Search

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire-Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults.

Contains fulltext : 221606.pdf (Publisher’s version ) (Open Access) Observability of threat-related spatial attentional biases may require previous-trial responses associated with threat-related locations. This carryover effect might affect reliability and correlations. In Study 1, a diagonalized Visual Probe Task was completed online (N=131) with colour, anger, fear and disgust stimuli, with questionnaires on aggression, anxiety, depression and impulsivity. Bias towards negative stimuli was found only following previous targets on the negative location. Study 2 aimed to test an interpretation in terms of cue-evoked attention. Task variants were completed (N=101) with and without removal of the cue when targets appeared. Anger and disgust stimuli and aggression, anxiety and depression scales were used. Carryover was replicated with no interaction with cue offset. Over both tasks, reliability was low and no robust correlations with questionnaires were found. Carryover thus determined whether attentional bias to negative facial expressions was observed, but analyses taking this into account did not improve reliability or reveal correlations. 11 p.

Self-regulation refers to the ability to monitor and modulate emotions, behavior, and cognition, which in turn allows us to achieve goals and adapt to ever changing circumstances. This trait develops from early infancy well into adulthood, and features both low-level executive functions such as reactive inhibition, as well as higher level executive functions such as proactive inhibition. Development of self-regulation is linked to brain maturation in adolescence and adulthood. However, how self-regulation in daily life relates to brain functioning in pre-adolescent children is not known. To this aim, we have analyzed data from 640 children aged 8–11, who performed a stop-signal anticipation task combined with functional magnetic resonance imaging, in addition to questionnaire data on self-regulation. We find that pre-adolescent boys and girls who display higher levels of self-regulation, are better able to employ proactive inhibitory control strategies, exhibit stronger frontal activation and more functional coupling between cortical and subcortical areas of the brain. Furthermore, we demonstrate that pre-adolescent children show significant activation in areas of the brain that were previously only associated with reactive and proactive inhibition in adults and adolescents. Thus, already in pre-adolescent children, frontal-striatal brain areas are active during self-regulatory behavior., Highlights • Children with higher levels of self-regulation employ more proactive inhibition. • During proactive inhibition, children aged 8–11 show activation in frontal-cortical areas. • Children higher in self-regulation exhibit more cortical-subcortical coupling. • Children aged 8–11 show similar brain activation as adults during inhibition.

Contains fulltext : 235990.pdf (Publisher’s version ) (Open Access) Concerns have been raised about the low reliability of measurements of spatial attentional bias via RT differences in dot-probe tasks. The anticipatory form of the bias, directed towards predicted future stimuli, appears to have relatively good reliability, reaching around 0.70. However, studies thus far have not attempted to experimentally control task-related influence on bias, which could further improve reliability. Evoking top-down versus bottom-up conflict may furthermore reveal associations with individual differences related to mental health. In the current study, a sample of 143 participants performed a predictive Visual Probe Task (predVPT) with angry and neutral face stimuli online. In this task, an automatic bias is induced via visually neutral cues that predict the location of an upcoming angry face. A task-relevant bias was induced via blockwise shifts in the likely location of target stimuli. The bias score resulting from these factors was calculated as RTs to target stimuli at locations of predicted but not actually presented angry versus neutral faces. Correlations were tested with anxiety, depression, self-esteem and aggression scales. An overall bias towards threat was found with a split-half reliability of 0.90, and 0.89 after outlier removal. Avoidance of threat in blocks with a task-relevant bias away from threat was correlated with anxiety, with correction for multiple testing. The same relationship was nominally significant for depression and low self-esteem. In conclusion, we showed high reliability of spatial attentional bias that was related to anxiety. 7 p.

Highlights • Dorsal attention network (DAN) centrality increased during stress recovery in healthy controls. • Healthy siblings of schizophrenia patients show a similar increase during stress recovery. • Bipolar disorder patients show no network changes during stress recovery., Stress is a major risk factor for the development of almost all psychiatric disorders. In addition to the acute stress response, an efficient recovery in the aftermath of stress is important for optimal resilience. Increased stress vulnerability across psychiatric disorders may therefore be related to altered trajectories during the recovery phase following stress. Such recovery trajectories can be quantified by changes in functional brain networks. This study therefore evaluated longitudinal functional network changes related to stress in healthy individuals (N = 80), individuals at risk for psychiatric disorders (healthy siblings of schizophrenia patients) (N = 39), and euthymic bipolar I disorder (BD) patients (N = 36). Network changes were evaluated before and at 20 and 90 min after onset of an experimental acute stress task (Trier Social Stress Test) or a control condition. Whole-brain functional networks were analyzed using eigenvector centrality as a proxy for network importance, centrality change over time was related to the acute stress response and recovery for each group. In healthy individuals, centrality of the dorsal attention network (DAN; p = 0.007) changed over time in relation to stress. More specifically, DAN centrality increased during the recovery phase after acute stress exposure (p = 0.020), while no DAN centrality change was observed during the initial stress response (p = 0.626). Such increasing DAN centrality during stress recovery was also found in healthy siblings (p = 0.016), but not in BD patients (p = 0.554). This study highlights that temporally complex and precise changes in network configuration are vital to understand the response to and recovery from stress.

Highlights • Test-retest reliability of structural MRI and DWI data was good. • Test-retest reliability of resting-state and task-related fMRI was moderate. • Overall, global brain measures are more reliable than local brain measures., The YOUth cohort study is a unique longitudinal study on brain development in the general population. As part of the YOUth study, 2000 children will be included at 8, 9 or 10 years of age and planned to return every three years during adolescence. Magnetic resonance imaging (MRI) brain scans are collected, including structural T1-weighted imaging, diffusion-weighted imaging (DWI), resting-state functional MRI and task-based functional MRI. Here, we provide a comprehensive report of the MR acquisition in YOUth Child & Adolescent including the test-retest reliability of brain measures derived from each type of scan. To measure test-retest reliability, 17 adults were scanned twice with a week between sessions using the full YOUth MRI protocol. Intraclass correlation coefficients were calculated to quantify reliability. Global brain measures derived from structural T1-weighted and DWI scans were reliable. Resting-state functional connectivity was moderately reliable, as well as functional brain measures for both the inhibition task (stop versus go) and the emotion task (face versus house). Our results complement previous studies by presenting reliability results of regional brain measures collected with different MRI modalities. YOUth facilitates data sharing and aims for reliable and high-quality data. Here we show that using the state-of-the art YOUth MRI protocol brain measures can be estimated reliably.

The loss of ventral striatal dopaminergic neurons in Parkinson's disease (PD) predicts an impact on the reward system. The ventrostriatal system is involved in motivational processing and its dysfunction may be related to non-motor symptoms such as depression and apathy. We previously documented that patients with PD had blunted Blood Oxygen Level Dependent functional magnetic resonance imaging (BOLD fMRI) reward task related activity during both reward anticipation (i.e., in the ventral striatum) and reward outcome (i.e., in the orbitofrontal cortex). Evidence for the modulation of brain function by dopaminergic genes in PD is limited. Genes implicated in dopamine transmission, such as the dopamine transporter gene (DAT1) may influence the clinical heterogeneity seen in PD, including reward processing. This study therefore sought to determine whether genetic differences in the DAT gene are associated with brain activity associated with response to reward in PD patients and controls. A sample of PD cases on treatment (n = 15) and non-PD controls (n = 30) from an ethnic group unique to South Africa were genotyped. We found a three-way interaction between GENOTYPE × BOLD fMRI REWARD × DIAGNOSIS [F (1, 40) = 4.666, p = 0.037, partial η2 = 0.104]. PD patients with the DAT1 homozygous 10/10 repeat genotype showed a relative decrease in orbitofrontal cortex reward outcome related activity compared to the patient group who did not have this repeat. PD patients with other genotypes showed an expected increase in orbitofrontal cortex reward outcome related activity compared to controls. Given the small sample size of the PD group with the 10/10 repeat, these results should be considered preliminary. Nevertheless, these preliminary findings highlight the potential modulation of dopamine transporter polymorphisms on orbitofrontal reward system activity in PD and highlight the need for further studies.

In the field of participatory health research (PHR) and related action research paradigms, limitations of standard ethical codes and institutional review processes have been identified. PHR is highly situational and relational, part of a hierarchical health care context and therefore ethics of care has been suggested as a helpful theoretical approach that emphasises responsibilities and relationships. The purpose of this article is to explore the value of Tronto’s second-generation ethics of care for reflection on ethical challenges experienced by academic researchers. Using the design of a collaborative auto-ethnography, this article starts from a story of a researcher who deals with dilemmas in responsibility to care for co-researchers with lived experiences during a PHR study in the field of acute psychiatric care. By analysing the challenges together with all co-researchers, using a framework of ethics of care, we discovered the importance of self-care and existential safety for an ethical PHR practice. The reflexive meta-narrative shows that the ethics of care lens is useful to untangle moral dilemmas in all participatory research-related paradigms for all engaged.

Schizophrenia is associated with frontostriatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients, indicating that these deficits are linked to a genetic vulnerability for the disorder. Frontostriatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder. However, to date, no studies have been performed to investigate frontostriatal tract connections in adolescents who are at increased familial risk for schizophrenia. In this study, we investigate the impact of familial risk on frontostriatal tract connections using diffusion tensor imaging in 27 adolescent offspring of schizophrenia patients and 32 matched control adolescents, aged 10-18 years. Mean fractional anisotropy (FA) was calculated for the tracts connecting the striatum (caudate nucleus, putamen, nucleus accumbens) and frontal cortex regions (DLPFC, medial orbital frontal cortex, inferior frontal gyrus). As expected, based on siblings data, we found an impact of familial risk on frontostriatal development: schizophrenia offspring showed increased FA in the tracts connecting nucleus accumbens and DLPFC as compared with control adolescents. Moreover, while FA increased across age in control adolescents, it did not in schizophrenia offspring. We did not find differences in FA in other frontostriatal tracts. These results indicate altered development of white matter in subjects who are at familial risk for schizophrenia and may precede frontostriatal white matter alterations in adult schizophrenia patients and siblings.

Stress is a major risk factor for almost all psychiatric disorders, however, the underlying neurobiological mechanisms remain largely elusive. In healthy individuals, a successful stress response involves an adequate neuronal adaptation to a changing environment. This adaptive response may be dysfunctional in vulnerable individuals, potentially contributing to the development of psychopathology. In the current study, we investigated brain responses to emotional stimuli following stress in healthy controls and at-risk individuals. An fMRI study was conducted in healthy male controls (N = 39) and unaffected healthy male siblings of schizophrenia patients (N = 39) who are at increased risk for the development of a broad range of psychiatric disorders. Brain responses to pictures from the International Affective Picture System (IAPS) were measured 33 min after exposure to stress induced by the validated trier social stress test (TSST) or a control condition. Stress-induced levels of cortisol, alpha-amylase, and subjective stress were comparable in both groups. Yet, stress differentially affected brain responses of schizophrenia siblings versus controls. Specifically, control subjects, but not schizophrenia siblings, showed reduced brain activity in key nodes of the default mode network (PCC/precuneus and mPFC) and salience network (anterior insula) as well as the STG, MTG, MCC, vlPFC, precentral gyrus, and cerebellar vermis in response to all pictures following stress. These results indicate that even in the absence of a psychiatric disorder, at-risk individuals display abnormal functional activation following stress, which in turn may increase their vulnerability and risk for adverse outcomes.

Background Studies of pre-and post-treatment striatal volume in schizophrenia have reported conflicting results. Materials and methods We assessed dorsal striatal (caudate and putamen) volumes bilaterally in 22 never-treated, non-substance-abusing patients with first-episode schizophrenia or schizophreniform disorder and 23 healthy controls matched for age, sex and educational status. Patients received either risperidone or flupenthixol long acting injection and were compared by structural MRI with controls at weeks 0, 4 and 13. T1-weighted data on a 3T MRI scanner were obtained and images were reconstructed using FreeSurfer. Treatment outcome was assessed by changes in psychopathology, insight, functionality, cognitive performance and motor symptoms. Results Caudate, but not putamen volumes was significantly larger in patients bilaterally at baseline (P = 0.01). Linear mixed effects repeated measures found no significant group × time interactions for any of the regions. Caudate volume was not significantly associated with improvements in psychotic symptoms. Also, the findings of a regression model were inconsistent insofar as larger caudate volume was associated with less improvement in depression scores, greater improvement in functionality and greater improvement in verbal learning but less improvement in reasoning and problem solving (left caudate) and composite cognitive score (right caudate). Conclusions The increased caudate volumes prior to treatment are contrary to previous reports in never-treated patients with first-episode schizophrenia, and together with our failure to demonstrate volume changes related to acute treatment, call into question previous proposals that enlarged caudate volume is a consequence of antipsychotic treatment.

The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with frontostriatal dysfunction. While frontostriatal systems play a key role in behavioral inhibition, there are to our knowledge no fMRI studies investigating the potential impact of HIV on systems involved during the inhibition of voluntary movement. A total of 17 combined antiretroviral therapy (cART) naïve HIV+ participants as well as 18 age, gender, ethnic, education matched healthy controls performed a modified version of the stop-signal paradigm. This paradigm assessed behavior as well as functional brain activity associated with motor execution, reactive inhibition (outright stopping) and proactive inhibition (anticipatory response slowing before stopping). HIV+ participants showed significantly slower responses during motor execution compared to healthy controls, whereas they had normal proactive response slowing. Putamen hypoactivation was evident in the HIV+ participants based on successful stopping, indicating subcortical dysfunction during reactive inhibition. HIV+ participants showed normal cortical functioning during proactive inhibition. Our data provide evidence that HIV infection is associated with subcortical dysfunction during reactive inhibition, accompanied by relatively normal higher cortical functioning during proactive inhibition. This suggests that HIV infection may primarily involve basic striatal-mediated control processes in cART naïve participants. (JINS, 2015, 21, 722–731)

OBJECTIVE: Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to investigate the effects of HIV infection on reward processing by examining the function of the ventral-striatal reward system during a monetary incentive delay task. DESIGN: This is a cross-sectional case-control study. METHODS: Eighteen combined antiretroviral therapy-naive HIV-positive (HIV+) participants, as well as 16 matched healthy controls, performed a monetary incentive delay task. This paradigm assesses behaviour as well as functional brain activity-associated reward anticipation and reward outcome. RESULTS: HIV+ participants showed a general decrease in activation associated with both neutral as well as potentially rewarding cues in their ventral striatum. We found normal activity related to reward outcome in the orbito-frontal cortex. Despite HIV+ participants' reaction times being significantly slower when independently measured from the reward paradigm, this performance deficit normalized during the performance of the reward task. CONCLUSION: HIV caused a decrease in activity during cue processing in the ventral striatum, with normal cortical functioning during reward outcome processing. Our results therefore suggest that HIV not only has an impact on fronto-striatal systems involved in executive functioning, but also has a direct impact on the function of the ventral-striatal reward system.

Healthy aging is associated with a progressive decline across a range of cognitive functions. An important factor underlying this decline may be the age-related impairment in stimulus-reward processing. Several studies have investigated age-related effects, but compared young versus old subjects. This is the first study to investigate the effect of aging on brain activation during reward processing within a continuous segment of the adult life span. We scanned 49 healthy adults aged 40-70 years, using functional MRI. We adopted a simple reward task, which allowed separate evaluation of neural responses to reward anticipation and receipt. The effect of reward on performance accuracy and speed was not related to age, indicating that all subjects could perform the task correctly. We identified a whole-brain significant age-related decline of ventral striatum activation during reward anticipation as compared to neutral anticipation. Importantly, the specificity of this finding was underscored by the observation that there was no general decline in activation during anticipation. Activation in the ventral striatum increased with age during reward receipt as compared to receiving neutral outcome. Finally, activation in the ventromedial prefrontal cortex during outcome was not affected by age. Our data demonstrate that the typical shift in striatal activation from reward receipt to reward anticipation in young adults disappears with healthy aging. These changes are consistent the well-ocumented age-related decline of striatal dopamine availability, and may provide a stepping stone for further research of age-related neurodegenerative diseases.

HIV-associated neurocognitive disorder (HAND) is a frequently occurring comorbidity of HIV infection. Evidence suggests this condition starts subclinical before a progression to a symptomatic stage. Blood oxygenated level dependent (BOLD) fMRI has shown to be a sensitive tool to detect abnormal brain function in an early stage and might therefore be useful to evaluate the effect of HIV infection on brain function. An extensive literature search was performed in June 2015. Eligibility criteria for included studies were as follows: (1) conducting with HIV-positive patients, (2) using BOLD fMRI, and (3) including a HIV-negative control group. A total of 19 studies were included in the review including 931 participants. Differences in activation between HIV-positive and -negative participants were found when testing multiple domains, i.e., attention, (working) memory, and especially executive functioning. Overall, HIV-positive patients showed hyperactivation in task-related brain regions despite equal performances as controls. Task performance was degraded only for the most complex tasks. A few studies investigated the effect of aging on fMRI, and most of them found no interaction with HIV infection. Only three studies evaluated the effect of combination antiretroviral therapy (cART) on functional data suggesting an increase in activation with the use of cART. fMRI is a sensitive instrument to detect subtle cognitive changes in HIV patients. Open questions remain regarding the effects of cART on fMRI and the effects of aging on fMRI. Electronic supplementary material The online version of this article (doi:10.1007/s13365-016-0483-y) contains supplementary material, which is available to authorized users.

Adolescence is a transitional period between childhood and adulthood and is characterized by emotional instability. Underlying this behavior may be an imbalance between the limbic subcortical areas and the prefrontal cortex. Here, we investigated differences in these regions during adolescence and young adulthood. Fifty subjects aged 10 to 24 viewed and rated neutral, negative, and positive pictures (IAPS: International Affective Picture System), while being scanned with functional MRI. Only those trials in which there was a match between the subject's response and the IAPS rating were included in the analyses. Task performance (matching accuracy, reaction times) did not differ across age. Activity in the amygdala and hippocampus decreased with age when processing emotional salient stimuli versus neutral stimuli. In contrast, activation in the ventrolateral prefrontal cortex increased with age. Importantly, we show for the first time that these age-related changes are paralleled by an increase in functional coupling of the amygdala and hippocampus with the orbitofrontal cortex and ventrolateral prefrontal cortex. These findings are in line with the general notion that brain development from childhood to adulthood is characterized by a gradual increase in frontal control over subcortical regions. Understanding these developmental changes is important as these may underlie typical adolescent behavior.

Functional MRI studies investigating the impact of HIV on the brain have implicated the involvement of fronto-striatal circuitry. However, to date there is no review and meta-analysis of this work. We systematically reviewed the literature and performed a meta-analysis of functional magnetic resonance imaging (fMRI) studies in HIV-infected individuals using a well validated tool recently developed for use in fMRI, 'GingerALE'. Twenty-one studies (468 HIV+, 270 HIV- controls) were qualitatively reviewed, of which six (105 HIV+, 102 controls) utilized fMRI paradigms engaging the fronto-striatal-parietal network, making a quantitative analysis possible. Our meta-analysis revealed consistent functional differences in the left inferior frontal gyrus and caudate nucleus between infected participants and controls across these studies. This fronto-striatal dysfunction was qualitatively related to cognitive impairment, disease progression and treatment effects. Although further work needs to be done to further delineate the potentially confounding influence of substance abuse and HIV-related comorbidities, as well as HIV's effect on functional haemodynamic vascular coupling, these findings indicate that further investigation of the fronto-striatal sub-networks in HIV-infected patients is warranted.

During adolescence, functional and structural changes in the brain facilitate the transition from childhood to adulthood. Because the cortex and the striatum mature at different rates, temporary imbalances in the frontostriatal network occur. Here, we investigate the development of the subcortical and cortical components of the frontostriatal network from early adolescence to early adulthood in 60 subjects in a cross-sectional design, using functional MRI and a stop-signal task measuring two forms of inhibitory control: reactive inhibition (outright stopping) and proactive inhibition (anticipation of stopping). During development, reactive inhibition improved: older subjects were faster in reactive inhibition. In the brain, this was paralleled by an increase in motor cortex suppression. The level of proactive inhibition increased, with older subjects slowing down responding more than younger subjects when anticipating a stop-signal. Activation increased in the right striatum, right ventral and dorsal inferior frontal gyrus, and supplementary motor area. Moreover, functional connectivity during proactive inhibition increased between striatum and frontal regions with age. In conclusion, we demonstrate that developmental improvements in proactive inhibition are paralleled by increases in activation and functional connectivity of the frontostriatal network. These data serve as a stepping stone to investigate abnormal development of the frontostriatal network in disorders such as schizophrenia and attention-deficit hyperactivity disorder.

Contains fulltext : 125332.pdf (Publisher’s version ) (Open Access) Typical adolescent behaviour such as increased risk-taking and novelty-seeking is probably related to developmental changes in the brain reward system. This functional MRI study investigated how brain activation related to two components of reward processing (Reward Anticipation and Reward Outcome) changes with age in a sample of 39 children, adolescents and young adults aged 10-25. Our data revealed age-related changes in brain activity during both components of reward processing. Activation related to Reward Anticipation increased with age, while activation related to Reward Outcome decreased in various regions of the reward network. This shift from outcome to anticipation was confirmed by subsequent analyses showing positive correlations between age and the difference in activation between Reward Anticipation and Reward Outcome. The shift was predominantly present in striatal regions and was accompanied by a significant effect of age on behaviour, with older participants showing more response speeding on potentially rewarding trials than younger participants. This study provides evidence for functional changes in the reward system which may underlie typical adolescent behaviour.

Item does not contain fulltext Learning from feedback involves a network of various cortical and subcortical regions. Although activation in this network has been shown to be especially strong in successful learners, it is currently unclear which of these regions are related to within-subject variation in learning performance. To this aim, 21 subjects performed a probabilistic feedback-learning task consisting of multiple independent Learning blocks and non-learning Control blocks, while functional magnetic resonance imaging data were acquired. In agreement with previous studies, activation in anterior, lateral and medial left prefrontal cortex, insula and superior and inferior parietal cortical regions were found when contrasting Learning and Control blocks. Furthermore, activation in the supplementary motor area, anterior cingulate cortex and bilateral striatum was associated specifically with the learning phase and not the application phase during Learning blocks. Finally, activation only in the ventral striatum was associated with within-subject learning performance across the Learning blocks. Taken together, these latter two results are argued to provide the answer to the main research question: ventral striatum activation is associated with within-subject variations in learning performance. The ventral striatum appears to play a vital role in learning by adjusting behavior based on feedback. 9 p.

In about 30–50% of patients with posttraumatic stress disorder (PTSD), symptoms persist after treatment. Although neurobiological research has advanced our understanding of PTSD, little is known about the neurobiology underlying persistence of PTSD. Two functional MRI scans were collected from 72 war veterans with and without PTSD over a 6- to 8-month interval, during which PTSD patients received trauma-focused therapy. All participants performed a trauma-unrelated emotional processing task in the scanner. Based on post-treatment symptom severity, a distinction was made between remitted and persistent patients. Behavioral and imaging measures of trauma-unrelated emotional processing were compared between the three groups (remitted patients, N=21; persistent patients, N=22; and combat controls, N=25) with repeated-measures (pre- and post-treatment) analyses. Second, logistic regression was used to predict treatment outcome. Before and after treatment, persistent patients showed a higher dorsal anterior cingulate cortex (dACC) and insula response to negative pictures compared with remitted patients and combat controls. Before treatment, persistent patients showed increased amygdala activation in response to negative pictures compared with remitted patients. The remitted patients and combat controls did not differ on the behavioral or imaging measures. Finally, higher dACC, insula, and amygdala activation before treatment were significant predictors of symptom persistence. Our results highlight a pattern of brain activation that may predict poor response to PTSD treatment. These findings can contribute to the development of alternative or additional therapies. Further research is needed to elucidate the heterogeneity within PTSD and describe how differences in neural function are related to treatment outcome. Such approaches are critical for defining parameters to customize PTSD treatment and improve treatment response rates.

Misattribution of symptoms is a common feature of schizophrenia, and likely involves impairment of metacognitive function that may be mediated by the frontal cortex. We aimed to compare frontal cortical thickness in first-episode schizophrenia (FES) patients with matched controls, and investigate its relationship with the symptom attribution dimension of insight in FES patients.We examined frontal cortical thickness in 92 minimally treated FES patients at baseline presentation and 93 healthy controls aged 16-45 years. We examined for correlations between symptom attribution as determined by the Birchwood Insight Scale (BIS) symptom relabeling subscale score and cortical thickness of frontal regions of interest (ROIs). We then examined for an association between symptom attribution and cortical thickness using multiple regression analysis.FES patients exhibited significantly reduced cortical thicknesses for a number of frontal regions, namely the left medial orbitofrontal, left superior frontal, left frontal pole, right rostral middle frontal, right lateral orbitofrontal and right superior frontal regions. Reduced cortical thickness in FES patients was associated with symptom misattribution for the left and right rostral middle frontal, left caudal anterior cingulate, right superior frontal, and left and right pars triangularis regions. Reduced left rostral middle frontal thickness and left anterior cingulate thickness remained significant on regression analysis.Our findings suggest that frontal neuroanatomical deficits that are present early in the disease process may be critical to the pathogenesis of symptom attribution in schizophrenia.

A recent Genome-Wide Association Study showed that the rs2514218 single nucleotide polymorphism (SNP) in close proximity to dopamine receptor D2 is strongly associated with schizophrenia. Further, an in silico experiment showed that rs2514218 has a cis expression quantitative trait locus effect in the basal ganglia. To date, however, the functional consequence of this SNP is unknown. Here, we used functional Magnetic resonance imaging to investigate the impact of this risk allele on striatal activation during proactive and reactive response inhibition in 45 unaffected siblings of schizophrenia patients. We included siblings to circumvent the illness specific confounds affecting striatal functioning independent from gene effects. Behavioral analyses revealed no differences between the carriers (n = 21) and noncarriers (n = 24). Risk allele carriers showed a diminished striatal response to increasing proactive inhibitory control demands, whereas overall level of striatal activation in carriers was elevated compared to noncarriers. Finally, risk allele carriers showed a blunted striatal response during successful reactive inhibition compared to the noncarriers. These data are consistent with earlier reports showing similar deficits in schizophrenia patients, and point to a failure to flexibly engage the striatum in response to contextual cues. This is the first study to demonstrate an association between impaired striatal functioning and the rs2514218 polymorphism. We take our findings to indicate that striatal functioning is impaired in carriers of the DRD2 risk allele, likely due to dopamine dysregulation at the DRD2 location.