Kesavan Muralidharan

Off label use of lithium in the treatment of Huntington's disease: A case series

Huntingtons disease is characterized by choreic movements, psychiatric disorders, striatal atrophy with selective small neuronal loss, and autosomal dominant inheritance. The genetic abnormality is CAG expansion in Huntingtin gene. Newer therapeutic strategies are evolving to treat this progressive disorder. The neuroprotective agents are one such group of drugs being tried. Lithium has been used to treat Huntingtons disease in the past due to its neuroprotective effects. Though the precise mechanism of action is not clear, Lithium can directly or indirectly modulate proteins involved in neuronal survival/differentiation which may account for its neuroprotective effects. We report three patients with Huntingtons disease in whom Lithium prevented the progression of chorea and also helped stabilize mood.

Abnormalities in cortical and transcallosal inhibitory mechanisms in subjects at high risk for alcohol dependence: a TMS study.

Central nervous system (CNS) hyperexcitability and a resulting state of behavioral undercontrol are thought to underlie the vulnerability to early‐onset alcohol dependence (AD). The aim of this study was to explore the differences in the functioning of cortical inhibitory systems, utilizing transcranial magnetic stimulation (TMS), in subjects at high risk (HR) and low risk (LR) for AD and to examine the relationship between CNS inhibition and behavioral undercontrol. Right‐handed HR (n = 15) and LR (n = 15) subjects, matched for age, gender, height, weight and education, were assessed for psychopathology and family history of alcoholism using the Semi‐Structured Assessment for the Genetics of Alcoholism and the Family Interview for Genetic Studies. Following single‐pulse TMS, an electromyogram recorded from the right opponens pollicis muscle was used to measure the silent periods at different stimulus intensities. HR subjects had significantly shorter contralateral and ipsilateral (iSP) silent periods and a relatively higher prevalence of ‘absent’ iSP. They had significantly higher mean externalizing symptoms scores (ESS) than LR subjects, and there was a significant negative correlation between iSP duration and ESS. These preliminary findings suggest that HR subjects have relative impairments in corticocortical and transcallosal inhibitory mechanisms. The consequent state of CNS hyperexcitability may be etiologically linked to the excess of externalizing behaviors observed in this population, which is thought to be a predisposition to a higher risk of developing early‐onset alcoholism.

Clinical efficacy and safety of repetitive transcranial magnetic stimulation in acute bipolar depression

Though bipolar disorder is characterized by episodes of mania/hypomania, depressive episodes pose the most burden for patients suffering from the disorder. Regrettably, few proven treatments exist for bipolar depression, and many patients either do not respond to, or have difficulty tolerating these treatments. Hence, novel, safe and effective treatments are urgently needed.

Are cognitive deficits similar in remitted early bipolar I disorder patients treated with lithium or valproate? Data from the STOP-EM study

In bipolar disorder (BD), lithium and valproate are both reportedly associated with mild cognitive deficits with impaired psychomotor speed and verbal memory ascribed to both while impairments in learning and attention are mainly attributed to valproate. However, there are few direct comparisons of the impact of lithium and valproate on cognitive function in early BD. Using data from the STOP-EM study, we compared neurocognitive functioning in BD patients, who had recently recovered from a first episode of mania, and were on treatment with lithium (n = 34) or valproate (n = 38), to a comparable sample of healthy controls (HC; n = 40), on the domains of processing speed, attention, verbal memory, nonverbal memory, working memory and executive functions. The three groups were comparable on socio-demographic (all p > 0.12) and clinical variables (all p > 0.08). MANOVA revealed a significant difference between the three groups on overall cognitive functioning (Wilks lambda = 0.644; F = 3.775; p < 0.001). On post-hoc Tukey test, the valproate group performed poorer on working memory compared to the lithium (p = 0.001) and HC groups (p < 0.001). There was no significant difference between the lithium and valproate groups on other cognitive domains (all p > 0.13). Treatment with valproate and not lithium may be associated with working memory deficits early in the course of BD.

Inhalant Dependence: Data from a Tertiary Care Center in South India

Background: This study aims to understand the sociodemographic and clinical profile of inhalant abusers seeking treatment from a tertiary care psychiatric hospital in South India. Materials and Methods: The clinical charts of patients who utilized the psychiatric services of a tertiary care center in India for over 10 years were examined for the study. Results: The sample had an urban predominance, was mostly unemployed, and was all male. Most of them had an adolescent age of onset of inhalant use (mean — 16.23 years). All patients reported the use of volatile solvents as inhalants. One other substance dependence was identified in more than half of the sample. The psychiatric comorbidity included psychosis and depression. A comparison was made between patients who presented with inhalant dependence only (I) and inhalant-dependent individuals who also used other psychoactive substances apart from nicotine (IP). The inhalant-only group (I) had an earlier mean age at onset of substance use as compared to the IP group. All patients in the I group reported withdrawal symptoms compared to 77% of patients in the (IP) group (P=0.048). The IP group reported a significantly higher occurrence of aggression (54.5 vs. 19%, P=0.02), externalizing symptoms (77.3 vs. 42.9%, P=0.03), and attention-deficit hyperactivity disorder (ADHD) (50 vs. 14.3%, P=0.02). Conclusion: Inhalant dependence is a serious health problem in adolescent subjects and is associated with high comorbidity of other substance dependence, psychiatric disorder, and externalizing spectrum disorder. There is a need for community-based prospective studies in this area from India.

Sex differences in cognitive functioning in patients with bipolar disorder who recently recovered from a first episode of mania: Data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM)

BACKGROUND Studies investigating bipolar disorder (BD) showed that healthy patterns of sex differences in cognitive functioning are altered within this population, but is it unknown whether these alterations are present in BD patients early in their course of illness. METHODS Patients with bipolar I disorder (36 males, 38 female), who had recently experienced their first manic or mixed episode were tested along with healthy controls (39 males, 59 females) similar in age, sex and premorbid IQ. Cognitive function was assessed through a comprehensive neuropsychological test battery. RESULTS Significant group effects were found in a majority of administered tests (p<0.05) with patients performing worse than healthy controls. Significant sex effects (p<0.05) were observed on tasks of spatial working memory and sustained attention, with males performing better than females. No significant group by sex interaction was found in any of the tasks administered. LIMITATIONS The cognitive battery employed in this study may not have been optimally sensitive in detecting sex differences. CONCLUSIONS The results suggest that unlike patients with long standing multi-episode BD or schizophrenia, healthy cognitive sex differences are maintained in patients with early BD, following recovery from a first-episode of mania. These findings highlight the progressive nature of the illness and provide justification for an early intervention.

Does catatonic schizophrenia improve faster with electroconvulsive therapy than other subtypes of schizophrenia

Objective. Electroconvulsive therapy (ECT) is generally recommended for treating catatonic schizophrenia. Non-catatonic schizophrenia patients also receive ECT. We compared the speed of response to ECT among patients with catatonic and other subtypes of schizophrenia. Methods and materials. Consecutive schizophrenia patients referred for ECT within 3 months of starting antipsychotic treatment were studied (19 with catatonic and 34 with non-catatonic schizophrenia). Nurses Observation Scale for Inpatient Evaluation (NOSIE-30) and Clinical Global Impression (CGI) were used to rate improvement. Referring psychiatrists stopped ECTs based on clinical impression of improvement. Total number of ECTs was taken as an indirect measure of speed of response. NOSIE-30 scores were compared using repeated measures analysis of variance. Results. Catatonic schizophrenia patients required significantly fewer ECTs to achieve clinically significant improvement. There was a significant group×occasion effect in NOSIE scores, suggesting faster response to ECT in the catatonia group (F=41.6; P<0.001). Survival analysis suggested that patients with catatonic schizophrenia required significantly fewer ECTs (one less session on an average) to achieve clinical improvement (Log-rank statistic =5.31; P=0.02). Conclusions. Catatonic schizophrenia responds faster to ECT than non-catatonic schizophrenia. However, the magnitude of the difference is modest.

The association between attention-deficit/hyperactivity disorder and early-onset alcohol dependence: A retrospective study

Background: Early onset (EO) alcohol dependence (AD) has been found to represent a subtype of alcoholism with a distinct profile and prognosis compared to late onset (LO) alcohol dependence. Externalizing disorders, especially attention deficit hyperactivity disorder (ADHD) that may continue as attention deficit hyperactivity disorder, residual type (ADD, RT) in adulthood, may increase susceptibility to early-onset AD. Aims: To examine the relationship between ADHD and ADD, RT symptoms and age at onset of AD in a sample of Indian male patients. 70 male subjects with AD presenting to the De-Addiction Services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, were studied. The study had a retrospective design. Materials and Methods: Patients were examined for evidence of past ADHD in childhood and current ADD, RT using structured instruments. Chi-square tests and odds ratios were used to express the relative risk of association of ADHD with early- and late-onset AD. Results: Significantly more EO alcoholics (19/30, 63.3%) had a history of ADHD in childhood compared to LO alcoholics (7/28, 25%, P < 0.05) ADD, RT was also over-represented in EO probands. Conclusions: The results of this study are consistent with previous research that shows a high incidence of ADHD in early-onset alcoholics. This may have important management implications.

Neurocognitive functioning in overweight and obese patients with bipolar disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

Objective: Obesity is frequent in people with bipolar I disorder (BD I) and has a major impact on the course of the illness. Although obesity negatively influences cognitive function in patients with BD, its impact in the early phase of the disorder is unknown. We investigated the impact of overweight and obesity on cognitive functioning in clinically stable patients with BD recently recovered from their first manic episode. Method: Sixty-five patients with BD (25 overweight or obese and 40 normal weight) recently remitted from a first episode of mania and 37 age- and sex-matched healthy control subjects (9 overweight or obese and 28 normal weight) were included in this analysis from the Systematic Treatment Optimization Program for Early Mania (commonly referred to as STOP-EM). All subjects had their cognitive function assessed using a standard neurocognitive battery. We compared cognitive function between normal weight patients, overweight-obese patients, and normal weight healthy control subjects. Results: There was a negative affect of BD diagnosis on the domains of attention, verbal memory, nonverbal memory, working memory, and executive function, but we were unable to find an additional effect of weight on cognitive functioning in patients. There was a trend for a negative correlation between body mass index and nonverbal memory in the patient group. Conclusions: These data suggest that overweight-obesity does not negatively influence cognitive function early in the course of BD. Given that there is evidence for a negative impact of obesity later in the course of illness, there may be an opportunity to address obesity early in the course of BD.

Childhood maltreatment and corpus callosum volume in recently diagnosed patients with bipolar I disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

Childhood trauma (CT) has been associated with abnormalities in the corpus callosum (CC). Decreased CC volumes have been reported in children and adolescents with trauma as well as adults with CT compared to healthy controls. CC morphology is potentially susceptible to the effects of Bipolar Disorder (BD) itself. Therefore, we evaluated the relationship between CT and CC morphology in BD. We using magnetic resonance imaging in 53 adults with BD recently recovered from their first manic episode, with (n = 23) and without (n = 30) CT, defined using the Childhood Trauma Questionnaire (CTQ) and 16 healthy controls without trauma. ANCOVA was performed with age, gender and intracranial volume as covariates in order to evaluate group differences in CC volume. The total CC volume was found to be smaller in BD patients with trauma compared to BD patients without trauma (p < .05). The differences were more pronounced in the anterior region of the CC. There was a significant negative correlation between CTQ scores and total CC volume in BD patients with trauma (p = .01). We did not find significant differences in the CC volume of patients with/without trauma compared to the healthy subjects. Our sample consists of patients recovered from a first episode of mania and are early in the course of illness and reductions in CC volume may occur late in the course of BD. It might mean there may be two sources of CC volume reduction in these patients: the reduction due to trauma, and the further reduction due to the illness.