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PubMed2022

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

BACKGROUND: Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses. METHOD: The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data. RESULTS: For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD). CONCLUSIONS: pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

Humans↗
PubMed1978

Tics and Tourette's: a continuum of symptoms?

Analysis of the families of 39 unselected children with Tourette syndrome revealed other members with tic disorders in twenty kindreds. In eight families there were 13 individuals with chronic multiple tics, usually motor, not vocal. Twelve different families contained 18 subjects with Tourette syndrome other than the index patient. In three of these families there were 6 additional individuals with chronic motor tics, forming a bridge to the first group. An autosomal dominant mode of inheritance was suggested in all cases. Tourette syndrome and chronic motor tics appear to represent conditions along a continuum and have, in many instances, a hereditary basis.

Child↗
PubMed1978

Chronic, multiple tics of Gilles de la Tourette's disease. CSF acid monoamine metabolites after probenecid administration.

Central nervous system metabolism in six children and one adult with the syndrome of chronic multiple tics was studied by measuring the accumulation of acid metabolites of dopamine and serotonin (homovanillic acid [HVA] and 5-hydroxyindole-acetic acid [5-HIAA], respectively) in the CSF following probenecid administration. The accumulation of 5-HIAA was reduced in patients with multiple tics in contrast with other pediatric patients (N = 27). The degree of reduction in 5-HIAA relative to HVA appeared to be associated with the severity of the tic disorder. With dextroamphetamine, tic symptoms worsened, CSF HVA level decreased, and CSF 5-HIAA concentration increased. These findings suggest an association in Gilles de la Tourette's disease of reduced functioning of inhibitory serotonergic mechanisms and functional dopaminergic overactivity.

Adolescent↗
PubMed1979

Clinical significance of monitoring plasma levels of psychotropic drugs.

The possible clinical significance of plasma level monitoring of psychotropic drugs in psychotic patients is described. In particular, data obtained with children and 'resistant' psychotic patients are presented. The results in children indicate the existence of a good relationship between side-effects and haloperidol plasma levels as well as between adverse effects and chlorimipramine plasma levels. Furthermore, an age effect on haloperidol clearance could be shown. Relationship between haloperidol and chlorimipramine concentration and effects could be observed for tics and enuresis respectively but not for psychotic reactions. Data in adult patients illustrate on the one hand possible causes of variability in plasma levels of haloperidol and, on the other hand, the fact that poor bioavailability is not the cause of lack of response in 'resistant' schizophrenic patients.

Adult↗