Williams syndrome: a relationship between genetics, brain morphology and behaviour.

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.

Correlations between sadness-induced cerebral activations and schizophrenia symptoms: an fMRI study of sex differences.

BACKGROUND: The 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. METHOD: Fifteen 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). RESULTS: Across 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. CONCLUSION: Present 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.

Violent persons with schizophrenia and comorbid disorders: a functional magnetic resonance imaging study.

The main goal of this functional Magnetic Resonance Imaging (fMRI) study was to verify the hypothesis that seriously violent persons with Sz and the co-morbid diagnoses of an Antisocial Personality Disorder (APD) and a Substance Use Disorder (Sz+APD+SUD) would present a different pattern of prefrontal functioning than seriously violent persons with Sz only. In support with the main hypothesis, frontal basal cortices were significantly less activated in persons with Sz+APD+SUD during the execution of a go/no-go task than in persons with Sz only and non-violent persons without a mental illness. In contrast, significantly higher activations in frontal motor, premotor and anterior cingulate regions were observed in the Sz+APD+SUD group than in the Sz-only group.

Increased extrapyramidal symptoms in patients with schizophrenia and a comorbid substance use disorder.

Few data have been gathered about the impact of psychoactive substances on extrapyramidal symptoms (EPS) in schizophrenia, and so far, inconsistent results have been reported. We studied 41 outpatients with schizophrenia (based on DSM-IV criteria), who were divided into two groups: with (n = 17) and without (n = 24) a substance use disorder (alcohol, cannabis, and/or cocaine). Both groups were matched for sociodemographic data and psychiatric symptoms (Positive and Negative Syndrome Scale). EPS were evaluated with the Extrapyramidal Symptoms Rating Scale and the Barnes Akathisia Scale, and all patients were stable on either quetiapine or clozapine. Patients receiving anticholinergic drugs were excluded. Analyses of variance were conducted on both groups and showed that schizophrenia patients with a comorbid substance use disorder (especially cocaine) displayed more EPS compared with non-abusing patients.

Negative socio-emotional resonance in schizophrenia: a functional magnetic resonance imaging hypothesis.

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.