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Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders.

Although women have a greater propensity than men to develop posttraumatic stress disorder (PTSD) following trauma, sex differences in neural activations to threat have received little investigation. This study tested the prediction that trauma would heighten activity in automatic fear-processing networks to a greater extent in women than in men. Functional magnetic resonance imaging (fMRI) data were recorded in 23 participants with PTSD (13 women, 10 men), 21 trauma-exposed controls (9 women, 12 men), and 42 non-trauma-exposed controls (22 women, 20 men) while they viewed masked facial expressions of fear. Exposure to trauma was associated with enhanced brainstem activity to fear in women, regardless of the presence of PTSD, but in men, it was associated only with the development of PTSD. Men with PTSD displayed greater hippocampal activity to fear than did women. Both men and women with PTSD showed enhanced amygdala activity to fear relative to controls. The authors conclude that greater brainstem activation to threat stimuli may contribute to the greater prevalence of PTSD in women, and greater hippocampal activation in men may subserve an enhanced capacity for contextualizing fear-related stimuli.

Measures of cognition support diagnostic and treatment decisions in attention deficit hyperactivity disorder. We used an integrative neuroscience framework to assess cognition and associated brain-function correlates in large attention deficit hyperactivity disorder and healthy groups. Matched groups of 175 attention deficit hyperactivity disorder children/adolescents and 175 healthy control subjects were assessed clinically, with the touch screen-based cognitive assessment battery "IntegNeuro" (Brain Resource Ltd., Sydney, Australia) and the "LabNeuro" (Brain Resource Ltd., Sydney, Australia) platform for psychophysiologic recordings of brain function and body arousal. IntegNeuro continuous performance task measures of sustained attention classified 68% of attention deficit hyperactivity disorder patients with 76% specificity, consistent with previous reports. Our additional cognitive measures of impulsivity, intrusive errors, inhibition, and response variability improved sensitivity to 88%, and specificity to 91%. Positive predictive power was 96%, and negative predictive power, 88%. These metrics were stable across attention deficit hyperactivity disorder subtypes and age. Consistent with their brain-based validity, cognitive measures were correlated with corresponding brain-function and body-arousal measures. We propose a combination of candidate cognitive "markers" that define a signature for attention deficit hyperactivity disorder: "sustained attention," "impulsivity," "inhibition," "intrusions," and "response variability." These markers offer a frame of reference to support diagnostic and treatment decisions, and an objective benchmark for monitoring outcomes of interventions.

OBJECTIVE:: To examine resting awake EEG in adolescent AN participants before and after refeeding to determine if EEG abnormalities in Anorexia Nervosa (AN) are reversible. METHOD:: In 37 adolescent first admission AN patients and 45 healthy controls, EEG was recorded during short duration "eyes open" and "eyes closed" awake resting conditions. Repeat testing occurred in 28 AN participants after refeeding and subsequent weight gain. RESULTS:: In "eyes open," underweight AN participants exhibit reduced relative alpha power and increased beta power in frontal brain regions. A significant increase in alpha, and decrease in beta and delta power was observed within participants after refeeding. In "eyes closed", underweight AN participants had elevated theta in parietal-occipital regions which remained after refeeding. DISCUSSION:: EEG abnormalities (reduced alpha/increased beta power) in AN normalizes with refeeding, while increased theta power persists in parietal-occipital regions in an eyes closed context. (c) 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2010).

There is overlap between the behavioural symptoms and disturbances associated with Attention-Deficit/Hyperactivity Disorder (AD/HD) and sleep problems. The aim of this study was to examine the extent of overlap in cognitive and electrophysiological disturbances identified in children experiencing sleep problems and children with AD/HD or both. Four groups (aged 7-18) were compared: children with combined AD/HD and sleep problems (n=32), children with AD/HD (n=52) or sleep problems (n=36) only, and children with neither disorder (n=119). Electrophysiological and cognitive function measures included: absolute EEG power during eyes open and eyes closed, event-related potential (ERP) components indexing attention and working memory processes (P3), and a number of standard neuropsychological tests. Children with symptoms of both AD/HD and sleep problems had a different profile from those of children with either AD/HD or sleep problems only. These findings suggest it is unlikely that disturbances in brain and cognitive functioning associated with sleep problems also give rise to AD/HD symptomatology and consequent diagnosis. Furthermore, findings suggest that children with symptoms of both AD/HD and sleep problems may have a different underlying aetiology than children with AD/HD-only or sleep problems-only, perhaps requiring unique treatment interventions.

The prevalence and nature of post-traumatic stress disorder (PTSD) following mild traumatic brain injury (MTBI) is controversial because of the apparent paradox of suffering PTSD with impaired memory for the traumatic event. In this study, 1167 survivors of traumatic injury (MTBI: 459, No TBI: 708) were assessed for PTSD symptoms and post-traumatic amnesia during hospitalization, and were subsequently assessed for PTSD 3 months later (N = 920). At the follow-up assessment, 90 (9.4%) patients met criteria for PTSD (MTBI: 50, 11.8%; No-TBI: 40, 7.5%); MTBI patients were more likely to develop PTSD than no-TBI patients, after controlling for injury severity (adjusted odds ratio: 1.86; 95% confidence interval, 1.78-2.94). Longer post-traumatic amnesia was associated with less severe intrusive memories at the acute assessment. These findings indicate that PTSD may be more likely following MTBI, however, longer post-traumatic amnesia appears to be protective against selected re-experiencing symptoms.

While posttraumatic stress disorder (PTSD) is often characterised by an excessive fear response and hyperarousal, research has generally neglected other clinical characteristics including hypoarousal. Findings indicate that concurrent autonomic activity is associated with increased non-conscious processing of fear, highlighting that autonomic responsivity may be an important determinant in the degree of activation within the brainstem-amygdala-MPFC (medial prefrontal cortex) network.

To examine the impact of environmental stress on grey matter volume in posttraumatic stress disorder (PTSD), we investigated the relationship between duration of PTSD and grey matter volume of hippocampus and anterior cingulate cortex. Twenty-one participants with PTSD and 17 trauma-exposed controls, matched for age and sex and with no history of substance dependence, underwent a T1-weighted structural MRI scan and voxel-based morphometry was employed. After controlling for age, depression and whole-brain volume, analysis of covariance revealed significant reductions in hippocampus and rostral anterior cingulate cortex in PTSD, and there was a significant negative correlation between right hippocampal volume and PTSD duration. This pattern suggests that prolonged PTSD may have cumulative adverse effects on hippocampal volume, highlighting the potential role of genetic-environmental interactions.

Various empirical data suggest that individuals with Panic Disorder (PD) fail to appropriately assign significance to sensory stimuli within the internal and external milieu, including those stimuli which are patently threat-neutral. The failure to appropriately discriminate 'signal' stimuli from among 'noise' signals [Gordon, E., Liddell, B.J., Brown, K.J., Bryant, R., Clark, C.R., Das, P., et al. 2007. Integrating objective gene-brain-behavior markers of psychiatric disorders. J. Integr. Neurosci. 6, 1-34.] results in disturbances of information processing and attentional deployment, which manifests across multiple levels of functioning (e.g., brain, behaviour, autonomic). The present event-related potential (ERP) study, therefore, investigated attentive information processing in PD, using a standard two-tone auditory oddball paradigm, to assess patients' response to infrequent 'target' tones (i.e., signals) and frequent 'non-target' tones (i.e., noise). Simultaneously-recorded autonomic data provided converging measures of the concomitants of disordered information processing. PD patients (n=50) showed increased N1 amplitude to frequent non-target tones and reduced P3 amplitude to infrequent targets, compared to matched controls (n=98). There were no between-group differences for N1 targets, N2 or P2. Patients additionally showed increased heart rate, fewer spontaneous skin conductance responses (trend) to significant stimuli, and reduced P3 latency compared to controls, although the latter result was accounted for by patients who frequently experienced depersonalization and/or derealisation during panic. Patients showed several disturbances of attentive information processing in a simple auditory discrimination task: Increased N1 to repeated stimuli suggests impaired stimulus filtering, whereas reduced P3 amplitude and latency represent the under-allocation of neural resources for infrequent, goal-relevant stimuli, and their increased speed of processing, respectively. These disturbances likely contribute to patients' aversive outcomes in stimulus-rich environments.

OBJECTIVE: Schizophrenia is characterized by a deficit in context processing, with physiological correlates of hypofrontality and reduced amplitude P3b event-related potentials. We hypothesized an additional physiological correlate: differences in the spatio-temporal dynamics of cortical activity along the anterior-posterior axis of the scalp. METHODS: This study assessed latency topographies of spatio-temporal waves under task conditions that elicit the P3b. EEG was recorded during separate auditory and visual tasks. Event-related spatio-temporal waves were quantified from scalp EEG of subjects with first episode schizophrenia (FES) and matched controls. RESULTS: The P3b-related task conditions elicited a peak in spatio-temporal waves in the delta band at a similar latency to the P3b event-related potential. Subjects with FES had fewer episodes of anterior to posterior waves in the 2-4 Hz band compared to controls. Within the FES group, a tendency for fewer episodes of anterior to posterior waves was associated with high Psychomotor Poverty symptom factor scores. CONCLUSIONS: Subjects with FES had altered global EEG dynamics along the anterior-posterior axis during task conditions involving context update. SIGNIFICANCE: The directional nature of this finding and its association with Psychomotor Poverty suggest this result is related to findings of hypofrontality in schizophrenia.

The INTEGRATE Model draws on the framework of 'integrative neuroscience' to bring together brain-body and behavioral concepts of emotion, thinking and feeling and their regulation. The key organizing principle is the drive to 'minimize danger and maximize reward' that determines what is significant to us at each point in time. Traits of 'negativity bias' reflect the tendency to perceive danger rather than reward related information, and this bias influences emotion, thinking and feeling processes. Here, we examined a self-report measure of Negativity Bias in relation to its impact on brain and body correlates of emotion processing. The contributions of the serotonin transporter (5-HTT-LPR) allelic variants and early life stress to both negativity bias and these correlates were also examined. Data were accessed in collaboration with the Brain Resource International Database (BRID) which provides standardized data across these domains of measurement. From an initial sample of 303 nonclinical subjects from the BRID, subjects scoring one standard deviation below (n=55) and above (n=47) the mean on the measure of negativity bias were identified as 'Negativity Bias' and 'Positivity Bias' groups for analysis, respectively. These subjects had been genotyped for 5-HTT-LPR Short allele versus LL homozygote status, and completed the early life stress scale, and recording of startle responses and heart rate for conscious and nonconscious fear conditions. A matched subset (n=39) of BRID subjects completed functional MRI with the same facial emotion tasks. The Negativity Bias (compared to Positivity Bias) group was distinguished by both arousal and brain function correlates: higher startle amplitude, higher heart rate for conscious and nonconscious fear conditions, and heightened activation in neural circuitry for both fear conditions. Regions of heightened activation included brainstem and bilateral amygdala, anterior cingulate and ventral and dorsal medial prefrontal cortex (mPFC) for conscious fear, and brainstem and right-sided amygdala, anterior cingulate and ventral, mPFC for nonconscious fear. The 5-HTT-LPR Short allele (versus LL) conferred a similar pattern of arousal and neural activation. For those with the 5-HTT-LPR Short allele, the addition of early life stress contributed to enhanced negativity bias, and to further effects on heart rate and neural activation for nonconscious fear in particular. These findings suggest that traits of negativity bias impact brain-body arousal correlates of fear circuitry. Both genetic variation and life stressors contribute to the impact of negativity bias. Given that negativity bias is a feature of conditions such as depression and associated biological alterations, the findings have implications for translation into clinical decision support.

BACKGROUND: Major depressive disorder is associated with a reduced ability to attend and concentrate, however, the extent to which attentional impairment is dependent on subtype remains to be clarified. METHODS: Event-related potentials (ERPs) associated with a well-validated auditory oddball, selective attention task, were recorded to determine the impact of melancholia (n=57) versus non-melancholia (n=48) relative to controls (n=116). RESULTS: The key findings were an exaggeration of the P200 to both non-target and target stimuli and a reduction in the P300 to targets in patients with melancholia, relative to patients with non-melancholia and controls. In addition, the N200/P300 complex was slowed in latency corresponding to the slowed behavioural responses to targets in melancholia. Stepwise regression analysis also revealed that depression severity, but not psychomotor slowing, contributed to increases in P200 amplitude. LIMITATIONS: This study is cross-sectional and cannot determine whether the observed ERP changes are a state or trait marker, highlighting the need for a longitudinal study of ERP characteristics in different subgroups of depressed patients. CONCLUSIONS: Results point to a difficulty in differentiating significant stimuli in the environment in the depressed individual. The combined disruption of early sensory processing (P200) and subsequent context processing (N200/P300 complex) may provide a potential mechanism for the attentional impairment that is frequently observed in depression, particularly in more severe depression.

OBJECTIVE: Two centuries of clinical observations have suggested that conversion symptoms are associated with strong emotions or situations that threaten the individual's physical or psychological integrity. This study tested the hypothesis that childhood conversion reactions reflect the motor-sensory components of two distinct emotional responses (one inhibitory, one excitatory) that develop as adaptations to recurring threats within intimate relationships. METHOD: Emotional responses to interpersonal threats were assessed in 28 children with conversion disorders using Dynamic-Maturational-Model (DMM) assessments of attachment. Attachment strategies (the inhibitory, Type A; the balanced, Type B; and the excitatory, Type C) provide information about (1) the child's behavioural (motor-sensory) organization in the face of interpersonal threats, and (2) the information processing that underpins this behavioural organization. RESULTS: Twelve children (43%) used an inhibitory attachment strategy. Twelve (43%) used an excitatory attachment strategy. A smaller group (14%) alternated between inhibitory and excitatory strategies, their conversion symptoms reflecting the latter. DISCUSSION: These data suggest that conversion reactions are not a single clinical entity and reflect the motor-sensory components of two distinct human emotional responses to threat. This distinction may help to account for the broad range of conversion symptoms seen in clinical practice, both those that involve loss of function and can be explained by a central inhibition hypothesis and those that involve positive symptoms and secondary gain.

Reduced ventral anterior cingulate (vACC) activity to threat is thought to reflect an impairment in regulating arousal networks in posttraumatic stress disorder (PTSD). Concurrent functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) recording were used to examine neural functioning when arousal networks are engaged. Eleven participants with PTSD and 11 age- and sex-matched non-traumatized controls performed an oddball task that required responding to salient, non-trauma-related auditory target tones embedded in lower frequency background tones. Averaged target-background analyses revealed significantly greater dorsal ACC, supramarginal gyrus, and hippocampal activity in PTSD relative to control participants.With-SCR target responses resulted in increased vACC activity in controls, and dorsal ACC activity in PTSD. PTSD participants had reduced vACC activity relative to controls to target tones when SCR responses were present. This reduction in vACC in PTSD relative to controls was not apparent in without-SCR responses. These findings suggest that a reduction in vACC in PTSD occurs specifically when arousal networks are engaged.

BACKGROUND: Schizophrenia may be understood as a disorder of neural synchrony. There is also increasing evidence that emotional and social cognitive impairments are central to this disorder. In patients with first-episode schizophrenia, we examined whether emotion perception is associated with disruptions to high-frequency (40 Hz) gamma synchrony and whether these disruptions predict self-regulatory adaptive compensations reflected in social cognitive behaviours. METHODS: We obtained electroencephalography recordings from 28 patients with first-episode schizophrenia and matched healthy controls during perception of facial emotion under both conscious and nonconscious conditions. We extracted gamma-band synchrony from the electroencephalogram. We also used behavioural measures of emotion identification, emotional intelligence, negativity bias and social function, along with ratings of first-episode schizophrenia symptoms. We analyzed group differences and predicted social cognition to assess the potential contribution of medication. RESULTS: Within 200 ms poststimulus, patients with first-episode schizophrenia showed alterations in gamma synchrony during both conscious and nonconscious emotion perception. Stimulus-locked synchrony was reduced in patients, particularly over the temporal cortex, whereas complementary enhancements in absolute gamma synchrony (independent of stimuli) were more distributed over temporal and left parieto-occipital regions. This pattern of altered synchrony predicted poor performance on each measure of social cognition among these patients. Medication dosage did not correlate significantly with either gamma synchrony or behavioural measures in this group. LIMITATIONS: Limitations to our study include the lack of comparison between medicated and unmedicated patients or between types of medication. CONCLUSION: These findings suggest that disruptions in integrative processing of motivationally important stimuli show promise as a potential biological marker of social cognitive impairments, present from the first episode of schizophrenia, and their outcomes.

Individual risk markers for depression and anxiety disorders have been identified but the explicit pathways that link genes and environment to these markers remain unknown. Here we examined the explicit interactions between the brain-derived neurotrophic factor (BDNF) Val66Met gene and early life stress (ELS) exposure in brain (amygdala-hippocampal-prefrontal gray matter volume), body (heart rate), temperament and cognition in 374 healthy European volunteers assessed for depression and anxiety symptoms. Brain imaging data were based on a subset of 89 participants. Multiple regression analysis revealed main effects of ELS for body arousal (resting heart rate, P=0.005) and symptoms (depression and anxiety, P<0.001) in the absence of main effects for BDNF. In addition, significant BDNF-ELS interactions indicated that BDNF Met carriers exposed to greater ELS have smaller hippocampal and amygdala volumes (P=0.013), heart rate elevations (P=0.0002) and a decline in working memory (P=0.022). Structural equation path modeling was used to determine if this interaction predicts anxiety and depression by mediating effects on the brain, body and cognitive measures. The combination of Met carrier status and exposure to ELS predicted reduced gray matter in hippocampus (P<0.001), and associated lateral prefrontal cortex (P<0.001) and, in turn, higher depression (P=0.005). Higher depression was associated with poorer working memory (P=0.005), and slowed response speed. The BDNF Met-ELS interaction also predicted elevated neuroticism and higher depression and anxiety by elevations in body arousal (P<0.001). In contrast, the combination of BDNF V/V genotype and ELS predicted increases in gray matter of the amygdala (P=0.003) and associated medial prefrontal cortex (P<0.001), which in turn predicted startle-elicited heart rate variability (P=0.026) and higher anxiety (P=0.026). Higher anxiety was linked to verbal memory, and to impulsivity. These effects were specific to the BDNF gene and were not evident for the related 5HTT-LPR polymorphism. Overall, these findings are consistent with the correlation of depression and anxiety, yet suggest that partially differentiated gene-brain cognition pathways to these syndromes can be identified, even in a nonclinical sample. Such findings may aid establishing an evidence base for more tailored intervention strategies.

We provide a systematic, evidence-based medicine (EBM) review of the field of electrophysiology in the anxiety disorders. Presently, electrophysiological studies of anxiety focus primarily on etiological aspects of brain dysfunction. The review highlights many functional similarities across studies, but also identifies patterns that clearly differentiate disorder classifications. Such measures offer clinical utility as reliable and objective indicators of brain dysfunction in individuals and indicate potential as biomarkers for the improvement of diagnostic specificity and for informing treatment decisions and prognostic assessments. Common to most of the anxiety disorders is basal instability in cortical arousal, as reflected in measures of quantitative electroencephalography (qEEG). Resting electroencephalographic (EEG) measures tend to correlate with symptom sub-patterns and be exacerbated by condition-specific stimulation. Also common to most of the anxiety disorders are condition-specific difficulties with sensory gating and the allocation and deployment of attention. These are clearly evident from evoked potential (EP) and event-related potential (ERP) electrical measures of information processing in obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder (PD), generalized anxiety disorder (GAD) and the phobias. Other'ERP measures clearly differentiate the disorders. However, there is considerable variation across studies, with inclusion and exclusion criteria, medication status and control group selection not standardized within condition or across studies. Study numbers generally preclude analysis for confound removal or for the derivation of diagnostic biomarker patterns at this time. The current trend towards development of databases of brain and cognitive function is likely to obviate these difficulties. In particular, electrophysiological measures of function are likely to play a significant role in the development and subsequent adaptations of DSM-V and assist critically in securing improvements in nosological and treatment specificity.

Association studies suggest that the low activity variant of the monoamine oxidase A (MAOA)-uVNTR polymorphism confers risk for emotional disturbances associated with antisocial traits, particularly in males. Here, we assessed the low (MAOA-L) activity variant in relation to both brain function and a behavioral index of antisocial traits. From an initial sample of 290 healthy participants, 210 had low (MAOA-L) or high (MAOA-H) activity variants. Participants underwent a brief assessment of personality traits and event-related potential (ERP) recording during an emotion-processing task. Genotype differences in ERPs were localized using LORETA. The MAOA-L genotype was distinguished by elevated scores on the index of antisocial traits. These traits were related to altered ERPs elicited 120-280ms post-stimulus, particularly for negative emotion. Altered neural processing of anger in MAOA-L genotypes was localized to medial frontal, parietal, and superior temporo-occipital regions in males, but only to the superior occipital cortex in females. The MAOA low activity variant may increase susceptibility to antisocial traits through alterations to the neural systems for processing threat-related emotion, especially for males. Monoamines such as noradrenalin and serotonin may modulate these relationships, given that their metabolism varies according to MAOA variants, and that they modulate both emotional brain systems and antisocial aggression.

OBJECTIVE: Previous studies using event-related potentials (ERPs) in post-traumatic stress disorder (PTSD) have demonstrated reduced P3 amplitude during target detection and working memory (WM) processes. This study investigated effects of psychotropic medication (primarily antidepressants) on these ERP components. METHODS: ERPs were recorded from 26 scalp sites in 34 PTSD patients (20 unmedicated, 14 medicated) with age- and gender-matched controls during a WM paradigm that involved detection of target letters on a visual display. RESULTS: As expected, PTSD patients showed a reduced amplitude P3wm component during WM updating and a reduced and delayed target P3 component. Contrary to expectation, these ERP effects were most apparent in the medicated subgroup of PTSD patients. The medicated PTSD subgroup showed a trend towards reduced P3wm amplitude compared with controls and a significant amplitude reduction and delay of target P3 component, while there was little difference between the non-medicated PTSD subgroup and controls. Neither ERP nor behavioural measures were related to Clinician Administered PTSD Scale (CAPS) symptom severity measures. CONCLUSIONS: These results are consistent with research that suggests antidepressant medication may impair working memory performance. SIGNIFICANCE: The present study illustrates the importance of monitoring medication effects on cognitive performance during clinical efficacy studies.

We applied a covariance-based multivariate analysis to functional magnetic resonance imaging (fMRI) data to investigate abnormalities in working memory (WM) systems in patients with post-traumatic stress disorder (PTSD). Patients (n=13) and matched controls (n=12) were scanned with fMRI while updating or maintaining trauma-neutral verbal stimuli in WM. A multivariate statistical analysis was used to investigate large-scale brain networks associated with these experimental tasks. For the control group, the first network reflected brain activity associated with WM updating and principally involved bilateral prefrontal and bilateral parietal cortex. Controls' second network was associated with WM maintenance and involved regions typically activated during storage and rehearsal of verbal material, including lateral premotor and inferior parietal cortex. In contrast, PTSD patients appeared to activate a single fronto-parietal network for both updating and maintenance tasks. This is indicative of abnormally elevated activity during WM maintenance and suggests inefficient allocation of resources for differential task demands. A second network in PTSD, which was not activated in controls, showed regions differentially activated between WM tasks, including the anterior cingulate, medial prefrontal cortex, fusiform and supplementary motor area. These activations may be linked to hyperarousal and abnormal reactivity, which are characteristic of PTSD.

Of the few studies that have directly investigated the neuroanatomical correlates of delusions in patients with recent-onset schizophrenia, a number have paradoxically reported a positive correlation between delusion severity and regional grey matter volume. In order to explore this relationship, 31 patients with first-episode schizophrenia (FES) underwent a clinical interview and a T1-weighted structural MRI scan. Patients' scores on the Delusions subscale of the Positive and Negative Syndrome Scale were correlated with the volume of every voxel in their grey matter images in SPM99. Patients' delusion scores were found to correlate with the volume of a cluster of voxels located in the dorso-medial frontal cortex, centred on the medial frontal gyrus. Post-hoc analysis revealed that this 'region-of-correlation' was volumetrically reduced in the FES patients relative to a group of 21 matched healthy controls. The results of this study support the hypothesis that while a certain level of structural brain atrophy is necessary for delusion formation in patients with FES, excessive structural atrophy may in fact preclude the formation of highly systematized delusions.

Efforts to identify genetic factors that confer an increased risk for the expression of psychiatric symptoms have focused on polymorphisms in variety of candidate genes, including the catechol-O-methyltransferase (COMT) gene. Results from previous studies that have examined associations between the functional COMT polymorphism (Val158Met) and mental health have been mixed. In the present study, we examined the relationships between COMT, early life stress, and personality in a healthy adult sample. Consistent with previous studies, we hypothesized that individuals with the low-activity genotype would have higher neuroticism and lower extraversion and that this effect would be more pronounced in females. In addition, we extended the previous literature by investigating the potential influence of early life stress. A total of 486 healthy adults underwent genetic testing and personality assessment. Results revealed that individuals homozygous for the COMT low enzyme activity allele had lower extraversion on the NEO-FFI and demonstrated a trend toward greater neuroticism. These relationships were not influenced by sex or the presence of reported early life stress. The finding that COMT genotype was associated with extraversion, and more weakly with neuroticism, is consistent with previous studies. Future research to clarify the influence of sex and gene-environmental interactions is warranted.

OBJECTIVE:: To determine the nature and severity of cognitive functioning impairment in adolescent anorexia nervosa (AN) when underweight and following weight gain. METHOD:: In 37 first admission adolescent (12-18 years) AN patients and 45 matched controls, general cognitive functions were assessed at baseline and follow-up using the IntegNeuro-computerized battery. AN participants were tested between days 3 and 10 of their admission when underweight, with retesting conducted after weight restoration. RESULTS:: When underweight, AN participants performed more poorly than controls on sensori-motor speed tasks and exhibited a susceptibility to interference, but had superior working memory. Once the weight is restored, individuals significantly improved relative to their own performance. Relative to controls, they were significantly faster on attention and executive function tasks, exhibited superior verbal fluency, working memory, and a significantly superior ability to inhibit well-learnt responses. DISCUSSION:: Cognitive impairments in adolescent AN appear to normalize with refeeding and weight gain. (c) 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009.

Both general and social cognition are important in providing endophenotypic markers and predicting real-world functional outcomes of clinical psychiatric disorders. However, to date, focus has been on general cognition, rather than on core domains of social/emotional cognition. This study sought to determine core domains of emotion processing for both explicit identification and implicit recognition and their relationships with core domains of general cognition. Age effects and sex differences were also investigated. A sample of 1,000 healthy individuals (6 to 91 years, 53.5% female) undertook the WebNeuro tests of emotion identification and recognition and tests of general cognitive function. Factor analysis revealed seven core domains of emotion processing: speed of explicit emotion identification, speed of implicit emotion recognition, implicit emotion recognition accuracy, "threat" processing, sadness-disgust identification, "positive emotion" processing, and general "face perception." Seven corresponding core domains of general cognition were identified: information-processing speed, executive function, sustained attention/vigilance, verbal memory, working-memory capacity, inhibition/impulsivity, and sensorimotor function. Factors of emotion processing generally showed positive associations with those of general cognitive function, suggesting commonality in processing speed in particular. Moreover, age had a consistent nonlinear impact on both emotion processing and general cognitive factors, while sex differences were more specific. These findings contribute to a normative and standardized structure for assessment of emotional and general cognition in clinical groups.

A number of psychiatric and neurological disorders are characterized by impairments in facial emotion recognition. Recognition of individual emotions has implicated limbic, basal ganglionic, and frontal brain regions. Since these regions are also implicated in age-related decline and sex differences in emotion processing, an understanding of normative variation is important for assessing deficits in clinical groups. An internet-based test ("WebNeuro") was administered to 1,000 healthy participants (6 to 91 years, 53% female) to assess explicit identification of basic expressions of emotion (happiness, sadness, fear, anger, disgust, neutral). A subsequent implicit recognition condition was based on a priming protocol, in which explicit identification provided the "study" phase. Responses were most accurate for happiness and slowest for fear in the explicit condition, but least accurate for happiness and fastest for fear in the implicit condition. The effects of age, by contrast, showed a similar pattern for both explicit and implicit conditions, following a nonlinear distribution in which performance improved from childhood through adolescence and early adulthood and declined in later adulthood. Females were better than males at explicit identification of fear in particular. These findings are consistent with the priority of threat-related signals, but indicate opposing biases depending on whether emotion processing is conscious or nonconscious. The lifespan trends in emotion processing over 10 decades point to an interaction of brain-based (maturation, stability, and then atrophy of cortical and subcortical systems) and experiential contributing factors. These findings provide a robust normative platform for assessing clinical groups.

This paper demonstrates a method for analyzing target evoked potentials in an auditory oddball task, using Wiener deconvolution to separate the brain's task-dependent properties from its task-invariant response. It is shown that a target response can be deconvolved, and the result contains two delta-like peaks separated by approximately 100 ms, implying that targets resemble a superposition of two standard responses. The latencies and areas of these delta-like peaks give quantitative measures of the evoked potential, providing a method of analysis that is simpler and more physiologically meaningful than peak scoring. This deconvolution method is applied to both synthetic and experimental evoked potential data, and is demonstrated to be applicable even when normal evoked potential features are not clearly visible.

Altered hippocampal volume, the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, and neuroticism have each been implicated in the etiology of psychiatric disorders, especially depression. However, the relationship between these variables is not well understood. Here, we determined the effects of the BDNF Val66met polymorphism on the five-factor personality dimensions (assessed using the NEO-FFI), trait depression (assessed with the DASS-21) in a cross-sectional cohort of 467 healthy volunteers. A large matched subset of this cohort was also assessed for grey matter volume of the hippocampus and contiguous temporal cortical regions using magnetic resonance imaging. In Met carriers, elevations in neuroticism and trait depression and stress were associated with lower mean hippocampal volume, but there were no such associations in Val homozygotes. Trait depression, in particular, was found to moderate the effects of BDNF genotypes on hippocampal volume. Met carriers with high trait depression showed a reduction in grey matter volume of the mean hippocampus compared with Val homozygotes. These findings suggest that even in otherwise healthy subjects, trait depression may contribute to the susceptibility of Met carriers to hippocampal grey matter loss.

Affective impairment is observed in children and adolescents with attention-deficit hyperactivity disorder (ADHD). Low levels of long-chain polyunsaturated fatty acids (LC-PUFA), specifically omega-3 (omega-3) fatty acids in blood measures have been linked to a range of behavioural and mood disorders including ADHD. However, nothing is known about the relationship between omega-3 and brain function in children with ADHD. In the current study, 20 adolescent boys with ADHD were assessed for total lipid fractions in red blood cells and their event-related potential (ERP) response to the presentation of facial expressions of happiness, sadness and fearfulness. The results supported the hypothesis of a positive association between eicosapentaenoic acid (EPA) and a cognitive bias in orientation to overt expressions of happiness over both sad and fearful faces as indexed by midline frontal P300 amplitude. Additional exploratory analyses revealed a positive association between levels of docosahexaenoic acid (DHA) and the right temporal N170 amplitude in response to covert expressions of fear. The arachidonic (AA)/DHA ratio was negatively associated with the right temporal N170 amplitude also to covert expressions of fear. These findings indicate that EPA and DHA may be involved in distinct aspects of affect processing in ADHD and have implications for understanding currently inconsistent findings in the literature on EFA supplementation in ADHD and depression.