Background: Obsessive-compulsive disorder (OCD) is heterogeneous, and differences in age at onset may be associated with important feature of distinct subtype. However, no studies have investigated the differences between early-and late-onset OCD using structural and functional multimodal neuroimaging methods that reflect different neurobiological backgrounds. Methods: Structural and resting-state functional magnetic resonance imaging data were obtained from 130 participants (76 medication-free patients with OCD and 54 healthy controls (HCs)). We investigated group differences among early-and late-onset OCD and HCs in the fractional amplitude of low-frequency fluctuation (fALFF) and local gyrification index (LGI). Results: In the fALFF analysis, group differences were detected in the left lateral occipital cortex and bilateral thalamus (a voxel-height threshold of p < 0.001 and a cluster-level threshold of p < 0.05, with a false discovery rate correction). Both patients with early-and late-onset OCD had significantly lower fALFF in the thalamus compared to HCs (Bonferroni corrected p < 0.01). Patients with early-onset OCD exhibited significantly lower fALFF in the lateral occipital cortex than those with late-onset OCD and HCs (Bonferroni corrected p < 0.01). No significant differences were observed in the LGI analysis (a nonparametric permutation approach (10 000 iterations)), a cluster-wise threshold of p < 0.05, and a cluster-defining threshold of p < 0.001). Limitations: Our cross-sectional data could limit the interpretation of our results. Conclusions: Our results emphasize the importance of the thalamus in the pathophysiology regardless of the age-of-onset subtype of OCD. In addition, altered fALFF in the lateral occipital cortex, not accompanied by deficits of LGI, could represent a disruption of normal functional developmental processes resulting from the OCD onset at a young age. Future study should examine the relationship between the alteration of fALFF in lateral occipital cortex and clinical and treatment-refractory features of early-onset OCD, potentially improving therapeutic strategies.
Background: The bed nucleus of the stria terminalis (BNST) plays a critical role in the neural processing of negative emotions. To date, no studies have investigated whether intrinsic connectivity of the BNST is associated with major depressive disorder (MDD) or with the severity of clinical symptoms in individuals with depression. Methods: Resting-state functional magnetic resonance imaging (7 Tesla (7T)) with seed-to-voxel-analysis was used to compare the intrinsic connectivity of the BNST between individuals with MDD (N = 17) and healthy volunteers (N = 29). Exploratory analyses were also conducted to determine whether intrinsic connectivity of the BNST was associated with the severity of clinical mood or anxiety symptoms in individuals with MDD, as assessed via scores on the clinician-administered Hamilton Anxiety Rating Scale and the Montgomery-Asberg Depression Rating Scale. Results: Compared to healthy volunteers, individuals with MDD exhibited reduced intrinsic connectivity between the BNST and regions of the right ventral striatum. No significant associations were noted between intrinsic connectivity and the severity of anxious or depressive symptoms in MDD participants. Limitations: The small sample size makes it difficult to assess whether clinical heterogeneity impacted these findings. Future studies that combine experimental paradigms with neuroimaging are needed to shed light on the functional implications of these results. Conclusions: Reduced intrinsic connectivity between the BNST and striatum may reflect altered activity in the neural circuits responsible for stress and reward processing. These findings can be used to guide future work investigating risk factors for MDD and provide potential targets for clinical intervention. Clinicaltrials.gov Identifier: NCT02543983, NCT02484456, NCT02122562
BACKGROUND:Inhibitory control deficits are a core feature of schizophrenia, yet their spectral and temporal characteristics remain poorly defined. This study investigates fast-response inhibition in first-episode schizophrenia (FES) by focusing on low gamma-band (30-50 Hz) oscillations within the right inferior frontal gyrus (rIFG)-pre-supplementary motor area (preSMA) circuit. METHODS:We conducted a magnetoencephalography (MEG) study involving FES, their first-degree relatives (FDR), and healthy controls (HCs), examining post-stimulus low gamma (30-50 Hz) and beta-band activity across rIFG-preSMA and preSMA-lM1 circuits. Power spectral density (PSD) and functional connectivity (FC) were segmented into middle (150-250 ms) and later (250-400 ms) stages. Behavioral data (BIS-11, DSST) were integrated with MEG features in two canonical discriminant models (Model 1: multimodal; Model 2: behavior-only), with independent temporal validation. RESULTS:FES patients showed early low gamma power reductions in rIFG and preSMA, followed by increased rIFG-preSMA connectivity during later stages-suggesting phase-specific disruption and compensatory adaptation. Model 1 achieved 95.2% classification accuracy (80.6% cross-validated), identifying rIFG-preSMA low gamma connectivity as the strongest neural discriminator. Model 2 retained 88.5% accuracy on temporally independent samples using only BIS and DSST measures. FDR occupied an intermediate position in both models, supporting a dimensional liability continuum. LIMITATIONS:The modest sample size, especially for the MEG recordings, may limit generalizability. Medication effects in the FES group and the cross-sectional design may also confound causal interpretation. CONCLUSION:This study delineates a frequency- and phase-specific disruption in fast-response inhibition in schizophrenia, centered on rIFG-preSMA low gamma desynchronization. The identified neural and behavioral signatures support a dimensional risk framework and may inform early detection strategies in clinical and familial populations.
Erythropoietin-producing hepatocellular (Eph) receptors are tyrosine kinase receptors that are canonically activated by their membrane tethered ligands, the ephrins. The Eph-ephrin system is critical in neurodevelopment, involved in processes such as neuronal growth and proliferation, axonal growth cone guidance, and cell survival. However, there is a significant knowledge gap in our understanding of the functional role of the Eph-ephrin system in later development, in both the adolescent and the adult brain. As various Eph receptor subtypes, and their associated ephrin ligands, are involved in the regulation of processes implicated in brain disorder pathogenesis, the Eph-ephrin system may represent an unexplored avenue for therapeutic target identification. Here, we will consolidate what is known about the Eph-ephrin system in synaptic plasticity, inflammation, and vascular permeability, linking the effects of specific ephrins and Eph receptors to depression and anxiety, autism, and schizophrenia. Novel insights into those Eph receptors with the most therapeutic promise will be provided and potential challenges of targeting these widely expressed receptor kinases discussed.
Background: Addiction is a multifaceted disorder driven by complex neurobiological and psychological mechanisms. The Addictions Neuroclinical Assessment (ANA) framework offers a dimensional mechanistic approach, focusing on three core domains: incentive salience, negative emotionality, and executive function. This study aimed to validate the ANA framework in relation to hazardous drinking using a machine learning approach, with the hypothesis that incentive salience and negative emotionality would be most strongly associated with drinking severity. Methods: We analysed two independent datasets: a cohort of 1260 nonclinical community-based adults ascertained in 2016-2018 and a cohort of 655 young adults reporting regular binge drinking ascertained in 2017-2018. The three ANA domains were operationalized using behavioural and self-report measures. Four machine learning models (elastic net, support vector machines, random forest, and gradient boosting machines) with nested five-fold cross-validation were used to assess relations between ANA domains and hazardous drinking as measured via the Alcohol Use Disorder Identification Test (AUDIT), a validated screening instrument. Results: Across both datasets, elastic net consistently outperformed other models. Incentive salience, largely reflecting alcohol's reinforcing value, was most robustly related to AUDIT score (R2 = 0.389-0.419), followed by negative emotionality (R2 = 0.293-0.317), largely reflecting drinking to cope. Executive function, reflecting impulsivity and inhibitory control, accounted for less variance (R2 = 0.098-0.109). Optimizing elastic net models via meta-learner further improved performance, explaining more than half of the variance (R2 = 0.539-0.549). Limitations: These findings may not generalize to individuals who are older or have severe AUD. Cross-sectional data limits longitudinal causal inferences. Conclusion: These results provide robust computational validation for the ANA framework, emphasizing incentive salience and negative emotionality as key domains linked to AUDIT score. Future research should explore diagnostic and longitudinal applications.
Background: Obsessive-compulsive disorder (OCD) remains refractory to conventional pharmacological and psychotherapeutic treatments in a substantial proportion of patients. Neuromodulation has emerged as a promising intervention, but optimal neural circuit targets remain unclear. This systematic review and meta-analysis aimed to evaluate the efficacy of invasive and non-invasive neuromodulation for OCD using a circuit-based framework and to translate these findings into clinical practice. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials investigating neuromodulation for OCD. PubMed/MEDLINE, Web of Science, and the Cochrane Library were searched from database inception to December 2023. Eligible studies included adult patients with a primary diagnosis of OCD receiving invasive or non-invasive neuromodulation, with symptom outcomes assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Random-or fixed-effects meta-analyses were performed using mean differences or standardized mean differences, depending on heterogeneity. The review was registered in PROSPERO (CRD42024518326). Results: Twenty-seven randomized controlled trials involving 868 patients met inclusion criteria. Overall, neuromodulation significantly reduced OCD symptoms compared with control conditions. Circuit-based subgroup analyses indicated that modulation of the fronto-limbic circuit--primarily via invasive deep brain stimulation--was associated with the largest and most consistent Y-BOCS improvements, while sensorimotor, dorsal cognitive, and ventral affective circuits also demonstrated significant but more heterogeneous effects. Invasive neuromodulation showed greater efficacy than non-invasive approaches. These findings informed a translational multi-target deep brain stimulation case, demonstrating clinically meaningful symptom improvement (Y-BOCS decreased from 25 to 16 after 6 months). Limitations: Heterogeneity across non-invasive studies, short follow-up durations, and limited circuit-specific data constrain interpretation of long-term and symptom-domain-specific effects. Conclusions: This systematic review, meta-analysis, and case study suggest that circuit-based neuromodulation--particularly targeting the fronto-limbic circuit--may offer the most consistent benefit for treatment-refractory OCD. Larger, longer-term, and circuit-informed trials are needed to optimize individualized neuromodulation strategies.
BACKGROUND:Late-life depression (LLD) is the major risk factor for elderly suicide, and suicidal ideation (SI) is a crucial stage for prevention. However, LLD are less likely openly express SI. Gamma oscillations, closely linked to cognition and mental processes, may contribute to the pathophysiology of LLD and suicidal behavior through their dysregulation within large-scale brain networks. The aim of our research was to investigate the cortical functional networks in the gamma band to better understand the neurobiological mechanisms underlying SI in LLD. METHODS:Electroencephalography (EEG) was recorded from 30 LLD with SI (LLD-SI), 32 LLD without SI (LLD-NSI), and 34 normal controls. We applied source-level graph theory based on functional connectivity in gamma band and utilized machine learning to differentiate between LLD-SI and LLD-NSI groups using network features. RESULTS:Significant diminished gamma functional connectivity, particularly involving the orbitofrontal cortex, was observed in both subtypes of the LLD group. In graph theory analysis, LLD-SI showed decreased average clustering coefficient (p < 0.001) and characteristic path length (p = 0.021), along with increased global efficiency (p = 0.015) compared to LLD-NSI. Compared to NC, LLD-SI also demonstrated reduced average clustering coefficient (p = 0.004), characteristic path length (p = 0.004), and higher global efficiency (p = 0.004). We also found several nodal metrics, which suggested potential hubs related to SI. The graph theorical method effectively distinguished SI in LLD, with an accuracy of 69.35%, sensitivity of 73.33%, and specificity of 65.63% based on gamma-band network features. LIMITATIONS:The sample sizes are relatively small. Higher-density EEG systems and interventional study designs should be included in future research. Future studies should incorporate external validation datasets to confirm the clinical utility of the proposed classification framework. CONCLUSION:Our research provides valuable insights into the brain connectome in gamma band of SI in LLD. Gamma-band network indices may serve as potential biomarkers for detecting SI and offer frequency-specific targets for neuromodulation in suicide prevention and treatment strategies for LLD patients.
Sex and gender can impact cannabis use and related harms, yet the field has historically centered men and male bodies. In our recent systematic review of sex differences in the acute cognitive effects of cannabis, just six of 29 human studies found evidence that female and male participants differed in cognitive responses to cannabis. The goal of this Commentary is to discuss methodological limitations of published studies that complicate interpretation of data and to suggest priorities for future research to move this topic forward. We highlight inadequate statistical power, poor definition and measurement of sex, lack of consideration of sex- or gender-related characteristics, and no inclusion of transgender and gender-diverse individuals in prior studies. Future research should take an intersectional perspective, incorporate hypothesis-driven sex- and gender-informed designs, ensure adequate power for interaction analyses, and consider sex-related variables across the lifespan. This approach is necessary to advance scientific rigor and promote equitable health outcomes related to cannabis use.
BACKGROUND:Suicide remains a critical public health issue, with self-report-based clinical assessments often failing to detect imminent risk. This study aimed to identify objective electroencephalography (EEG)-based neurobiological markers for differentiating a suicide attempt (SA) from suicidal ideation (SI) using EEG microstate and microstate-based functional connectivity (FC) analyses. METHODS:From 2017 to 2020, this study enrolled 130 medication-naïve major depressive disorder patients (68 SA, evaluated within 7 days of the attempt; 62 SI) at Soonchunhyang University Cheonan Hospital. Resting-state EEG data were analyzed using microstate analysis to explore temporal dynamics of brain topography and microstate-based FC to assess connectivity in theta, alpha, and beta bands. Correlations between EEG features and psychological measures (e.g., suicidal ideation, depression, emotion regulation) were examined. RESULTS:Compared with the SI group, the SA group showed a marginally lower frequency of occurrence for microstates A (auditory/language processing) and B (visual processing) (p = 0.078 for both). The SA group demonstrated significantly higher alpha-band FC during microstate E (linked to the default mode network (DMN)) for several electrode pairs (e.g., F7-C5, p = 0.009; FC5-C5, p = 0.005). The SA group also exhibited marginally higher FC in the alpha band during microstates C (DMN-related) and B, and in the theta band during microstate E. A subsequent within-group analysis revealed that in the SI group, alpha-band FC during microstate E positively correlated with scores for difficulties in emotion regulation (r = 0.433, p = 0.017). LIMITATIONS:Findings are limited by potential physiological confounds in the SA group and by the limited anatomical specificity inherent in sensor-space EEG analysis. CONCLUSION:EEG microstate dynamics and microstate-based FC differ between patients with SA and SI. Specifically, enhanced alpha-band connectivity during microstate E in the SA group potentially reflects condition-specific DMN functions. These EEG-based measures show promise as objective markers that complement clinical suicide risk assessment and inform early intervention strategies.
BACKGROUND:Despite the effectiveness of specialized therapies, people with borderline personality disorder (BPD) continue to face substantial psychosocial challenges, which may be partially attributed to neuropsychological deficits arising from imbalances in the corticolimbic system. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (DLPFC) could enhance impulse control, emotional regulation, and cognitive functions; thus, we sought to explore the effectiveness of tDCS combined with online cognitive training on cognitive functions, BPD symptoms, and psychosocial functioning among patients with BPD. METHODS:This open-label study recruited adults with BPD who were not undergoing psychotherapy. Participants completed informational psychoeducation sessions, followed by 10 daily sessions of 20-minute tDCS over 2 weeks. Stimulation involved a continuous 2-mA current with the anode over the left DLPFC and the cathode over the right DLPFC. During each session, participants simultaneously engaged in online cognitive training using the Lumosity app (aspredicted.org no. 206 001). RESULTS:We included 29 participants. We noted significant improvements in cognitive functions, including the Towers of London task (Cohen d = -0.38 to -0.78), the Corsi Block-Tapping direct and total scores (d = -0.41 and -0.42, respectively), and the Stroop Interference and Alternance tests (d = 0.80 and 0.94, respectively). Emotional dysregulation showed a substantial reduction (d = 0.44), while impulsivity did not change significantly. Symptoms of BPD decreased (d = 0.69), while general functioning (d = 0.33) and the internal component of BPD functioning improved (d = -0.51). LIMITATIONS:Although these preliminary findings are encouraging, further controlled studies are necessary to validate the efficacy and long-term effect of the intervention. CONCLUSION:This combined approach appears to be well tolerated and produced promising short-term improvements in cognitive performance, BPD symptoms, and overall functioning. The results underscore the relevance of the left DLPFC in developing neuropsychologically integrative interventions for BPD.
BACKGROUND:Although the processes underlying the relationship between developmental trauma and psychosis remain to be elucidated, alterations in hippocampal-dependent memory (HDM) processing may underlie this relationship. We hypothesized that exposure to developmental trauma would be negatively associated with HDM and hippocampal volume and positively associated with intrusive memories among people with psychosis. METHODS:We conducted a systematic search of studies published from Dec. 18, 2020, to Nov. 14, 2023, using the search terms "childhood," "trauma," "psychosis," and "memory processing" in Embase, PsycINFO, MEDLINE, OpenGrey, Google Scholar, and PTSDpubs. We conducted meta-analyses of studies that measured developmental trauma (self-report questionnaires or interviews), HDM (episodic memory performance and trauma-memory intrusions), semantic and recognition-memory performance, and hippocampal volume among people with psychosis. Subsample analysis determined whether these associations differed across the psychosis spectrum or for specific abuse types. RESULTS:We included 26 studies. Meta-analyses found that developmental trauma was not associated with total hippocampal volume (n = 4, outcomes = 6, d = -0.12, standard error [SE] = 0.20, p = 0.2), episodic memory performance (n = 10, outcomes = 42, d = 0.11, SE = 0.19, p = 0.5), recognition (n = 3, outcomes = 4, d = -0.55, SE = 0.58, p = 0.3), or semantic memory performance (n = 4, outcomes = 6, d = 0.08, SE = 0.13, p = 0.6) in participants across the psychosis spectrum. One study found that developmental trauma was associated with impaired episodic memory performance in participants with schizotypal disorder and participants with a mixed phenotype of affective and psychotic symptoms. Two studies found developmental trauma to be associated with increased involuntary memory intrusions in a sample of people with psychosis. LIMITATIONS:We did not control for age of trauma, sex, or chronicity of trauma. Results should be considered with caution, given the high publication bias and study heterogeneity seen within meta-analyses. CONCLUSION:The association between developmental trauma and memory processing may not affect HDM more than the psychotic symptoms already experienced by affected individuals. However, future studies should focus on the effects of developmental trauma on involuntary memory among people with psychosis.
BACKGROUND:Both cerebral blood flow (CBF) and fractional anisotropy (FA) are altered in bipolar disorder (BD). We sought to investigate the unexplored CBF-FA association in relation to youth BD. METHODS:We recruited youth with BD, high-risk youth with a family history of BD, and healthy controls. Using 3 T magnetic resonance imaging, we measured global and regional grey matter CBF using arterial spin labelling and we measured regional FA using diffusion tensor imaging. We explored the CBF-FA association across groups, between groups, and by sex. Analyses of the BD group further examined mood effects. We conducted region-of-interest analyses of global CBF and FA, anterior cingulate cortex (ACC) CBF, and cingulate FA. RESULTS:We included 59 youth with BD, 19 high-risk youth with a family history of BD, and 47 healthy controls. There were no significant CBF-FA associations in the overall sample. Within the BD group, higher ACC CBF was associated with higher cingulum FA (β-weight 0.30, p = 0.03), with larger effect sizes among females and asymptomatic participants. Among controls, higher global CBF was associated with lower global FA (β-weight -0.40, p = 0.05). Within-sex analyses in the overall sample revealed a small effect size association between ACC CBF and cingulum FA among females only. LIMITATIONS:Our small sample size limited power, and our cross-sectional observational design precluded directional inferences about CBF-FA associations. CONCLUSION:We found preliminary evidence that ACC CBF was positively associated with cingulum FA among youth with BD, which may be driven by asymptomatic female participants. These associations may relate to differences in cerebral metabolism or white matter perfusion. Prospective and experimental studies are warranted to better understand CBF-FA associations in BD.
BACKGROUND:Brain-derived neurotrophic factor (BDNF) is a key factor in neurodevelopment of autism spectrum disorder (ASD), yet the variability of peripheral BDNF levels in ASD remains debated. We sought to investigate the relationship between circulating oxidative stress and peripheral BDNF in children with ASD. METHODS:We analyzed plasma BDNF levels and redox status in both plasma and peripheral blood mononuclear cells (PBMCs) among children with ASD and typically developing (TD) children aged 2-5 years. We generated an autism-like mouse model via prenatal exposure to medroxyprogesterone acetate (MPA). To modulate circulating redox balance, we employed tyrosine kinase-driven lentiviral expression of superoxide dismutase 2 (Sod2) and hematopoietic stem cell (HSC) transplantation with Sod2 overexpression. We then assessed circulating redox balance, gene expression, epigenetic changes, peripheral BDNF levels, and autism-like behaviours in offspring. RESULTS:We included 78 children in the ASD group and 63 children in the TD group. Children with ASD exhibited elevated plasma BDNF levels and an altered redox balance compared with TD controls. In the mouse model, MPA-exposed autism-like offspring demonstrated increased peripheral BDNF levels and heightened oxidative stress in hematopoietic stem cells, endothelial cells, and PBMCs. Tyrosine kinase-Sod2 lentiviral expression in the endothelium fully normalized peripheral BDNF levels, while HSC transplantation with Sod2 overexpression not only reduced plasma BDNF levels, but also alleviated autism-like behaviours. LIMITATIONS:This study's cross-sectional data limit causal inference between oxidative stress and BDNF levels among children with ASD. The mouse model, while informative, may not fully recapitulate human ASD heterogeneity. CONCLUSION:In ASD, elevated peripheral BDNF levels are associated with circulating oxidative stress. Prenatal progestin exposure induces both increased peripheral BDNF and oxidative stress, effects that can be completely reversed through SOD2 modulation in circulation among mouse offspring.
BACKGROUND:A history of trauma increases risk for excessive and problematic cannabis use, and this relationship may involve conditioned cannabis craving to trauma cues arising through classical and operant conditioning. Alterations in functional connectivity (FC) after trauma reminders within or between brain regions associated with reward processing may potentiate this link; however, the underlying neural mechanisms remain unstudied. METHODS:We recruited cannabis users with trauma histories from February 2021 to August 2022. Participants completed a semi-structured interview about a personally relevant traumatic experience, a typical cannabis use situation unrelated to trauma or stress, and an emotionally neutral situation, with responses informing development of 3-minute audiovisual cues. Using a randomized cross-over design, we presented personalized audio recordings and images of the neutral, cannabis-related, and trauma-related situations to participants in counterbalanced order using a cue reactivity paradigm adapted for the magnetic resonance imaging (MRI) environment. Participants self-reported on subjective cannabis craving and positive and negative affect after each cue presentation. We measured FC between striatal, cortical, and limbic regions via functional MRI during each cue. RESULTS:We included 27 cannabis users with trauma histories (74.1% female, average age 32.2 years, standard deviation 10.5 years). Trauma cues increased cannabis craving and negative affect and decreased positive affect relative to other cues. Cannabis cues increased craving relative to neutral and baseline cues. Trauma cues increased FC within the striatum and between striatal-cortical regions relative to neutral cues and increased striatocortical FC relative to cannabis cues. Cannabis cues increased cortical and corticolimbic FC relative to trauma cues and increased striatocortical FC relative to neutral cues. LIMITATIONS:The sample was small in size and not formed exclusively of participants with diagnoses of posttraumatic stress disorder or cannabis use disorder. CONCLUSION:Findings suggested potential neural mechanisms underlying the link between trauma and cannabis use. Trauma- and cannabis-related cues may potentiate cannabis craving through altered reward circuit FC.
BACKGROUND:Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) often show cognitive deficits. Given that some evidence has suggested transcranial direct current stimulation (tDCS) as a potential alternative or adjunct to psychostimulants, we sought to perform a meta-analysis and systematic review to evaluate the effects of tDCS on clinical symptoms and cognitive function among children and adolescents with ADHD, as well as to summarize associated adverse effects. METHODS:We searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library up to May 7, 2025 for randomized controlled trials (RCTs) involving children and adolescents with ADHD who underwent tDCs therapy. The outcome included specific cognitive function assessments and clinical symptoms. RESULTS:We included 18 RCTs that involved 496 children and adolescents with ADHD, of which 14 trials (n = 388) were included in the meta-analysis. The results indicated that there was no significant improvement in clinical symptoms (standardized mean difference [SMD] 0.012, 95% confidence interval [CI] -0.235 to 0.259) and processing speed (SMD 0.063, 95% CI -0.145 to 0.27) compared with controls. For cognitive function, those who underwent tDCS showed significant improvement effects in attention (SMD 0.207, 95% CI 0.011 to 0.403) and inhibitory control (SMD 0.222, 95% CI 0.045 to 0.399). Subgroup analyses revealed that stimulation at the F3 site was more effective in improving attention, inhibitory control, and processing speed. A current intensity of 1 mA outperformed currents of 1.5 mA and 2 mA in enhancing inhibitory control, and the cathode was more effective than the anode. A single stimulation session appeared effective in improving attention and inhibitory control, although further studies are needed to confirm these findings. LIMITATIONS:Some subgroup analyses included few studies, lacked ADHD subtype delineation, and involved only single-dimensional analysis, which limited comprehensive conclusions. CONCLUSION:Overall, tDCS may improve the attention and inhibitory abilities of children and adolescents with ADHD, particularly with optimal stimulation parameters (F3 site, a current intensity of 1 mA, cathodal stimulation, and single-session stimulation). These findings suggest therapeutic potential but require larger clinical validation.
BACKGROUND:Mood disorders, including depressive and bipolar disorders, begin in late adolescence to early adulthood, tend to run in families, and present early with subthreshold symptoms. They have been associated with differential connectivity in 3 core networks: the default mode network (DMN), cognitive executive network (CEN), and salience network (SN), but it remains unclear whether differences in connectivity in the DMN, CEN, and SN are associated with familial risk for mood disorders. METHODS:We recruited youth aged 9-19 years, including offspring of parents with major depressive or bipolar disorders (familial high risk [FHR]) and offspring of parents with no mood disorder (controls) for a resting-state functional magnetic resonance imaging study. We tested associations between family history of major mood disorders and connectivity within and between the DMN, CEN, and SN. RESULTS:We included 215 youth: 126 at FHR with a mean age of 13.38 (standard deviation [SD] 2.91) years and 79 controls with a mean age of 13.17 (SD 2.67) years. Mean connectivity in the DMN (β = 0.003, 95% confidence interval [CI] -0.023 to 0.029), CEN (β = -0.009, 95% CI, -0.070 to 0.089), and SN (β = -0.010, 95% CI -0.071 to 0.051) in the FHR group was similar to that of controls. Moreover, DMN, CEN, and SN connectivity was not significantly associated with depressive symptoms. LIMITATIONS:Given that brain connectivity changes over the developmental period, longitudinal studies would improve understanding of how this change occurs in familial risk groups to identify critical time periods for intervention or prevention of mood disorders. CONCLUSION:Connectivity within and between the DMN, CEN, and SN is not a neural indicator of familial risk for major mood disorders.
BACKGROUND:Although it has been suggested that the hippocampus and amygdala (HA) are involved in the neurobiology of obsessive-compulsive disorder (OCD), volumetric findings have been inconsistent, and little work has been undertaken on the volumetry of the heterogeneous anatomic units of HA, with their specific functions and cytoarchitecture, in OCD. We sought to explore potential sources of heterogeneity in brain volumes by performing a separate analysis for people with and without psychotropic medication use, as well as the association of subfield volumes with OCD symptom severity. METHODS:We segmented T 1-weighted images from people with OCD and healthy controls in the OCD Brain Imaging Consortium to produce 12 hippocampal subfields and 9 amygdala subfields using Free-Surfer 6.0. We assessed between-group differences in subfield volume using a mixed-effects model adjusted for age and quadratic effects of age, sex, site, and whole HA volume. We also performed subgroup analyses to examine subfield volume in relation to comorbid anxiety and depression, medication status, and symptom severity. We corrected all analyses for multiple comparisons using the false discovery rate (FDR). RESULTS:We included images from 381 people with OCD and 338 healthy controls. These groups did not significantly differ in HA subfield volumes. However, medicated people with OCD had significantly smaller volumes in the hippocampal dentate gyrus (p FDR = 0.04, d = -0.26) and molecular layer (p FDR = 0.04, d = -0.29), and larger volumes in the lateral (p FDR = 0.049, d = 0.23) and basal (p FDR = 0.049, d = 0.25) amygdala subfields, than healthy controls. Unmedicated people with OCD had significantly smaller volumes in the hippocampal cornu ammonis sector 1 (p FDR = 0.02, d = -0.28) than controls. We did not detect associations between any subfield volume and OCD severity. LIMITATIONS:We used cross-sectional data, which limits the interpretation of our analysis. CONCLUSION:Differences in HA subfields between people with OCD and healthy controls are dependent on medication status, in line with previous work on other brain volumetric alterations in OCD. This emphasizes the importance of considering psychotropic medication in neuroimaging studies of OCD.
BACKGROUND:Numerous neuroimaging studies investigating the neural substrates of obsessive-compulsive disorder (OCD) have yielded inconsistent findings, and growing evidence suggests that psychiatric disorders are more accurately localized to brain networks rather than discrete brain regions. We sought to identify brain network localization in OCD. METHODS:We initially examined brain locations of structural and functional alterations among patients with OCD and healthy controls using neuroimaging studies. Employing a novel technique called functional connectivity network mapping (FCNM) and large-scale human brain connectome data, we mapped these damaged brain regions to 2 brain impairment networks in OCD. RESULTS:We included 62 neuroimaging studies involving 2578 patients with OCD and 2502 healthy controls. For FCNM, we used data from 556 healthy adults. Among patients with OCD, the grey matter volume (GMV) and resting-state activity impairment networks encompassed a broad range of brain regions, primarily involving the default mode, sensorimotor, and limbic networks, as well as the bilateral middle frontal gyrus and bilateral middle temporal gyrus. Additionally, the GMV impairment network specifically involved bilateral inferior frontal gyrus. LIMITATIONS:We used large-scale human brain connectome data from healthy people, rather than the samples clinically and demographically matched to the original study participants, to examine brain networks in OCD. CONCLUSION:Our study integrated an FCNM method with large-scale human brain connectome data to map heterogeneous abnormal brain locations of OCD to structural and functional impairment networks. Our findings deepen our understanding of the neuropathological mechanisms of OCD from a network perspective and may inform future neuromodulation treatment.
BACKGROUND:Despite the prevalence and impact of body dysmorphic concerns on psychosocial functioning, there remains a scarcity of research examining the neurobiological and psychological correlates of these symptoms in healthy individuals. Given that previous studies on clinical body dysmorphic disorder (BDD) revealed brain structural and functional differences in limbic, frontal, and visual processing areas, as well as cognitive and emotional deficits, we sought to investigate the associations between grey matter volume (GMV), subclinical body dysmorphic symptom severity, alexithymia, and rumination. METHODS:We assessed GMV using structural magnetic resonance imaging (MRI) in a sample of healthy participants. We employed a region-of-interest (ROI) approach, including the medial orbital superior frontal gyrus (SFG), precuneus, amygdala, hippocampus, anterior cingulate cortex (ACC), and inferior occipital gyrus (IOG). We analyzed associations between ROIs and body dysmorphic symptoms, with particular emphasis on the impact of gender on these associations. We corrected p values using threshold-free cluster enhancement and established a conservative family-wise error (FWE) threshold value of 0.05. RESULTS:We included 219 participants. Our analysis revealed an interaction effect between body dysmorphic symptom score and gender in the right amygdala (p FWE = 0.01), bilateral hippocampus (right p FWE = 0.02; left p FWE = 0.04), and right IOG (p FWE = 0.01), reflecting a trend toward positive associations between body dysmorphic symptoms and GMV among men and negative associations among women. No significant relationships were found in the SFG, ACC, and precuneus. Women exhibited elevated levels of body dysmorphic symptoms compared with men, and body areas of concern differed between genders. Additionally, alexithymia predicted body dysmorphic symptom severity among women only. LIMITATIONS:The specificities of structural MRI measurements and cross-sectional study designs should be taken into account when interpreting these results. CONCLUSION:Our findings suggest an association between subclinical body dysmorphic symptoms and brain structure in limbic and visual areas moderated by gender. Insights into body dysmorphic symptomatology drawn from subclinical samples may offer valuable insights into predisposing factors in the etiology of BDD and may aid in developing targeted prevention strategies.
BACKGROUND:Suicide risk is a major concern for patients with major depressive disorder (MDD). Neuroimaging studies have demonstrated that patients with MDD with suicidal ideation or suicide attempt (MDD-S) are accompanied by neurostructural or functional abnormalities, but there is no consensus of opinion on neural substrate alterations involved in MDD-S. METHODS:We performed a whole-brain multimodal meta-analysis of existing magnetic resonance imaging (MRI) studies to identify conjoint and separate alterations of grey matter volume (GMV) and spontaneous brain activity characteristics (regional homogeneity and amplitude of low-frequency fluctuations) between patients with MDD-S and patients with MDD without suicidal ideation or suicidal attempt (MDD-NS) via the seed-based d mapping software. We excluded studies that used other modalities, had overlapping data, or had insufficient information. RESULTS:Our systematic search identified 13 structural MRI studies (471 patients with MDD-S and 508 patients with MDD-NS) and 16 resting-state functional MRI studies (704 patients with MDD-S and 554 patients with MDD-NS) published up to Dec. 5, 2023. Compared with patients with MDD-NS, those with MDD-S showed increased GMV with hypoactivity in the left postcentral gyrus, decreased GMV with hypoactivity in the right inferior parietal gyri, decreased GMV with hyperactivity in the right insula, and separate GMV and functional changes within the bilateral parietal, occipital, and frontal lobes, and the left thalamus. LIMITATIONS:We were unable to analyze the association between brain features and clinical detail because of a lack of data. Included studies showed considerable heterogeneity and publication bias. CONCLUSION:These findings provide a comprehensive overview of brain morphological and spontaneous functional impairments linked to impulsivity, impaired positive reward modulation, emotional disturbances, abnormal emotional processing, and cognitive deficits in MDD-S. These results support an understanding of the relationship between neural substrates and clinical symptoms in MDD-S, and these alterations provide useful insight into pathophysiological mechanisms and intervention strategies to decrease suicide risk in MDD.
