Showing papers by "Andrea Mechelli published in 2010"

Short-term Effects of Antipsychotic Treatment on Cerebral Function in Drug-Naive First-Episode Schizophrenia Revealed by “Resting State” Functional Magnetic Resonance Imaging

Abstract: Context: Most of what we know about antipsychotic drug effects is at the receptor level, distal from the neural system effects that mediate their clinical efficacy. Studying cerebral function in antipsychotic-naive patients with schizophrenia before and after pharmacotherapy can enhance understanding of the therapeutic mechanisms of these clinically effective treatments.

Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol.

Abstract: Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in animals and humans. Although recent studies have helped provide a better understanding of the neurofunctional correlates of these effects, indicating the involvement of the amygdala and cingulate cortex, their reciprocal influence is still mostly unknown. In this study dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to explore the effects of pure compounds of C. sativa [600 mg of cannabidiol (CBD) and 10 mg Delta 9-tetrahydrocannabinol (Delta 9-THC)] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind randomized, placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety. In the placebo condition, BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit. CBD but not Delta 9-THC disrupted forward connectivity between these regions during the neural response to fearful faces. This is the first study to show that the disruption of prefrontal-subocritical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties.

High-Field Magnetic Resonance Imaging of Suicidality in Patients With Major Depressive Disorder

Abstract: Objective: Suicide is a major social and public health problem, but its neurobiology in major depressive disorder is poorly understood. The purpose of this study was to use magnetic resonance diffusion tensor imaging to characterize abnormalities of white matter integrity in major depressive disorder patients with and without a history of suicide attempts. Method: Participants were 52 patients with major depressive disorder, with (N=16) and without (N=36) a history of suicide attempts, and 52 healthy comparison subjects matched for age, gender, education, and ethnicity. Diffusion tensor imaging in a 3.0 Tesla magnetic resonance scanner was performed. Wholebrain voxel-based analysis was used to compare fractional anisotropy across the three groups and analyze the correlation with symptom severity. A region-of-interest analysis was applied to the bilateral hippocampus, thalamus, and lentiform nucleus Results: Fractional anisotropy was decreased in the left anterior limb of the internal capsule in suicide attempters relative to both nonattempters and healthy comparison subjects, in the right frontal lobe relative to comparison subjects only, and in the right lentiform nucleus relative to nonattempters only. There was no signifi cant correlation with symptom severity. Conclusions: Decreased fractional anisotropy in the left anterior limb of the internal capsule appears to characterize patients with major depressive disorder who have a history of attempting suicide. Longitudinal studies are required to validate this as a potential marker that may inform the development of strategies for reducing suicide.

Schizotypy and brain structure: a voxel-based morphometry study.

Abstract: Background. Schizotypy is conceptualized as a subclinical manifestation of the same underlying biological factors that give rise to schizophrenia and other schizophrenia spectrum disorders. Individuals with psychometric schizotypy (PS) experience subthreshold psychotic signs and can be psychometrically identified among the general population. Previous research using magnetic resonance imaging (MRI) has shown gray-matter volume (GMV) abnormalities in chronic schizophrenia, in subjects with an at-risk mental state (ARMS) and in individuals with schizotypal personality disorder (SPD). However, to date, no studies have investigated the neuroanatomical correlates of PS. Method. Six hundred first-and second-year university students completed the Community Assessment of Psychic Experiences (CAPE), a self-report instrument on psychosis proneness measuring attenuated positive psychotic experiences. A total of 38 subjects with high and low PS were identified and subsequently scanned with MRI. Voxel-based morphometry (VBM) was applied to examine GMV differences between subjects with high and low positive PS. Results. Subjects with high positive PS showed larger global volumes compared to subjects with low PS, and larger regional volumes in the medial posterior cingulate cortex (PCC) and the precuneus. There were no regions where GMV was greater in low than in high positive PS subjects. Conclusions. These regions, the PCC and precuneus, have also been sites of volumetric differences in MRI studies of ARMS subjects and schizophrenia, suggesting that psychotic or psychotic-like experiences may have common neuroanatomical correlates across schizophrenia spectrum disorders.

The Impact of Second Language Learning on Semantic and Nonsemantic First Language Reading

Abstract: The relationship between orthography (spelling) and phonology (speech sounds) varies across alphabetic languages. Consequently, learning to read a second alphabetic language, that uses the same letters as the first, increases the phonological associations that can be linked to the same orthographic units. In subjects with English as their first language, previous functional imaging studies have reported increased left ventral prefrontal activation for reading words with spellings that are inconsistent with their orthographic neighbors (e.g., PINT) compared with words that are consistent with their orthographic neighbors (e.g., SHIP). Here, using functional magnetic resonance imaging (fMRI) in 17 Italian--English and 13 English--Italian bilinguals, we demonstrate that left ventral prefrontal activation for first language reading increases with second language vocabulary knowledge. This suggests that learning a second alphabetic language changes the way that words are read in the first alphabetic language. Specifically, first language reading is more reliant on both lexical/semantic and nonlexical processing when new orthographic to phonological mappings are introduced by second language learning. Our observations were in a context that required participants to switch between languages. They motivate future fMRI studies to test whether first language reading is also altered in contexts when the second language is not in use.

Heritable variations in gray matter concentration as a potential endophenotype for psychopathic traits

Abstract: CONTEXT: Genetic vulnerability to psychopathic traits is likely to also manifest at the neural level. We have recently reported increased gray matter concentration in several brain areas in boys with psychopathic traits. OBJECTIVE: To explore whether these gray matter concentration differences can be regarded as endophenotypes for psychopathic traits by (1) assessing their heritability and (2) examining the etiology of the co-occurrence of psychopathic traits and increased gray matter concentration. DESIGN: Community twin sample. SETTING: On-campus neuroimaging facility. Patients or Other PARTICIPANTS: One hundred twenty-three male twins (56 monozygotic and 67 dizygotic individuals; mean age 11.55 years; range, 10-13 years). MAIN OUTCOME MEASURES: We analyzed structural magnetic resonance imaging scans. Voxel-based morphometry analyses were used to obtain gray matter concentration values that were analyzed in a biometrical genetic twin model. RESULTS: Left posterior cingulate and right dorsal anterior cingulate gray matter concentrations were found to be the strongest endophenotype markers, with heritability estimates of 46% and 37%, respectively, and common genes explaining the phenotypic relationship between these regions and psychopathic traits. No significant heritabilities were found for several regions, including the right orbitofrontal cortex and insula. CONCLUSIONS: These findings suggest that structural endophenotypes, in the form of variations in gray matter concentration, reflect genetic vulnerability for psychopathic traits. Specifically, gray matter concentration in the left posterior cingulate and right dorsal anterior cingulate, brain areas implicated in empathy, moral processing, and introspection, are potential candidate endophenotypes for psychopathic traits.

How neuroscience and behavioral genetics improve psychiatric assessment: report on a violent murder case

Abstract: Despite the advances in the understanding of neural and genetic foundations of violence, the investigation of the biological bases of a mental disorder is rarely included in psychiatric evaluation of mental insanity. Here we report on a case in which cognitive neuroscience and behavioral genetics methods were applied to a psychiatric forensic evaluation conducted on a young woman, J.F., tried for a violent and impulsive murder. The defendant had a history of multidrug and alcohol abuse and non-forensic clinical evaluation concluded for a diagnosis of borderline personality disorder. We analyzed the defendant's brain structure in order to underlie possible brain structural abnormalities associated with pathological impulsivity. Voxel-based morphometry indexed a reduced gray matter volume in the left prefrontal cortex, in a region specifically associated with response inhibition. Furthermore, J.F.'s DNA was genotyped in order to identify genetic polymorphisms associated with various forms of violence and impulsive behavior. Five polymorphisms that are known to be associated with impulsivity, violence, and other severe psychiatric illnesses were identified in J.F.'s DNA. Taken together, these data provided evidence for the biological correlates of a mental disorder characterized by high impulsivity and aggressive tendencies. Our claim is that the use of neuroscience and behavioral genetics do not change the rationale underlying the determination of criminal liability, which must be based on a causal link between the mental disorder and the crime. Rather, their use is crucial in providing objective data on the biological bases of a defendant's mental disorder.

Attachment style, affective loss and gray matter volume: A voxel-based morphometry study

Abstract: Early patterns of infant attachment have been shown to be an important influence on adult social behavior. Animal studies suggest that patterns of early attachment influence brain development, contributing to permanent alterations in neural structure; however, there are no previous studies investigating whether differences in attachment style are associated with differences in brain structure in humans. In this study, we used Magnetic Resonance Imaging (MRI) and voxel-based morphometry (VBM) to examine for the first time the association between attachment style, affective loss (for example, death of a loved one) and gray matter volume in a healthy sample of adults (n = 32). Attachment style was assessed on two dimensions (anxious and avoidant) using the ECR-Revised questionnaire. High attachment-related anxiety was associated with decreased gray matter in the anterior temporal pole and increased gray matter in the left lateral orbital gyrus. A greater number of affective losses was associated with increased gray matter volume in the cerebellum; in this region, however, the impact of affective losses was significantly moderated by the level of attachment-related avoidance. These findings indicate that differences in attachment style are associated with differences in the neural structure of regions implicated in emotion regulation. It is hypothesized that early attachment experience may contribute to structural brain differences associated with attachment style in adulthood; furthermore, these findings point to a neuronal mechanism through which attachment style may mediate individual differences in responses to affective loss.

Influence of Neuregulin1 Genotype on Neural Substrate of Perceptual Matching in Children

Abstract: Adult psychopathology is often rooted early in life and first emerges during childhood and adolescence. However, as most imaging genetic research to date has involved adult participants, little is known about how risk genes affect brain function to influence biological vulnerability in childhood. We examined the impact of neuregulin1 (NRG1), a probable susceptibility gene for schizophrenia and bipolar disorder, on brain function in a sample of 102 healthy 10-12 year old boys including 18 pairs of monozygotic twins, 24 pairs of dizygotic twins and 18 singletons. Each participant performed a perceptual matching task, while brain responses were measured using functional magnetic resonance imaging. Response accuracy and reaction times did not differ as a function of NRG1 genotype; however, individuals with two high-risk alleles showed relatively increased brain activation in a distributed network comprising the precuneus bilaterally, and the left cuneus, middle occipital gyrus, angular gyrus and caudate nucleus. These results indicate that genetic variation in NRG1 significantly affects cortical function during perceptual and monitoring processes in healthy children as young as 10-12 years of age.

Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schzophrenia revealed by rFMRI

Abstract: Context Most of what we know about antipsychotic drug effects is at the receptor level, distal from the neural systemeffects that mediate their clinical efficacy. Studying cerebral function in antipsychotic-naive patients with schizophreniabefore and after pharmacotherapy can enhance understanding of the therapeutic mechanisms of these clinically effective treatments. Objective To examine alterations of regional and neural network function in antipsychotic-naive patients with first-episodeschizophrenia before and after treatment with second-generation antipsychotic medication. Design Case-control study. Setting Huaxi MR Research Center and Mental Health Centre of the West China Hospital. Participants Thirty-four antipsychotic-naive patients with first-episode schizophrenia were scanned using gradient-echoecho-planar imaging while in a resting state. After 6 weeks of antipsychotic treatment, patients were rescanned. Thirty-fourmatched healthy control subjects were studied at baseline for comparison purposes. Main Outcome Measures The amplitude of low-frequency fluctuations (ALFF) of blood oxygen level–dependent signals, believed to reflect spontaneous neural activity, was used to characterize regional cerebral function. Functional connectivity across brain regions was evaluated using a seed voxel correlation approach and an independent component analysis. Changes in these measures after treatment were examined to characterize effects of antipsychotic drugs on regional function and functional integration. Results After short-term treatment with second-generation antipsychotic medications, patients showed increased ALFF, particularly in the bilateral prefrontal and parietal cortex, left superior temporal cortex, and right caudate nucleus. Increased regional ALFF was associated with a reduction of clinical symptoms, and a widespread attenuation in functional connectivity was observed that was correlated with increased regional ALFF. Conclusions We demonstrate for the first time, to our knowledge, that widespread increased regional synchronous neural activity occurs after antipsychotic therapy, accompanied by decreased integration of function across widely distributed neural networks. These findings contribute to the understanding of the complex systems-level effects of antipsychotic drugs.