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Background: The finding that transcranial magnetic stimulation (TMS) can enhance memory performance via stimulation of parietal sites within the Cortical-Hippocampal Network counts as one of the most exciting findings in this field in the past decade. However, the first independent effort aiming to fully replicate this finding found no discernible influence of TMS on memory performance., Objective: We examined whether this might relate to interindividual spatial variation in brain connectivity architecture, and the capacity of personalisation methodologies to overcome the noise inherent across independent scanners and cohorts., Methods: We implemented recently detailed personalisation methodology to retrospectively compute individual-specific parietal targets and then examined relation to TMS outcomes., Results: Closer proximity between actual and novel fMRI-personalized targets associated with greater improvement in memory performance., Conclusion: These findings demonstrate the potential importance of aligning brain stimulation targets according to individual-specific differences in brain connectivity, and extend upon recent findings in prefrontal cortex., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure and response prevention (ERP) is the current first-line psychological treatment for Obsessive-compulsive disorder (OCD). However, substantial inter-individual variability exists in treatment outcomes, including inadequate symptom improvements, and notable refusal and attrition rates. These are driven, in part, by impracticalities in simulating intrusive thoughts within clinical settings. Virtual reality (VR) offers the potential of overcoming these limitations in a manner that allows for finely controlled anxiety-provoking scenarios to be created within supportive clinical settings. To validate the potential of VR for treating contamination-based OCD, 22 patients undertook a VR ERP session and a matched session of the current gold-standard of in vivo ERP. In VR, patients were immersed within a contamination environment that permitted flexible delivery of customisable, graded exposure tasks. The VR environment utilised HTC Vive hardware, to allow for patients to both interact with, and physically move through the environment. Subjective and objective measures of distress were recorded, including heart and respiration rates. These measures indicate virtual and in vivo ERP sessions provoke consistent anxiety profiles across an exposure hierarchy. Virtual exposure was advantageous for engagement and adherence to tasks, and the therapeutic alliance was upheld. VR is a promising mechanism for ERP in contamination OCD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Gender-related differences in the susceptibility, progression and clinical outcomes of alcohol dependence are well-known. However, the neurobiological substrates underlying such differences remain unclear. Therefore, this study aimed to investigate gender differences in the neuroanatomy (i.e. regional brain volumes) of alcohol dependence. We examined the volume of a priori regions of interest (i.e., orbitofrontal cortex, hippocampus, amygdala, nucleus accumbens, caudate, putamen, pallidum, thalamus, corpus callosum, cerebellum) and global brain measures (i.e., total grey matter (GM), total white matter (WM) and cerebrospinal fluid). Volumes were compared between 660 people with alcohol dependence (228 women) and 326 controls (99 women) recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age and education years. Compared to controls, individuals with alcohol dependence on average had (3-9%) smaller volumes of the hippocampus (bilateral), putamen (left), pallidum (left), thalamus (right), corpus callosum, total GM and WM, and cerebellar GM (bilateral), the latter more prominently in women (right). Alcohol-dependent men showed smaller amygdala volume than control men, but this effect was unclear among women. In people with alcohol dependence, more monthly standard drinks predicted smaller amygdala and larger cerebellum GM volumes. The neuroanatomical differences associated with alcohol dependence emerged as gross and widespread, while those associated with a specific gender may be confined to selected brain regions. These findings warrant future neuroscience research to account for gender differences in alcohol dependence to further understand the neurobiological effects of alcohol dependence., (Copyright © 2021. Published by Elsevier Inc.)

Background and Objectives: Neurocognitive processes are key drivers of addictive and compulsive disorders. The current study examined whether reward-related attentional capture and cognitive inflexibility are associated with impulsive and/or compulsive personality traits, and whether these cognitive characteristics interact to predict greater compulsivity-related problems across obsessive-compulsive and drinking behaviors., Methods: One-hundred and seventy-three participants (mean age = 34.5 years, S.D = 8.4, 42% female) completed an online visual search task to measure reward-related attentional capture and its persistence following reversal of stimulus-reward contingencies. Participants also completed questionnaires to assess trait impulsivity, compulsivity, alcohol use, and obsessive-compulsive behaviors., Results: Greater reward-related attentional capture was associated with trait compulsivity, over and above all impulsivity dimensions, while greater cognitive inflexibility was associated with higher negative urgency (distress-elicited impulsivity). Reward-related attentional capture and cognitive inflexibility interacted to predict greater compulsivity-related problems among participants who reported obsessive-compulsive behaviors in the past month (n = 57) as well as current drinkers (n = 88). Follow-up analyses showed that, for OCD behaviors, this interaction was driven by an association between higher reward-related attentional capture and more problematic behaviors among cognitively inflexible participants only. For drinking, the same pattern was seen, albeit at trend level., Limitations: This study includes a non-clinical, online sample and is cross-sectional, thus its findings need to be interpreted with these limitations in mind., Conclusions: Reward-related attentional capture and cognitive flexibility are related to trait compulsivity and impulsivity (negative urgency) respectively, and interact to determine more problematic behaviors., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent neuroimaging studies in OCD have reported structural alterations in the brain, not limited to frontostriatal regions. While Diffusion Tensor Imaging (DTI) is typically used to interrogate WM microstructure in OCD, additional imaging metric, such as Magnetization Transfer Imaging (MTI), allows for further identification of subtle but important structural changes across both GM and WM. In this study, both MTI and DTI were utilised to investigate the structural integrity of the brain, in OCD in relation to healthy controls. 38 adult OCD patients were recruited, along with 41 age- and gender-matched controls. Structural T1, MTI and DTI data were collected. Case-control differences in Magnetization Transfer Ratio (MTR) and DTI metrics (FA, MD) were examined, along with MTR/DTI-related associations with symptom severity in patients. No significant group differences were found across MTR, FA, and MD. However, OCD symptom severity was positively correlated with MTR in a distributed network of brain regions, including the striatum, cingulate, orbitofrontal area and insula. Within the same regions, OCD symptoms were also positively correlated with FA in WM, and negatively correlated with MD in GM. These results indicate a greater degree of myelination in certain cortical and subcortical regions in the more severe cases of OCD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cannabis exerts its psychoactive effect through cannabinoid receptors that are widely distributed across the cortical surface of the human brain. It is suggested that cannabis use may contribute to structural alterations across the cortical surface. In a large, multisite dataset of 120 controls and 141 cannabis users, we examined whether differences in key characteristics of the cortical surface - including cortical thickness, surface area, and gyrification index were related to cannabis use characteristics, including (i) cannabis use vs. non-use, (ii) cannabis dependence vs. non-dependence vs. non-use, and (iii) early adolescent vs. late adolescent onset of cannabis use vs. non-use. Our results revealed that cortical morphology was not associated with cannabis use, dependence, or onset age. The lack of effect of regular cannabis use, including problematic use, on cortical structure in our study is contrary to previous evidence of cortical morphological alterations (particularly in relation to cannabis dependence and cannabis onset age) in cannabis users. Careful reevaluation of the evidence on cannabis-related harm will be necessary to address concerns surrounding the long-term effects of cannabis use and inform policies in a changing cannabis regulation climate., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

Background: Error processing and inhibitory control enable the adjustment of behaviors to meet task demands. Functional magnetic resonance imaging studies report brain activation abnormalities in patients with obsessive-compulsive disorder (OCD) during both processes. However, conclusions are limited by inconsistencies in the literature and small sample sizes. Therefore, the aim here was to perform a meta-analysis of the existing literature using unthresholded statistical maps from previous studies., Methods: A voxelwise seed-based d mapping meta-analysis was performed using t-maps from studies comparing patients with OCD and healthy control subjects (HCs) during error processing and inhibitory control. For the error processing analysis, 239 patients with OCD (120 male; 79 medicated) and 229 HCs (129 male) were included, while the inhibitory control analysis included 245 patients with OCD (120 male; 91 medicated) and 239 HCs (135 male)., Results: Patients with OCD, relative to HCs, showed longer inhibitory control reaction time (standardized mean difference = 0.20, p = .03, 95% confidence interval = 0.016, 0.393) and more inhibitory control errors (standardized mean difference = 0.22, p = .02, 95% confidence interval = 0.039, 0.399). In the brain, patients showed hyperactivation in the bilateral dorsal anterior cingulate cortex, supplementary motor area, and pre-supplementary motor area as well as right anterior insula/frontal operculum and anterior lateral prefrontal cortex during error processing but showed hypoactivation during inhibitory control in the rostral and ventral anterior cingulate cortices and bilateral thalamus/caudate, as well as the right anterior insula/frontal operculum, supramarginal gyrus, and medial orbitofrontal cortex (all seed-based d mapping z value >2, p < .001)., Conclusions: A hyperactive error processing mechanism in conjunction with impairments in implementing inhibitory control may underlie deficits in stopping unwanted compulsive behaviors in the disorder., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The current study examined amygdala and orbitofrontal cortex (OFC) volumes as mediators of the relationship between externalizing symptoms and daily smoking in adolescence. Externalizing behaviors are among the most robust predictors of adolescent smoking, and there is emerging evidence that volume reductions in the amygdala and OFC are associated with risk for substance misuse as well as aggressive, impulsive, and disinhibited tendencies. Using a prospective longitudinal design, we recruited 109 adolescents who provided data on brain volume and externalizing behaviors at age 12, and on smoking at age 18. Daily smoking at age 18 (n = 27) was predicted by externalizing behaviors (measured by the self-report Child Behavior Checklist, CBCL) as well as smaller right amygdala volumes. Right amygdala volumes mediated the relationship between externalizing symptoms and later smoking. These findings provide important insight into the neurobiological risk factors associated with adolescent smoking, and, more generally, into factors that may be associated with vulnerability to substance use disorders and related psychopathology., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Dopaminergic medication can induce severe addictive behaviours (e.g., pathological gambling) in susceptible Parkinson's disease (PD) patients. It is still unknown which particular neurocognitive processes become exacerbated or dysfunctional in PD patients with addictive behaviours. We sought to systematically review the relevant literature to identity potential neurocognitive correlates of medication-induced addictive behaviours in PD. We framed our review around neurocognitive processes central to four dominant accounts of substance addiction: 'aberrant learning', 'incentive sensitization', 'impulsivity to compulsivity' and 'impaired response inhibition and salience attribution'. Searches of the PubMed and Scopus databases were completed on June 23, 2017. To be included, studies were required to involve: (a) medicated PD patients, without a history of deep brain stimulation, with and without addictive behaviours; (b) a reward-related or decision-making task; and (c) statistical comparison of addictive and non-addictive groups' 'on' medication performance on the task(s). Studies were summarised qualitatively with statistically significant (p<.05) group differences and effect sizes (Cohen's d) highlighted. 35 studies were included. Findings showed that the extant literature is highly heterogeneous. The domains of reward and punishment learning, reflection impulsivity and disadvantageous decision-making exemplify this. More homogeneity exists in domains in which (a) neurocognitive dysfunction is not apparent (motor control, cognitive/attentional flexibility and cognitive control) or (b) typical neurocognitive processes appear exacerbated by medication (reward motivation and choice impulsivity). Future large-scale neurocognitive studies are still required to develop our scientific understanding of addictive behaviours in PD and aid their clinical treatment and prediction., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

Magnetic resonance spectroscopy (MRS) was utilized to investigate sex differences in gamma-aminobutyric acid (GABA) between adults with autism spectrum disorder (ASD) and neurotypical (NT) controls. GABA at the right superior temporal sulcus (STS) is reported for 12 ASD and 14 NT participants. The results show no group differences in GABA. There was, however, a significant positive association between GABA at the STS and autism-related social impairments in females with ASD. These findings provide preliminary support for sex differences in GABAergic distribution and processes that contribute to social functioning in ASD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Patients with obsessive-compulsive disorder (OCD) exhibit abnormal neural responses when they experience particular emotions or when they evaluate stimuli with emotional value. Whether these brain responses are sufficiently distinctive to discriminate between OCD patients and healthy controls is unknown. The present study is the first to investigate the discriminative power of multivariate pattern analysis of regional fMRI responses to moral and non-moral emotions., Method: To accomplish this goal, we performed a searchlight-based multivariate pattern analysis to unveil brain regions that could discriminate 18 OCD patients from 18 matched healthy controls during provoked guilt, disgust, compassion, and anger. We also investigated the existence of distinctive neural patterns while combining those four emotions (herein termed multiemotion analysis)., Results: We found that different frontostriatal regions discriminated OCD patients from controls based on individual emotional experiences. Most notably, the left nucleus accumbens (NAcc) discriminated OCD patients from controls during both disgust and the multiemotion analysis. Among other regions, the angular gyrus responses to anger and the lingual and the middle temporal gyri in the multi-emotion analysis were highly discriminant between samples. Additional BOLD analyses supported the directionality of these findings., Conclusions: In line with previous studies, differential activity in regions beyond the frontostriatal circuitry differentiates OCD from healthy volunteers. The finding that the response of the left NAcc to different basic and moral emotions is highly discriminative for a diagnosis of OCD confirms current pathophysiological models and points to new venues of research.

Drug use is a choice with immediate positive outcomes, but long-term negative consequences. Thus, the repeated use of drugs in the face of negative consequences suggests dysfunction in the cognitive mechanisms underpinning decision-making. This cognitive dysfunction can be mapped into three stages: the formation of preferences involving valuation of decision options; choice implementation including motivation, self-regulation and inhibitory processes; and feedback processing implicating reinforcement learning. This article reviews behavioral studies that have examined alterations in these three stages of decision-making in people with substance use disorders. Relative to healthy individuals, those with alcohol, cannabis, stimulant and opioid use disorders value risky options more highly during the formation of preferences; have a greater appetite for superficially attractive rewards during choice implementation; and are both more efficient in learning from rewards and less efficient in learning from losses during feedback processing. These observed decision-making deficits are most likely due to both premorbid factors and drug-induced effects. Because decision-making deficits have been prospectively associated with a greater risk of drug relapse, we advocate for greater research on modulating the component stages that give rise to dysfunctional decision-making in disorders of addiction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Anhedonia is prevalent among substance-dependent populations. The hedonic allostasis model suggests this is due to the effects of addictive substances on neural substrates of reward processing. However, previous research may have been confounded by other factors likely to influence anhedonia, including tobacco use, psychopathology, and history of trauma and other stressors. Thus it remains unclear whether elevated anhedonia in substance-dependent populations is caused by substance use itself, or is due to other correlates of substance dependence., Methods: Multivariate analysis of covariance was conducted to test whether opioid-dependent participants' anhedonia scores were elevated, relative to a non-dependent control group, after controlling for psychosocial factors likely to influence anhedonia. Correlational analyses within opioid-dependent participants were also conducted to examine whether anhedonia was associated with recent illicit opioid use or duration of abstinence., Results: There was a modest, but significant, elevation in anhedonia in opioid-dependent participants, relative to controls (Partial η 2 =0.034, p=0.041) after controlling for psychosocial variables that were associated with anhedonia. Depressive symptoms and history of post-traumatic stress disorder also remained significantly associated with anhedonia in the adjusted model. Among participants on opioid pharmacotherapy, there were significant associations between frequency of recent illicit opioid use and scores on anhedonia measures (all r s >0.25, p<0.013), but among abstinent opioid-dependent participants, relationships between duration of abstinence and anhedonia were not significant (all r s <0.24, p>0.22)., Conclusion: These findings support the hypothesis that use of opioids can cause anhedonia, although other psychosocial factors may also contribute to the high prevalence of anhedonia among opioid-dependent populations., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Most evidence for structural brain abnormalities associated with adolescent depression is based on cross-sectional study designs that do not take into account the dynamic course of depressive symptoms and brain maturation across adolescence. In this study, a longitudinal design was used to investigate the association between different trajectories of depressive symptoms and longitudinal changes in brain structure throughout adolescence., Method: One hundred forty-nine adolescents were assessed on depressive symptoms and underwent structural magnetic resonance imaging at 12 years of age and were followed up multiple times until 19 years. Three depressive symptom trajectories (low-stable [n = 97], early-decreasing [n = 33], late-increasing [n = 19]) were identified, and effects of group and group by time on hippocampus and amygdala volume and prefrontal cortical thickness and surface area were evaluated., Results: The early-decreasing symptoms group exhibited differences in cortical surface area compared to the low-stable and late-increasing symptoms groups, moderated by sex. Specifically, females in the early-decreasing symptoms group showed lower anterior cingulate and orbitofrontal cortex surface areas across adolescence compared to females in the other groups. Males in the early-decreasing symptoms group showed lower right orbitofrontal cortex surface area expansion over time compared to males in the low-stable and late-increasing symptoms groups. No effects were found for cortical thickness or for hippocampus and amygdala volume., Conclusion: Alterations in cortical surface area were specifically observed in young people experiencing depressive symptoms in early adolescence. These findings suggest that early adolescence is a particularly sensitive period for cortical surface area abnormalities associated with depressive symptoms and could provide a critical window for treatment of (subthreshold) depressive symptoms., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Neuroscientific explanations of gambling disorder can help people make sense of their experiences and guide the development of psychosocial interventions. However, the societal perceptions and implications of these explanations are not always clear or helpful. Two workshops in 2013 and 2014 brought together multidisciplinary researchers aiming to improve the clinical and policy-related effects of neuroscience research on gambling. The workshops revealed that neuroscience can be used to improve identification of the dangers of products used in gambling. Additionally, there was optimism associated with the diagnostic and prognostic uses of neuroscience in problem gambling and the provision of novel tools (eg, virtual reality) to assess the effectiveness of new policy interventions before their implementation. Other messages from these workshops were that neuroscientific models of decision making could provide a strong rationale for precommitment strategies and that interdisciplinary collaborations are needed to reduce the harms of gambling., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Olfactory deficits have been reported in major depressive disorder (MDD). However, it remains largely unknown whether MDD is associated with abnormalities in olfactory sulcus morphology, a potential marker of olfactory system development. This magnetic resonance imaging study investigated the length and depth of the olfactory sulcus in 29 currently depressed patients, 27 remitted depressed patients, and 33 age- and gender-matched healthy control subjects. Both current and remitted MDD patients had significantly shallower olfactory sulci bilaterally as compared with controls. Only for male subjects, the right olfactory sulcus was significantly shorter in remitted MDD patients than in controls. The right sulcus depth was negatively correlated with number of depressive episodes in the entire MDD group and with residual depressive symptoms in the remitted MDD group. Medication status, presence of melancholia, and comorbidity with anxiety disorders did not affect the sulcus morphology. These findings suggest that abnormality of the olfactory sulcus morphology, especially its depth, may be a trait-related marker of vulnerability to major depression., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users. However, the evidence has been mixed and contested, and no systematic reviews of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings. We systematically review the empirical research published in the past decade (from January 2004 to February 2015) on acute and chronic effects of cannabis and cannabinoids and on persistence or recovery after abstinence. We summarize the findings into the major categories of the cognitive domains investigated, considering sample characteristics and associations with various cannabis use parameters. Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis. Psychomotor function is most affected during acute intoxication, with some evidence for persistence in chronic users and after cessation of use. Impaired verbal memory, attention, and some executive functions may persist after prolonged abstinence, but persistence or recovery across all cognitive domains remains underresearched. Associations between poorer performance and a range of cannabis use parameters, including a younger age of onset, are frequently reported. Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis. Evidence for potential protection from harmful effects by cannabidiol continues to increase but is not definitive. In light of increasing trends toward legalization of cannabis, the knowledge gained from this body of research needs to be incorporated into strategies to minimize harm., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The past few decades have seen a marked change in the composition of commonly smoked cannabis. These changes primarily involve an increase of the psychoactive compound ∆(9)-tetrahydrocannabinol (THC) and a decrease of the potentially therapeutic compound cannabidiol (CBD). This altered composition of cannabis may be linked to persistent neuroanatomic alterations typically seen in regular cannabis users. In this review, we summarize recent findings from human structural neuroimaging investigations. We examine whether neuroanatomic alterations are 1) consistently observed in samples of regular cannabis users, particularly in cannabinoid receptor-high areas, which are vulnerable to the effects of high circulating levels of THC, and 2) associated either with greater levels of cannabis use (e.g., higher dosage, longer duration, and earlier age of onset) or with distinct cannabinoid compounds (i.e., THC and CBD). Across the 31 studies selected for inclusion in this review, neuroanatomic alterations emerged across regions that are high in cannabinoid receptors (i.e., hippocampus, prefrontal cortex, amygdala, cerebellum). Greater dose and earlier age of onset were associated with these alterations. Preliminary evidence shows that THC exacerbates, whereas CBD protects from, such harmful effects. Methodologic differences in the quantification of levels of cannabis use prevent accurate assessment of cannabis exposure and direct comparison of findings across studies. Consequently, the field lacks large "consortium-style" data sets that can be used to develop reliable neurobiological models of cannabis-related harm, recovery, and protection. To move the field forward, we encourage a coordinated approach and suggest the urgent development of consensus-based guidelines to accurately and comprehensively quantify cannabis use and exposure in human studies., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

We assessed correlates of obsessive-compulsive (OCPD), schizotypal (SPD) and borderline (BPD) personality disorders in 110 obsessive-compulsive disorder (OCD) patients. We found OCD patients with OCPD (20.9%) to exhibit higher rates of hoarding and bipolar disorders, increased severity of hoarding and symmetry, lower prevalence of unacceptable thoughts involving sex and religion and less non-planning impulsivity. Conversely, OCD patients with SPD (13.6%) displayed more frequently bipolar disorder, increased severity of depression and OCD neutralization, greater prevalence of "low-order" behaviors (i.e., touching), lower low-planning impulsivity and greater "behavioral" compulsivity. Finally, in exploratory analyses, OCD patients with BPD (21.8%) exhibited lower education, higher rates of several comorbid psychiatric disorders, greater frequency of compulsions involving interpersonal domains (e.g. reassurance seeking), increased severity of depression, anxiety and OCD dimensions other than symmetry and hoarding, more motor and non-planning impulsivity, and greater "cognitive" compulsivity. These findings highlight the importance of assessing personality disorders in OCD samples., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study investigated the relationship between the development of effortful control (EC), a temperamental measure of self-regulation, and concurrent development of three regions of the prefrontal cortex (anterior cingulate cortex, ACC; dorsolateral prefrontal cortex, dlPFC; ventrolateral prefrontal cortex, vlPFC) between early- and mid-adolescence. It also examined whether development of EC mediated the relationship between cortical maturation and emotional and behavioral symptoms. Ninety-two adolescents underwent baseline assessments when they were approximately 12 years old and follow-up assessments approximately 4 years later. At each assessment, participants had MRI scans and completed the Early Adolescent Temperament Questionnaire-Revised, as well as measures of depressive and anxious symptoms, and aggressive and risk taking behavior. Cortical thicknesses of the ACC, dlPFC and vlPFC, estimated using the FreeSurfer software, were found to decrease over time. EC also decreased over time in females. Greater thinning of the left ACC was associated with less reduction in EC. Furthermore, change in effortful control mediated the relationship between greater thinning of the left ACC and improvements in socioemotional functioning, including reductions in psychopathological symptoms. These findings highlight the dynamic association between EC and the maturation of the anterior cingulate cortex, and the importance of this relationship for socioemotional functioning during adolescence., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The hippocampus and amygdala have received much attention with regard to the deleterious effects of childhood maltreatment. However, it is not known if and when these effects emerge during adolescence and whether comorbid psychopathology is more likely to explain these effects. This study investigated whether childhood maltreatment was associated with hippocampal and amygdala development from early to midadolescence and whether the experience of psychopathology during this period mediated the relation., Method: One hundred seventeen (60 male) adolescents, recruited as part of a broader adolescent development study, participated in magnetic resonance imaging assessments during early and midadolescence (mean age at baseline 12.62 years, SD 0.44 years; mean follow-up period 3.78 years, SD 0.20 years), and completed self-report measurements of childhood maltreatment and diagnostic interviews assessing DSM-IV mental disorders., Results: Childhood maltreatment was associated with larger baseline left hippocampal volumes and retarded growth of the left amygdala over time and was indirectly associated, through the experience of psychopathology, with retarded growth of the left hippocampus and accelerated growth of the left amygdala over time. Exploratory cortical analysis showed that maltreatment influenced thickening of the superior parietal region through the experience of psychopathology., Conclusions: Childhood maltreatment was associated with altered brain development during adolescence. The experience of Axis I psychopathology during adolescence may be one mechanism by which childhood maltreatment has continuing effects on brain development during the adolescent years. These findings highlight the importance of early intervention for individuals who have experienced childhood maltreatment., (Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: There is growing evidence that long-term, heavy cannabis use is associated with alterations in regional brain volumes. Although these changes are frequently attributed to the neurotoxic effects of cannabis, it is possible that some abnormalities might predate use and represent markers of vulnerability. To date, no studies have examined whether structural brain abnormalities are present before the onset of cannabis use. This study aims to determine whether adolescents who have initiated cannabis use early (i.e., before age 17 years) show premorbid structural abnormalities in the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex., Methods: Participants (n = 121) were recruited from primary schools in Melbourne, Australia, as part of a larger study examining adolescent emotional development. Participants underwent structural magnetic resonance imaging at age 12 years and were assessed for cannabis use 4 years later, at age 16 years. At the follow-up assessment, 28 participants had commenced using cannabis (16 female subjects [57%]), and 93 had not (43 female subjects [46%])., Results: Smaller orbitofrontal cortex volumes at age 12 years predicted initiation of cannabis use by age 16 years. The volumes of other regions (amygdala, hippocampus, and anterior cingulate cortex) did not predict later cannabis use., Conclusions: These findings suggest that structural abnormalities in the orbitofrontal cortex might contribute to risk for cannabis exposure. Although the results have important implications for understanding neurobiological predictors of cannabis use, further research is needed to understand their relationship with heavier patterns of use in adulthood as well as later abuse of other substances., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

We evaluated whether traumatic events are associated with a distinctive pattern of socio-demographic and clinical features of obsessive-compulsive disorder (OCD). We compared socio-demographic and clinical features of 106 patients developing OCD after post-traumatic stress disorder (PTSD; termed post-traumatic OCD), 41 patients developing OCD before PTSD (pre-traumatic OCD), and 810 OCD patients without any history of PTSD (non-traumatic OCD) using multinomial logistic regression analysis. A later age at onset of OCD, self-mutilation disorder, history of suicide plans, panic disorder with agoraphobia, and compulsive buying disorder were independently related to post-traumatic OCD. In contrast, earlier age at OCD onset, alcohol-related disorders, contamination-washing symptoms, and self-mutilation disorder were all independently associated with pre-traumatic OCD. In addition, patients with post-traumatic OCD without a previous history of obsessive-compulsive symptoms (OCS) showed lower educational levels, greater rates of contamination-washing symptoms, and more severe miscellaneous symptoms as compared to post-traumatic OCD patients with a history of OCS., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Studies of depressed patients have demonstrated increased amygdala activation to negative affective stimuli. In this study, we used a paradigm that employed personally relevant social stimuli, which are known to strongly activate the amygdala, to test whether the amygdala demonstrated aberrant activity in depressed participants as they responded to stimuli with positive valence., Methods: Nineteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. They completed a novel functional magnetic resonance imaging task in which they received social feedback from people who they believed had evaluated them. Voxelwise statistical parametric maps of brain response to positive social feedback and to a control feedback condition were compared to test the hypothesis that differences in neural response between depressed and control participants would arise in the amygdala., Results: Depressed participants showed increased neural response to the positive- versus control-feedback condition in the amygdala (p < .05, corrected). An exploratory analysis showed that depressed participants responded to faces from both feedback conditions with increased activity in regions subserving social appraisal (ventrolateral prefrontal cortex and inferior parietal cortex) and affective processing (pregenual anterior cingulate cortex and anterior insular cortex; p < .001, uncorrected)., Conclusions: Depressed patients responded to positive social feedback with increased amygdala activation, demonstrating that amygdala hyperresponsivity in depression is not restricted to negatively-valenced stimuli. The heightened sensitivity of depressed participants to social evaluation may help explain symptoms of depression such as social withdrawal., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

While long-term heroin addiction is associated with hypothalamus-pituitary-adrenal (HPA) axis dysregulation, few studies have used in vivo brain imaging to examine the impact on pituitary gland volume (PGV) or its relationship with substitution pharmacotherapy. We examined 28 heroin users stable on methadone or buprenorphine and 28 healthy controls. Heroin users exhibited larger PGVs than healthy controls, and this was particularly evident among the buprenorphine-treated group. These findings indicate that substitution pharmacotherapy may have differential effects on normalising HPA axis activity., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: We conducted a meta-analysis of gray matter abnormalities in bipolar disorder (BD) using voxel-based morphometry studies to help clarify the structural abnormalities underpinning this condition., Methods: A systematic review was conducted for voxel-based morphometry studies of patients with BD. Meta-analyses of gray matter differences between BD and control subjects were undertaken using "signed differential mapping," a novel method that, in contrast to previously used techniques, allows inclusion of negative findings and ensures that single studies do not exert undue influence on the results. Meta-regression and subgroup analyses were used to examine the effect of moderator variables on gray matter abnormalities., Results: A total of 21 studies comparing gray matter volumes of 660 BD patients and 770 healthy control subjects were included. Gray matter reduction in left rostral anterior cingulate cortex (ACC) and right fronto-insular cortex was associated with BD. Fronto-insular cortex abnormality was not evident in early phases of the illness. In chronic patients, longer duration of illness was associated with increased gray matter in a cluster that included basal ganglia, subgenual ACC, and amygdala. Lithium treatment was associated with enlargement of ACC gray matter volumes, which overlapped with the region where gray matter was reduced in BD., Conclusions: The most robust gray matter reductions in BD occur in anterior limbic regions, which may be related to the executive control and emotional processing abnormalities seen in this patient population. Clinical factors such as illness duration and lithium treatment also impact on case-control comparisons of gray matter volume., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis., Methods: Participants underwent baseline magnetic resonance imaging and were followed-up over 12-24 months to ascertain diagnostic outcomes. Baseline ACC morphometry was then compared between UHR individuals who developed psychosis (UHR-P; n = 35), those who did not (UHR-NP; n = 35), and healthy control subjects (n = 33)., Results: Relative to control subjects, UHR-P individuals displayed bilateral thinning of a rostral paralimbic ACC region that was negatively correlated with negative symptoms, whereas UHR-NP individuals displayed a relative thickening of dorsal and rostral limbic areas that was correlated with anxiety ratings. Baseline ACC differences between the two UHR groups predicted time to psychosis onset, independently of symptomatology. Subdiagnostic comparisons revealed that changes in the UHR-P group were driven by individuals subsequently diagnosed with a schizophrenia spectrum psychosis., Conclusions: These findings indicate that anatomic abnormalities of the ACC precede psychosis onset and that baseline ACC differences distinguish between UHR individuals who do and do not subsequently develop frank psychosis. They also indicate that prepsychotic changes are relatively specific to individuals who develop a schizophrenia spectrum disorder, suggesting they may represent a diagnostically specific risk marker.

Objective: Temperament refers to enduring behavioral characteristics that underpin individual differences in human behavior, including risk for psychopathology. Research attempting to investigate the neurobiological basis of temperament represents an important step toward elucidating the biological mechanisms underlying these individual differences. In the present study, we examined the relation between four core temperament dimensions and anatomically defined regions of the limbic and prefrontal cortices., Method: We used a cross-sectional design to examine a large sample (N = 153; mean age 12.6 years, SD 0.4, range 11.4-13.7) of healthy early adolescents who were selected from a larger sample to maximize variation in temperament. The main outcome measures were psychometric measures of temperament (four factors: effortful control, negative affectivity, surgency, and affiliativeness) based on the Early Adolescent Temperament Questionnaire-Revised, and volumetric measures of a priori brain regions of interest (anterior cingulate cortex [ACC], orbitofrontal cortex, amygdala, and hippocampus)., Results: We found regional brain volumes to account for small but significant amounts of the variance in self-reported temperament scores. Specifically, higher effortful control was associated with larger volume of the left orbitofrontal cortex and hippocampus. Higher negative affectivity was associated with smaller volume of the left dorsal paralimbic relative to limbic portion of the ACC. Higher affiliativeness was associated with larger volume of the right rostral/ventral limbic portion of the ACC. Affiliativeness and surgency also showed a number of female-specific associations, primarily involving the rostral/ventral ACC., Conclusions: Our results provide support for a neuroanatomical basis for individual differences in temperament and have implications for understanding the neurobiological mechanisms underlying the development of a number of psychiatric disorders.

Background: Our previous work on sulcal-gyral brain morphology in healthy volunteers revealed that males were characterized by greater cortical folding in the left versus right anterior cingulate cortex. Given the evidence showing an absence or reversal of normal anatomical asymmetries in patients with schizophrenia, the current study examined the anterior cingulate cortex sulcal-gyral patterns in patients with schizophrenia., Methods: Using high-resolution magnetic resonance imaging, we examined anterior cingulate cortex surface morphology in a group of 55 patients with established schizophrenia and 75 healthy controls. All subjects were male and right-handed. Depending on the presence of a paracingulate sulcus and its antero-posterior extent, three types of anterior cingulate cortex sulcal patterns were identified: "prominent," "present," and "absent." Measures of overall cerebral hemispheric folding were used as independent variables and as covariates to ascertain the specificity of the findings to the anterior cingulate cortex., Results: Examination of anterior cingulate cortex morphology showed that, compared with controls, patients with schizophrenia lacked the leftward anterior cingulate cortex sulcal asymmetry, which was explained by reduced folding in the left anterior cingulate cortex. These differences were over and above differences in cortical folding across the entire left hemisphere., Conclusions: These findings suggest that, in male patients with schizophrenia, there is a disturbance in the neurodevelopment of the left anterior cingulate cortex, as well as a more general aberration of left hemisphere development.