Spontaneous slow wave oscillations in extracellular field potential recordings reflect the alternating dominance of excitation and inhibition.

In the resting state, cortical neurons can fire action potentials spontaneously but synchronously (Up state), followed by a quiescent period (Down state) before the cycle repeats. Extracellular recordings in the infragranular layer of cortex with a micro-electrode display a negative deflection (depth-negative) during Up states and a positive deflection (depth-positive) during Down states. The resulting slow wave oscillation (SWO) has been studied extensively during sleep and under anaesthesia. However, recent research on the balanced nature of synaptic excitation and inhibition has highlighted our limited understanding of its genesis. Specifically, are excitation and inhibition balanced during SWOs? We analyse spontaneous local field potentials (LFPs) during SWOs recorded from anaesthetised rats via a multi-channel laminar micro-electrode and show that the Down state consists of two distinct synaptic states: a Dynamic Down state associated with depth-positive LFPs and a prominent dipole in the extracellular field, and a Static Down state with negligible ( ≈ 0 mV $ \approx 0{\mathrm{\;mV}}$ ) LFPs and a lack of dipoles extracellularly. We demonstrate that depth-negative and -positive LFPs are generated by a shift in the balance of synaptic excitation and inhibition from excitation dominance (depth-negative) to inhibition dominance (depth-positive) in the infragranular layer neurons. Thus, although excitation and inhibition co-tune overall, differences in their timing lead to an alternation of dominance, manifesting as SWOs. We further show that Up state initiation is significantly faster if the preceding Down state is dynamic rather than static. Our findings provide a coherent picture of the dependence of SWOs on synaptic activity. KEY POINTS: Cortical neurons can exhibit repeated cycles of spontaneous activity interleaved with periods of relative silence, a phenomenon known as 'slow wave oscillation' (SWO). During SWOs, recordings of local field potentials (LFPs) in the neocortex show depth-negative deflection during the active period (Up state) and depth-positive deflection during the silent period (Down state). Here we further classified the Down state into a dynamic phase and a static phase based on a novel method of classification and revealed non-random, stereotypical sequences of the three states occurring with significantly different transitional kinetics. Our results suggest that the positive and negative deflections in the LFP reflect the shift of the instantaneous balance between excitatory and inhibitory synaptic activity of the local cortical neurons. The differences in transitional kinetics may imply distinct synaptic mechanisms for Up state initiation. The study may provide a new approach for investigating spontaneous brain rhythms.

Smoking, tobacco dependence, and neurometabolites in the dorsal anterior cingulate cortex.

Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warrants further investigation. The goal of this project therefore was to validate and extend evidence of hypoinflammation related to smoking, and to examine the potential contribution of inflammation to clinical features of smoking. Using magnetic resonance spectroscopy, we measured levels of neurometabolites that are putative neuroinflammatory markers. N-acetyl compounds (N-acetylaspartate + N-acetylaspartylglutamate), glutamate, creatine, choline-compounds (phosphocholine + glycerophosphocholine), and myo-inositol, have all been linked to neuroinflammation, but they have not been examined as such with respect to smoking. We tested whether people who smoke cigarettes have brain levels of these metabolites consistent with decreased neuroinflammation, and whether clinical features of smoking are associated with levels of these metabolites. The dorsal anterior cingulate cortex was chosen as the region-of-interest because of previous evidence linking it to smoking and related states. Fifty-four adults who smoked daily maintained overnight smoking abstinence before testing and were compared with 37 nonsmoking participants. Among the smoking participants, we tested for associations of metabolite levels with tobacco dependence, smoking history, craving, and withdrawal. Levels of N-acetyl compounds and glutamate were higher, whereas levels of creatine and choline compounds were lower in the smoking group as compared with the nonsmoking group. In the smoking group, glutamate and creatine levels correlated negatively with tobacco dependence, and creatine correlated negatively with lifetime smoking, but none of the metabolite levels correlated with craving or withdrawal. The findings indicate a link between smoking and a hypoinflammatory state in the brain, specifically in the dorsal anterior cingulate cortex. Smoking may thereby increase vulnerability to infection and brain injury.

Neurobiology of subtypes of trichotillomania and skin picking disorder.

BACKGROUND: Trichotillomania (TTM) and skin picking disorder (SPD) are common and often debilitating mental health conditions, grouped under the umbrella term of body-focused repetitive behaviors (BFRBs). Recent clinical subtyping found that there were three distinct subtypes of TTM and two of SPD. Whether these clinical subtypes map on to any unique neurobiological underpinnings, however, remains unknown. METHODS: Two hundred and fifty one adults [193 with a BFRB (85.5% [n = 165] female) and 58 healthy controls (77.6% [n = 45] female)] were recruited from the community for a multicenter between-group comparison using structural neuroimaging. Differences in whole brain structure were compared across the subtypes of BFRBs, controlling for age, sex, scanning site, and intracranial volume. RESULTS: When the subtypes of TTM were compared, low awareness hair pullers demonstrated increased cortical volume in the lateral occipital lobe relative to controls and sensory sensitive pullers. In addition, impulsive/perfectionist hair pullers showed relative decreased volume near the lingual gyrus of the inferior occipital-parietal lobe compared with controls. CONCLUSIONS: These data indicate that the anatomical substrates of particular forms of BFRBs are dissociable, which may have implications for understanding clinical presentations and treatment response.

Alcohol Craving and Severity are Associated with Dorsal Anterior Cingulate Choline Levels in Individuals with an Alcohol Use Disorder.

AIMS: Magnetic resonance spectroscopy (MRS) has been used to probe inflammation in the brain. While altered MRS metabolite levels have previously been found in individuals with alcohol use disorder (AUD), the relationship between potential metabolite markers of inflammation and the clinical correlates of AUD remains understudied. Therefore, this exploratory study sought to elucidate the clinical significance of inflammation in AUD by examining relationships between metabolites, AUD severity, alcohol consumption, and craving in individuals with AUD. METHODS: Data for this secondary analysis are derived from a two-week clinical trial of ibudilast to treat AUD. Forty-three non-treatment-seeking individuals with an AUD (26M/17F) completed an MRS scan and alcohol-related questionnaires. MRS was performed using a multi-voxel array placed above the corpus callosum, extending from the pregnenual anterior cingulate to premotor cortex. The dorsal anterior cingulate was selected as the volume of interest. Metabolite levels of choline-compounds (Cho), myo-inositol (mI), and creatine+phosphocreatine (Cr) were quantified. Separate hierarchical regression models were used to evaluate the independent effects of metabolite levels on alcohol craving, alcohol problem severity, and alcohol consumption. RESULTS: Dorsal anterior cingulate Cho predicted alcohol craving and alcohol problem severity over and above demographics, medication, and alcohol consumption measures. mI and Cr did not predict alcohol craving or alcohol problem severity. Metabolite markers were not predictive of alcohol consumption. CONCLUSIONS: This preliminary study indicates that dACC Cho is sensitive to clinical characteristics of AUD. This is a further step in advancing neurometabolites, particularly Cho, as potential biomarkers and treatment targets for AUD.

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration.

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Higher glutamatergic activity in the medial prefrontal cortex in chronic ketamine users.

BACKGROUND: The medial prefrontal cortex (mPFC) plays an important role in depression and addiction. Previous studies have shown alterations in glutamatergic activity in the mPFC following the administration of ketamine in patients with depression and healthy controls. However, it remains unclear whether chronic, nonmedical use of ketamine affects metabolites in the mPFC. METHODS: Using proton magnetic resonance spectroscopy, we measured metabolites (glutamate and glutamine [Glx]; phosphocreatine and creatine [PCr+Cr]; myo-inositol; N-acetyl-aspartate; and glycerophosphocholine and phosphocholine [GPC+PC]) in the mPFC of chronic ketamine users (n = 20) and healthy controls (n = 43). Among ketamine users, 60% consumed ketamine once per day or more, 10% consumed it every 2 days and 30% consumed it every 3 or more days. Using analysis of covariance, we evaluated between-group differences in the ratios of Glx:PCr+Cr, myo-inositol:PCr+Cr, N-acetyl-aspartate:PCr+Cr and GPC+PC:PCr+Cr. RESULTS: Chronic ketamine users showed significantly higher Glx:PCr+Cr ratios than healthy controls (median 1.05 v. 0.95, p = 0.008). We found no significant differences in myoinositol:PCr+Cr, N-acetyl-aspartate:PCr+Cr or GPC+PC:PCr+Cr ratios between the 2 groups. We found a positive relationship between N-acetyl-aspartate:PCr+Cr and Glx:PCr+Cr ratios in the healthy control group (R = 0.345, p = 0.023), but the ketamine use group failed to show such an association (ρ = 0.197, p = 0.40). LIMITATIONS: The cross-sectional design of this study did not permit causal inferences related to higher Glx:PCr+Cr ratios and chronic ketamine use. CONCLUSION: This study provides the first evidence that chronic ketamine users have higher glutamatergic activity in the mPFC than healthy controls; this finding may provide new insights relevant to the treatment of depression with ketamine.

Clinical MRI morphological analysis of functional seizures compared to seizure-naïve and psychiatric controls.

PURPOSE: Functional seizures (FS), also known as psychogenic nonepileptic seizures (PNES), are physical manifestations of acute or chronic psychological distress. Functional and structural neuroimaging have identified objective signs of this disorder. We evaluated whether magnetic resonance imaging (MRI) morphometry differed between patients with FS and clinically relevant comparison populations. METHODS: Quality-screened clinical-grade MRIs were acquired from 666 patients from 2006 to 2020. Morphometric features were quantified with FreeSurfer v6. Mixed-effects linear regression compared the volume, thickness, and surface area within 201 regions-of-interest for 90 patients with FS, compared to seizure-naïve patients with depression (n = 243), anxiety (n = 68), and obsessive-compulsive disorder (OCD, n = 41), respectively, and to other seizure-naïve controls with similar quality MRIs, accounting for the influence of multiple confounds including depression and anxiety based on chart review. These comparison populations were obtained through review of clinical records plus research studies obtained on similar scanners. RESULTS: After Bonferroni-Holm correction, patients with FS compared with seizure-naïve controls exhibited thinner bilateral superior temporal cortex (left 0.053 mm, p = 0.014; right 0.071 mm, p = 0.00006), thicker left lateral occipital cortex (0.052 mm, p = 0.0035), and greater left cerebellar white-matter volume (1085 mm3, p = 0.0065). These findings were not accounted for by lower MRI quality in patients with FS. CONCLUSIONS: These results reinforce prior indications of structural neuroimaging correlates of FS and, in particular, distinguish brain morphology in FS from that in depression, anxiety, and OCD. Future work may entail comparisons with other psychiatric disorders including bipolar and schizophrenia, as well as exploration of brain structural heterogeneity within FS.

Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial.

Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro-inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and potential central markers of inflammation in individuals with AUD. This study also explored the predictive relationship of neurometabolite markers with subsequent drinking in the trial. Non-treatment-seeking individuals with an AUD (n = 52) were randomized to receive oral ibudilast (n = 24) or placebo (n = 28) for 2 weeks. Plasma levels of peripheral inflammatory markers were measured at baseline and after 1 and 2 weeks of medication. At study mid-point, proton magnetic resonance spectroscopy was performed to measure potential neurometabolite markers of inflammation: choline-compounds (Cho), myo-inositol (MI) and creatine + phosphocreatine (Cr) in frontal and cingulate cortices from 43 participants (ibudilast: n = 20; placebo: n = 23). The treatment groups were compared on peripheral and central markers. Ibudilast-treated participants had lower Cho in superior frontal white matter and nominally lower MI in pregenual anterior cingulate cortex. Ibudilast-treated participants had nominally lower C-reactive protein levels at visit 2 and nominally lower TNF-α/IL-10 ratios, relative to placebo. C-reactive protein and Cho levels were correlated, controlling for medication. Superior frontal white matter Cho predicted drinking in the following week. Micro-longitudinal ibudilast treatment may induce peripheral and putative central anti-inflammatory responses in patients with AUD. The neurometabolite responses may be associated with reduction in drinking, suggesting an anti-inflammatory component to the therapeutic action of ibudilast.

Clinical Characteristics of Youth with Trichotillomania (Hair-Pulling Disorder) and Excoriation (Skin-Picking) Disorder.

Body-focused repetitive disorders (BFRBDs) are understudied in youth and understanding of their underlying mechanisms is limited. This study evaluated BFRBD clinical characteristics, and two factors commonly implicated in their maintenance - emotion regulation and impulsivity - in 53 youth aged 11 to 17 years: 33 with BFRBDs and 20 controls. Evaluators administered psychiatric diagnostic interviews. Participants rated BFRBD severity, negative affect, quality of life, family functioning, emotion regulation, distress tolerance, and impulsivity. Youth with BFRBDs showed poorer distress tolerance and quality of life, and higher impulsivity and negative affect than controls, with no differences in family impairment. BFRBD distress/impairment, but not BFRBD severity, correlated with anxiety and depression, and poorer distress tolerance. Findings suggest youth with BFRBDs show clinical patterns aligning with prior research; highlight the role of distress tolerance in child BFRBDs; and suggest the utility of acceptance and mindfulness-based therapies for unpleasant emotions in BFRBDs. Continued research should evaluate factors underlying BFRBDs in youth.

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.

Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder.

Cognitive behavioral therapy (CBT) is an effective treatment for many with obsessive-compulsive disorder (OCD). However, response varies considerably among individuals. Attaining a means to predict an individual's potential response would permit clinicians to more prudently allocate resources for this often stressful and time-consuming treatment. We collected resting-state functional magnetic resonance imaging from adults with OCD before and after 4 weeks of intensive daily CBT. We leveraged machine learning with cross-validation to assess the power of functional connectivity (FC) patterns to predict individual posttreatment OCD symptom severity. Pretreatment FC patterns within the default mode network and visual network significantly predicted posttreatment OCD severity, explaining up to 67% of the variance. These networks were stronger predictors than pretreatment clinical scores. Results have clinical implications for developing personalized medicine approaches to identifying individual OCD patients who will maximally benefit from intensive CBT.

Identification of a polymorphism within the Rosa multiflora muRdr1A gene linked to resistance to multiple races of Diplocarpon rosae W. in tetraploid garden roses (Rosa × hybrida).

KEY MESSAGE: A QTL for resistance to several races of black spot co-located with the known Rrd1 locus in Rosa. A polymorphism in muRdr1A linked to black spot resistance was identified and molecular markers were designed. Black spot, caused by Diplocarpon rosae, is one of the most serious foliar diseases of landscape roses that reduces the marketability and weakens the plants against winter survival. Genetic resistance to black spot (BS) exists and race-specific resistance is a good target to implement marker-assisted selection. High-density single nucleotide polymorphism-based genetic maps were created for the female parent of a tetraploid cross between 'CA60' and 'Singing in the Rain' using genotyping-by-sequencing following a two-way pseudo-testcross strategy. The female linkage map was generated based on 227 individuals and included 31 linkage groups, 1055 markers, with a length of 1980 cM. Race-specific resistance to four D. rosae races (5, 7, 10, 14) was evaluated using a detached leaf assay. BS resistance was also evaluated under natural infection in the field. Resistance to races 5, 10 and 14 of D. rosae and field resistance co-located on chromosome 1. A unique sequence of 32 bp in exon 4 of the muRdr1A gene was identified in 'CA60' that co-segregates with D. rosae resistance. Two diagnostic markers, a presence/absence marker and an INDEL marker, specific to this sequence were designed and validated in the mapping population and a backcross population derived from 'CA60.' Resistance to D. rosae race 7 mapped to a different location on chromosome 1.

Disrupted-in-schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization.

Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single-unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted-in-Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein aggregation, disturbances in the dopaminergic system and attention-related deficits. Recordings were performed during exploration of familiar and novel open field environments and during sleep, allowing investigation of neuronal abnormalities in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited smaller place fields and decreased speed-modulation of their firing rates, demonstrating altered spatial coding and deficits in encoding location-independent sensory inputs. Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase locking strength during novelty, limiting their phase coding ability. However, their mean theta phases were more variable at the population level, reducing oscillatory network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty-induced shift in their preferred theta and gamma firing phases, indicating deficits in coding of novel environments with oscillatory firing. By combining single cell and neuronal population analyses, we link DISC1 protein pathology with abnormal hippocampal neural coding and network synchrony, and thereby gain a more comprehensive understanding of CMI mechanisms.

N-Acetyl and Glutamatergic Neurometabolites in Perisylvian Brain Regions of Methamphetamine Users.

Background: Methamphetamine induces neuronal N-acetyl-aspartate synthesis in preclinical studies. In a preliminary human proton magnetic resonance spectroscopic imaging investigation, we also observed that N-acetyl-aspartate+N-acetyl-aspartyl-glutamate in right inferior frontal cortex correlated with years of heavy methamphetamine abuse. In the same brain region, glutamate+glutamine is lower in methamphetamine users than in controls and is negatively correlated with depression. N-acetyl and glutamatergic neurochemistries therefore merit further investigation in methamphetamine abuse and the associated mood symptoms. Methods: Magnetic resonance spectroscopic imaging was used to measure N-acetyl-aspartate+N-acetyl-aspartyl-glutamate and glutamate+glutamine in bilateral inferior frontal cortex and insula, a neighboring perisylvian region affected by methamphetamine, of 45 abstinent methamphetamine-dependent and 45 healthy control participants. Regional neurometabolite levels were tested for group differences and associations with duration of heavy methamphetamine use, depressive symptoms, and state anxiety. Results: In right inferior frontal cortex, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate correlated with years of heavy methamphetamine use (r = +0.45); glutamate+glutamine was lower in methamphetamine users than in controls (9.3%) and correlated negatively with depressive symptoms (r = -0.44). In left insula, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate was 9.1% higher in methamphetamine users than controls. In right insula, glutamate+glutamine was 12.3% lower in methamphetamine users than controls and correlated negatively with depressive symptoms (r = -0.51) and state anxiety (r = -0.47). Conclusions: The inferior frontal cortex and insula show methamphetamine-related abnormalities, consistent with prior observations of increased cortical N-acetyl-aspartate in methamphetamine-exposed animal models and associations between cortical glutamate and mood in human methamphetamine users.

Dorsolateral prefrontal γ-aminobutyric acid in patients with treatment-resistant depression after transcranial magnetic stimulation measured with magnetic resonance spectroscopy

Background: The therapeutic mechanism of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) may involve modulation of γ-aminobutyric acid (GABA) levels. We used proton magnetic resonance spectroscopy (MRS) to assess changes in GABA levels at the site of rTMS in the left dorsolateral prefrontal cortex (DLPFC). Methods: In 26 adults with TRD, we used Mescher­Garwood point-resolved spectroscopy (MEGA-PRESS) spectral-editing MRS to measure GABA in the left DLPFC before and after standard clinical treatment with rTMS. All participants but 1 were medicated, including 12 patients on GABA agonist agents. Results: Mean GABA in the DLPFC increased 10.0% (p = 0.017) post-rTMS in the overall sample. As well, GABA increased significantly in rTMS responders (n = 12; 23.6%, p = 0.015) but not in nonresponders (n = 14; 4.1%, p = not significant). Changes in GABA were not significantly affected by GABAergic agonists, but clinical response was less frequent (p = 0.005) and weaker (p = 0.035) in the 12 participants who were receiving GABA agonists concomitant with rTMS treatment. Limitations: This study had an open-label design in a population receiving naturalistic treatment. Conclusion: Treatment using rTMS was associated with increases in GABA levels at the stimulation site in the left DLPFC, and the degree of GABA change was related to clinical improvement. Participants receiving concomitant treatment with a GABA agonist were less likely to respond to rTMS. These findings were consistent with earlier studies showing the effects of rTMS on GABA levels and support a GABAergic model of depression.

Comparing OCD-affected youth with and without religious symptoms: Clinical profiles and treatment response.

BACKGROUND: Childhood obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric condition, with varied symptom presentations that have been differentially associated with clinical characteristics and treatment response. One OCD symptom cluster of particular interest is religious symptoms, including fears of offending religious figures/objects; patients affected by these symptoms have been characterized as having greater overall OCD severity and poorer treatment response. However, the extant literature primarily examines this symptom subtype within adults, leaving a gap in our understanding of this subtype in youth. METHOD: Consequently, this study examined whether presence of religious symptoms in OCD-affected children and adolescents (N = 215) was associated with greater clinical impairments across OCD symptoms and severity, insight, other psychiatric comorbidity, family variables, or worse treatment response. RESULTS: Results found that youth with religious OCD symptoms presented with higher OCD symptom severity and exhibited more symptoms in the aggressive, sexual, somatic, and checking symptom cluster, as well as the symmetry, ordering, counting, and repeating cluster. Religious OCD symptoms were also significantly associated with poorer insight and higher family expressiveness. No differences in treatment response were observed in youths with versus without religious OCD symptoms. CONCLUSION: Ultimately, youths with religious OCD symptoms only differed from their OCD-affected counterparts without religious symptoms on a minority of clinical variables; this suggests they may be more comparable to youths without religious OCD symptoms than would be expected based on the adult OCD literature and highlights the importance of examining these symptoms within a pediatric OCD sample.

Relationships between obsessive-compulsive disorder, depression and functioning before and after exposure and response prevention therapy.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is associated with impaired functioning and depression. Our aim was to examine relationships between OCD symptoms, depression and functioning before and after exposure and response prevention (ERP), a type of cognitive-behavioural therapy for OCD, specifically examining whether functioning, depression and other cognitive factors like rumination and worry acted as mediators. METHODS: Forty-four individuals with OCD were randomised to 4 weeks of intensive ERP treatment first (n = 23) or waitlist then treatment (n = 21). We used a bootstrapping method to examine mediation models. RESULTS: OCD symptoms, depression and functioning significantly improved from pre- to post-intervention. Functioning mediated the relationship between OCD symptoms and depression and the relationship between functioning and depression was stronger at post-treatment. Depression mediated the relationship between OCD symptoms and functioning, but only at post-intervention. Similarly, rumination mediated the relationship between OCD symptoms and depression at post-intervention. CONCLUSIONS: Our findings suggest that after ERP, relationships between depression and functioning become stronger. Following ERP, treatment that focuses on depression and functioning, including medication management for depression, cognitive approaches targeting rumination, and behavioural activation to boost functionality may be important clinical interventions for OCD patients.

Distinguishing Fear Versus Distress Symptomatology in Pediatric OCD.

Prior research has identified OCD subtypes or "clusters" of symptoms that differentially relate to clinical features of the disorder. Given the high comorbidity between OCD and anxiety, OCD symptom clusters may more broadly associate with fear and/or distress internalizing constructs. This study examines fear and distress dimensions, including physical concerns (fear), separation anxiety (fear), perfectionism (distress), and anxious coping (distress), as predictors of previously empirically-derived OCD symptom clusters in a sample of 215 youth diagnosed with primary OCD (ages 7-17, mean age = 12.25). Self-reported separation fears predicted membership in Cluster 1 (aggressive, sexual, religious, somatic obsessions, and checking compulsions) while somatic/autonomic fears predicted membership in Cluster 2 (symmetry obsessions and ordering, counting, repeating compulsions). Results highlight the diversity of pediatric OCD symptoms and their differential association with fear, suggesting the need to carefully assess both OCD and global fear constructs that might be directly targeted in treatment.

Effects of gender and executive function on visuospatial working memory in adult obsessive-compulsive disorder.

Visuospatial working memory (VSWM) is the ability of the brain to transiently store and manipulate visual information. VSWM deficiencies have been reported in obsessive-compulsive disorder (OCD), but not consistently, perhaps due to variability in task design and clinical patient factors. To explore this variability, this study assessed effects of the design factors task difficulty and executive organizational strategy and of the clinical factors gender, OCD symptom dimension, and duration of illness on VSWM in OCD. The CANTAB spatial working memory, spatial recognition memory, delayed matching to sample, and stop signal tasks were administered to 42 adult OCD patients and 42 age- and sex-matched healthy controls. Aims were to detect a possible VSWM deficit in the OCD sample, to evaluate influences of the above task and patient factors, to determine the specificity of the deficit to the visuospatial subdomain, and to examine effects of sustained attention as potential neurocognitive confound. We confirmed previous findings of a VSWM deficit in OCD that was more severe for greater memory load (task difficulty) and that was affected by task strategy (executive function). We failed to demonstrate significant deficits in neighboring or confounding neurocognitive subdomains (visual object recognition or visual object short-term memory, sustained attention). Notably, the VSWM deficit was only significant for female patients, adding to evidence for sexual dimorphism in OCD. Again as in prior work, more severe OCD symptoms in the symmetry dimension (but no other dimension) significantly negatively impacted VSWM. Duration of illness had no significant effect on VSWM. VSWM deficits in OCD appear more severe with higher task load and may be mediated through poor task strategy. Such deficits may present mainly in female patients and in (male and female) patients with symmetry symptoms.

Glutamatergic neurometabolites during early abstinence from chronic methamphetamine abuse.

BACKGROUND: The acute phase of abstinence from methamphetamine abuse is critical for rehabilitation success. Proton magnetic resonance spectroscopy has detected below-normal levels of glutamate+glutamine in anterior middle cingulate of chronic methamphetamine abusers during early abstinence, attributed to abstinence-induced downregulation of the glutamatergic systems in the brain. This study further explored this phenomenon. METHODS: We measured glutamate+glutamine in additional cortical regions (midline posterior cingulate, midline precuneus, and bilateral inferior frontal cortex) putatively affected by methamphetamine. We examined the relationship between glutamate+glutamine in each region with duration of methamphetamine abuse as well as the depressive symptoms of early abstinence. Magnetic resonance spectroscopic imaging was acquired at 1.5 T from a methamphetamine group of 44 adults who had chronically abused methamphetamine and a control group of 23 age-, sex-, and tobacco smoking-matched healthy volunteers. Participants in the methamphetamine group were studied as inpatients during the first week of abstinence from the drug and were not receiving treatment. RESULTS: In the methamphetamine group, small but significant (5-15%, P<.05) decrements (vs control) in glutamate+glutamine were observed in posterior cingulate, precuneus, and right inferior frontal cortex; glutamate+glutamine in posterior cingulate was negatively correlated (P<.05) with years of methamphetamine abuse. The Beck Depression Inventory score was negatively correlated (P<.005) with glutamate+glutamine in right inferior frontal cortex. CONCLUSIONS: Our findings support the idea that glutamatergic metabolism is downregulated in early abstinence in multiple cortical regions. The extent of downregulation may vary with length of abuse and may be associated with severity of depressive symptoms emergent in early recovery.