Emotional face processing correlates with depression/anxiety symptoms but not wellbeing in non-clinical adults: An event-related potential study.

Whilst alterations in emotional face processing, as indicated by event-related potentials (ERPs), are associated with depression and anxiety symptoms in clinical and non-clinical samples, it has remained unclear whether they are related to mental wellbeing. The current study aimed to address this question in a non-clinical sample. The analysis included 402 adult twins from the TWIN-E study. The COMPAS-W and the Depression Anxiety Stress Scale (DASS-42) were used to measure mental wellbeing and depression/anxiety symptoms, respectively. Participants viewed facial expressions under Unmasked (conscious) and Masked (subliminal) conditions while ERPs were recorded. The associations of emotion processing with mental wellbeing and depression/anxiety symptoms were assessed using multivariate linear mixed models. There was a strong association between depression/anxiety symptoms and the N170 amplitude difference for the Fear - Happy contrast in the Masked condition after controlling for wellbeing scores (B = 0.34, p < .001). Specifically, higher depression/anxiety symptoms were associated with a lack of differentiation between fearful and happy faces. No associations were found between emotional face processing and mental wellbeing scores. These results indicate that even within a non-clinical sample, alterations in emotional ERPs, namely the N170, reflect differences in depression/anxiety symptoms rather than differences in wellbeing. Furthermore, this effect was limited to automatic processing, rather than conscious processing of emotional stimuli, suggesting the observed differences apply only to the subconscious pathway.

Electroencephalography profiles as a biomarker of wellbeing: A twin study.

Alterations to electroencephalography (EEG) power have been reported for psychiatric conditions such as depression and anxiety, but not for mental wellbeing in a healthy population. This study examined the resting EEG profiles associated with mental wellbeing, and how genetics and environment contribute to these associations using twin modelling. Mental wellbeing was assessed using the COMPAS-W Wellbeing Scale which measures both subjective and psychological wellbeing. In 422 healthy adult monozygotic and dizygotic twins aged 18-61 years, we examined the association between mental wellbeing and EEG power (alpha, beta, theta, delta) using linear mixed models. This was followed by univariate and multivariate twin modelling to assess the heritability of wellbeing and EEG power, and whether the association was driven by shared genetics or environment. A significant association between wellbeing and an interaction of alpha, beta, and delta (ABD) power was found (ß = -0.33, p < 0.001) whereby a profile of high alpha and delta and low beta was associated with higher wellbeing, independent of depression and anxiety symptoms. This finding was supported by a five-fold cross-validation analysis. A significant genetic correlation (rG = -0.43) was found to account for 94% of the association between wellbeing and the EEG power interaction. Together, this study has identified a novel EEG profile with a common genetic component that may be a potential biomarker of mental wellbeing. Future studies need to clarify the causal direction of this association.

Neurofeedback and Attention-Deficit/Hyperactivity-Disorder (ADHD) in Children: Rating the Evidence and Proposed Guidelines.

Stimulant medication and behaviour therapy are the most often applied and accepted treatments for Attention-Deficit/Hyperactivity-Disorder (ADHD). Here we explore where the non-pharmacological clinical intervention known as neurofeedback (NFB), fits on the continuum of empirically supported treatments, using standard protocols. In this quantitative review we utilized an updated and stricter version of the APA guidelines for rating 'well-established' treatments and focused on efficacy and effectiveness using effect-sizes (ES) and remission, with a focus on long-term effects. Efficacy and effectiveness are compared to medication and behaviour therapy using benchmark studies. Only recent systematic reviews and meta-analyses as well as multi-centre randomized controlled trials (RCT's) will be included. Two meta-analyses confirmed significant efficacy of standard neurofeedback protocols for parent and teacher rated symptoms with a medium effect size, and sustained effects after 6-12 months. Four multicenter RCT's demonstrated significant superiority to semi-active control groups, with medium-large effect sizes end of treatment or follow-up and remission rates of 32-47%. Effectiveness in open-label studies was confirmed, no signs of publication bias were found and no significant neurofeedback-specific side effects have been reported. Standard neurofeedback protocols in the treatment of ADHD can be concluded to be a well-established treatment with medium to large effect sizes and 32-47% remission rates and sustained effects as assessed after 6-12 months.

A negative association between brainstem pontine grey-matter volume, well-being and resilience in healthy twins

Background: Associations between well-being, resilience to trauma and the volume of grey-matter regions involved in affective processing (e.g., threat/reward circuits) are largely unexplored, as are the roles of shared genetic and environmental factors derived from multivariate twin modelling. Methods: This study presents, to our knowledge, the first exploration of well-being and volumes of grey-matter regions involved in affective processing using a region-of-interest, voxel-based approach in 263 healthy adult twins (60% monozygotic pairs, 61% females, mean age 39.69 yr). To examine patterns for resilience (i.e., positive adaptation following adversity), we evaluated associations between the same brain regions and well-being in a trauma-exposed subgroup. Results: We found a correlated effect between increased well-being and reduced grey-matter volume of the pontine nuclei. This association was strongest for individuals with higher resilience to trauma. Multivariate twin modelling suggested that the common variance between the pons volume and well-being scores was due to environmental factors. Limitations: We used a cross-sectional sample; results need to be replicated longitudinally and in a larger sample. Conclusion: Associations with altered grey matter of the pontine nuclei suggest that basic sensory processes, such as arousal, startle, memory consolidation and/or emotional conditioning, may have a role in well-being and resilience.

Genetic correlations between wellbeing, depression and anxiety symptoms and behavioral responses to the emotional faces task in healthy twins.

Currently there is a very limited understanding of how mental wellbeing versus anxiety and depression symptoms are associated with emotion processing behaviour. For the first time, we examined these associations using a behavioural emotion task of positive and negative facial expressions in 1668 healthy adult twins. Linear mixed model results suggested faster reaction times to happy facial expressions was associated with higher wellbeing scores, and slower reaction times with higher depression and anxiety scores. Multivariate twin modelling identified a significant genetic correlation between depression and anxiety symptoms and reaction time to happy facial expressions, in the absence of any significant correlations with wellbeing. We also found a significant negative phenotypic relationship between depression and anxiety symptoms and accuracy for identifying neutral emotions, although the genetic or environment correlations were not significant in the multivariate model. Overall, the phenotypic relationships between speed of identifying happy facial expressions and wellbeing on the one hand, versus depression and anxiety symptoms on the other, were in opposing directions. Twin modelling revealed a small common genetic correlation between response to happy faces and depression and anxiety symptoms alone, suggesting that wellbeing and depression and anxiety symptoms show largely independent relationships with emotion processing at the behavioral level.

The shared and unique genetic relationship between mental well-being, depression and anxiety symptoms and cognitive function in healthy twins.

Alterations to cognitive function are often reported with depression and anxiety symptoms, yet few studies have examined the same associations with mental well-being. This study examined the association between mental well-being, depression and anxiety symptoms and cognitive function in 1502 healthy adult monozygotic (MZ) and dizygotic (DZ) twins, and the shared/unique contribution of genetic (G) and environmental (E) variance. Using linear mixed models, mental well-being was positively associated (p < .01) with sustained attention (ß = 0.127), inhibition (ß = 0.096), cognitive flexibility (ß = 0.149), motor coordination (ß = 0.114) and working memory (ß = 0.156), whereas depression and anxiety symptoms were associated (p < .01) with poorer sustained attention (ß = -0.134), inhibition (ß = -0.139), cognitive flexibility (ß = -0.116) and executive function (ß = -0.139). Bivariate twin modelling showed well-being shared a small environmental correlation with motor coordination and a small genetic correlation with working memory. Trivariate twin modelling showed well-being shared a small genetic correlation with inhibition, whereas depression and anxiety symptoms shared a small environmental correlation with inhibition. The remaining variance was mostly driven by unique G and/or E variance. Overall, well-being and depression and anxiety symptoms show both independent and shared relationships with cognitive functions but this is largely attributable to unique G or E variance and small shared G/E variance between pairs of variables.

Electroencephalographic correlates of states of concentrative meditation.

Meditative techniques aim for and meditators report states of mental alertness and focus, concurrent with physical and emotional calm. We aimed to determine the electroencephalographic (EEG) correlates of five states of Buddhist concentrative meditation, particularly addressing a correlation with meditative level. We studied 12 meditators and 12 pair-matched meditation-naïve participants using high-resolution scalp-recorded EEG. To maximise reduction of EMG, data were pre-processed using independent component analysis and surface Laplacian transformed data. Two non-meditative and five meditative states were used: resting baseline, mind-wandering, absorptions 1, 2, 3, 4 and 5 (corresponding to four levels of absorption and an absorption with a different object of focus, otherwise equivalent to level 4; these five meditative states produce repeatable, distinctly different experiences for experienced meditators). The experimental protocol required participants to experience the states in the order listed above, followed immediately by the reverse. We then calculated EEG power in standard frequency bands from 1 to 80Hz. We observed decreases of central scalp beta (13-25Hz), and central low gamma (25-48Hz) power in meditators during deeper absorptions. In contrast, we identified increases in frontal midline and temporo-parietal theta power in meditators, again, during deeper absorptions. Alpha activity was increased over all meditative states, not depth-related. This study demonstrates that the subjective experiences of deepening meditation partially correspond to measures of EEG. Our results are in accord with prior studies on non-graded meditative states. These results are also consistent with increased theta correlating with tightness of focus, and reduced beta/gamma with the desynchronization associated with enhanced alertness.

Shared versus distinct genetic contributions of mental wellbeing with depression and anxiety symptoms in healthy twins.

Mental wellbeing and mental illness symptoms are typically conceptualized as opposite ends of a continuum, despite only sharing about a quarter in common variance. We investigated the normative variation in measures of wellbeing and of depression and anxiety in 1486 twins who did not meet clinical criteria for an overt diagnosis. We quantified the shared versus distinct genetic and environmental variance between wellbeing and depression and anxiety symptoms. The majority of participants (93%) reported levels of depression and anxiety symptoms within the healthy range, yet only 23% reported a wellbeing score within the "flourishing" range: the remainder were within the ranges of "moderate" (67%) or "languishing" (10%). In twin models, measures of wellbeing and of depression and anxiety shared 50.09% of variance due to genetic factors and 18.27% due to environmental factors; the rest of the variance was due to unique variation impacting wellbeing or depression and anxiety symptoms. These findings suggest that an absence of clinically-significant symptoms of depression and anxiety does not necessarily indicate that an individual is flourishing. Both unique and shared genetic and environmental factors may determine why some individuals flourish in the absence of symptoms while others do not.

Anxiety in young people with ADHD: clinical and self-report outcomes.

OBJECTIVE: (a) To determine the prevalence of comorbid anxiety disorder in ADHD, defined by diagnostic criteria and (b) to compare anxiety as reported by parents and participants with clinician assessment. METHOD: Children with ADHD were assessed for comorbid anxiety disorder using the Anxiety Disorder Interview Schedule for Children. Parent report (Conners' Parent Rating Scale-Revised: Long version) and self-report (State-Trait Anxiety Inventory and Brain Resource Inventory for Screening Cases-Child version) scales were used to assess anxiety. The ADHD-Rating Scale IV was used to measure ADHD symptoms. RESULTS: Of 134 participants (11.0 ± 2.6 years), 31.3% had comorbid anxiety disorder. Comorbid anxiety disorder was associated with greater severity of ADHD. Anxiety symptoms from parent reports (p < .05) but not from child/self-report (p > .05) correlated with clinician assessment. CONCLUSION: Assessment for comorbid anxiety disorder and inclusion of parent rating in this assessment are important components of ADHD treatment in children and adolescents.

The relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD - a monozygotic twin study.

BACKGROUND: PTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD. METHODS: Our study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins. RESULTS: There were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD. CONCLUSIONS: These findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.

Comorbid externalising behaviour in AD/HD: evidence for a distinct pathological entity in adolescence.

While the profiling of subtypes of Attention Deficit Hyperactivity Disorder (AD/HD) have been the subject of considerable scrutiny, both psychometrically and psychophysiologically, little attention has been paid to the effect of diagnoses comorbid with AD/HD on such profiles. This is despite the greater than 80% prevalence of comorbidity under the DSM-IV-TR diagnostic definitions. Here we investigate the event related potential (ERP) and psychometric profiles of Controls, AD/HD, and comorbid AD/HD (particularly AD/HD+ODD/CD) groups on six neurocognitive tasks thought to probe the constructs of selective and sustained attention, response inhibition and executive function. Data from 29 parameters extracted from a child group (age range 6 to 12; 52 Controls and 64 AD/HD) and from an adolescent group (age range 13 to 17; 79 Controls and 88 AD/HD) were reduced via a Principal Components Analysis, the 6 significant eigenvectors then used as determinants of cluster membership via a Two-Step Cluster Analysis. Two clusters were found in the analysis of the adolescent age group--a cluster dominated by Control and AD/HD participants without comorbidity, while the second cluster was dominated by AD/HD participants with externalising comorbidity (largely oppositional defiant/conduct disorder ODD/CD). A similar segregation within the child age group was not found. Further analysis of these objectively determined clusters in terms of their clinical diagnoses indicates a significant effect of ODD/CD comorbidity on a concurrent AD/HD diagnosis. We conclude that comorbid externalising behaviour in AD/HD constitutes a distinct pathological entity in adolescence.

The TWIN-E project in emotional wellbeing: study protocol and preliminary heritability results across four MRI and DTI measures.

Despite the significant advancements being made in the neurogenetics for mental health, the identification and validation of potential endophenotype markers of risk and resilience remain to be confirmed. The TWIN-E study (The Twin study in Wellbeing using Integrative Neuroscience of Emotion) aims to validate endophenotype markers of mental health across cognitive, brain, and autonomic measures by testing the heritability, clinical plausibility, and reliability of each of these measures in a large adult twin cohort. The specific gene and environmental mechanisms that moderate prospective links between endophenotype-phenotype markers and the final outcome of wellbeing will also be identified. TWIN-E is a national prospective study with three phases: I) baseline testing on a battery of online questionnaires and cognitive tasks, and EEG, MRI, and autonomic testing; II) 12-month follow-up testing on the online assessments; and III) randomized controlled trial of brain training. Minimum target numbers include 1,500 male/female twins (18-65 years) for the online assessments (Phase I and II), 300 twins for the EEG testing component, and 244 twins for the MRI testing component. For Phase III, each twin out of the pair will be randomized to either the treatment or waitlist control group to test the effects of brain training on mental health over a 30-day period, and to confirm the gene-environment and endophenotype contributions to treatment response. Preliminary heritability results are provided for the first 50% of the MRI subgroup (n = 142) for the grey matter volume, thickness, and surface area measures, and white matter diffuse tensor imaging fractional anisotropy.

Assessing cognition in schizophrenia: a comparison of clinician and computerized test administration.

Cognitive impairment is recognized as an important determinant of outcome in schizophrenia, but mental health services generally have little capacity to provide detailed neuropsychological assessments. Computerized testing would overcome this difficulty, provided that such testing was equivalent to testing by a clinician. Given that negative symptoms can include impaired motivation and attention, it is also important to know whether computerized testing is valid in people with more severe negative symptoms. Our study was designed to compare clinician-administered and computerized testing of two domains commonly impaired in schizophrenia, verbal memory and verbal fluency. We also evaluated the effect of negative symptoms on performance on computerized cognitive tests. Sixty-two participants with schizophrenia completed clinician-administered and computerized verbal memory and verbal fluency tasks. The Positive and Negative Syndrome Scale assessed negative symptom severity. The study found no difference in cognitive performance associated with the method of test administration. This finding held regardless of the severity of negative symptoms. We found that computerized cognitive testing was equivalent to clinician-delivered testing in assessing verbal memory and verbal fluency. This finding was not affected by the presence of negative symptoms. Our results support the use of computerized cognitive testing for people with schizophrenia.

Visual Experiences during Paralysis.

RATIONALE: Paralyzed human volunteers (n = 6) participated in several studies the primary one of which required full neuromuscular paralysis while awake. After the primary experiment, while still paralyzed and awake, subjects undertook studies of humor and of attempted eye-movement. The attempted eye-movements tested a central, intentional component to one's internal visual model and are the subject of this report. METHODS: Subjects reclined in a supportive chair and were ventilated after paralysis (cisatracurium, 20 mg intravenously). In illumination, subjects were requested to focus alternately on the faces of investigators standing on the left and the right within peripheral vision. In darkness, subjects were instructed to look away from a point source of light. Subjects were to report their experiences after reversal of paralysis. RESULTS: During attempted eye-movement in illumination, one subject had an illusion of environmental movement but four subjects perceived faces as clearly as if they were in central vision. In darkness, four subjects reported movement of the target light in the direction of attempted eye-movements and three could control the movement of the light at will. CONCLUSION: The hypothesis that internal visual models receive intended ocular-movement-information directly from oculomotor centers is strengthened by this evidence.

A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): rationale and design.

BACKGROUND: The ACTION study (Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study. METHODS: Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo. RESULTS: The methodology for the ACTION study has been detailed. CONCLUSIONS: The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ANZCTRN12607000535471.

Regional heterogeneity in limbic maturational changes: evidence from integrating cortical thickness, volumetric and diffusion tensor imaging measures.

Magnetic resonance imaging (MRI) studies of structural brain development have suggested that the limbic system is relatively preserved in comparison to other brain regions with healthy aging. The goal of this study was to systematically investigate age-related changes of the limbic system using measures of cortical thickness, volumetric and diffusion characteristics. We also investigated if the "relative preservation" concept is consistent across the individual sub-regions of the limbic system. T1 weighted structural MRI and Diffusion Tensor Imaging data from 476 healthy participants from the Brain Resource International Database was used for this study. Age-related changes in grey matter (GM)/white matter (WM) volume, cortical thickness, diffusional characteristics for the pericortical WM and for the fiber tracts associated with the limbic regions were quantified. A regional variability in the aging patterns across the limbic system was present. Four important patterns of age-related changes were highlighted for the limbic sub-regions: 1. early maturation of GM with late loss in the hippocampus and amygdala; 2. an extreme pattern of GM preservation in the entorhinal cortex; 3. a flat pattern of reduced GM loss in the anterior cingulate and the parahippocampus and; 4. accelerated GM loss in the isthmus and posterior cingulate. The GM volumetric data and cortical thickness measures proved to be internally consistent, while the diffusional measures provided complementary data that seem consistent with the GM trends identified. This heterogeneity can be hypothesized to be associated with age-related changes of cognitive function specialized for that region and direct connections to the other brain regions sub-serving these functions.

An integrative assessment of brain and body function 'at rest' in panic disorder: a combined quantitative EEG/autonomic function study.

We conducted a quantitative electroencephalographic (QEEG) and autonomic assessment of panic disorder (PD). The study samples comprised 52 individuals meeting DSM-IV criteria for PD (with or without agoraphobia) and 104 age-, gender-, and handedness-matched controls. EEG data were acquired from 16 scalp sites during resting eyes-open (REO) and eyes-closed (REC) conditions, and spectral power was assessed within 4 frequency bands: theta, alpha-1, alpha-2, and beta. The main findings were an overall reduction of spectral power in PD, compared to controls (Group main effect, p=.011), which was most apparent during REC (Group Condition interaction, p=.014), and within the alpha-1 frequency band (8-11 Hz; Group Band interaction, p=.014). Alpha-1 desynchronization occurs in response to increases in non-specific information processing, and aspects of attention such as alertness. Other findings were region-specific alterations of spectral power at frontal and temporal scalp sites, including a frontal alpha-1 asymmetry (R

Default network connectivity during a working memory task.

The default network exhibits correlated activity at rest and has shown decreased activation during performance of cognitive tasks. There has been little investigation of changes in connectivity of this network during task performance. In this study, we examined task-related modulation of connectivity between two seed regions from the default network posterior cingulated cortex (PCC) and medial prefrontal cortex (mPFC) and the rest of the brain in 12 healthy adults. The purpose was to determine (1) whether connectivity within the default network differs between a resting state and performance of a cognitive (working memory) task and (2) whether connectivity differs between these nodes of the default network and other brain regions, particularly those implicated in cognitive tasks. There was little change in connectivity with the other main areas of the default network for either seed region, but moderate task-related changes in connectivity occurred between seed regions and regions outside the default network. For example, connectivity of the mPFC with the right insula and the right superior frontal gyrus decreased during task performance. Increased connectivity during the working memory task occurred between the PCC and bilateral inferior frontal gyri, and between the mPFC and the left inferior frontal gyrus, cuneus, superior parietal lobule, middle temporal gyrus and cerebellum. Overall, the areas showing greater correlation with the default network seed regions during task than at rest have been previously implicated in working memory tasks. These changes may reflect a decrease in the negative correlations occurring between the default and task-positive networks at rest.

Impact of the HTR3A gene with early life trauma on emotional brain networks and depressed mood.

BACKGROUND: The risk for mental illnesses such as depression is increasingly conceptualized as the product of gene-environment interactions and their impact on brain structure and function. The role of serotonin 3A receptor gene (HTR3A -42C>T polymorphism) and its interaction with early life stress (ELS) was investigated in view of the receptor's localization to brain regions central to emotion processing. METHODS: Fronto-limbic grey matter (GM) loss was measured using magnetic resonance imaging and assessed using voxel-based morphometry analysis in 397 nonclinical individuals from the Brain Resource International Database. Negative mood symptoms were also assessed. RESULTS: The HTR3A CC genotype group, compared to the T carriers, demonstrated comparative loss to GM in hippocampal structures, which extended to the frontal cortices for those CC genotype individuals also exposed to ELS. Elevations in depressed mood were also evident. CONCLUSIONS: These findings suggest that the HTR3A CC genotype may be associated with alterations in brain structures central to emotion processing, particularly when exposed to stress, and further highlight the potential role of the serotonin system in the pathophysiology of affective disorders. In contrast, those individuals with the T allele, in particular the TT genotype, may be more protected from such alterations combined with minimal exposure to ELS events.

Early life stress combined with serotonin 3A receptor and brain-derived neurotrophic factor valine 66 to methionine genotypes impacts emotional brain and arousal correlates of risk for depression.

BACKGROUND: Depression will be the second largest burden of disease by 2020. Developing new tools for identifying risk and ultimately prevention of depression relies on elucidating the integrative relationships between susceptibility markers from gene-stress interactions and how they impact emotional brain and arousal systems. They have largely been studied in isolation. METHODS: We examined how genetic (brain-derived neurotrophic factor [BDNF] valine 66 to methionine [Val66Met] and serotonin receptor gene 3A [HTR3A]) and early life stress susceptibility factors interact in predicting electroencephalogram (EEG) asymmetry, emotion-elicited heart rate, and self-reported negativity bias, each correlates of risk for depression. Caucasian volunteers (n = 363) were derived from the Brain Resource International Database, via the Brain Research And Integrative Neuroscience Network. RESULTS: Individuals with both BDNF methionine and HTR3A CC risk genotypes and early life stressors demonstrated a profile of elevated emotion-elicited heart rate and right frontal hyper-activation with right parietotemporal hypoactivation in EEG asymmetry. Elevations in heart rate were a moderator of negativity bias. CONCLUSIONS: The findings provide new evidence that these gene-stress susceptibility factors contribute to a brain-arousal profile indicative of risk for depression. They are a step toward identifying biological markers for detecting risk before overt symptoms. It would be valuable for future studies to examine comorbidity and specificity issues; for instance, whether these gene-stress factors contribute in different ways to the partially distinct EEG asymmetry profiles found with anxiety.