Neurocircuit models of obsessive-compulsive disorder: limitations and future directions for research

Obsessive-compulsive disorder (OCD) is a common psychiatric condition classically characterized by obsessions (recurrent, intrusive and unwanted thoughts) and compulsions (excessive, repetitive and ritualistic behaviors or mental acts). OCD is heterogeneous in its clinical presentation and not all patients respond to first-line treatments. Several neurocircuit models of OCD have been proposed with the aim of providing a better understanding of the neural and cognitive mechanisms involved in the disorder. These models use advances in neuroscience and findings from neuropsychological and neuroimaging studies to suggest links between clinical profiles that reflect the symptoms and experiences of patients and dysfunctions in specific neurocircuits. Several models propose that treatments for OCD could be improved if directed to specific neurocircuit dysfunctions, thereby restoring efficient neurocognitive function and ameliorating the symptomatology of each associated clinical profile. Yet, there are several important limitations to neurocircuit models of OCD. The purpose of the current review is to highlight some of these limitations, including issues related to the complexity of brain and cognitive function, the clinical presentation and course of OCD, etiological factors, and treatment methods proposed by the models. We also provide suggestions for future research to advance neurocircuit models of OCD and facilitate translation to clinical application.

Neuroimaging and electroencephalographic (EEG) methods for investigating neural circuits in mental disorders / Métodos de neuroimagem e eletroencefalografia (EEG) para investigação de circuitos neurais em transtornos mentais

It is increasingly recognised that dysfunction in neural circuits plays a key role in the neurobiological basis of mental disorders. The efficacy of pharmacological and behavioural treatments for mental disorders could therefore be improved by targeting dysfunctions in neurocircuits. However, to achieve this, a better understanding of the specific alterations in neural circuits involved in different mental disorders is required. Such understanding can be acquired by using advanced neuroscience methods to examine the pathways and function of neurocircuits in both typically developing individuals and in those with mental disorders. This article provides an overview of currently available neuroscience methods of investigating neural circuits, including advantages and limitations of different techniques, and highlights the importance of using multi-modal imaging in future research.

É cada vez mais reconhecido que a disfunção nos circuitos neurais desempenha um papel fundamental na base neurobiológica dos transtornos mentais. A eficácia dos tratamentos farmacológicos e comportamentais para os transtornos mentais pode, portanto, ser melhorada por direcionar as disfunções nos neurocircuitos. No entanto, para isso, é necessário um melhor entendimento das alterações específicas nos circuitos neurais envolvidos em diferentes transtornos mentais. Tal entendimento pode ser adquirido usando-se métodos avançados de neurociência para examinar as vias e a função dos neurocircuitos em indivíduos com desenvolvimento típico e naqueles com transtornos mentais. Este artigo fornece uma visão geral dos métodos da neurociência atualmente disponíveis na investigação de circuitos neurais, incluindo vantagens e limitações de diferentes técnicas, e destaca a importância do uso de imagens multimodais em pesquisas futuras.

Theoretical models of Obsessive-Compulsive Disorder (OCD): a perspective on future approaches

Obsessive-Compulsive disorder (OCD) is a common psychiatric condition that leads to significant impairment in everyday life. Advancements in neurobiological investigations contributed to a better understanding of pathophysiological mechanisms behind OCD, leading to the understanding that current models employed to conceptualize OCD are not adequate and might be a significant factor in precluding further advancements in how OCD is treated. In this paper, we will use OCD as a model to discuss the limitations of the current diagnostic systems in Psychiatry and to present the novel perspectives based on neurobiological findings that might lead to considerable advancements in treatments for OCD.

No evidence of attentional bias toward angry faces in patients with obsessive-compulsive disorder

Objective: Although attentional bias (AB) toward angry faces is well established in patients with anxiety disorders, it is still poorly studied in obsessive-compulsive disorder (OCD). We investigated whether OCD patients present AB toward angry faces, whether AB is related to symptom severity and whether AB scores are associated with specific OCD symptom dimensions. Method: Forty-eight OCD patients were assessed in clinical evaluations, intelligence testing and a dot-probe AB paradigm that used neutral and angry faces as stimuli. Analyses were performed with a one-sample t-test, Pearson correlations and linear regression. Results: No evidence of AB was observed in OCD patients, nor was there any association between AB and symptom severity or dimension. Psychiatric comorbidity did not affect our results. Conclusion: In accordance with previous studies, we were unable to detect AB in OCD patients. To investigate whether OCD patients have different brain activation patterns from anxiety disorder patients, future studies using a transdiagnostic approach should evaluate AB in OCD and anxiety disorder patients as they perform AB tasks under functional neuroimaging protocols.

The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil

Objective: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. Methods: Two psychiatrists, working independently, evaluated 92 adults with DS ≥ 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAMDEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. Results: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. Conclusion: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research.

Clinical and molecular neuroimaging characteristics of Brazilian patients with Parkinson's disease and mutations in PARK2 or PARK8 genes / Características clínicas e de neuroimagem molecular de pacientes brasileiros com doença de Parkinson e mutações nos genes PARK2 ou PARK8

OBJECTIVE: To describe clinical and neuroimaging (SPECT) characteristics of Brazilian patients with Parkinson's disease (PD) and mutations in PARK2 or PARK8 genes. METHOD: A total of 119 patients meeting clinical criteria for PD were evaluated. RESULTS: Of all patients studied, 13 had mutations in either PARK2 (n=9) or PARK8 genes (n=4). No statistically significant differences in clinical characteristics in both groups were seen. SPECT with [99mTc] TRODAT-1 showed significant differences between patient and control and the most remarkable difference was between PARK2 and control. CONCLUSION: The study found a frequency of mutation of 10.1 percent and it was most commonly seen in women. These patients had long disease course and high rates of dyskinesia after L-DOPA use. PARK8 patients did not have a relevant family history of PD.

OBJETIVO: Descrever as características clínicas e de neuroimagem (SPECT) de pacientes brasileiros com doença de Parkinson e mutações PARK2 e PARK8. MÉTODO: Foram avaliados 119 pacientes com critérios clínicos para a doença de Parkinson. RESULTADO: Entre os pacientes avaliados foram encontrados 13 pacientes com mutação nos genes PARK2 (n=9) ou PARK8 (n=4). Não houve diferença significativa na avaliação das características clínicas entre os dois grupos. Os resultados de SPECT mostraram diferenças significativas quanto ao potencial de ligação do [99mTc] TRODAT-1 SPECT entre pacientes vs. controle, sendo a diferença mais pronunciada entre PARK2 e controle. CONCLUSÃO: A freqüência de mutação encontrada foi 10,1 por cento, sendo mais comum em mulheres. Estes pacientes apresentavam longo tempo de doença e alta prevalência de discinesias associadas ao uso da levodopa. Nossos pacientes com PARK8 não apresentaram uma história familiar relevante de doença de Parkinson.

Dopamine transporter density by [99mTc]-TRODAT-1 SPECT and neurocognitive performance - a preliminary pilot study

Introducción: los déficits cognitivos están relacionados con el deterioro funcional y con la baja calidad de vida en la enfermedad de Parkinson (EP). El sistema dopaminérgico de los ganglios basales es importante para el funcionamiento cognitivo y motor. Radiomarcadores de transportador de Dopamina (TAD) han sido utilizados para calcular la pérdida neuronal dopaminérgica en humanos. Objetivos: estudiar la relación entre el deterioro cognitivo y la pérdida neuronal dopaminérgica estriatal en pacientes con EP. Métodos: quince pacientes fueron escaneados con [99mTc]-TRODAT-1 y SPECT. El estriado (STR) y el lóbulo occipital (BKG) fueron definidos como regiones de interés (RIs) para la obtención del potencial de ligación (PL = [STR - BKG] / BKG). Exámenes neurocognitivos fueron aplicados, incluyendo el Rey Auditory Verbal Learning Test (RAVLT), Wisconsin Card Sorting Test (WCST), Ravens Progressive Matrices, Digit Span y Tavis 3. Resultados: El PL fue correlacionado negativamente con los exámenes de RAVLT 4 y 5, que evalúan el aprendizaje verbal. El PL también fue correlacionado negativamente con el artículo de aprendizaje de WCST y los artículos de Tavis 3, el error de acción y el número de aciertos. Conclusiones: este estudio indica que la pérdida de TAD estriatal está asociada con un desempeño mas pobre en tareas de flexibilidad cognitiva y aprendizaje verbal. Estos resultados están de acuerdo con un estudio previo con participantes sanos que encontró una relación entre la densidad de TAD del caudado y el desempeño en tareas de aprendizaje verbal. La segmentación del caudado/putamen en una muestra mayor está en desarrollo y podrá proveer más información sobre déficits cognitivos y pérdida de TAD estriatal.