scholarly journals The functional coding variant Asn107Ile of the neuropeptide S receptor gene (NPSR1) influences age at onset of obsessive–compulsive disorder

2013 ◽  
Vol 16 (9) ◽  
pp. 1951-1958 ◽  
Author(s):  
Leonhard Lennertz ◽  
Petra E. Franke ◽  
Hans Jörgen Grabe ◽  
Friederike Rampacher ◽  
Svenja Schulze-Rauschenbach ◽  
...  

Abstract Neuropeptide S (NPS) is a novel central acting neuropeptide that modulates several brain functions. NPS has shown strong anxiolytic-like effects and interactions with other central transmitter systems, including serotonin and glutamate. A coding variation (Asn107Ile) of the NPS receptor gene (NPSR1) was associated with panic disorder and schizophrenia. Based on these encouraging findings, the present study aimed at exploring a potential role of NPSR1 in obsessive–compulsive disorder (OCD). A sample of 232 OCD patients was successfully genotyped for the NPSR1 Asn107Ile variant (rs324981). Age at onset was taken into account to address the heterogeneity of the OCD phenotype. The NPSR1 genotype significantly affected age at onset of the OCD patients, with a mean age at onset approximately 4 yr earlier in homozygous carriers of the low-functioning Asn107 variant compared to patients with at least one Ile107 variant (p = 0.032). Case–control analyses with 308 healthy control subjects reveal a highly significant association of the Asn107 variant with early onset OCD (odds ratio = 2.36, p = 0.0004) while late onset OCD or the OCD group as a whole were unrelated to the NPSR1 genotype. Based on our association finding relating NPSR1 genotype to early onset OCD, we suggest a differential role of the NPS system in OCD. In particular, the early onset OCD subtype seems to be characterized by a genetically driven low NPS tone, which might affect other OCD-related transmitter systems, including the serotonin and glutamate systems. In agreement with preclinical research, we suggest that NPS may be a promising pharmacological candidate with anti-obsessional properties.

2005 ◽  
Vol 35 (2) ◽  
pp. 237-243 ◽  
Author(s):  
RICHARD DELORME ◽  
JEAN-LOUIS GOLMARD ◽  
NADIA CHABANE ◽  
BRUNO MILLET ◽  
MARIE-ODILE KREBS ◽  
...  

Background. Age at onset (AAO) has been useful to explore the clinical, neurobiological and genetic heterogeneity of obsessive–compulsive disorder (OCD). However, none of the various thresholds of AAO used in previous studies have been validated, and it remains an unproven notion that AAO is a marker for different subtypes of OCD. If AAO is a clinical indicator of different biological subtypes, then subgroups based on distinct AAOs should have separate normal distributions as well as different clinical characteristics.Method. Admixture analysis was used to determine the best-fitting model for the observed AAO of 161 OCD patients.Results. The observed distribution of AAO in OCD is a mixture of two Gaussian distributions with mean ages of 11·1±4·1 and 23·5±11·1 years. The first distribution, defined by early-onset OCD, had increased frequency of Tourette's syndrome and increased family history of OCD. The second distribution, defined by late-onset OCD, showed elevated prevalence of general anxiety disorder and major depressive disorder.Conclusions. These results, based on a statistically validated AAO cut-off and those of previous studies on AAO in OCD, suggest that AAO is a crucial phenotypic characteristic in understanding the genetic basis of this disorder.


CNS Spectrums ◽  
2009 ◽  
Vol 14 (7) ◽  
pp. 362-370 ◽  
Author(s):  
Maria Alice de Mathis ◽  
Juliana B. Diniz ◽  
Roseli G. Shavitt ◽  
Albina R. Torres ◽  
Ygor A. Ferrão ◽  
...  

ABSTRACTIntroduction: Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations.Objective: The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated.Methods: Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the “early onset” group (EOG): before 11 years of age, 75 patients hadResults: The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the “aggression/violence” and “miscellaneous” dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the “contamination/cleaning” dimension.Conclusion: The current results disentangle some of the clinical overlap between early onset OCD with and without tics.


1991 ◽  
Vol 158 (2) ◽  
pp. 260-263 ◽  
Author(s):  
Homa F. Noshirvani ◽  
Yiannis Kasvikis ◽  
Isaac M. Marks ◽  
Fivos Tsakiris ◽  
William O. Monteiro

Among 307 adults with OCD, early onset (age 5–15 years) was more common in men and later onset (age 26–35 years) in women. Early onset was associated with more checking, and late onset with more washing. More women than men had a history of treated depression; 12% of the women but none of the men had a history of anorexia. More women than men were married. Gender-divergent features may reflect differential aetiological factors. Our sample resembled others in the literature in its slight overall female preponderance, low rate of marriage and low fertility, onset mainly before age 35 years, chronicity, and common present and past depression.


CNS Spectrums ◽  
2000 ◽  
Vol 5 (S4) ◽  
pp. 40-46 ◽  
Author(s):  
Donald W. Black

AbstractThis manuscript summarizes presentations by an international panel of experts, representing Brazil, Israel, Italy, Mexico, Portugal, Spain, and the United States, at a symposium on obsessive-compulsive disorder (OCD) and its possible subtypes. Presentations concerned both OCD proper, as well as putative obsessive-compulsive-spectrum disorders (autistic disorders, eating disorders, pathological gambling, and schizo-obsessive disorder). Projects discussed included a study assessing impulsive temperament in eating disorder patients, a study on serotonin receptor sensitivity in autism, a study of sleep EEG abnormalities in OCD, a study of dissociation in pathological gamblers, papers on aspects of schizo-obsessive patients, a study addressing biological alterations in OCD, data from a new family study on OCD, data from a molecular genetic study of OCD, a factor analytic study of Tourette disorder, a study hypothesizing the existence of an OCD continuum, and, finally, a paper on early- vs late-onset OCD. General discussion followed leading to a consensus that 1) OCD is likely heterogeneous with multiple subtypes; 2) division of patients by age-at-onset probably represents a robust and valid subtyping scheme; 3) the presence of schizophrenic features probably identifies a valid subtype; 4) the validation of subtypes in the future will be informed by both family-genetic studies, as well as studies of biological alterations in OCD; and 5) the study of obsessive-compulsive spectrum disorders adds to our understanding of the OCD phenomenon, and helps in our search to identify valid subtypes.


CNS Spectrums ◽  
2021 ◽  
pp. 1-7
Author(s):  
Giacomo Grassi ◽  
Chiara Cecchelli ◽  
Gloria Mazzocato ◽  
Luisa Vignozzi

Abstract Moving from a behavioral-based to a biological-based classification of mental disorders is a crucial step toward a precision-medicine approach in psychiatry. In the last decade, a big effort has been made in order to stratify genetic, immunological, neurobiological, cognitive, and clinical profiles of patients. Making the case of obsessive–compulsive disorder (OCD), a lot have been made in this direction. Indeed, while the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of OCD aimed to delineate a homogeneous group of patients, it is now clear that OCD is instead an heterogeneous disorders both in terms of neural networks, immunological, genetic, and clinical profiles. In this view, a convergent amount of literature, in the last years, indicated that OCD patients with an early age at onset seem to have a specific clinical and biological profile, suggesting it as a neurodevelopmental disorder. Also, these patients tend to have a worse outcome respect to adult-onset patients and there is growing evidence that early-interventions could potentially improve their prognosis. Therefore, the aim of the present paper is to review the current available genetic, immunological, neurobiological, cognitive, and clinical data in favor of a more biologically precise subtype of OCD: the early-onset subtype. We also briefly resume current available recommendations for the clinical management of this specific population.


2017 ◽  
Vol 38 (1) ◽  
pp. 41 ◽  
Author(s):  
SaharEl Emam Gad ◽  
WafaaMohamed El Emshaty ◽  
HananEl-sayed Hussein ◽  
OsamaAhmed El-Boraie ◽  
MohammedAli Ezzat El-Hadid

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