RESUMO
Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition that is difficult to treat due to our limited understanding of its pathophysiology. Functional connectivity in brain networks, as evaluated through neuroimaging studies, plays a pivotal role in understanding OCD. While both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been extensively employed in OCD research, few have fully synthesized their findings. To bridge this gap, we reviewed 166 studies (10 EEG, 156 fMRI) published up to December 2023. In EEG studies, OCD exhibited lower connectivity in delta and alpha bands, with inconsistent findings in other frequency bands. Resting-state fMRI studies reported conflicting connectivity patterns within the default mode network (DMN) and sensorimotor cortico-striato-thalamo-cortical (CSTC) circuitry. Many studies observed decreased resting-state connectivity between the DMN and salience network (SN), implicating the 'triple network model' in OCD. Task-related hyperconnectivity within the DMN-SN and hypoconnectivity between the SN and frontoparietal network suggest OCD-related cognitive inflexibility, potentially due to triple network dysfunction. In conclusion, our review highlights diverse connectivity differences in OCD, revealing complex brain network interplay that contributes to symptom manifestation. However, the presence of conflicting findings underscores the necessity for targeted research to achieve a comprehensive understanding of the pathophysiology of OCD.
Assuntos
Encéfalo , Eletroencefalografia , Imageamento por Ressonância Magnética , Rede Nervosa , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Conectoma/métodosRESUMO
A large-scale biophysical network model for the isolated striatal body is developed to optimise potential intrastriatal deep brain stimulation applied to, e.g. obsessive-compulsive disorder. The model is based on modified Hodgkin-Huxley equations with small-world connectivity, while the spatial information about the positions of the neurons is taken from a detailed human atlas. The model produces neuronal spatiotemporal activity patterns segregating healthy from pathological conditions. Three biomarkers were used for the optimisation of stimulation protocols regarding stimulation frequency, amplitude and localisation: the mean activity of the entire network, the frequency spectrum of the entire network (rhythmicity) and a combination of the above two. By minimising the deviation of the aforementioned biomarkers from the normal state, we compute the optimal deep brain stimulation parameters, regarding position, amplitude and frequency. Our results suggest that in the DBS optimisation process, there is a clear trade-off between frequency synchronisation and overall network activity, which has also been observed during in vivo studies.
Assuntos
Estimulação Encefálica Profunda , Modelos Neurológicos , Estimulação Encefálica Profunda/métodos , Humanos , Corpo Estriado/fisiologia , Neurônios/fisiologia , Rede Nervosa/fisiologia , Transtorno Obsessivo-Compulsivo/terapia , Transtorno Obsessivo-Compulsivo/fisiopatologiaRESUMO
Obsessive-compulsive disorder is a neuropsychiatric condition with notable genetic involvement. Against this background, laboratory-housed deer mice of both sexes varyingly present with excessive and persistent large nesting behavior (LNB), which has been validated for its resemblance of clinical compulsivity. Although LNB differs from normal nesting behavior (NNB) on both a biological and cognitive level, it is unknown to what extent the expression of LNB and NNB is related to familial background. Here, we randomly selected 14 NNB- and 14 LNB-expressing mice (equally distributed between sexes) to constitute 7 breeding pairs of each phenotype. Pairs were allowed to breed two successive generations of offspring, which were raised until adulthood (12 weeks) and assessed for nesting expression. Remarkably, our findings show that offspring from LNB-expressing pairs build significantly larger nests compared to offspring from NNB-expressing pairs and the nesting expression of the offspring of each breeding pair, irrespective of parental phenotype or litter, is family specific. Collectively, the results of this investigation indicate that LNB can be explored for its potential to shed light on heritable neurocognitive mechanisms that may underlie the expression of specific persistent behavioral phenotypes.
Assuntos
Comportamento de Nidação , Peromyscus , Animais , Comportamento de Nidação/fisiologia , Masculino , Feminino , Peromyscus/fisiologia , Camundongos , Modelos Animais de Doenças , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/genética , Comportamento Compulsivo/fisiopatologia , Fenótipo , Comportamento Animal/fisiologiaRESUMO
While previous research has shown that compulsivity is related to an imbalance between goal-directed and habitual learning systems, very little is known about whether this effect is due to the impairment of a single system or the impairment of the arbitration mechanism that determines which system controls behaviour at any given moment; the current study aims to address this disagreement. Nineteen alcohol use disorder, 30 obsessive-compulsive disorder (OCD) and 20 major depressive disorder patients and corresponding sex- and age-matched controls performed two-choice, three-stage Markov decision-making paradigm. Model-based and mode-free reinforcement learning models were used to independently fitted their behavioural data. Alcohol use disorder and OCD patients showed less model-based strategy choice than healthy controls in task conditions where the model-based strategy was optimal. Only OCD patients showed higher behavioural control system switching in task conditions where model-free use was optimal. Major depressive disorder patients did not differ from the matched control in both. These findings suggest that dysfunction in arbitration control between dual systems may be the basis for diverse disorders involving compulsivity.
Assuntos
Tomada de Decisões , Transtorno Depressivo Maior , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/psicologia , Masculino , Feminino , Adulto , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Pessoa de Meia-Idade , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Reforço Psicológico , Estudos de Casos e Controles , Comportamento Compulsivo/psicologia , Cadeias de Markov , Aprendizagem/fisiologia , Comportamento de EscolhaRESUMO
Obsessive-compulsive disorder (OCD) is a clinically challenging and refractory psychiatric disorder characterized by pathologically hyperactivated brain activity. Continuous theta burst stimulation (cTBS) is considered a potentially non-invasive treatment for inducing inhibitory effects on the underlying cortex. Numerous studies showed an unsatisfactory efficacy of cTBS for OCD. Accordingly, it seems that cTBS is ineffective for OCD. However, the neglect of varying OCD severities, modest sample size, absence of a multicenter design incorporating inpatients and outpatients, and lack of personalized imaging-guided targeting may constrain the conclusive findings of cTBS efficacy for OCD. In the preliminary experiment, 50 inpatients with OCD were enrolled to receive cTBS (10 sessions/day for five continuous days) or sham over the personalized right pre-supplementary motor area determined by the highest functional connectivity with the subthalamic nucleus according to our prior study. In the extension experiment, 32 outpatients with OCD received cTBS to generalize the treatment effects. The Yale-Brown Obsessive-Compulsive Scale (YBOCS) was assessed before and after treatment. In the preliminary experiment, the response rates in the cTBS group were 56.52%, respectively, significantly higher than those in the sham group. Further analysis revealed significant YBOCS improvement in patients with moderate OCD symptoms than those with severe OCD symptoms. In the extension experiment, the response rates were 50.00%. Additionally, a significant decrease in YBOCS scores was only found in patients with moderate OCD symptoms. This is the first study with an external validation design across two centers to identify OCD symptoms as playing an important role in cTBS treatment effects, especially in patients with moderate OCD symptoms.
Assuntos
Transtorno Obsessivo-Compulsivo , Estimulação Magnética Transcraniana , Humanos , Transtorno Obsessivo-Compulsivo/terapia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Masculino , Feminino , Adulto , Estimulação Magnética Transcraniana/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem , Córtex Motor/fisiopatologia , Ritmo TetaRESUMO
Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors, with childhood trauma recognized as a contributing factor to its pathophysiology. This study aimed to delineate brain functional aberrations in OCD patients and explore the association between these abnormalities and childhood trauma, to gain insights into the neural underpinnings of OCD. Forty-eight drug-naive OCD patients and forty-two healthy controls (HC) underwent resting-state functional magnetic resonance imaging and clinical assessments, including the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Childhood Trauma Questionnaire-Short Form (CTQ-SF). Compared to HCs, OCD patients exhibited significantly decreased amplitude of low-frequency fluctuations (ALFF) in the right cerebellum, decreased regional homogeneity (ReHo) in the right cerebellum and right superior occipital lobes (FWE-corrected p < 0.05), which negatively correlated with Y-BOCS scores (p < 0.05). Furthermore, cerebellar ALFF negatively correlated with the CTQ emotional abuse subscale (r = - 0.514, p < 0.01). Mediation analysis revealed that cerebellar ALFF mediated the relationship between CTQ-emotional abuse and Y-BOCS (good model fit: R2 = 0.231, MSE = 14.311, F = 5.721, p < 0.01; direct effect, c' = 0.153, indirect effect, a*b = 0.191). Findings indicated abnormal spontaneous and regional cerebellar activity in OCD, suggesting childhood trauma impacts OCD symptoms through cerebellar neural remodeling, highlighting its importance for clinical treatment selection.
Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Masculino , Feminino , Adulto , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Cerebelo/fisiopatologia , Cerebelo/diagnóstico por imagem , Mapeamento Encefálico , Adulto Jovem , Estudos de Casos e ControlesRESUMO
Patients with mental illnesses, particularly psychosis and obsessiveâcompulsive disorder (OCD), frequently exhibit deficits in executive function and visuospatial memory. Traditional assessments, such as the ReyâOsterrieth Complex Figure Test (RCFT), performed in clinical settings require time and effort. This study aimed to develop a deep learning model using the RCFT and based on eye tracking to detect impaired executive function during visuospatial memory encoding in patients with mental illnesses. In 96 patients with first-episode psychosis, 49 with clinical high risk for psychosis, 104 with OCD, and 159 healthy controls, eye movements were recorded during a 3-min RCFT figure memorization task, and organization and immediate recall scores were obtained. These scores, along with the fixation points indicating eye-focused locations in the figure, were used to train a Long Short-Term Memory + Attention model for detecting impaired executive function and visuospatial memory. The model distinguished between normal and impaired executive function, with an F1 score of 83.5%, and identified visuospatial memory deficits, with an F1 score of 80.7%, regardless of psychiatric diagnosis. These findings suggest that this eye tracking-based deep learning model can directly and rapidly identify impaired executive function during visuospatial memory encoding, with potential applications in various psychiatric and neurological disorders.
Assuntos
Aprendizado Profundo , Função Executiva , Tecnologia de Rastreamento Ocular , Humanos , Função Executiva/fisiologia , Feminino , Masculino , Adulto , Adulto Jovem , Testes Neuropsicológicos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtornos Mentais/fisiopatologia , Transtornos Mentais/diagnóstico , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Memória de Curto Prazo/fisiologia , Adolescente , Movimentos Oculares/fisiologia , Atenção/fisiologiaRESUMO
BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling disorder in which the temporal variability of regional brain connectivity is not well understood. The aim of this study was to investigate alterations in static and dynamic intrinsic neural activity (INA) in first-episode OCD and whether these changes have the potential to reflect neurotransmitters. METHODS: A total of 95 first-episode OCD patients and 106 matched healthy controls (HCs) were included in this study. Based on resting-state functional magnetic resonance imaging (rs-fMRI), the static and dynamic local connectivity coherence (calculated by static and dynamic regional homogeneity, sReHo and dReHo) were compared between the two groups. Furthermore, correlations between abnormal INA and PET- and SPECT-derived maps were performed to examine specific neurotransmitter system changes underlying INA abnormalities in OCD. RESULTS: Compared with HCs, OCD showed decreased sReHo and dReHo values in left superior, middle temporal gyrus (STG/MTG), left Heschl gyrus (HES), left putamen, left insula, bilateral paracentral lobular (PCL), right postcentral gyrus (PoCG), right precentral gyrus (PreCG), left precuneus and right supplementary motor area (SMA). Decreased dReHo values were also found in left PoCG, left PreCG, left SMA and left middle cingulate cortex (MCC). Meanwhile, alterations in INA present in brain regions were correlated with dopamine system (D2, FDOPA), norepinephrine transporter (NAT) and the vesicular acetylcholine transporter (VAChT) maps. CONCLUSION: Static and dynamic INA abnormalities exist in first-episode OCD, having the potential to reveal the molecular characteristics. The results help to further understand the pathophysiological mechanism and provide alternative therapeutic targets of OCD.
Assuntos
Imageamento por Ressonância Magnética , Neurotransmissores , Transtorno Obsessivo-Compulsivo , Humanos , Masculino , Feminino , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Adulto , Adulto Jovem , Neurotransmissores/metabolismo , Tomografia por Emissão de Pósitrons , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Estudos de Casos e Controles , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismoRESUMO
BACKGROUND: Compulsive- and anxiety-like behaviour can be efficiently modelled in SAPAP3 knockout (KO) mice, a preclinical model of relevance to obsessive-compulsive disorder (OCD). Although there is emerging evidence in the clinical literature of gastrointestinal dysfunction in OCD, no previous studies have investigated gut function in preclinical models of relevance to OCD. Similarly, the effects of voluntary exercise (EX) or environmental enrichment (EE) have not yet been explored in this context. METHOD: We comprehensively phenotyped the SAPAP3 KO mouse model, including the assessment of grooming microstructure, anxiety- and depressive-like behaviour, and gastrointestinal function. Mice were exposed to either standard housing (SH), exercise (EX, provided by giving mice access to running wheels), or environmental enrichment (EE) for 4 weeks to investigate the effects of enriched housing conditions in this animal model relevant to OCD. FINDINGS: Our study is the first to assess grooming microstructure, perseverative locomotor activity, and gastrointestinal function in SAPAP3 KO mice. We are also the first to report a sexually dimorphic effect of grooming in young-adult SAPAP3 KO mice; along with changes to grooming patterning and indicators of gut dysfunction, which occurred in the absence of gut dysbiosis in this model. Overall, we found no beneficial effects of voluntary exercise or environmental enrichment interventions in this mouse model; and unexpectedly, we revealed a deleterious effect of wheel-running exercise on grooming behaviour. We suspect that the detrimental effects of experimental housing in our study may be indicative of off-target effects of stress-a conclusion that warrants further investigation into the effects of chronic stress in this preclinical model of compulsive behaviour.
Assuntos
Comportamento Compulsivo , Modelos Animais de Doenças , Asseio Animal , Camundongos Knockout , Transtorno Obsessivo-Compulsivo , Animais , Asseio Animal/fisiologia , Camundongos , Masculino , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/genética , Comportamento Compulsivo/fisiopatologia , Comportamento Compulsivo/genética , Feminino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/deficiência , Comportamento Animal/fisiologia , Ansiedade/fisiopatologia , Depressão/fisiopatologia , Gastroenteropatias/fisiopatologia , Meio Ambiente , Condicionamento Físico Animal/fisiologiaRESUMO
Compulsive behaviour may often be triggered by Pavlovian cues. Assessing how Pavlovian cues drive instrumental behaviour in obsessive-compulsive disorder (OCD) is therefore crucial to understand how compulsions develop and are maintained. An aversive Pavlovian-to-Instrumental transfer (PIT) paradigm, particularly one involving avoidance/cancellation of negative outcomes, can enable such investigation and has not previously been studied in clinical-OCD. Forty-one participants diagnosed with OCD (21 adults; 20 youths) and 44 controls (21 adults; 23 youths) completed an aversive PIT task. Participants had to prevent the delivery of unpleasant noises by moving a joystick in the correct direction. They could infer these correct responses by learning appropriate response-outcome (instrumental) and stimulus-outcome (Pavlovian) associations. We then assessed whether Pavlovian cues elicited specific instrumental avoidance responses (specific PIT) and induced general instrumental avoidance (general PIT). We investigated whether task learning and confidence indices influenced PIT strength differentially between groups. There was no overall group difference in PIT performance, although youths with OCD showed weaker specific PIT than youth controls. However, urge to avoid unpleasant noises and preference for safe over unsafe stimuli influenced specific and general PIT respectively in OCD, while PIT in controls was more influenced by confidence in instrumental and Pavlovian learning. Thus, in OCD, implicit motivational factors, but not learnt knowledge, may contribute to the successful integration of aversive Pavlovian and instrumental cues. This implies that compulsive avoidance may be driven by these automatic processes. Youths with OCD show deficits in specific PIT, suggesting cue integration impairments are only apparent in adolescence. These findings may be clinically relevant as they emphasise the importance of targeting such implicit motivational processes when treating OCD.
Assuntos
Aprendizagem da Esquiva , Condicionamento Clássico , Condicionamento Operante , Sinais (Psicologia) , Transtorno Obsessivo-Compulsivo , Transferência de Experiência , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/psicologia , Masculino , Adulto , Adolescente , Feminino , Condicionamento Clássico/fisiologia , Aprendizagem da Esquiva/fisiologia , Transferência de Experiência/fisiologia , Adulto Jovem , Condicionamento Operante/fisiologia , Comportamento Compulsivo/psicologia , Comportamento Compulsivo/fisiopatologiaRESUMO
Background and Objectives: Fibromyalgia syndrome (FMS) is defined as a chronic pain syndrome that is characterized by widespread pain, tenderness, and diffuse stiffness. In addition, neuropsychological symptoms such as fatigue, sleep disorders, poor mood, cognitive impairment, and headaches are often reported. Many reports have addressed the coexistence of affective disorders and anxiety with FMS, yet few have focused on its association with obsessive compulsive disorder (OCD). We investigated the occurrence of classical patterns of OCD in participants with FMS and assessed their effect on pain perception and functional impairment. Material and Methods: The research population included 37 patients diagnosed with FMS, treated at the Rheumatology Clinic in the Sheba Medical Center, Tel-Hashomer, Israel. We used validated questionnaires including a demographic questionnaire, a questionnaire on average and maximal pain intensity, the Eysenck Personality Questionnaire-Revised (EPQ-R), the Perceived Stress Scale, the Pain Catastrophizing Scale, the Pain Obsessive questionnaire, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: Patients with FMS were found to have intrusive and obsessive thoughts regarding pain for several hours every day, causing a high degree of anxiety and high levels of pain, catastrophizing, and magnification, leading to helplessness and functional impairment. In total, 27% of the patients reported severe malfunction due to pain and pain ideation, and 49% demonstrated mild obsessive compulsive symptoms that were strongly correlated with pain intensity and functional impairment. Conclusions: Obsessive compulsive thinking patterns contribute to pain magnification and to the cognitive aspects of fibromyalgia syndrome.
Assuntos
Fibromialgia , Transtorno Obsessivo-Compulsivo , Humanos , Fibromialgia/psicologia , Fibromialgia/complicações , Fibromialgia/fisiopatologia , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/complicações , Inquéritos e Questionários , Israel/epidemiologia , Medição da Dor/métodos , Catastrofização/psicologia , Ansiedade/psicologia , Ansiedade/complicações , Ansiedade/etiologiaRESUMO
ABSTRACT: Wolfram syndrome 1 (WS1) is a rare, autosomal recessive neurodegenerative disorder characterized by diabetes insipidus, insulin-dependent diabetes mellitus, optic atrophy, and deafness resulting from loss-of-function genetic variants in the WFS1 gene. Individuals with WS1 manifest a spectrum of neuropsychiatric disorders. Here, we report a pediatric case of WS1, which stemmed from a novel biallelic WFS1 loss-of-function genetic variant. The individual initially presented with obsessive-compulsive disorder, which was successfully managed by fluvoxamine. After 2 months, the child manifested excessive daytime sleepiness. Clinical evaluation and sleep recordings revealed a diagnosis of narcolepsy type 2. Excessive daytime sleepiness was improved with methylphenidate. To the best of our knowledge, this is the first report of narcolepsy in WS1, which possibly arose during a progressive neurodegenerative process. We emphasize the need for in-depth screening for neuropsychiatric phenotypes and sleep-related disorders in WS1, for clinical management, which significantly improves the quality of life.
Assuntos
Narcolepsia , Transtorno Obsessivo-Compulsivo , Síndrome de Wolfram , Humanos , Feminino , Síndrome de Wolfram/diagnóstico , Síndrome de Wolfram/genética , Síndrome de Wolfram/fisiopatologia , Síndrome de Wolfram/complicações , Narcolepsia/diagnóstico , Narcolepsia/fisiopatologia , Narcolepsia/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/fisiopatologia , Criança , Proteínas de Membrana/genéticaRESUMO
It is increasingly evident that structural and functional changes in brain regions associated with obsessive-compulsive disorder (OCD) are often related to the development of the disease. However, limited research has been conducted on how the progression of OCD may lead to an imbalance between goal-directed and habit-learning systems. This study employs resting-state functional imaging to examine the relationship between illness duration and abnormal brain function in goal-directed/habitual-learning systems. Demographic, clinical, and multimodal fMRI data were collected from participants. Our findings suggest that, compared to healthy controls, individuals with OCD exhibit abnormal brain functional indicators in both goal-directed and habit-learning brain regions, with a more pronounced reduction observed in the goal-directed regions. Additionally, abnormal brain activity is associated with illness duration, and the abnormalities observed in goal-directed regions are more effective in distinguishing different courses of OCD patients. Patients with different durations of OCD have functional abnormalities in the goal-directed and habitual-learning brain regions. There are differences in the degree of abnormality in different brain regions, and these abnormalities may disrupt the balance between goal-directed and habitual-learning systems, leading to increasing reliance on repetitive behaviors.
Assuntos
Encéfalo , Objetivos , Hábitos , Aprendizagem , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Masculino , Feminino , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Adulto , Aprendizagem/fisiologia , Adulto Jovem , Mapeamento Encefálico , Progressão da Doença , Descanso/fisiologiaRESUMO
Serotonin (5-HT) regulates working memory within the prefrontal cortex network, which is crucial for understanding obsessive-compulsive disorder. However, the mechanisms how network dynamics and serotonin interact in obsessive-compulsive disorder remain elusive. Here, we incorporate 5-HT receptors (5-HT1A, 5-HT2A) and dopamine receptors into a multistable prefrontal cortex network model, replicating the experimentally observed inverted U-curve phenomenon. We show how the two 5-HT receptors antagonize neuronal activity and modulate network multistability. Reduced binding of 5-HT1A receptors increases global firing, while reduced binding of 5-HT2A receptors deepens attractors. The obtained results suggest reward-dependent synaptic plasticity mechanisms may attenuate 5-HT related network impairments. Integrating serotonin-mediated dopamine release into circuit, we observe that decreased serotonin concentration triggers the network into a deep attractor state, expanding the domain of attraction of stable nodes with high firing rate, potentially causing aberrant reverse learning. This suggests a hypothesis wherein elevated dopamine concentrations in obsessive-compulsive disorder might result from primary deficits in serotonin levels. Findings of this work underscore the pivotal role of serotonergic dysregulation in modulating synaptic plasticity through dopamine pathways, potentially contributing to learned obsessions. Interestingly, serotonin reuptake inhibitors and antidopaminergic potentiators can counteract the over-stable state of high-firing stable points, providing new insights into obsessive-compulsive disorder treatment.
Assuntos
Transtorno Obsessivo-Compulsivo , Córtex Pré-Frontal , Serotonina , Córtex Pré-Frontal/metabolismo , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/metabolismo , Serotonina/metabolismo , Humanos , Dopamina/metabolismo , Modelos Neurológicos , Receptores Dopaminérgicos/metabolismo , Rede Nervosa/metabolismo , Rede Nervosa/fisiopatologia , Simulação por Computador , Receptor 5-HT2A de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Plasticidade Neuronal/fisiologia , Receptor 5-HT1A de Serotonina/metabolismoRESUMO
BACKGROUND: Obsessive-compulsive disorder (OCD) is a highly prevalent neuropsychiatric disorder. Recently, there has been a growing interest in investigating the association between pro-inflammatory cytokines and the pathogenesis of OCD. However, studies targeting interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in OCD are limited. Therefore, the present study aimed to explore the potential role of pro-inflammatory cytokines IL-1ß and IL-6 in the pathophysiology and development of OCD. METHODS: This study recruited 58 OCD patients and 30 age-sex-matched healthy controls (HCs). A qualified psychiatrist diagnosed OCD patients and assessed HCs based on the Diagnostic and Statistical Manual for Mental Health Disorders, 5th edition (DSM-5) criteria. We measured the severity of OCD using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Serum IL-1ß and IL-6 levels were measured using ELISA kits following the appropriate methods. RESULTS: The results showed that serum IL-1ß levels were significantly elevated in OCD patients compared to HCs (23.68±1.65 pg/ml vs. 15.75±1.02 pg/ml; p = 0.002). Similarly, OCD patients exhibited significantly higher serum IL-6 levels than HCs (44.97±0.73 pg/ml vs. 37.04±0.35 pg/ml; p<0.001). We observed both cytokines were positively correlated with the Y-BOCS scores in OCD patients (IL-1ß: r = 0.380, p = 0.015; IL-6: r = 0.324, p = 0.026) which indicates their role in disease pathophysiology. CONCLUSION: These results suggest that serum IL-1ß and IL-6 levels may be associated with the pathophysiology of OCD. Also, these cytokines levels in blood samples can serve as early risk assessment tools for the development of OCD. We recommend further studies in a large and homogeneous population to support these findings.
Assuntos
Interleucina-1beta , Interleucina-6 , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/sangue , Transtorno Obsessivo-Compulsivo/fisiopatologia , Interleucina-1beta/sangue , Interleucina-6/sangue , Feminino , Masculino , Adulto , Estudos de Casos e Controles , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) are psychiatric disorders that often co-occur. We aimed to investigate whether their high comorbidity could be traced not only by clinical manifestations, but also at the level of functional brain activity. In this paper, we examined the differences in functional connectivity (FC) at the whole-brain level and within the default mode network (DMN). Resting-state EEG was obtained from 43 controls, 26 OCD patients, and 34 MDD patients. FC was analyzed between 68 cortical sources, and between-group differences in the 4-30 Hz range were assessed via the Network Based Statistic method. The strength of DMN intra-connectivity was compared between groups in the theta, alpha and beta frequency bands. A cluster of 67 connections distinguished the OCD, MDD and control groups. The majority of the connections, 8 of which correlated with depressive symptom severity, were found to be weaker in the clinical groups. Only 3 connections differed between the clinical groups, and one of them correlated with OCD severity. The DMN strength was reduced in the clinical groups in the alpha and beta bands. It can be concluded that the high comorbidity of OCD and MDD can be traced at the level of FC.
Assuntos
Transtorno Depressivo Maior , Eletroencefalografia , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Masculino , Feminino , Adulto , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Eletroencefalografia/métodos , Pessoa de Meia-Idade , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Adulto Jovem , Conectoma/métodos , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , DescansoRESUMO
Obsessive-compulsive disorder (OCD) affects 2-3% of people worldwide. Although antidepressants are the standard pharmachological treatment of OCD, their effect on the brain of individuals with OCD has not yet been fully clarified. We conducted a systematic search on PubMed, Scopus, Embase, and Web of Science to explore the effects of antidepressants on neuroimaging findings in OCD. Thirteen neuroimaging investigations were included. After antidepressant treatment, structural magnetic resonance imaging studies suggested thalamic, amygdala, and pituitary volume changes in patients. In addition, the use of antidepressants was associated with alterations in diffusion tensor imaging metrics in the left striatum, the right midbrain, and the posterior thalamic radiation in the right parietal lobe. Finally, functional magnetic resonance imaging highlighted possible changes in the ventral striatum, frontal, and prefrontal cortex. The small number of included studies and sample sizes, short durations of follow-up, different antidepressants, variable regions of interest, and heterogeneous samples limit the robustness of the findings of the present review. In conclusion, our review suggests that antidepressant treatment is associated with brain changes in individuals with OCD, and these results may help to deepen our knowledge of the pathophysiology of OCD and the brain mechanisms underlying the effects of antidepressants.
Assuntos
Antidepressivos , Encéfalo , Neuroimagem , Transtorno Obsessivo-Compulsivo , Humanos , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/patologia , Antidepressivos/uso terapêutico , Antidepressivos/farmacologia , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Imageamento por Ressonância MagnéticaRESUMO
Anxiety symptoms vary moment-to-moment within a day. One factor that may influence these variations is chronotype. Evening chronotypes prefer to engage in activities (e.g., sleep, physical and social activity) later in the day, and evening chronotype is implicated in psychopathology, including anxiety-related disorders. However, it is unknown whether chronotype influences diurnal variation in anxiety symptoms and whether these effects are amplified in individuals with a probable anxiety-related disorder. We examined the diurnal variation in anxiety symptoms and daily activities in morning and evening chronotypes with and without probable generalized anxiety disorder (GAD) or obsessive-compulsive disorder (OCD) in a community sample of adults (N = 410). Evening chronotypes reported higher anxiety symptoms, particularly in the evening hours, and lower engagement in daily activities, predominantly in the morning hours. Evening chronotypes with probable GAD or OCD reported worse anxiety symptoms in the evening. Our findings indicate that anxiety symptoms and engagement in daily activities fluctuate considerably across the day, and these patterns differ depending on chronotype. Evening chronotypes have more anxiety symptoms in the evening, despite preferring this time of day. Personalized treatment approaches that consider chronotype and target certain times of day may be efficient in alleviating peaks in anxiety symptoms.
Assuntos
Transtornos de Ansiedade , Ansiedade , Ritmo Circadiano , Humanos , Masculino , Feminino , Adulto , Ritmo Circadiano/fisiologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Ansiedade/fisiopatologia , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto Jovem , Sono/fisiologia , Atividades Cotidianas , Adolescente , CronotipoRESUMO
BACKGROUND: Transcranial direct current stimulation (tDCS) is a safe, accessible, and promising therapeutic approach for obsessive-compulsive disorder (OCD). AIMS: This study aimed to evaluate the effect of tDCS on electroencephalography (EEG) microstates and identify potential biomarkers to predict efficacy. METHODS: A total of 24 individuals diagnosed with OCD underwent ten sessions of tDCS targeting the orbitofrontal cortex, while 27 healthy individuals were included as controls. Microstates A, B, C, and D were extracted before and after tDCS. A comparative analysis of microstate metrics was performed between the OCD and the healthy control groups, as well as within the OCD group before and after tDCS. Multiple linear regression analysis was performed to identify potential biomarkers of tDCS. RESULTS: Comparison to healthy controls, the OCD group exhibited a significantly reduced duration of microstate A and increased occurrence of microstate D. The transition between microstates A and C was significantly different between patients with OCD and healthy controls and was no longer observed following tDCS. Multiple linear regression analysis revealed that the duration of microstate C was associated with an improvement OCD symptom after tDCS. CONCLUSIONS: The results revealed an aberrant large-scale EEG brain network that could be modulated by tDCS. In particular, the duration of EEG microstate C may be a neurophysiological characteristic associated with the therapeutic effects of tDCS on OCD.