Challenges in Testing Intranasal Ketamine in Obsessive-Compulsive Disorder.
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ABSTRACT:
SUBMITTER: Rodriguez CI
PROVIDER: S-EPMC7401001 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Challenges in Testing Intranasal Ketamine in Obsessive-Compulsive Disorder.
Rodriguez Carolyn I CI Lapidus Kyle A B KAB Zwerling Jordana J Levinson Amand A Mahnke Amanda A Steinman Shari A SA Kalanthroff Eyal E Simpson Helen Blair HB
The Journal of clinical psychiatry 20170401 4
Similar Datasets
Project description:Treatments for obsessive-compulsive disorder (OCD) usually lead to incomplete symptom relief and take a long-time to reach full effect. Convergent evidence suggests that glutamate abnormalities contribute to the pathogenesis of OCD. Ketamine is a potent noncompetitive antagonist of the N-methyl-D-aspartate glutamate receptor. Trials have reported rapid antidepressant effects after low-dose ketamine infusion.We conducted an open-label trial of ketamine (.5 mg/kg IV over 40 min) in 10 subjects with treatment-refractory OCD. Response was defined as >35% improvement in OCD symptoms and >50% improvement in depression symptoms from baseline at any time between 1 and 3 days after infusion.None of 10 subjects experienced a response in OCD symptoms in the first 3 days after ketamine. Four of seven patients with comorbid depression experienced an antidepressant response to ketamine in the first 3 days after infusion. Both OCD and depression symptoms demonstrated a statistically significant improvement in the first 3 days after infusion compared with baseline, but the OCD response was <12%. The percentage reduction in depressive symptoms in the first 3 days after ketamine infusion was significantly greater than the reduction in OCD symptoms.Ketamine effects on OCD symptoms, in contrast to depressive symptoms, did not seem to persist or progress after the acute effects of ketamine had dissipated.
| S-EPMC3667652 | biostudies-literature
Project description:Neurogenetics of Obsessive-Compulsive Disorder
| PRJNA588486 | ENA
Project description:Neurogenetics of Obsessive-Compulsive Disorder
| PRJNA588485 | ENA
Project description:Obsessive-compulsive disorder (OCD) is a highly prevalent and chronic condition that is associated with substantial global disability. OCD is the key example of the 'obsessive-compulsive and related disorders', a group of conditions which are now classified together in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the International Classification of Diseases, 11th Revision, and which are often underdiagnosed and undertreated. In addition, OCD is an important example of a neuropsychiatric disorder in which rigorous research on phenomenology, psychobiology, pharmacotherapy and psychotherapy has contributed to better recognition, assessment and outcomes. Although OCD is a relatively homogenous disorder with similar symptom dimensions globally, individualized assessment of symptoms, the degree of insight, and the extent of comorbidity is needed. Several neurobiological mechanisms underlying OCD have been identified, including specific brain circuits that underpin OCD. In addition, laboratory models have demonstrated how cellular and molecular dysfunction underpins repetitive stereotyped behaviours, and the genetic architecture of OCD is increasingly understood. Effective treatments for OCD include serotonin reuptake inhibitors and cognitive-behavioural therapy, and neurosurgery for those with intractable symptoms. Integration of global mental health and translational neuroscience approaches could further advance knowledge on OCD and improve clinical outcomes.
| S-EPMC7370844 | biostudies-literature
Project description:Obsessive-compulsive disorder (OCD) has been seen to run in families and genetics help to understand its heritability. In this review, we summarize older studies which focused on establishing the familial nature of OCD, including its various dimensions of symptoms, and we focus on recent findings from studies using both the candidate gene approach and genome-wide association study (GWAS) approach. The family studies and twin studies establish the heritability of OCD. Candidate gene approaches have implicated genes in the serotonergic, glutamatergic, and dopaminergic pathways. GWAS has not produced significant results possibly due to the small sample size. Newer techniques such as gene expression studies in brain tissue, stem cell technology, and epigenetic studies may shed more light on the complex genetic basis of OCD.
| S-EPMC6343406 | biostudies-literature
Project description:Neuromodulation shows increasing promise in the treatment of psychiatric disorders, particularly obsessive-compulsive disorder (OCD). Development of tools and techniques including deep brain stimulation, transcranial magnetic stimulation, and electroconvulsive therapy may yield additional options for patients who fail to respond to standard treatments. This article reviews the motivation for and use of these treatments in OCD. We begin with a brief description of the illness followed by discussion of the circuit models thought to underlie the disorder. These circuits provide targets for intervention. Basal ganglia and talamocortical pathophysiology, including cortico-striato-thalamo-cortical loops is a focus of this discussion. Neuroimaging findings and historical treatments that led to the use of neuromodulation for OCD are presented. We then present evidence from neuromodulation studies using deep brain stimulation, electroconvulsive therapy, and transcranial magnetic stimulation, with targets including nucleus accumbens, subthalamic nucleus inferior thalamic peduncle, dorsolateral prefrontal cortex, supplementary motor area, and orbitofrontal cortex. Finally, we explore potential future neuromodulation approaches that may further refine and improve treatment.
| S-EPMC4121444 | biostudies-literature
Project description:Patients with obsessive-compulsive disorder (OCD) exhibit abnormal neural responses when they experience particular emotions or when they evaluate stimuli with emotional value. Whether these brain responses are sufficiently distinctive to discriminate between OCD patients and healthy controls is unknown. The present study is the first to investigate the discriminative power of multivariate pattern analysis of regional fMRI responses to moral and non-moral emotions.To accomplish this goal, we performed a searchlight-based multivariate pattern analysis to unveil brain regions that could discriminate 18 OCD patients from 18 matched healthy controls during provoked guilt, disgust, compassion, and anger. We also investigated the existence of distinctive neural patterns while combining those four emotions (herein termed multiemotion analysis).We found that different frontostriatal regions discriminated OCD patients from controls based on individual emotional experiences. Most notably, the left nucleus accumbens (NAcc) discriminated OCD patients from controls during both disgust and the multiemotion analysis. Among other regions, the angular gyrus responses to anger and the lingual and the middle temporal gyri in the multi-emotion analysis were highly discriminant between samples. Additional BOLD analyses supported the directionality of these findings.In line with previous studies, differential activity in regions beyond the frontostriatal circuitry differentiates OCD from healthy volunteers. The finding that the response of the left NAcc to different basic and moral emotions is highly discriminative for a diagnosis of OCD confirms current pathophysiological models and points to new venues of research.
| S-EPMC6051311 | biostudies-other
Project description:BACKGROUND:Despite evidence that obsessive-compulsive disorder (OCD) is a familial neuropsychiatric condition, progress aimed at identifying genetic determinants of the disorder has been slow. The OCD Collaborative Genetics Study (OCGS) has identified several OCD susceptibility loci through linkage analysis. METHODS:In this study we investigate two regions on chromosomes 15q and 1q by first refining the linkage region using additional short tandem repeat polymorphic (STRP) markers. We then performed association analysis on single nucleotide polymorphisms (SNP) genotyped (markers placed every 2-4?kb) in the linkage regions in the OCGS sample of 376 rigorously phenotyped affected families. RESULTS:Three SNPs are most strongly associated with OCD: rs11854486 (P?=?0.00005 [0.046 after adjustment for multiple tests]; genetic relative risk (GRR)?=?11.1 homozygous and 1.6 heterozygous) and rs4625687 [P?=?0.00007 (after adjustment?=?0.06); GRR?=?2.4] on 15q; and rs4387163 (P?=?0.0002 (after adjustment?=?0.08); GRR?=?1.97) on 1q. The first SNP is adjacent to NANOGP8, the second SNP is in MEIS2, and the third is 150?kb between PBX1 and LMX1A. CONCLUSIONS:All the genes implicated by association signals are homeobox genes and are intimately involved in neurodevelopment. PBX1 and MEIS2 exert their effects by the formation of a heterodimeric complex, which is involved in development of the striatum, a brain region involved in the pathophysiology of OCD. NANOGP8 is a retrogene of NANOG, a homeobox transcription factor known to be involved in regulation of neuronal development. These findings need replication; but support the hypothesis that genes involved in striatal development are implicated in the pathogenesis of OCD.
| S-EPMC3250212 | biostudies-literature
Project description: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.
| S-EPMC3181958 | biostudies-literature
Project description:OCD is a psychiatric disorder with a lifetime prevalence of 1-3% and is a significant cause of disability worldwide. Family studies indicate that OCD has a significant hereditable component, with relatives of OCD cases being 4 times more likely to develop the disorder than the general population. Linkage studies in OCD have generally been underpowered and have failed to reach the statistical threshold for genome-wide significance, but they have nevertheless been useful for revealing potential regions of interest for future candidate gene studies. Candidate gene studies in OCD have thus far focused on genes involved in the serotonergic, dopaminergic, and glutamatergic pathways. These studies have been for the most part inconclusive, and failures to replicate have been the norm until very recently. The only genetic association replicated by multiple groups was with a glutamate transporter gene (SLC1A1). Genome-wide association studies in OCD are in progress, but final results have not yet been reported. As with the study of many other psychiatric disorders, an improved understanding of OCD will only be achieved (1) with larger collaborative efforts involving more probands, (2) the use of probands and controls drawn from epidemiologically-based populations rather than clinical samples, (3) developing a more precise phenotypic description of OCD and (4) measuring important environmental influences that affect OCD pathogenesis and severity.
| S-EPMC3747631 | biostudies-literature