Microstructural Correlates of Resilience against Major Depressive Disorder: Epigenetic Mechanisms?

Mental disorders are a major cause of long-term disability and are a direct cause of mortality, with approximately 800.000 individuals dying from suicide every year worldwide - a high proportion of them related to major depressive disorder (MDD)^1^. Healthy relatives of patients with major depressive disorder (MDD) are at risk to develop the disease. This higher vulnerability is associated with structural^2-4^ and functional brain changes^5^. However, we found using high angular resolution diffusion imaging (HARDI) with 61 diffusion directions that neuron tracts between frontal cortices and limbic as well as temporal and parietal brain regions are characterized by better diffusion coefficients in unaffected relatives (UHR), who managed to stay healthy, compared to healthy volunteers without any family history for a psychiatric disease (HC). Moreover, those UHR with stronger fibre connections better managed incidences of adversity in early life without later developing depression, while in HC axonal connections were found to be decreased when they had early-life adversity. Altogether these findings indicate the presence of stronger neural fibre connections in UHR, which seem to be associated with resilience against environmental stressors, which we suggest occur through epigenetic mechanisms

Neurochemical substrates and neuroanatomical generators of the event-related P300

The present review focuses on the current knowledge of the neurochemical processes and neuronal structures involved in the generation of P300. The increasing knowledge in this area facilitates the physiological interpretation of P300 findings as well as the link between P300 research and other research findings in biological psychiatry. Concerning the question of neurochemical substrates, the glutamatergic, GABAergic, cholinergic, noradrenergic, dopaminergic and serotonergic influences on P300 are reviewed. The knowledge of the generating structures of P300 is summarized from intracranial studies, magnetoencephalographic investigations, lesion and animal studies

Overlap between Autism Spectrum Disorder and Bipolar Affective Disorder

Background: At present there is a substantial uncertainty regarding the extent and nature of autism spectrum disorder (ASD) and bipolar affective disorder (BPAD) co-occurrence due to disparate findings in previous studies. This paper aimed to find and review original studies on co-occurrence rates of ASD with BPAD, assess them, synthesize the findings in a systematic way, present an overview and make recommendations for future research. Methods: Systematic literature searches were performed using several databases. Selected articles had to describe an original study that provided prevalence and/or incidence analysis on ASD co-occurring together with BPAD. Results and Conclusion: A significant minority of patients (7%) with ASD suffers from BPAD. An accurate detection of co-occurring ASD and BPAD can lead to a more targeted treatment and improve the patients' functioning and quality of life

Breathomics profiling of metabolic pathways affected by major depression: Possibilities and limitations

BackgroundMajor depressive disorder (MDD) is one of the most common psychiatric disorders with multifactorial etiologies. Metabolomics has recently emerged as a particularly potential quantitative tool that provides a multi-parametric signature specific to several mechanisms underlying the heterogeneous pathophysiology of MDD. The main purpose of the present study was to investigate possibilities and limitations of breath-based metabolomics, breathomics patterns to discriminate MDD patients from healthy controls (HCs) and identify the altered metabolic pathways in MDD.MethodsBreath samples were collected in Tedlar bags at awakening, 30 and 60 min after awakening from 26 patients with MDD and 25 HCs. The non-targeted breathomics analysis was carried out by proton transfer reaction mass spectrometry. The univariate analysis was first performed by T-test to rank potential biomarkers. The metabolomic pathway analysis and hierarchical clustering analysis (HCA) were performed to group the significant metabolites involved in the same metabolic pathways or networks. Moreover, a support vector machine (SVM) predictive model was built to identify the potential metabolites in the altered pathways and clusters. The accuracy of the SVM model was evaluated by receiver operating characteristics (ROC) analysis.ResultsA total of 23 differential exhaled breath metabolites were significantly altered in patients with MDD compared with HCs and mapped in five significant metabolic pathways including aminoacyl-tRNA biosynthesis (p = 0.0055), branched chain amino acids valine, leucine and isoleucine biosynthesis (p = 0.0060), glycolysis and gluconeogenesis (p = 0.0067), nicotinate and nicotinamide metabolism (p = 0.0213) and pyruvate metabolism (p = 0.0440). Moreover, the SVM predictive model showed that butylamine (p = 0.0005, pFDR=0.0006), 3-methylpyridine (p = 0.0002, pFDR = 0.0012), endogenous aliphatic ethanol isotope (p = 0.0073, pFDR = 0.0174), valeric acid (p = 0.005, pFDR = 0.0162) and isoprene (p = 0.038, pFDR = 0.045) were potential metabolites within identified clusters with HCA and altered pathways, and discriminated between patients with MDD and non-depressed ones with high sensitivity (0.88), specificity (0.96) and area under curve of ROC (0.96).ConclusionAccording to the results of this study, the non-targeted breathomics analysis with high-throughput sensitive analytical technologies coupled to advanced computational tools approaches offer completely new insights into peripheral biochemical changes in MDD

Cerebral differences in explicit and implicit emotional processing - An fMRI study

The processing of emotional facial expression is a major part of social communication and understanding. In addition to explicit processing, facial expressions are also processed rapidly and automatically in the absence of explicit awareness. We investigated 12 healthy subjects by presenting them with an implicit and explicit emotional paradigm. The subjects reacted significantly faster in implicit than in explicit trials but did not differ in their error ratio. For the implicit condition increased signals were observed in particular in the thalami, the hippocampi, the frontal inferior gyri and the right middle temporal region. The analysis of the explicit condition showed increased blood-oxygen-level-dependent signals especially in the caudate nucleus, the cingulum and the right prefrontal cortex. The direct comparison of these 2 different processes revealed increased activity for explicit trials in the inferior, superior and middle frontal gyri, the middle cingulum and left parietal regions. Additional signal increases were detected in occipital regions, the cerebellum, and the right angular and lingual gyrus. Our data partially confirm the hypothesis of different neural substrates for the processing of implicit and explicit emotional stimuli. Copyright (c) 2007 S. Karger AG, Basel

Neuroanatomical correlates of aggressiveness: a case-control voxel- and surface-based morphometric study

Aggression occurs across the population ranging on a symptom continuum. Most previous studies have used magnetic resonance imaging in clinical/forensic samples, which is associated with several confounding factors. The present study examined structural brain characteristics in two healthy samples differing only in their propensity for aggressive behavior. Voxel- and surface-based morphometry (SBM) analyses were performed on 29 male martial artists and 32 age-matched male controls. Martial artists had significantly increased mean gray matter volume in two frontal (left superior frontal gyrus and bilateral anterior cingulate cortex) and one parietal (bilateral posterior cingulate gyrus and precuneus) brain clusters compared to controls (whole brain: p < 0.001, cluster level: family-wise error (FWE)-corrected). SBM analyses revealed a trend for greater gyrification indices in martial artists compared to controls in the left lateral orbital frontal cortex and the left pars orbitalis (whole brain: p < 0.001, cluster level: FWE-corrected). The results indicate brain structural differences between martial artists and controls in frontal and parietal brain areas critical for emotion processing/inhibition of emotions as well as empathic processes. The present study highlights the importance of studying healthy subjects with a propensity for aggressive behavior in future structural MRI research on aggression

Testosterone causes both prosocial and antisocial status-enhancing behaviors in human males

Although popular discussion of testosterone’s influence on males often centers on aggression and antisocial behavior, contemporary theorists have proposed that it instead enhances behaviors involved in obtaining and maintaining a high social status. Two central distinguishing but untested predictions of this theory are that testosterone selectively increases status-relevant aggressive behaviors, such as responses to provocation, but that it also promotes nonaggressive behaviors, such as generosity toward others, when they are appropriate for increasing status. Here, we tested these hypotheses in healthy young males by injecting testosterone enanthate or a placebo in a double-blind, between-subjects, randomized design (n = 40). Participants played a version of the Ultimatum Game that was modified so that, having accepted or rejected an offer from the proposer, participants then had the opportunity to punish or reward the proposer at a proportionate cost to themselves. We found that participants treated with testosterone were more likely to punish the proposer and that higher testosterone levels were specifically associated with increased punishment of proposers who made unfair offers, indicating that testosterone indeed potentiates aggressive responses to provocation. Furthermore, when participants administered testosterone received large offers, they were more likely to reward the proposer and also chose rewards of greater magnitude. This increased generosity in the absence of provocation indicates that testosterone can also cause prosocial behaviors that are appropriate for increasing status. These findings are inconsistent with a simple relationship between testosterone and aggression and provide causal evidence for a more complex role for testosterone in driving status-enhancing behaviors in males

BDNF Val66Met polymorphism in patterns of neural activation in individuals with MDD and healthy controls.

BACKGROUND: Rs6265 single nucleotide polymorphism, which influences brain-derived neurotrophic factor (BDNF) levels in the cortical and subcortical brain structures, may result in distinguished patterns of neural activation during a major depressive disorder (MDD) episode. Valine homozygotes with high levels of BDNF and methionine carriers with lower levels of BDNF may present specific neural correlates of MDD. In our study we have tested differences in blood oxygen level dependant (BOLD) signal between individuals with MDD and healthy controls for both allelic variants. METHODS: Individuals with MDD (N = 37) and healthy controls (N = 39) were genotyped for rs6265 and compared separately in each allelic variant for BOLD response in a functional magnetic resonance imaging experiment examining appraisal of emotional scenes. The two allelic variants were also compared separately for both individuals with MDD and healthy controls. RESULTS: In the homozygous valine group MDD was associated with decreased neural activation in areas responsible for cognitive appraisal of emotional scenes. In the methionine group MDD was related to increased activation in subcortical regions responsible for visceral reaction to emotional stimuli. During an MDD episode methionine carriers showed more activation in areas associated with cognitive appraisal of emotional information in comparison to valine homozygotes. LIMITATIONS: Small sample size of healthy controls carrying methionine (N=8). CONCLUSION: Our results suggest that allelic variations in the rs6265 gene lead to specific neural correlates of MDD which may be associated with different mechanisms of MDD in the two allelic groups. This may have potential importance for screening and treatment of patients.Funding for this study was provided by the Science Foundation Ireland (Grant Number: SFI/07SK/B1214C). Health Research Board (HRB) Ireland provided funding for magnetic resonance imaging infrastructure at the Centre of Advanced Medical Imaging (CAMI) at St. James’s Hospital in Dublin.This is the author accepted manuscript. The final version is available from Elsevier at http://www.jad-journal.com/article/S0165-0327%2815%2900383-3/abstract

Usability of the IDDEAS prototype in child and adolescent mental health services: A qualitative study for clinical decision support system development

Introduction: Child and adolescent mental health services (CAMHS) clinical decision support system (CDSS) provides clinicians with real-time support as they assess and treat patients. CDSS can integrate diverse clinical data for identifying child and adolescent mental health needs earlier and more comprehensively. Individualized Digital Decision Assist System (IDDEAS) has the potential to improve quality of care with enhanced efficiency and effectiveness. Methods: We examined IDDEAS usability and functionality in a prototype for attention deficit hyperactivity disorder (ADHD), using a user-centered design process and qualitative methods with child and adolescent psychiatrists and clinical psychologists. Participants were recruited from Norwegian CAMHS and were randomly assigned patient case vignettes for clinical evaluation, with and without IDDEAS. Semi-structured interviews were conducted as one part of testing the usability of the prototype following a five-question interview guide. All interviews were recorded, transcribed, and analyzed following qualitative content analysis. Results: Participants were the first 20 individuals from the larger IDDEAS prototype usability study. Seven participants explicitly stated a need for integration with the patient electronic health record system. Three participants commended the step-by-step guidance as potentially helpful for novice clinicians. One participant did not like the aesthetics of the IDDEAS at this stage. All participants were pleased about the display of the patient information along with guidelines and suggested that wider guideline coverage will make IDDEAS much more useful. Overall, participants emphasized the importance of maintaining the clinician as the decision-maker in the clinical process, and the overall potential utility of IDDEAS within Norwegian CAMHS. Conclusion: Child and adolescent mental health services psychiatrists and psychologists expressed strong support for the IDDEAS clinical decision support system if better integrated in daily workflow. Further usability assessments and identification of additional IDDEAS requirements are necessary. A fully functioning, integrated version of IDDEAS has the potential to be an important support for clinicians in the early identification of risks for youth mental disorders and contribute to improved assessment and treatment of children and adolescents