Thennarasu Kandavel

Cognitive endophenotypes in OCD: a study of unaffected siblings of probands with familial OCD.

BACKGROUND Impairments in executive functions and non-verbal memory are considered potential endophenotype markers of obsessive-compulsive disorder (OCD). For the neuropsychological deficits to be considered endophenotypes, they should be demonstrable in unaffected family members. AIM To compare the neuropsychological performance in unaffected siblings of probands with familial OCD with that of individually matched healthy controls. METHODS Twenty-five unaffected siblings of OCD probands with familial OCD, and 25 individually matched healthy controls were assessed with tests of attention, executive function, memory and intelligence. RESULTS Unaffected siblings showed significant deficits in tests of decision making and behavioural reversal i.e., the Iowa Gambling Task (IGT) and the Delayed Alternation Test (DAT) respectively, but performed adequately in other tests. CONCLUSIONS Our study suggests that the deficits in decision making and behavioural reversal could be potential endophenotypes in OCD. These deficits are consistent with the proposed neurobiological model of OCD involving the orbitofrontal cortex. Future studies could couple cognitive and imaging strategies to identify neurocognitive endophenotypes in homogenous samples of OCD.

Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder

OBJECTIVES Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls. METHODS We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education. RESULTS Unaffected siblings performed poorly on the Tower of London test (TOL), the Reys auditory verbal learning test (RAVLT), and the Reys complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001). CONCLUSIONS Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.

Neuropsychological functioning in obsessive-compulsive disorder: are executive functions the key deficit?

OBJECTIVE Although several studies have examined neuropsychological functions in obsessive-compulsive disorder (OCD), findings are not conclusive, predominantly due to small samples and assessment of limited domains. We aim to map the neuropsychological profile of OCD in a large sample with a comprehensive battery of tests. METHOD Neuropsychological functions were tested in 150 subjects with DSM-IV OCD and 205 healthy control subjects. RESULTS Subjects with OCD performed significantly worse than healthy control subjects on Colour Trails 1 time, Tower of Hanoi 3-disk time, Wisconsin Card Sorting Test categories completed, Iowa Gambling Task, Complex Figure Test immediate and delayed recall (p<0.001). CONCLUSIONS Subjects with OCD evince deficits in scanning, planning time, concept formation, decision making and encoding of non-verbal memory after controlling for the effects of age, gender and education. The profile is suggestive of a predominantly executive dysfunction, with difficulties in strategizing and organizing stimuli and cognitive resources for maximum efficiency. The findings implicate dorsolateral prefrontal, superior medial prefrontal and anterior cingulate cortices, suggesting that OCD might not be a purely orbitofronto-striatal disorder as previously conceptualized.

Neuropsychological performance in OCD: a study in medication-naïve patients.

BACKGROUND Obsessive-compulsive disorder (OCD) is associated with impairments in multiple neuropsychological domains but the findings are rather inconsistent across studies. One potential reason for poor replication is the confounding influence of medications. There is limited research on neuropsychological performance in medication-naïve, never treated OCD patients. METHODS In this study, we assessed 31 medication-naïve, never-treated, DSM-IV OCD patients free of comorbid major depression and 31 healthy controls individually matched for age, gender and years of education, with tests of attention, executive function, memory reasoning and visuo-spatial function. RESULTS Medication-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Patients performed somewhat poorly only on the highest goal hierarchy of the Tower of London (TOL) test (p=0.001, effect size=0.68). CONCLUSIONS It is intriguing to find that symptomatic, drug-naïve OCD patients did not significantly differ from healthy controls on most neuropsychological tests. Our finding of medium effect size on TOL highest goal hierarchy test suggests that brain regions outside the affective orbitofrontal loop may also be perhaps involved in OCD. This finding however needs replication because of modest effect size. Future studies should focus on studying medication-naïve, co-morbidity-free patients and relatives using symptom dimensions for consistent and robust findings.

Neuropsychological correlates of insight in obsessive–compulsive disorder

Kashyap H, Kumar JK, Kandavel T, Reddy YCJ. Neuropsychological correlates of insight in obsessive–compulsive disorder.

Impact of age of onset of illness on clinical phenotype in OCD

BACKGROUND This study aims to examine the demographic, clinical and comorbid patterns in a large sample of adult OCD subjects at a specialty OCD clinic in India. METHODS Consecutive patients (n=545) who consulted a specialty OCD Clinic over 5 years at a large psychiatric hospital in India were evaluated with the Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive-Compulsive Scale, and the Clinical Global Impression scale. RESULTS Earlier age onset of OCD (years) was characterized by male preponderance (19.61±7.98 vs. 25.19±10.39, U=23453.5, p=<0.001), positive family history of OCD (19.60±10.02 vs. 22.27±9.20, U=16590.5, p<0.001) and presence of tic disorder (16.28±8.21 vs. 22.01±9.38, OR=0.86, p=0.001). In addition, early age of onset was associated with presence of sexual obsessions (18.92±7.49 vs. 22.88±9.82, OR=0.96, p=0.02), hoarding (19.61±9.32 vs. 22.21±9.36, OR=0.95, p=0.009), repeating rituals (19.76±8.37 vs. 23.29±9.84, OR=0.95, p=0.006) and need to touch compulsions (16.40±7.19 vs. 22.36±9.43, OR=0.89, p<0.001). CONCLUSIONS Our findings from a large sample not only confirm that early onset OCD could be a valid and distinct subtype of OCD but also support the cross-cultural similarity of early onset phenotype.

Impact of depressive and anxiety disorder comorbidity on the clinical expression of obsessive-compulsive disorder.

BACKGROUND The identification of distinct subtypes based on comorbidity offers potential utility in understanding variations in the clinical expression of obsessive-compulsive disorder (OCD). Hence, we examined the hypothesis whether patients with OCD with major depressive disorder (MDD) or anxiety disorder comorbidity would differ from those without in terms of phenomenology. METHODS A total of 545 consecutive patients who consulted a specialty OCD clinic during the period 2004 to 2009 at a psychiatric hospital in India formed the sample. They were evaluated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS), the Mini International Neuropsychiatric Interview, and the Clinical Global Impression scale. RESULTS Among 545 patients, 165 (30%) had current MDD, and 114 (21%) had current anxiety disorder comorbidity. Patients with OCD with MDD were mostly women who had a greater severity of OCD symptoms, more of obsessions (especially religious), greater occurrence of miscellaneous compulsions (need to confess or need to touch), higher suicidal risk, and past suicidal attempts. Patients with OCD with anxiety disorder had an earlier onset of illness that was associated with prior life events, less of compulsions, more of aggressive and hoarding obsessions, pathologic doubts, checking, and cognitive compulsions. CONCLUSIONS Obsessive-compulsive disorder, when comorbid with MDD, is more severe and is associated with higher suicidal risk. On the other hand, anxiety disorder comorbidity seems to influence not so much the morbidity but the phenotypic expression of OCD.

DRD4 gene and obsessive compulsive disorder: Do symptom dimensions have specific genetic correlates?

INTRODUCTION The dopamine D4 receptor (DRD4) is a promising candidate gene in obsessive compulsive disorder (OCD). A 48-bp variable number of tandem repeats (VNTR) sequence in exon 3 has been studied previously, and alleles containing 2-11 repeats (2R-11R) have been identified. We investigated the association of DRD4 VNTR polymorphism with OCD and its relationship with various clinical parameters (age of onset, gender, family history, co-morbidity, factor-analyzed symptom dimensions and insight). METHODOLOGY One hundred and seventy three South Indian OCD patients (DSM-IV) recruited from a specialty OCD clinic were evaluated using the Yale-Brown obsessive compulsive scale (YBOCS), YBOCS item-11 for insight, Mini International Neuropsychiatric Interview (MINI) plus, tic disorder subsection of the MINI-KID and Clinical Global Impression scale. 201 healthy controls were evaluated using MINI plus. All subjects were genotyped for the DRD4 VNTR polymorphism. RESULTS Genotype frequencies did not deviate significantly from the Hardy-Weinberg equilibrium. Case-control association analysis revealed that the 7R allele frequency was significantly greater in OCD patients than controls. This difference was restricted to the women subsample when performing the gender sub-analysis. Among other clinical variables examined, factor 3 (symmetry) was associated with presence of 2R allele. Linear regression analysis confirmed the association of symmetry dimension with the 2R allele (Beta=0.23, t=2.96, p=0.004, CI=0.19-0.95). CONCLUSIONS Our data provides further evidence that DRD4 VNTR polymorphism is associated with OCD. Furthermore, the presence of the 2R allele was significantly associated with the symmetry dimension. This dimension may represent a more homogeneous subtype of OCD with a genetic etiology.

Does insight have specific correlation with symptom dimensions in OCD

OBJECTIVE To study relationship between insight and clinical characteristics in subjects with obsessive-compulsive disorder (OCD). METHOD Sample included 545 consecutive patients with a primary diagnosis of DSM-IV OCD who consulted a specialty OCD Clinic at a tertiary psychiatric hospital in India between January 2004 and December 2009. They had been evaluated with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) symptom checklist, severity rating scale and the item 11 for insight, the Mini International Neuropsychiatric Interview (MINI) and the Clinical Global Impression scale (CGI). Regression analyses were performed to identify predictors of insight. RESULTS The sample had 498 (91%) subjects with good insight (score≤2) and 47 (9%) subjects with poor insight (score>2) as per the Y-BOCS item11. Poor insight group had a significantly higher score on the Y-BOCS compulsions (p<0.001) and total score (p=0.001), the CGI-Severity (p=0.001) and a higher rate of contamination fears (p<0.001) and washing compulsions (p<0.001). Good insight group had a significantly higher frequency of aggressive obsessions (p<0.001). In linear regression, contamination dimension (p=0.007) and Y-BOCS total score (p<0.001) predicted poorer insight and presence of forbidden thoughts (p=0.006) predicted better insight. LIMITATIONS Study sample is from a specialty OCD clinic of a major psychiatric hospital in India and therefore, generalizability to other clinical settings may be limited. CONCLUSION Poor insight is associated with severe form of OCD, and is associated with contamination dimension. That degree of insight has specific correlation with certain symptom dimensions adds to the growing knowledge on the dimensional aspect of OCD. Insight has to be systematically assessed in all OCD subjects particularly in those with contamination fears. Failure to systematically assess insight may have treatment implications.

Family accommodation of obsessional symptoms and naturalistic outcome of obsessive–compulsive disorder

Accommodation of symptoms by families and expressed emotion (EE) may have a negative impact on the outcome of obsessive-compulsive disorder (OCD). The study examines the effect of family accommodation (FA) and EE on the 1-year naturalistic outcome of OCD. Patients with OCD who met the criteria for the Diagnostic and Statistical Manual of Mental Disorders-IV, text revision (DSM-IV TR; N=94) were followed up for 1 year and assessed every 3 months. Assessments included measurement of symptom severity, FA, EE and family burden. By the 12th month, the cumulative probability of remission was 58%. Non-remitters compared with remitters had a significantly higher FA, EE and family burden at the baseline and did not report significant reductions on any of the family variables over the year. In a Cox proportional hazard regression analysis, a higher FA at the baseline significantly predicted time to remission. FA of symptoms has a significant negative impact on the naturalistic outcome of OCD. This emphasises the need to design specific interventions to reduce FA for a better outcome.