Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts’ maps could uncover functionally and clinically related genes.Molecular Psychiatry advance online publication, 31 May 2016; doi:10.1038/mp.2016.84

Effects of Cerebellar tDCS on Inhibitory Control: Evidence from a Go/NoGo Task

Response inhibition as an executive function refers to the ability to suppress inappropriate but prepotent responses. Several brain regions have been implicated in the process underlying inhibitory control, including the cerebellum. The aim of the present study was to explore the role of the cerebellum in executive functioning, particularly in response inhibition. For this purpose, we transitorily inhibited cerebellar activity by means of cathodal tDCS and studied the effects of this inhibition on ERP components elicited during a Go/NoGo task in healthy subjects. Sixteen healthy subjects underwent a Go/NoGo task prior to and after cathodal and sham cerebellar tDCS in separate sessions. A reduction in N2-NoGo amplitude and a prolongation in N2-NoGo latency emerged after cathodal tDCS whereas no differences were detected after sham stimulation. Moreover, commission errors in NoGo trials were significantly higher after cathodal tDCS than at the basal evaluation. No differences emerged between performances in Go trials and those after sham stimulation. These data indicate that cerebellar inhibition following cathodal stimulation alters the ability to allocate attentional resources to stimuli containing conflict information and the inhibitory control. The cerebellum may regulate the attentional mechanisms of stimulus orientation and inhibitory control both directly, by making predictions of errors or behaviors related to errors, and indirectly, by controlling the functioning of the cerebral cortical areas involved in the perception of conflict signals and of the basal ganglia involved in the inhibitory control of movement

Cardiovascular reactivity of mitral valve prolapse patients during experimental stress exposure: Evidence for a functional nature of cardiovascular symptoms

We studied a group of 18 patients with mitral valve prolapse (MVP) and a group of 20 healthy controls. Subjects in both groups were subjected to a 1-h experimental stress exposure during which Holter-ECG monitoring was performed and was then continued for the following 24 h. MVP patients complained of significant cardiac palpitation during the stress session, but ECG examination did not reveal significant inter-group differences. However, the two groups did show statistically significant differences in some psychometric measurements (Toronto Alexithymia Scale, Anxiety Sensitivity Index, Fear Questionnaire, Beck Depression Inventory, and Harm Avoidance subscale of Tridimensional Personality Questionnaire) that underlie personality traits known to be important in the process fostering functional somatic symptoms, according to the somatosensory amplification model. As no objective signs of cardiac rhythm modification were found in MVP patients under stress, we postulate that the symptoms for which these patients were referred have a functional nature, and that there is no pathogenetic link with the underlying valvular defect

The role of cerebellum in unipolar and bipolar depression: a review of the main neurobiological findings.

Evidences from studies on patients with overt cerebellar diseases as well as on healthy individuals suggest a possible role for the cerebellum in cognition, mood and behaviour. The aim of the present study is to review those neuroimaging studies examining the cerebellum in Bipolar Disorder (BD) and Major Depressive Disorder (MDD) and to illustrate a possible role of cerebellum in their pathophysiological mechanisms. Cellular and molecular findings from post mortem studies such as mitochondria abnormalities, brain-derived neurotrophic factor and its high affinity receptor tyrosine kinase B, transcription factor specificity protein 4, the glial fibrillary acidic protein have also been reviewed. In total 28 studies have been included in the review; among these, 12 studies were related to structural and functional neuroimaging of cerebellum in BD, 13 studies to structural and functional neuroimaging in MDD and 4 studies to cellular and molecular issues. This wealth of evidence from contemporary studies, indicating that the cerebellum (vermis in particular) is engaged in the modulation of emotional processing, provides strong support for the clinical relevance of cerebellar-limbic connections, and is in agreement with earlier clinical and electrophysiological studies that lead to the indication of the cerebellum as an "emotional pacemaker"

Cognitive remediation for the treatment of neuropsychological disturbances in subjects with euthymic bipolar disorder: findings from a controlled study

Introduction: Individuals with euthymic Bipolar Disorder (BD) can experience deteriorated cognitive functioning, with such deterioration being associated with functional impairment. Cognitive remediation (CR) is considered an effective add-on intervention for neuropsychological impairments, but relatively few CR controlled studies have been performed on BD. In the present study the efficacy of a CR intervention designed for the improvement of cognition and functioning in patients with euthymic BD was tested. Methods: Patients (n = 54) with euthymic BD were assigned to receive active (n = 27) or control (n = 27) intervention. The active intervention (i.e. the Cognitive Remediation in Integrated Treatment – CRIIT – protocol) was made of 20 individual sessions focused on the treatment of attention, memory and executive functioning through the COGPACK software; each session was integrated with psychoeducation and rehabilitation interventions implemented through a metacognitive approach aimed at ameliorating personal agency. Results: A significant (p ≤ 0.015) time x group interaction at repeated measures MANOVA was observed on Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Wisconsin Card Sorting Test, Trail Making Test, Visual Search, Life Skills Profile, and Barratt Impulsiveness Scale. Limitations: A single-blind approach was used. Discussion: The results showed that patients undergoing active intervention improved in domains related to executive functions, attention, memory, functioning and impulsivity more significantly than patients undergoing control interventions. This study adds to the evidence that CR improves neurocognition in BD, and suggests that CRIIT protocol represents an add-on intervention of potential relevance to increase cognition and functioning in BD euthymic patients

Tinnitus: clinical experience of the psychosomatic connection.

The connection between psychopathology and tinnitus is complex and not adequately studied. The aim of this study is to investigate the relationship between tinnitus and psychiatric comorbidities from different points of view: categorical, dimensional, temperamental, and perceived stress level.Two hundred and thirty-nine patients affected by tinnitus were recruited between January and October 2012. Patients underwent a preliminary battery of tests including the Tinnitus Handicap Inventory (THI), Symptom Check List (SCL90-R), Temperament and Character Inventory (TCI), and Stress-Related Vulnerability Scale (VRS), and eventually a full psychiatric evaluation.One hundred and fourteen patients (48\% of the total sample) presented psychiatric comorbidity. Among these, a higher prevalence of depression, somatization, obsession, and anxiety was found. More than 41\% of patients affected by decompensated tinnitus reported a family history of psychiatric disorders. Significant positive correlations between the psychopathological screening tools (SCL90-R and VRS) and THI were found. Patients affected by comorbid psychiatric disorder showed specific temperamental and characterial predispositions.Psychiatric comorbidity in subjects affected by tinnitus is frequent. Stress can be considered as a factor leading to damage and dysfunction of the auditory apparatus. The vulnerability to neurotic disorders and the lack of coping capabilities can play a critical role in the clinical history of patients affected by severe tinnitus

Effect of affective temperament on illness characteristics of subjects with bipolar disorder and major depressive disorder

Background: Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder (BD) or major depressive disorder (MDD) has been described. However, the strength of such relationship should be tested while considering other factors influencing the diagnosis of BD/MDD. Literature also lacks a comprehensive description of the interplay between affective temperament and characteristics of mood disorders. The aim of the present study is to address these issues. Methods: This is a multicentric observational study including 7 Italian university sites. Five-hundred-fifty-five euthymic subjects with BD/MDD were enrolled and further divided in those with hyperthymic (Hyper, N = 143), cyclothymic (Cyclo, N = 133), irritable (Irr, N = 49), dysthymic (Dysth, N = 155), and anxious (Anx N = 76) temperaments. Linear, binary, ordinal and logistic regressions were performed to assess the association between affective temperaments and i) diagnosis of BD/MDD; ii) characteristics of illness severity and course. Results: Hyper, Cyclo and Irr were more likely to be associated with BD, together with earlier age of onset and presence of a first-degree relative with BD. Anx and Dysth were more associated with MDD. Differences in association between affective temperaments and characteristics of BD/MDD were observed for hospital admissions, phase-related psychotic symptoms, length and type of depression, comorbidity and pharmacological intake. Limitations: Small sample size, cross-sectional design, recall biases. Conclusion: Specific affective temperaments were associated to certain characteristics of illness severity and course of BD or MDD. Evaluation of affective temperaments might help a deeper understanding of mood disorders