scholarly journals Pathophysiology of Obsessive–Compulsive Disorder: Affected Brain Regions and Challenge Towards Discovery of Novel Drug Treatment

Author(s):  
Uday Gaikwad
Author(s):  
Murad Atmaca ◽  
Ebru Onalan ◽  
Hanefi Yildirim ◽  
Huseyin Yuce ◽  
Mustafa Koc ◽  
...  

2006 ◽  
Vol 30 (6) ◽  
pp. 1051-1057 ◽  
Author(s):  
Murad Atmaca ◽  
Hanefi Yildirimb ◽  
Huseyin Ozdemirb ◽  
Ayşe Aydinb ◽  
Ertan Tezcana ◽  
...  

2019 ◽  
Vol 236 (8) ◽  
pp. 2325-2336 ◽  
Author(s):  
Graham K. Murray ◽  
Franziska Knolle ◽  
Karen D. Ersche ◽  
Kevin J. Craig ◽  
Sanja Abbott ◽  
...  

2017 ◽  
Vol 51 (06) ◽  
pp. 229-242 ◽  
Author(s):  
Přemysl Vlček ◽  
Jakub Polák ◽  
Martin Brunovský ◽  
Jiří Horáček

AbstractObsessive-compulsive disorder (OCD) is a chronic psychiatric illness and 1 of the most common anxiety disorders with the prevalence of 3%. Although its pathogenesis remains unclear, the traditional model focused on alternations in the serotonin system. Selective serotonin reuptake inhibitors provide the most effective treatment; however, as much as 40–60% of patients do not respond to antidepressants therapy. Thus, attention has shifted towards other neurotransmitter systems and related neuroanatomical structures. Recently, there is extensive evidence showing a key role of glutamate pathways abnormalities within the cortico-striatal-thalamo-cortical circuitry and temporal lobes in OCD pathogenesis. In this review, we link together the existent neuroanatomical, neurophysiological, and neuropsychological evidence to argue for potential benefits of adjuvant treatment with glutamatergic agents, especially memantine. By a targeted de-excitation effect on the glutamatergic system in the temporal lobes and connected brain regions, memantine might further alleviate OCD symptoms. This effect should be even more pronounced in certain subtypes of patients with specific cognitive deficits and maladaptive compensatory memory processes (e.g., checkers).


1995 ◽  
Vol 166 (4) ◽  
pp. 424-443 ◽  
Author(s):  
Marco Piccinelli ◽  
Stefano Pini ◽  
Cesario Bellantuono ◽  
Greg Wilkinson

BackgroundA review of the efficacy of antidepressant drug treatment in patients with obsessive–compulsive disorder (OCD), using a meta-analytic approach.MethodRandomised double-blind clinical trials of antidepressant drugs, carried out among patients with OCD and published in peer-reviewed journals between 1975 and May 1994, were selected together with three studies currently in press. Forty-seven trials were located by searching the Medline and Excerpta Medica – Psychiatry data bases, scanning psychiatric and psychopharmacological journals, consulting recent published reviews and bibliographies, contacting pharmaceutical companies and through cross-references. Hedges' g was computed in pooled data at the conclusion of treatment under double-blind conditions or at the latest reported point of time during this treatment period. For each trial, effect sizes were computed for all available outcome measures of the following dependent variables: obsessive–compulsive symptoms considered together; obsessions; compulsions; depression; anxiety; global clinical improvement; psychosocial adjustment; and physical symptoms.ResultsClomipramine was superior to placebo in reducing both obsessive–compulsive symptoms considered together (g = 1.31; 95% CI = 1.15 to 1.47) as well as obsessions (g = 0.89, 95% CI = 0.36 to 1.42) and compulsions (g = 0.79; 95% CI = 0.34 to 1.24) taken separately. Also, selective serotonin re-uptake inhibitors (SSRIs) as a class were superior to placebo, weighted mean g being respectively 0.47 (95% CI = 0.33 to 0.61), 0.54 (95% CI = 0.34 to 0.74) and 0.52 (95% CI = 0.34 to 0.70) for obsessive–compulsive symptoms considered together, and obsessions and compulsions taken separately. Although on Y–BOCS the increase in improvement rate over placebo was 61.3%, 28.5%, 28.2% and 21.6% for clomipramine, fluoxetine, fluvoxamine, and sertraline respectively, the trials testing clomipramine against fluoxetine and fluvoxamine showed similar therapeutic efficacy between these drugs. Finally, both clomipramine and fluvoxamine proved superior to antidepressant drugs with no selective serotonergic properties.ConclusionAntidepressant drugs are effective in the short-term treatment of patients suffering from OCD; although the increase in improvement rate over placebo was greater for clomipramine than for SSRIs, direct comparison between these drugs showed that they had similar therapeutic efficacy on obsessive–compulsive symptoms; clomipramine and fluvoxamine had greater therapeutic efficacy than antidepressant drugs with no selective serotonergic properties; concomitant high levels of depression at the outset did not seem necessary for clomipramine and for SSRIs to improve obsessive–compulsive symptoms.


2004 ◽  
Vol 19 (4) ◽  
pp. 202-208 ◽  
Author(s):  
V. Ravi Kishore ◽  
R. Samar ◽  
Y.C. Janardhan Reddy ◽  
C.R. Chandrasekhar ◽  
K. Thennarasu

AbstractThe DSM-IV criteria recognize the existence of obsessive–compulsive disorder (OCD) with poor insight. However, there is paucity of literature on the clinical correlates and treatment response in poor and good insight OCD. In this study, insight is measured by using the Brown Assessment of Beliefs Scale (BABS) developed specifically to assess insight. One hundred subjects with DSM-IV OCD were ascertained from the OCD clinic of a large psychiatric hospital in India. All subjects were evaluated extensively by using structured instruments and established measures of psychopathology. The subjects were treated with adequate doses of drugs for adequate period. The results showed that 25% of the subjects had poor insight. Poor insight was associated with earlier age-at-onset, longer duration of illness, more number of obsessive–compulsive symptoms, more severe illness and higher comorbidity rate, particularly major depression. Of the subjects who were treated adequately (N = 73), 44 (60%) were treatment responders. Poor insight was associated with poor response to drug treatment. In the step-wise logistic regression analysis, baseline BABS score was highly predictive of poor treatment response. Poor insight appears to be associated with specific clinical correlates and poor response to drug treatment. Further studies are needed in larger samples to replicate our findings.


2010 ◽  
Vol 12 (2) ◽  
pp. 187-197 ◽  

Knowledge of pharmacotherapeutic treatment options in obsessive-compulsive disorder (OCD) has grown considerably over the past 40 years. Serotonergic antidepressants, such as selective serotonin reuptake inhibitors (SSRls) and clomipramine, are the established pharmacologic first-line treatment of OCD. Medium to large dosages and acute treatment for at least 3 months are recommended until efficacy is assessed. In case of significant improvement, maintenance treatment is necessary, Unfortunately, about half of the patients do not respond sufficiently to oral serotonergic antidepressants; augmentation with atypical antipsychotics is an established second-line drug treatment strategy. Alternatives include intravenous serotonergic antidepressants and combination with or switch to cognitive behavioral psychotherapy. Remarkably, a considerable proportion of OCD patients still do not receive rational drug treatment. Novel research approaches, such as preliminary treatment studies with glutamatergic substances, and trials with further drugs, as well as needed aspects of future research, are reviewed.


Author(s):  
M. M Vaghi ◽  
T. W Robbins

The neurobiological basis of Obsessive Compulsive Disorder (OCD) has been probed using functional magnetic resonance in hundreds of studies over three decades. This complex literature can be syntheized using a theory-informed approach. At a theoretical level, separable, independent, constructs of relevance to OCD have been identified. At the experimental level, extensive translational evidence has provided an account that relates specific brain systems to these neuropsychological constructs. Parallels between neural substrates implicated in OCD and functional specialization of different brain regions suggest that abnormalities within fronto-striatal circuitry impinge on executive functions, and their subcomponents, and on goal-directed learning and habit formation. In OCD, this is reflected at a functional level in patterns of abnormal activations in particular brain regions during specific cognitive tasks. However, many issues still need to be addressed. The authors suggest that the experimental context might represent a pivotal variable that should be taken into account.


Author(s):  
Brian P. Brennan ◽  
Scott L. Rauch

Studies using functional neuroimaging have played a critical role in the current understanding of the neurobiology of obsessive-compulsive disorder (OCD). Early studies using positron emission tomography (PET) identified a core cortico-striatal-thalamo-cortical circuit that is dysfunctional in OCD. Subsequent studies using behavioral paradigms in conjunction with functional magnetic resonance imaging (fMRI) have provided additional information about the neural substrates underlying specific psychological processes relevant to OCD. More recently, studies utilizing resting state fMRI have identified abnormal functional connectivity within intrinsic brain networks including the default mode and frontoparietal networks in OCD patients. Although these studies, as a whole, clearly substantiate the model of cortico-striatal-thalamo-cortical circuit dysfunction in OCD and support the continued investigation of neuromodulatory treatments targeting these brain regions, there is also growing evidence that brain regions outside this core circuit, particularly frontoparietal regions involved in cognitive control processes, may also play a significant role in the pathophysiology of OCD.


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