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IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subjects’ data from 29 cohorts in five countries (n=3439).MethodsUsing Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN.ResultsNotable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comorbid PTSD and MDD showed higher CT-based centrality in the right anterior cingulate gyrus, right parahippocampal gyrus and lower SA-based centrality in left insular gyrus.ConclusionUnlike previous studies with smaller sample sizes (≤318), our study found differences in centrality measures using a sample size of 3439 subjects. This is the first cross-sectional study to examine SCN interactions with age, sex, and comorbid MDD. Although limited to group level inferences, centrality measures offer insights into a node’s relationship to the entire functional connectome unlike approaches like seed-based connectivity or independent component analysis. Nodes having higher centrality have greater structural or functional connections, lending them invaluable for translational treatments like neuromodulation.

AimsMethamphetamine Use Disorder is prevalent in South Africa. This analysis uses data from a contingency management (CM) pilot study in South Africa to replicate and expand on a U.S.-based study showing that CM voucher spending was associated with drug abstinence behavior.DesignParticipants with methamphetamine-use disorder were enrolled in an 8-week CM trial requiring thrice weekly visits and received cash vouchers in exchange for stimulant-negative urines at each visit.ParticipantsParticipants were 33 treatment-seeking individuals with methamphetamine use disorder including 22 men (66.7%) and 11 women (33.3%) with a mean age of 34years (S.D.=7.7). Participants reported using methamphetamine for a mean of 11.7years (S.D.=4.9).SettingAll study procedures took place in South Africa between August 2016 and May 2018.MeasurementsA time-lagged counting process Cox Proportional Hazards model for recurrent event survival analysis examined the relationship between frequency of and participant-categorized type of CM expenditures (hedonic, utilitarian, consumable or durable) and drug abstinence.FindingsAfter controlling for severity of baseline methamphetamine use and accumulated CM earnings (proxied by cumulative negative urines), those spending CM earnings at a previous visit ("spenders") were more likely to produce stimulant-negative urine samples subsequently, compared to those who did not ("savers") [OR=1.23, CI=1.08-1.53, p=.002]. There were significantly more cumulative stimulant-negative results among spenders vs. savers, p&nbsp

Author(s): Lake, Marilyn T; Shoptaw, Steven; Ipser, Jonathan C; Takada, Sae; van Nunen, Lara J; Lipinska, Gosia; Stein, Dan J; London, Edythe D | Abstract: Background:Individuals with substance use disorders exhibit maladaptive decision-making on the Iowa Gambling Task (IGT), which involves selecting from card decks differing in the magnitudes of rewards, and the frequency and magnitude of losses. We investigated whether baseline IGT performance could predict responses to contingency management (CM) by treatment-seeking individuals with methamphetamine use disorder (MA Use Disorder) in Cape Town, South Africa. Methods:Twenty-nine individuals with MA Use Disorder underwent an 8-week, escalating reinforcement, voucher-based CM treatment in a study on the suitability of CM therapy for the South African context. Along with 20 healthy control participants, they performed a computerized version of the IGT before starting CM treatment. Seventeen participants maintained abstinence from methamphetamine throughout the trial (full responders), and 12 had an incomplete response (partial responders). Performance on the IGT was scored for magnitude effect (selection of large immediate rewards with high long-term loss) and for frequency effect (preference for frequent rewards and avoidance of frequent losses). Group differences were investigated using linear mixed-effect modeling. Results:Partial responders made more selections from decks providing large, immediate rewards and long-term losses than healthy controls [p = 0.038, g = -0.77 (-1.09: -0.44)]. Full responders showed a greater, nonsignificant preference for frequent rewards and aversion to frequent losses than partial responders [p = 0.054, g = -0.63 (-0.95: -0.29)]. Conclusions:A predilection for choices based on the size and immediacy of reward may reflect a cognitive strategy that works against CM. Pretesting with a decision-making task, such as the IGT, may help in matching cognitive therapies to clients with MA Use Disorder.

Muscle fatigue is a disturbed homeostatic state characterized by a temporary inability to maintain force output and has lasting effects on the brain in the period immediately after exercise, such as decreased interhemispheric functional connectivity (FC). Stimulants that increase dopamine and norepinephrine neurotransmission can enhance performance during muscle fatiguing exercise (i.e. are ergogenic). We recently demonstrated that methylphenidate (MPH) increased force output and increased FC between the insular (IC) and hand motor cortex during a fatiguing handgrip task. However, whether resting FC is altered in the recovery period after enhanced force is unknown. The objective of these follow-up analyses was to examine the effects of performing a fatiguing handgrip task with MPH on subsequent resting state FC. In a double-blind counter-balanced design, participants ingested placebo or MPH and in a magnetic resonance imaging scanner performed: a six-minute pre-task resting scan, a fatiguing handgrip task during scanning, and then a six-minute post-task resting scan. We investigated task-related force and resting state FC pre- and post-task between: (1) interhemispheric motor cortices (M1) and (2) the right IC and left hand motor area. We found 1) a post-task reduction in M1 interhemispheric FC and that the extent of reduciton was negatively correlated with enhanced mean trial force in MPH conditions. 2) MPH but not placebo increased post-task FC between the right IC and left hand motor area. This study demonstrates that using MPH during a muscle fatiguing task has lasting effects on the brain that are markedly different from drug naïve conditions.

Background Methamphetamine use among pregnant women has become a significant problem. Research delineating the cognitive outcomes of prenatal methamphetamine exposure (PME) in early childhood is limited, however. The aim of this study was to examine effects of PME on cognition in six-to-seven-year-old children. Methods PME children ( n = 23) and unexposed controls ( n = 22) completed a battery of neurocognitive tests, which included the Kaufman Assessment Battery for Children, Boston Naming Test, Beery Developmental Test of Visual-Motor Integration, and Grooved Pegboard Test. Results Independent samples t -tests revealed that PME children scored significantly worse than controls on the measures of IQ, learning and memory, confrontation naming, visual-motor integration, and fine motor coordination. Hierarchical regression analyses that included potential confounding sociodemographic, co-exposure and anthropometric variables confirmed that PME impacts negatively on cognitive performance. Conclusions The study confirms that PME has deleterious effects on cognition in several broad cognitive domains, likely by altering underlying brain circuitry in development. These effects may be particularly pronounced at the time when children enter formal schooling. Extended follow-ups into late childhood might help elucidate the developmental trajectory of cognitive dysfunction in PME, and subsequent effects on everyday functioning.

In substance use and psychotic disorders, socially problematic behaviours, such as high aggression may, in part, be explained by deficits in social cognition skills, like the detection of emotions or intentions in others. The aim of this study was to assess the magnitude of social cognition impairment and its association with aggression in individuals with methamphetamine (MA) dependence, methamphetamine-associated psychosis (MAP), and healthy controls (CTRL). A total of 20 MAP participants, 21 MA-dependent participants without psychosis, and 21 CTRL participants performed a facial morphing emotion recognition task (ERT) across four basic emotions (anger, fear, happiness and sadness) and the reading the mind in the eyes task (RMET), and completed the aggression questionnaire. Both MA-dependent groups showed impairment in social cognition in terms of lower RMET scores relative to CTRL participants (MA; p = .047; MAP: p

Chronic methamphetamine use is associated with executive functioning deficits that suggest dysfunctional cognitive control networks (CCNs) in the brain. Likewise, abnormal connectivity between intrinsic CCNs and default mode networks (DMNs) has also been associated with poor cognitive function in clinical populations. Accordingly, we tested the extent to which methamphetamine use predicts abnormal connectivity between these networks, and whether, as predicted, these abnormalities are compounded in patients with a history of methamphetamine-associated psychosis (MAP). Resting-state fMRI data were acquired from 46 methamphetamine-dependent patients [19 with MAP, 27 without (MD)], as well as 26 healthy controls (CTRL). Multivariate network modelling and whole-brain voxel-wise connectivity analyses were conducted to identify group differences in intrinsic connectivity across four cognitive control and three DMN networks identified using an independent components analysis approach (meta-ICA). The relationship of network connectivity and psychotic symptom severity, as well as antipsychotic treatment and methamphetamine use variables, was also investigated. Robust evidence of hyper-connectivity was observed between the right frontoparietal and anterior DMN networks in MAP patients, and 'normalized' with increased duration of treatment with antipsychotics. Attenuation of anticorrelated anterior DMN-dorsal attention network activity was also restricted to this group. Elevated coupling detected in MD participants between anterior and posterior DMN networks became less apparent with increasing duration of abstinence from methamphetamine. In summary, we observed both alterations of RSN connectivity between DMN networks with chronic methamphetamine exposure, as well as DMN-CCN coupling abnormalities consistent with possible MAP-specific frontoparietal deficits in the biasing of task-appropriate network activity.

Background There is a shortage of trained mental health workers in spite of the significant contribution of psychiatric disorders to the global disease burden. Task shifting, through the delegation of health care tasks to less specialised health workers such as community health workers (CHWs), is a promising approach to address the human resource shortage. CHWs in the Western Cape province of South Africa provide comprehensive chronic support which includes that for mental illness, but have thus far not received standardized mental health training. It is unknown whether a structured mental health training programme would be acceptable and feasible, and result improved knowledge, confidence and attitudes amongst CHWs. Methods We developed and piloted a mental health training programme for CHWs, in line with the UNESCO guidelines; the WHO Mental Health Gap Action Programme and the South African National framework for CHW training. In our quasi-experimental (before-after) cohort intervention study we measured outcomes at the start and end of training included: 1) Mental health knowledge, measured through the use of case vignettes and the Mental Health Knowledge Schedule; 2) confidence, measured with the Mental Health Nurse Clinical Confidence Scale; and 3) attitudes, measured with the Community Attitudes towards the Mentally Ill Scale. Knowledge measures were repeated 3 months later. Acceptability data were obtained from daily evaluation questionnaires and a training evaluation questionnaire, while feasibility was measured by participant attendance at training sessions. Results Fifty-eight CHWs received the training, with most (n = 56, 97.0%) attending at least 7 of the 8 sessions. Most participants (n = 29, 63.04%) demonstrated significant improvement in knowledge, which was sustained at 3-months. There was significant improvement in confidence, along with changes in attitude, indicating improved benevolence, reduced social restrictiveness, and increased tolerance to rehabilitation of the mentally ill in the community but there was no change in authoritarian attitudes. The training was acceptable and feasible. Conclusions Mental health training was successful in improving knowledge, confidence and attitudes amongst trained CHWs. The training was acceptable and feasible. Further controlled studies are required to evaluate the impact of such training on patient health outcomes. Trial registration PACTR PACTR201610001834198 , Registered 26 October 2016.

In rodents, there is abundant evidence for the involvement of the opioid system in the processing of reward cues, but this system has remained understudied in humans. In humans, the happy facial expression is a pivotal reward cue. Happy facial expressions activate the brain's reward system and are disregarded by subjects scoring high on depressive mood who are low in reward drive. We investigated whether a single 0.2 mg administration of the mixed mu-opioid agonist/kappa-antagonist, buprenorphine, would influence short-term memory for happy, angry or fearful expressions relative to neutral faces. Healthy human subjects ( n 38) participated in a randomized placebo-controlled within-subject design, and performed an emotional face relocation task after administration of buprenorphine and placebo. We show that, compared to placebo, buprenorphine administration results in a significant improvement of memory for happy faces. Our data demonstrate that acute manipulation of the opioid system by buprenorphine increases short-term memory for social reward cues.

Although specific phobia is a prevalent anxiety disorder, evidence regarding its underlying functional neuroanatomy is inconsistent. A meta-analysis was undertaken to identify brain regions that were consistently responsive to phobic stimuli, and to characterize changes in brain activation following cognitive behavioral therapy (CBT). We searched the PubMed, SCOPUS and PsycINFO databases to identify positron emission tomography and functional magnetic resonance imaging studies comparing brain activation in specific phobia patients and healthy controls. Two raters independently extracted study data from all the eligible studies, and pooled coordinates from these studies using activation likelihood estimation, a quantitative meta-analytic technique. Resulting statistical parametric maps were compared between patients and healthy controls, in response to phobic versus fear-evoking stimuli, and before and after therapy. Thirteen studies were included, comprising 327 participants. Regions that were consistently activated in response to phobic stimuli included the left insula, amygdala, and globus pallidus. Compared to healthy controls, phobic subjects had increased activation in response to phobic stimuli in the left amygdala/globus pallidus, left insula, right thalamus (pulvinar), and cerebellum. Following exposure-based therapy widespread deactivation was observed in the right frontal cortex, limbic cortex, basal ganglia and cerebellum, with increased activation detected in the thalamus. Exposure to phobia-specific stimuli elicits brain activation that is consistent with current understandings of the neuroanatomy of fear conditioning and extinction. There is evidence that the effects of CBT in specific phobia may be mediated through the same underlying neurocircuitry.

Background/Aims: Acute and chronic consumption of nicotine alters brain function at rest. In this chapter, we summarize the effect of nicotine exposure on default mode, executive control, and salience network (DMN, ECN, and SN, respectively) connectivity. Method: We provide a review of resting-state functional magnetic resonance imaging studies of acute versus chronic smokers. Results: Nineteen studies and 1452 participants were eligible for inclusion in the review. Networks incorporating dorsal anterior cingulate, insular cortex, and the frontoparietal regions were most implicated. Results show that acute nicotine exposure is associated with reduced synchronicity in DMN and enhanced activation patterns within limbic connectivity. Data on functional connectivity following chronic nicotine exposure are less consistent. Conclusions: Acute nicotine exposure may temporarily improve cognitive processes associated with attention networks by influencing both the SN and ECN.

Panksepp’s separation-distress model of depression posits that endogenous opioid systems become dysregulated subsequent to early social trauma and that this dysregulation constitutes a risk factor for depression. We tested an aspect of this model by recruiting medically and psychiatrically healthy young adults (N = 32) who differed on one key criterion—exposure to early social trauma. In terms of core affective personality traits as measured by the Affective Neuroscience Personality Scales (ANPS), those not exposed to early social trauma scored significantly higher on SEEKING; the groups did not differ on SADNESS. Importantly, the groups also responded differently to a low-dose opioid challenge (0.2 mg sublingual buprenorphine vs. placebo). Buprenorphine administration had little effect on emotion in controls, but it reduced experience of both positive and negative emotion in trauma-exposed participants. The latter also showed a significant negative bias in social cognition that was not attenuated by bupr...

In rodents, the endogenous opioid system has been implicated in emotion regulation, and in the reduction of fear in particular. In humans, while there is evidence that the opioid antagonist naloxone acutely enhances the acquisition of conditioned fear, there are no corresponding data on the effect of opioid agonists in moderating responses to fear. We investigated whether a single 0.2mg administration of the mu-opioid agonist buprenorphine would decrease fear sensitivity with an emotion-recognition paradigm. Healthy human subjects participated in a randomized placebo-controlled within-subject design, in which they performed a dynamic emotion recognition task 120min after administration of buprenorphine and placebo. In the recognition task, basic emotional expressions were morphed between their full expression and neutral in 2% steps, and presented as dynamic video-clips with final frames of different emotional intensity for each trial, which allows for a fine-grained measurement of emotion sensitivity. Additionally, visual analog scales were used to investigate acute effects of buprenorphine on mood. Compared to placebo, buprenorphine resulted in a significant reduction in the sensitivity for recognizing fearful facial expressions exclusively. Our data demonstrate, for the first time in humans, that acute up-regulation of the opioid system reduces fear recognition sensitivity. Moreover, the absence of an effect of buprenorphine on mood provides evidence of a direct influence of opioids upon the core fear system in the human brain.

In the antiretroviral era, youth perinatally infected with HIV (PHIV+) are surviving into adulthood and are at risk for emotional and behavioural problems. Few studies of these problems have been conducted in low- and middle-income countries and even fewer in sub-Saharan Africa. The aims of this study were to provide a quantitative description of emotional and behavioural problems in a group of PHIV+ youth (n = 78) in South Africa compared with a group of demographically matched HIV-negative controls (n = 30) and to identify correlates of emotional and behavioural problems. A cross-sectional study was conducted employing participants from community and hospital-based clinics. Emotional and behavioural problems were assessed using the Child Behaviour Checklist (CBCL). Several measures were used to assess demographic, biological, cognitive and contextual correlates of problem behaviours. Youth were compared by HIV status on demographic, cognitive and contextual variables as well as the Total Problems and subscale scores of the CBCL. Multivariate comparisons of the influence of contextual and cognitive variables on CBCL Total Problems scores were performed using a stepwise linear regression analytic procedure. In this study, there were no significant differences in between-group comparisons for the prevalence of Internalizing, Externalizing and Total Problems in the PHIV+ youth and control group at the clinical and borderline cut-off ranges of the CBCL. Caregiver depression was the only significant predictor of greater Total Problems scores in the full model, after controlling for age and gender (F = 8.57, df = 5.102, P .01). An interaction between HIV status and caregiver depression was observed (t = -2.20, P = .03), with follow-up within-group analyses confirming that caregiver depression predicted greater Total Problems scores both in HIV-negative youth (β = 0.61, P .001), and to a lesser extent, in HIV-positive youth (β = 0.25, P .001). This study highlights the need for adequate screening of depression in the caregivers of HIV-infected youth.

We conducted a systematic review and meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies comparing autism spectrum disorder (ASD) patients with healthy controls, with the aim of profiling ASD-associated changes in the metabolites N-acetyl-aspartate (NAA) and Creatine (Cr). Meta-regression models of NAA and Cr levels were employed, using data from 20 eligible studies (N = 852), to investigate age-dependent differences in both global brain and region-specific metabolite levels, while controlling for measurement method (Cr-ratio versus absolute concentrations). Decreased NAA concentrations that were specific to children were found for whole-brain grey and white matter. In addition, a significant decrease in NAA was evident across age categories in the parietal cortex, the cerebellum, and the anterior cingulate cortex. Higher levels of Cr were observed for ASD adults than children in global grey matter, with specific increases for adults in the temporal lobe and decreased Cr in the occipital lobe in children. No differences were found for either NAA or Cr in the frontal lobes. These data provide some evidence that ASD is characterized by age-dependent fluctuations in metabolite levels across the whole brain and at the level of specific regions thought to underlie ASD-associated behavioural and affective deficits. Differences in Cr as a function of age and brain region suggests caution in the interpretation of Cr-based ratio measures of metabolites. Despite efforts to control for sources of heterogeneity, considerable variability in metabolite levels was observed in frontal and temporal regions, warranting further investigation.

Post-traumatic stress disorder (PTSD) is a prevalent and disabling disorder. Recognition of neurobiological abnormalities associated with this condition suggests the potential efficacy of medication in its treatment. Nevertheless, questions regarding the efficacy of medications remain, despite general endorsement by clinical practice guidelines of selective serotonin reuptake inhibitors (SSRIs) as first-line agents in treating PTSD. This paper reviews evidence from randomized controlled trials (RCTs) for the efficacy of acute and long-term pharmacotherapy for PTSD, including the treatment of refractory PTSD. In addition, we conducted a systematic meta-analysis to compare the efficacy of different medications in treating PTSD. The effects of methodological study features (including year of publication, duration, number of centres) and sample characteristics (proportion of combat veterans, gender composition) were also tested. The largest body of evidence for short- and long-term efficacy of medication currently exists for SSRIs, with promising initial findings for the selective noradrenergic reuptake inhibitor venlafaxine and the atypical antipsychotic risperidone. Treatment effect was predicted by number of centres and recency of the study, with little evidence that sample characteristics predicted response. Evidence for the effectiveness of benzodiazepines is lacking, despite their continued use in clinical practice. Finally, the α1 antagonist prazosin and the atypical antipsychotics show some efficacy in treatment-resistant PTSD. Adequately powered trials that are designed in accordance with best-practice guidelines are required to provide conclusive evidence of clinically relevant differences in efficacy between agents in treating PTSD, and to help estimate clinical and methodological predictors of treatment response.

Background Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. Methods Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. Results Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. Conclusions Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children.

Objectives: Research into the neural basis of social anxiety disorder (SAD) suggests alterations in prefrontal networks, which may in turn disrupt regulation of the limbic system. Better understanding of the disturbed interface between these networks may improve current pathogenic models of this disorder. Methods: Applying group independent component analysis (ICA) to recordings of fMRI resting-state, connectivity in the executive control network was studied in 18 patients with SAD and 15 age- and sex-matched healthy controls. Results: Results revealed a dissociation within the left executive control network, with SAD patients showing decreased connectivity of the orbitofrontal gyrus and increased connectivity of the middle frontal gyrus compared to healthy controls. In a subsequent seed-based functional connectivity analysis, patients with SAD displayed increased connectivity between the left orbitofrontal gyrus and the left amygdala. Conclusions: Findings suggest that hypo-connectivity in the executive control network and hyper-connectivity between the orbitofrontal cortex and the amygdala may reflect a disturbance in the balance between top-down and bottom-up control processes, potentially contributing to the development of SAD.

A vast amount of information describing health interventions is available on the Internet. This paper describes the systematic retrieval and quality assessment of websites containing information on the treatment of anxiety disorders. Separate searches were conducted for information on generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and specific phobia. The Google, Yahoo, and MSN search engines yielded 540 results, 110 of which were eligible for inclusion. Sixty-seven unique websites were identified. The DISCERN scale was used to evaluate quality of content. The authors also compared the websites in terms of popularity, readability, and a range of technical criteria. Websites were generally of poor to moderate quality. Higher-quality scores were obtained for websites whose authors attributed their sources and provided a clear statement of the purpose of the website. The paper closes by considering limitations of the review and possible future research avenues.

Background: Many randomized controlled trials of the pharmacotherapy and psychotherapy of obsessive-compulsive disorder (OCD) have been undertaken. Several meta-analyses of these trials, and a number of expert consensus guidelines, have been published. This article summarizes these works, and suggests future research directions.Methods: Meta-analyses of OCD were assessed with the QUORUM statement and the Oxman and Guyatt rating scale, and consensus guidelines on the treatment of OCD were assessed with the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. Current principles in the treatment of OCD, and gaps in our knowledge, were reviewed.Results: Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy are currently viewed as the first-line treatments of choice for adult and pediatric OCD.There is also good evidence for the efficacy of atypical antipsychotics in the augmentation of patients refractory to SSRIs. Important questions remain for the field.Conclusions: There have been significant advances in both the pharmacotherapy and psychotherapy of OCD. Nevertheless, there is a paucity of longer-term trials, data on symptom remission and functional improvement, and data on treatment effectiveness in wider clinical practice. It is hoped that improved understanding of the mechanisms underlying OCD will lead to future advances.

HIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the association of HIV infection with functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Fifteen HIV-positive and 15 demographically matched control participants underwent 6 min of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). HIV – associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (N=9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was also associated with reduced frontostriatal connectivity. In conclusion, our data indicate that HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies. (JINS, 2015, 21, 1–11)

Pharmacotherapy is frequently considered in the treatment of disruptive behavior disorders (DBDs) in children and adolescents. There are, however, no systematic reviews of this literature. The aim of this work is to determine whether medication is effective in treating pediatric disruptive behavior disorders and related problems of impulse control, as well as to examine differences in the treatment response and tolerability of different medication classes and agents. Randomized controlled trials of the pharmacotherapy of DBDs in children and adolescents were reviewed, and a meta-analysis of 14 trials (823 participants) was conducted. There is some evidence of the effectiveness of medication in treating DBDs, with positive outcomes for lithium and risperidone in particular. Pharmacotherapy also demonstrated some efficacy in reducing symptoms of aggression. Medication was relatively well-tolerated, as indicated by equivalent dropout rates in medication and comparison groups. There are relatively few controlled trials of the pharmacotherapy of disruptive behavior disorders or other impulse control disorders, despite the importance of research in this area. Given the potential adverse effects of agents such as lithium and risperidone, a careful risk–benefit analysis is needed for each patient.

Although animal evidence indicates that early life trauma results in pervasive hippocampal deficits underlying spatial and cognitive impairment, visuo-spatial data from adult humans with early childhood adversity are lacking. We administered 4 tests of visuo-spatial ability from the Cambridge Neuorpsychological Test Automated Battery (CANTAB) to adults with a history of childhood trauma (measured by the Childhood Trauma Questionnaire) and a matched sample of healthy controls (trauma/control = 27/28). We observed a significant effect of trauma history on spatial/pattern learning. These effects could not be accounted for by adverse adult experiences, and were sex-specific, with prior adversity improving performance in men but worsening performance in women, relative to controls. Limitations include the small sample size and reliance of our study design on a retrospective, self report measure. Our results suggest that early adversity can lead to specific and pervasive deficits in adult cognitive function.

Background:Social anxiety disorder (SAD) is characterised by abnormal fear and anxiety in social situations. Functional magnetic resonance imaging (fMRI) is a brain imaging technique that can be used to illustrate neural activation to emotionally salient stimuli. However, no attempt has yet been made to statistically collate fMRI studies of brain activation, using the activation likelihood-estimate technique, in response to emotion recognition tasks in individuals with social anxiety disorder. Methods:A systematic search of fMRI studies of neural responses to socially emotive cues in SAD and GSP was undertaken. Activation likelihood-estimate (ALE) meta-analysis, a voxel based meta-analytic technique, was used to estimate the most significant activations during emotional recognition. Results: 7 studies were eligible for inclusion in the meta-analysis, constituting a total of 91 subjects with SAD or GSP, and 93 healthy controls. The most significant areas of activation during emotional recognition versus neutral stimuli in individuals with social anxiety disorder compared to controls were: bilateral amygdala, left medial temporal lobe encompassing the entorhinal cortex, left medial aspect of the inferior temporal lobe encompassing perirhinal cortex and parahippocampus, right anterior cingulate, right globus pallidus, and distal tip of right postcentral gyrus.Conclusion:The results are consistent with neuroanatomic models of the role of the amygdala in fear conditioning, and the importance of the limbic circuitry in mediating anxiety symptoms.

Panic disorder is a debilitating and distressing disorder characterized by recurrent and spontaneous episodes of fear, worry, or distress. These panic attacks are accompanied by at least four anxiety-related symptoms (e.g., palpitations, fear of dying, trembling), and may vary in their phenomenology, incidence, and severity. The presentation of this disorder is further complicated by the frequent presence of psychiatric comorbidity. Nevertheless, recent advances in our understanding of the psychobiology of fear and developments in clinical research (e.g., structural functional imaging, neurogenetics) promise to clarify our understanding of this heterogeneous condition. This article will examine the psychobiological and biological theories of panic disorder, focusing on its underlying neurocircuitry and neurochemistry. The role of gene–environment interactions in the development of panic disorder, and its subsequent diagnosis and treatment, will also be reviewed.

Introduction Literature on the ability of patients with obsessive–compulsive disorder (OCD) to recognize static facial expressions of disgust is not consistent. We aimed to investigate whether OCD is associated with deficits in the recognition of disgust in a dynamic task, and if so, whether the acute administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram would result in the normalization of such deficits. Methods OCD patients ( n = 20) and matched healthy controls ( n = 20) received a single dose of escitalopram 20 mg on one day, and a single dose of placebo on another day, in randomized order, under double-blind conditions. Accuracy (i.e. the percentage of correct answers) and sensitivity to disgust stimuli (defined as the lowest level of emotional intensity expressed on the photo image after which no errors were made in the recognition of disgust for subsequent trials of increasing intensity) were compared in OCD patients and controls, with a repeated measures analysis of variance using a mixed model approach. Results On placebo, the accuracy of, and sensitivity to, disgust stimuli were similar across groups. OCD patients had more accurate and more sensitive recognition of disgust after acute SSRI administration than after placebo, while controls had less accurate recognition and less sensitive recognition of disgust after acute SSRI administration than after placebo. Conclusions The use of a dynamic facial recognition task demonstrated altered responses to disgust in OCD patients compared to healthy controls after a pharmacological challenge with escitalopram. These findings suggest that the serotonergic system plays a role in disgust recognition.

Summary Grooming disorders, such as trichotillomania (TTM), nail biting, and skin picking, are receiving increasing attention from researchers and clinicians. This is in part due to their possible link to obsessive–compulsive disorder (OCD). It is imperative that these disorders are categorized correctly in order to facilitate research and aid diagnosis and treatment. However, within current psychiatric classification systems TTM is currently conceptualized as an impulse control disorder and nail biting, lip biting, and skin picking are not yet included in the official nomenclature. It is therefore unclear whether these grooming disorders should form a category on their own (i.e., “grooming disorders” or “pathological grooming behaviors”), or whether they should be classified as obsessive–compulsive spectrum disorders (OCSD), impulse control disorders, or as body-focused repetitive behaviors. This chapter will discuss these diagnostic and taxonomic issues particularly as they pertain to clinical practice, fostering further discussion on the psychopathology of aberrant grooming behaviors. Introduction The positioning of TTM and other conditions characterized by self-directed repetitive behaviors (e.g., nail biting and pathological skin picking [PSP]) within existing psychiatric classification systems has recently been debated (e.g., Stein et al . 2007). Trichotillomania is classified in the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; APA, 2000) as an impulse control disorder. However, some researchers suggest that TTM is an OCSD (Swedo and Leonard 1992).

Social anxiety disorder (SAD) is a prevalent, disabling disorder. We aimed to assess the effects of pharmacotherapy for SAD and to determine whether particular classes of medication are more effective and/or better tolerated than others. A systematic review and meta-analysis was conducted of all published and unpublished placebo-controlled randomized controlled trials (RCTs) undertaken between 1966 and 2007. A rigorous search, which included searching the Cochrane CCDANTR, MEDLINE and PsycINFO electronic databases, yielded a total of 51 RCTs (9914 participants) considered eligible for inclusion in the review. On average, over half of trial participants responded to medication, as assessed with the improvement item of the Clinical Global Impressions scale (55.2%), with approximately four participants having to be treated for an average of 12 weeks before an additional person responded to medication, relative to placebo (number needed to benefit = 4.19). There was substantial variation across medication classes in the number of dropouts due to adverse events, with an average number needed to harm of 14.4. Maintenance and relapse prevention studies confirm the value of longer-term medication in treatment responders. Medication was also effective in reducing SAD symptoms, comorbid depressive symptoms and associated disability. However, evidence for the efficacy of beta-blockers in treating performance anxiety was lacking. Taken together, trials of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors provide the largest evidence base for agents that are both effective and well tolerated. This review is an updated version of a Cochrane Review in The Cochrane Library, Issue 4, 2004. Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review.

Convincing evidence from placebo-referenced randomized controlled trials supports efficacy for clomipramine and selective serotonin reuptake inhibitors for acute treatment of obsessive-compulsive disorder. It remains less conclusively understood whether these agents maintain efficacy over the longer term. This paper systematically reviews long-term medication studies in obsessive-compulsive disorder. Studies of clomipramine, fluoxetine and sertraline investigated 'responders' from acute treatment trials and extended treatment up to 12 months versus placebo. Responses to medication were sustained. A 24-week placebo-controlled trial of escitalopram (10 mg or 20 mg/day) and paroxetine (40 mg/day) demonstrated ongoing efficacy for all three treatments. Studies that randomized treated cases to placebo demonstrated reemergence of symptoms in the placebo-treated cohort. Six relapse prevention trials were found by systematic search. Some, but not all, revealed significant advantages for remaining on medication. Paroxetine (20-60 mg/day) and escitalopram (10 or 20 mg/day) were each found to outperform placebo in preventing relapse during 24 weeks of double-blind, randomized follow-up. Meta-analysis, using Review Manager software (4.2.8), detected overall superiority of selective serotonin reuptake inhibitors to placebo in preventing relapse among adult treatment-responders. Worsening by five Yale-Brown Obsessive Compulsive Scale points emerged from the review as a suggested threshold for relapse. Viewed collectively, these results suggest that selective serotonin reuptake inhibitors are effective long-term treatments and relapse prevention represents the treatment target for obsessive-compulsive disorder.

The opioid systems play an important role in mediating both physical pain and negative affects (eg, the pain of social isolation). From an evolutionary perspective, it is not surprising that the neurocircuitry and neurochemistry of physical pain would overlap with that involved in complex social emotions. Exposure to trauma as well as a range of gene variants in the opioid system may be associated with alterations in opioid systems function, with changes in reward processing, and with vulnerability to substance abuse. A role for interventions with opioid agents in depression and anxiety disorders has been suggested.