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Abstract: Background: Few studies have used neuroimaging to characterize treatment-refractory obsessive–compulsive disorder (OCD). This study sought to explore gray matter structure in patients with treatment-refractory OCD and compare it with that of healthy controls. Methods: A total of 18 subjects with treatment-refractory OCD and 26 healthy volunteers were analyzed by MRI using a 3.0-T scanner and voxel-based morphometry (VBM). Diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) was used to identify structural changes in gray matter associated with treatment-refractory OCD. A partial correlation model was used to analyze whether morphometric changes were associated with Yale–Brown Obsessive–Compulsive Scale scores and illness duration. Results: Gray matter volume did not differ significantly between the two groups. Treatment-refractory OCD patients showed significantly lower gray matter density than healthy subjects in the left posterior cingulate cortex (PCC) and mediodorsal thalamus (MD) and significantly higher gray matter density in the left dorsal striatum (putamen). These changes did not correlate with symptom severity or illness duration. Conclusions: Our findings provide new evidence of deficits in gray matter density in treatment-refractory OCD patients. These patients may show characteristic density abnormalities in the left PCC, MD and dorsal striatum (putamen), which should be verified in longitudinal studies. [Copyright &y& Elsevier]

Abstract: Objectives: Obsessive–compulsive symptoms (OCSs) and disorder (OCD) are often underdiagnosed in the out-patient epilepsy clinic. This work aimed at determining the risks and comorbidities (psychopathological and neurobiological correlates) of OCSs in treated adults with idiopathic epilepsy recruited from a university hospital. Methods: Psychiatric evaluation was done using DSM-IV (The Diagnostic and Statistical Manual of Mental Health Disorders). Obsessive–compulsive disorder was identified using the Mini International Neuropsychiatric Interview (MINI). The Beck Depression Inventory (BDI-II), Hamilton Anxiety Rating Scale (HAM-A), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) were used to determine the severity of the related psychiatric symptoms. Results: Out of 474 patients screened, included in this study were 107 with no psychiatric symptoms and 188 with OCSs [classified as those with at least OCSs=93; mild OCSs=36; moderate, severe, and extreme OCSs=59]. A hundred healthy subjects were included as controls. Blood concentrations of serotonin, adrenaline, noradrenaline, and dopamine were measured. Compared with controls, patients with OCSs had higher frequencies of depression and anxiety. Low concentrations of serotonin, adrenaline, noradrenaline, and dopamine were reported regardless of the presence or the absence of psychiatric symptoms, OCS severities, and antiepileptic drug (AED)-related variables (dose and serum drug level). Significant correlations were identified between Y-BOCS, BDI-II, and HAM-A scores, age, age at onset, and concentrations of noradrenaline. Conclusion: This study indicates that a) OCSs are common in patients with epilepsy. Male sex, age, duration of illness, seizure focus, lateralization, and intractability to AEDs are its main risks; b) depression and anxiety are comorbid psychopathologies; and c) serotonin, catecholamines, and dopamine are linked to epilepsy-related variables and its comorbid psychopathies but not to its medications. [Copyright &y& Elsevier]

Atypical antipsychotics (APs) are now widely in use in clinical practice. They exert a beneficial effect in patients with schizophrenic disorders, including cases resistant to traditional APs and negative symptoms. They have also enhanced the ratio of therapeutic efficacy to adverse effects. Atypical APs, mainly risperidone and olanzapine, have been used as adjunctive treatment in (selective) serotonin reuptake inhibitor [(S)SRI]-refractory cases with obsessive symptoms. However, de novo emergence or exacerbation of obsessive–compulsive (OC) symptoms during treatment with clozapine, risperidone, olanzapine and quetiapine has been described in the literature. The reported cases and the possible pathogenetic mechanisms involved in their occurrence are discussed and reviewed. [Copyright &y& Elsevier]

Radiosurgery for psychiatric disorders has been performed for more than 50 years. The use of deep brain stimulation has recently been expanded to the investigational treatment of specific psychiatric disorders. A literature review of past studies incorporating radiosurgical stereotactic lesions for psychiatric disorders was performed to provide historic context and possible guidance for current and future attempts at treating psychiatric disorders, especially by gamma capsulotomy. The anatomic target localization, dose selection, and the outcome of the radiosurgical procedures were reviewed, and the evolutions of lesioning strategies were analyzed with particular emphasis on the dose selection. Large-scale prospective studies with strict inclusion and well-defined, objective outcome criteria are necessary for defining the role of radiosurgery for the treatment of psychiatric disorders. [Copyright &y& Elsevier]

Interest in using neuromodulation to treat psychiatric disorders is rapidly increasing. The development of novel tools and techniques, such as deep brain stimulation (DBS), increases precision and minimizes risk. This article reviews the history of psychosurgical interventions and recent developments of DBS to provide a framework for understanding current options and future goals. We begin by discussing early approaches to psychosurgery, focusing on the widespread use of lobotomy and the subsequent backlash from the public and professionals in the field. Next, we discuss the development of stereotaxis. This technique allows for more targeted, precise interventions that produce discrete subcortical lesions. We focus on four stereotactic procedures that were developed using this technique: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. We subsequently review contemporary theory and approaches with relevance to psychosurgery. We discuss the systems and neurocircuitry that are thought to be involved in psychiatric illness and provide targets for intervention. This discussion includes presentation of basal ganglia thalamocortical pathophysiology including cortico-striato-thalamo-cortical loops. We focus the discussion on two psychiatric disorders that have been targets of neurosurgical interventions: obsessive-compulsive disorder and mood disorders such as major depressive disorder. Evidence from studies of DBS in psychiatric disorders, including efficacy and tolerability, is reviewed. Finally, we look to the future, exploring the possibilities for these approaches to increase understanding, transform societal views of mental illness, and improve treatment. [Copyright &y& Elsevier]