Brain activation during fear extinction recall in unmedicated patients with obsessive-compulsive disorder.

Specific brain activation patterns during fear conditioning and the recall of previously extinguished fear responses have been associated with obsessive-compulsive disorder (OCD). However, further replication studies are necessary. We measured skin-conductance response and blood oxygenation level-dependent responses in unmedicated adult patients with OCD (n = 27) and healthy participants (n = 22) submitted to a two-day fear-conditioning experiment comprising fear conditioning, extinction (day 1) and extinction recall (day 2). During conditioning, groups differed regarding the skin conductance reactivity to the aversive stimulus (shock) and regarding the activation of the right opercular cortex, insular cortex, putamen, and lingual gyrus in response to conditioned stimuli. During extinction recall, patients with OCD had higher responses to stimuli and smaller differences between responses to conditioned and neutral stimuli. For the entire sample, the higher the response delta between conditioned and neutral stimuli, the greater the dACC activation for the same contrast during early extinction recall. While activation of the dACC predicted the average difference between responses to stimuli for the entire sample, groups did not differ regarding the activation of the dACC during extinction recall. Larger unmedicated samples might be necessary to replicate the previous findings reported in patients with OCD.

Polygenic risk score for attention-deficit/hyperactivity disorder and brain functional networks segregation in a community-based sample.

Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.

Neuroimaging of Dopamine Transporter Density in the Striatum of Disordered Gamblers.

The aim of the present research was to add to the growing literature on dopamine and gambling disorder (GD) by assessing whether GD is associated with dopamine transporter (DAT) density in the ventral striatum compared to healthy controls and whether DAT density was associated with key characteristics of GD (e.g., abstinence, craving). In a cross-sectional investigation using single-photon emission computed tomography with a technetium-99m-labeled tropane derivative as a radiotracer with SPECT imaging, fifteen participants with GD and 15 controls (non-gambling individuals, matched for age, gender, handedness, and smoking status) were measured. The GD group completed self-reported questionnaires regarding gambling. Striatal DAT density did not differ between the two groups. Conversely, striatal DAT density correlated significantly with various measures of recent gambling, but not with measures of chronic gambling. Multivariate analysis, adjusted for age and smoking status, showed that DAT density in the left striatum correlated positively with time spent gambling and gambling craving in the last month, whereas DAT density in the right striatum correlated negatively with abstinence self-efficacy. The results suggests that DAT density in the striatum is associated with recent gambling activity and gambling expectation.

Evaluation of dopamine transporter density in healthy Brazilians using Tc-99m TRODAT-1 SPECT.

ABSTRACT: The presynaptic dopamine transporter (DAT) modulates the uptake of dopamine by regulating its concentration in the central nervous system. We aimed to evaluate the DAT binding potential (DAT-BP) in a sample of healthy Brazilians through technetium-99 metastable TRODAT-1 single-photon emission computed tomography imaging.We selected 126 healthy individuals comprising 72 men and 54 women, aged 18 to 80 years. We conducted semi-quantitative evaluation in transaxial slices, following which we identified the regions of interest in the striatal region using the occipital lobe as a region of non-specific DAT-BP.We found a decrease in DAT-BP in healthy individuals aged over 30 years, culminating in a 42% mean reduction after 80 years. There was no difference in the decrease by age group between the right (linear regression test [R2] linear = 0.466) and left striatum (R2 linear = 0.510). Women presented a higher DAT-BP than men (women: R2 linear = 0.431; men: R2 linear = 0.457); nonetheless, their decrease by age group was equal to that in men.Our study sheds light on important DAT-BP findings in healthy Brazilian subjects. Our results will facilitate understanding of brain illnesses that involve the dopamine system, such as neuropsychiatric disorders.

Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls. RESULTS: There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences. CONCLUSIONS: DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.

Association Between Obsessive-Compulsive Symptom Dimensions in Mothers and Psychopathology in Their Children.

Background: The non-clinical presentation of obsessive-compulsive symptoms (OCS) in women may impact not only their daily lives and well-being but also increase the risk for emotional and behavioral problems in their children. This study aims to investigate the OCS dimension distribution in a large sample of mothers from a cohort of school age children and the association between these OCS dimensions with their own psychopathology, and with the presence of OCS and other psychopathology in their children. Method: Our final sample consisted of 2,511 mother-children dyads recruited from the elementary schools of two large cities. Throughout multiple regression analysis, we examined the correlations between demographic and clinical variables of mothers assessed by the Mini International Psychiatric Interview (MINI) and the Dimensional Yale-Brown Obsessive-Compulsive Scale-Short Version (DY-BOCS-SV) with children's psychopathology status reported by the Child Behavior Checklist (CBCL). Results: The overall prevalence of mothers who reported experiencing at least one OCS was 40% (N = 1,004). "Aggression/violence" was the most frequent symptom dimension (32.2%), followed by the "symmetry/ordering" (16.4%) and the "sexual/religious" dimensions (13.8%). There was a significant correlation between the presence of OCS and maternal psychopathology in general (p < 0.001, r = 0.397). Not only the presence but also the severity of the mother's OCS were strongly correlated to the total (p < 0.001), internalizing (p < 0.001), externalizing (p < 0.001), and OCS subscale scores (p < 0.001) on the CBCL. Conclusion: OCS dimensions are highly prevalent in women. Presence and severity of maternal OCS are related to children's psychopathology and behavioral problems.

Neuropsychiatric Symptoms of Alzheimer's Disease in Down Syndrome and Its Impact on Caregiver Distress.

BACKGROUND: Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. OBJECTIVE: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). METHODS: We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). RESULTS: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2 = 0.627, F(15,76) = 8.510, p < 0.001). CONCLUSION: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.

Risk factors for obsessive-compulsive symptoms. Follow-up of a community-based youth cohort.

Environmental factors are at least as important as genetic factors for the development of obsessive-compulsive symptoms (OCS), but the identification of such factors remain a research priority. Our study aimed to investigate the association between a broad scope of potential risk factors and OCS in a large community cohort of children and adolescents. We evaluated 1877 participants and their caregivers at baseline and after 3 years to assess various demographic, prenatal, perinatal, childhood adversity, and psychopathological factors. Mean age at baseline was 10.2 years (SD 1.9) and mean age at follow-up was 13.4 years (SD 1.9). Reports of OCS at baseline and follow-up were analyzed using latent variable models. At preliminary regression analysis, 15 parameters were significantly associated with higher OCS scores at follow-up. At subsequent regression analysis, we found that eight of these parameters remained significantly associated with higher follow-up OCS scores while being controlled by each other and by baseline OCS scores. The significant predictors of follow-up OCS were: lower socioeconomic status (p = 0.033); lower intelligence quotient (p = 0.013); lower age (p < 0.001); higher maternal stress level during pregnancy (p = 0.028); absence of breastfeeding (p = 0.017); parental baseline OCS (p = 0.038); youth baseline anxiety disorder (p = 0.023); and youth baseline OCS scores (p < 0.001). These findings may better inform clinicians and policymakers engaged in the mental health assessment and prevention in children and adolescents.

Neuroimaging Association Scores: reliability and validity of aggregate measures of brain structural features linked to mental disorders in youth.

In genetics, aggregation of many loci with small effect sizes into a single score improved prediction. Nevertheless, studies applying easily replicable weighted scores to neuroimaging data are lacking. Our aim was to assess the reliability and validity of the Neuroimaging Association Score (NAS), which combines information from structural brain features previously linked to mental disorders. Participants were 726 youth (aged 6-14) from two cities in Brazil who underwent MRI and psychopathology assessment at baseline and 387 at 3-year follow-up. Results were replicated in two samples: IMAGEN (n = 1627) and the Healthy Brain Network (n = 843). NAS were derived by summing the product of each standardized brain feature by the effect size of the association of that brain feature with seven psychiatric disorders documented by previous meta-analyses. NAS were calculated for surface area, cortical thickness and subcortical volumes using T1-weighted scans. NAS reliability, temporal stability and psychopathology and cognition prediction were analyzed. NAS for surface area showed high internal consistency and 3-year stability and predicted general psychopathology and cognition with higher replicability than specific symptomatic domains for all samples. They also predicted general psychopathology with higher replicability than single structures alone, accounting for 1-3% of the variance, but without directionality. The NAS for cortical thickness and subcortical volumes showed lower internal consistency and less replicable associations with behavioural phenotypes. These findings indicate the NAS based on surface area might be replicable markers of general psychopathology, but these links are unlikely to be causal or clinically useful yet.

Testing the Stability and Validity of an Executive Dysfunction Classification Using Task-Based Assessment in Children and Adolescents.

OBJECTIVE: It is unclear if pediatric executive dysfunction assessed only with cognitive tasks predicts clinically relevant outcomes independently of psychiatric diagnoses. This study tested the stability and validity of a task-based classification of executive function. METHOD: A total of 2,207 individuals (6-17 years old) from the Brazilian High-Risk Cohort Study participated in this study (1,930 at baseline, 1,532 at follow-up). Executive function was measured using tests of working memory and inhibitory control. Dichotomized age- and sex-standardized performances were used as input in latent class analysis and receiver operating curves to create an executive dysfunction classification (EDC). The study tested EDC's stability over time, association with symptoms, functional impairment, a polymorphism in the CADM2 gene, polygenic risk scores (PRS), and brain structure. Analyses covaried for age, sex, social class, IQ, and psychiatric diagnoses. RESULTS: EDC at baseline predicted itself at follow-up (odds ratio [OR] = 5.11; 95% CI 3.41-7.64). Participants in the EDC reported symptoms spanning several domains of psychopathology and exhibited impairment in multiple settings, including more adverse school events (OR = 2.530; 95% CI 1.838-3.483). Children in the EDC presented higher attention-deficit/hyperactivity disorder and lower educational attainment PRS at baseline; higher schizophrenia PRS at follow-up; and lower chances of presenting a polymorphism in a gene previously linked to high performance in executive function (CADM2 gene). They also exhibited smaller intracranial volumes and smaller bilateral cortical surface areas in several brain regions. CONCLUSION: Task-based executive dysfunction is associated with several validators, independently of psychiatric diagnoses and intelligence. Further refinement of task-based assessments might generate clinically useful tools.

Brain white matter microstructure in obese women with binge eating disorder.

OBJECTIVE: Research on potential brain circuit abnormalities in binge eating disorder (BED) is limited. Here, we assess white matter (WM) microstructure in obese women with BED. METHOD: Diffusion tensor imaging data were acquired, and tract-based spatial statistics used to examine WM in women with BED who were obese (n = 17) compared to normal-weight (NWC) (n = 17) and to women who were obese (OBC) (n = 13). Body mass index (BMI) was a covariate in the analyses. RESULTS: The BED group (vs. NWC) had greater axial diffusion (AD) in the forceps minor, anterior thalamic radiation, superior and inferior longitudinal fasciculus, that is, in pathways connecting fronto-limbic regions. Microstructures differences in AD between the BED and OBC groups were seen in fronto-limbic pathways extending to temporoparietal pathways. The BED (vs. OBC) group had greater fractional anisotropy in the forceps minor and greater AD in the superior longitudinal fasciculus, cingulate gyrus, and corpus callosum, consistent with fronto-tempoparietal pathways. CONCLUSION: Women with BED show WM alterations in AD in fronto-limbic and parietal pathways that are important in decision-making processes. As BMI was a covariate in the analyses, alterations in BED may be part of the pathology, but whether they are a cause or effect of illness is unclear.

Cognitive performance in children and adolescents at high-risk for obsessive-compulsive disorder.

BACKGROUND: Cognitive performance has been studied in adults with obsessive-compulsive symptoms (OCS) and in adult relatives of patients with obsessive-compulsive disorder (OCD) Meanwhile, few studies have been conducted with children under the same conditions. This study compared the neurocognitive domains previously associated with dysfunction in OCD, especially visuoconstructive ability, visuospatial memory, executive functions, and intelligence, in children and adolescents at high risk (HR) for OCD (n = 18) and non-OCD controls (NOC) (n = 31). METHODS: For the HR group, we considered the first-degree relatives of patients with OCD that present OCS, but do not meet diagnostic criteria for OCD. Psychiatric diagnosis was assessed by experienced clinicians using the Structured Clinical Interview for DSM-IV and OCS severity was measured by the Yale-Brown Obsessive-Compulsive Scale. Neurocognitive assessment was performed with a comprehensive neuropsychological battery. Performance on the cognitive domains was compared between groups using Multivariate Analysis of Variance, whereas performance on the neuropsychological variables was compared between groups using independent t-tests in a cognitive subdomain analysis. RESULTS: The cognitive domain analysis revealed a trend towards significance for impairments in the motor and processing speed domain (p = 0.019; F = 3.12) in the HR group. Moreover, the cognitive subdomain analysis identified a statistically significant underperformance in spatial working memory in the HR group when compared to the NOC group (p = 0.005; t = - 2.94), and a trend towards significance for impairments in non-verbal memory and visuoconstructive tasks in the HR group. CONCLUSIONS: Our results suggest impairments in spatial working memory and motor and processing speed in a non-clinical sample of HR participants. Considering the preliminary nature of our findings, further studies investigating these neurocognitive domains as potential predictors of pediatric OCD are warranted.

Exploring response inhibition and error monitoring in obsessive-compulsive disorder.

Behavioral evidence of impaired response inhibition (RI) and hyperactive error monitoring (EM) in obsessive-compulsive disorder (OCD) is inconsistent. Recent neuroimaging work suggests that EM plays a role in RI impairments in OCD, but this has rarely been investigated using behavioral measures. The aims of this study were to (1) compare RI and EM performance between adults with OCD and non-psychiatric controls (NPC) while investigating possible moderators, and (2) assess whether excessive EM influences RI in OCD. We compared RI and EM performance on the Stop-Signal Task (SST) between 92 adults with OCD and 65 NPC from two Brazilian sites. We used linear regression to investigate which variables (group, age, medication use, clinical symptomatology) influenced performance, as well as to examine possible associations between RI and EM. OCD and NPC did not differ in RI and EM. However, age moderated RI performance in OCD with a medium effect size, reflecting differential effects of age on RI between groups: age was positively associated with RI in OCD but not NPC. Further, OCD severity predicted EM with a medium to large effect size, suggesting that more symptomatic patients showed greater monitoring of their mistakes. Finally, group moderated the relationship between RI and EM with a small effect size. Our findings suggest that demographic factors may influence RI, whereas clinical factors may influence EM. Further, we found preliminary behavioral evidence to indicate that impaired RI and excessive EM are related in OCD.

Association between spontaneous activity of the default mode network hubs and leukocyte telomere length in late childhood and early adolescence.

The impact of early life stress on mental health and telomere length shortening have been reported. Changes in brain default mode network (DMN) were found to be related to a myriad of psychiatric conditions in which stress may play a role. In this context, family environment and adverse childhood experiences (ACEs) are potential causes of stress. This is a hypothesis-driven study focused on testing two hypotheses: (i) there is an association between telomere length and the function of two main hubs of DMN: the posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC); (ii) this association is modulated by family environment and/or ACEs. To the best of our knowledge, this is the first study investigating these hypotheses. Resting-state functional magnetic resonance imaging data and blood sample were collected from 389 subjects (6-15 age range). We assessed DMN fractional amplitude of low-frequency fluctuations (fALFF) and leukocyte telomere length (LTL). We fitted general linear models to test the main effects of LTL on DMN hubs and the interaction effects with Family Environment Scale (FES) and ACEs. The results did not survive a strict Bonferroni correction. However, uncorrected p-values suggest that LTL was positively correlated with fALFF in PCC and a FES interaction between FES and LTL at mPFC. Although marginal, our results encourage further research on the interaction between DMN hubs, telomere length and family environment, which may play a role on the biological embedding of stress.

Genetic risk for Alzheimer's disease and functional brain connectivity in children and adolescents.

Research suggested accumulation of tau proteins might lead to the degeneration of functional networks. Studies investigating the impact of genetic risk for Alzheimer's disease (AD) on early brain connections might shed light on mechanisms leading to AD development later in life. Here, we aim to investigate whether the polygenic risk score for Alzheimer's disease (AD-PRS) influences the connectivity among regions susceptible to tau pathology during childhood and adolescence. Participants were youth, aged 6-14 years, and recruited in Porto Alegre (discovery sample, n = 332) and São Paulo (replication sample, n = 304), Brazil. Subjects underwent genotyping and 6-min resting state funcional magnetic resonance imaging. Connections between the local maxima of tau pathology networks were used as dependent variables. The AD-PRS was associated with the connectivity between the right precuneus and the right superior temporal gyrus (discovery sample: ß = 0.180, padjusted = 0.036; replication sample: ß = 0.202, p = 0.031). This connectivity was also associated with inhibitory control (ß = 0.157, padjusted = 0.035) and moderated the association between the AD-PRS and both immediate and delayed recall. These findings suggest the AD-PRS may affect brain connectivity in youth, which might impact memory performance and inhibitory control in early life.

Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome.

There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (≥30 years of age), divided into 3 groups by diagnosis-stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apathy) by an informant using the Frontal Systems Behavior Scale. Informant-reported behaviors related to frontal lobe dysfunction were found to correlate negatively with executive function performance. Disinhibition and executive dysfunction were associated with the clinical stage of dementia. The odds of having Alzheimer's disease increased in parallel with increases in the domain and total Frontal Systems Behavior Scale scores (p ≤ 0.5). Disinhibition, executive dysfunction and apathy should be taken into consideration during the clinical evaluation of adults with DS, and future studies should consider the intersection of neuropathology, brain connectivity, and behavior.

Association Between Fractional Amplitude of Low-Frequency Spontaneous Fluctuation and Degree Centrality in Children and Adolescents.

The fractional amplitude of low-frequency fluctuations (fALFFs) of the BOLD signal have been successfully applied as exploratory tools in neuroimaging. This metric has been useful in mapping brain functional changes in many clinical populations. However, little is known about the neurophysiological correlates of fALFF. This study aimed at demonstrating that fALFF is related to local network centrality during childhood and adolescence. The establishment of this relationship is fundamental to provide a more meaningful explanation to previous clinical and neurodevelopmental studies based on fALFF. Our findings show a correlation of ∼0.5 between these two metrics at a group level, which is a finding replicated in four large independent samples. However, when considering the across-subject and intra-subject correlations between the two metrics, the correlation is much lower, probably due to the low signal-to-noise ratio. Moreover, we found that regions with high fALFF and degree centrality overlapped modestly, particularly the posterior cingulate/precuneus and lateral parietal cortices.

Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis.

Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.

Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive-compulsive disorder.

Neurobiological models have provided consistent evidence of the involvement of cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.

Associations between children's family environment, spontaneous brain oscillations, and emotional and behavioral problems.

The family environment in childhood has a strong effect on mental health outcomes throughout life. This effect is thought to depend at least in part on modifications of neurodevelopment trajectories. In this exploratory study, we sought to investigate whether a feasible resting-state fMRI metric of local spontaneous oscillatory neural activity, the fractional amplitude of low-frequency fluctuations (fALFF), is associated with the levels of children's family coherence and conflict. Moreover, we sought to further explore whether spontaneous activity in the brain areas influenced by family environment would also be associated with a mental health outcome, namely the incidence of behavioral and emotional problems. Resting-state fMRI data from 655 children and adolescents (6-15 years old) were examined. The quality of the family environment was found to be positively correlated with fALFF in the left temporal pole and negatively correlated with fALFF in the right orbitofrontal cortex. Remarkably, increased fALFF in the temporal pole was associated with a lower incidence of behavioral and emotional problems, whereas increased fALFF in the orbitofrontal cortex was correlated with a higher incidence.