cerebral physiology responsible for schizophrenia.

The aim of the present study is to use neuroscience theories about brain function (mirror-neurons MN) to draw inferences about the mechanisms supporting emotional resonance in two different groups of schizophrenia patients (with flat affect FA+ n = 13 and without flat affect FA- n = 11). We hypothesize that FA+ will not activate key brain areas involved in emotional processing. Conversely, FA- will have a functional mirror system for emotional resonance confirmed by activation of the prefrontal cortex and behavioral results. To test this hypothesis, we compared the two groups using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) displaying a passive visual task (44 negative IAPS pictures and 44 neutral pictures). A random-effects analysis, for schizophrenia patients FA-, revealed significant loci of activation in the left mesial prefrontal (MPFC), right orbitofrontal (OFC) and left anterior cingulate cortices (ACC). Correlational analyses carried out between self-report ratings of negative feelings and BOLD signal changes revealed the existence of positive correlation in the LACC, LMPFC and ROFC. Conversely, FA+ did not show significant activation in the prefrontal cortex. We propose that negative emotional resonance induced by passively viewing negative pictures may be a form of "mirroring" that grounds negative feelings via an experiential mechanism. Hence, it could be argued that FA- were able to 'feel' emotions through this resonance behavior. Conversely, we suggest that the dysfunction seen in the FA+ group is a failure or distortion in the development of the MN system. This could be due to genetic or other endogenous causes, which affected prefrontal cortex MN involved in emotional resonance.

Legs Activity Cry Consolability [FLACC], Faces or Rulers scales; range 0–10) were lower in the nitrous oxide group, despite the greater number of injections, than in the midazolam group. The majority of the children in our Entonox group were able to score their own pain experience, as they were verbal and older than the midazolam group. No adverse effects were noted in either group. Two procedures within our Entonox group were very unsatisfactory (pain score 10) due to failure to anticipate the high levels of pre-procedural anxiety of both children. We conclude that for older children who can comply with verbal instructions and require a limited number of injections, self-administered Entonox can provide a similar level of procedural pain control to the continuous flow nitrous oxide ⁄oxygen system used by Zier et al. It has other advantages in terms of potentially fewer adverse effects and lower resource overheads. Finally, the pain control was not ideal for all children (e.g. pain score >5) using any of the sedation ⁄analgesia above. We are developing a pre-procedural score to improve the choice and level of sedation based on child and intervention factors, e.g. child’s previous response to pain, number of injections, etc.