Vivek H. Phutane

Cardiovascular risk in a first-episode psychosis sample: a ‘critical period’ for prevention?

OBJECTIVE Studies in first episode psychosis samples about status of cardiovascular risk factors have shown discordant results. We aimed to determine the 10-year risk of developing coronary heart disease in a sample of first episode psychosis patients referred to an early intervention clinic and compared the same with age, gender, and race matched controls from the U.S. National Health and Nutrition Examination Survey (NHANES). METHOD We conducted a cross-sectional analysis of baseline data of 56 subjects enrolled in first episode psychosis clinic from April 2006 to January 2010. This sample was compared with age, gender, and race matched 145 individuals drawn from NHANES 2005-2006 database. Sociodemographic and clinical variables were collected. Physical examination including laboratory evaluation was used to screen for common medical illnesses. The 10-year risk of developing coronary heart disease was calculated by using a tool developed by the National Cholesterol Education Program (NCEP-ATP III). RESULTS There were elevated rates of smoking (46%) and hypertension (11%) albeit statistically significant differences from the control could not be demonstrated for these measures or weight, body mass index, or total or HDL cholesterol, fasting plasma glucose, status of diabetes and impaired fasting plasma glucose, HbA1C level. The 10-year median (range) risk of developing coronary heart disease in patients and controls was 1 (0-5)% and 0 (0-9)% respectively. The difference was not statistically significant. CONCLUSIONS First episode psychosis patients do not present with significantly higher cardiovascular risk than age and race-matched controls despite clinically significant prevalence of individual risk factors. This sample presents an opportunity for early intervention for the primary prevention of cardiovascular morbidity and mortality.

First-Episode Services for Psychotic Disorders in the U.S. Public Sector: A Pragmatic Randomized Controlled Trial

OBJECTIVE This study sought to determine the effectiveness of a comprehensive first-episode service, the clinic for Specialized Treatment Early in Psychosis (STEP), in an urban U.S. community mental health center by comparing it with usual treatment. METHODS This pragmatic randomized controlled trial enrolled 120 patients with first-episode psychosis within five years of illness onset and 12 weeks of antipsychotic exposure. Referrals were mostly from inpatient psychiatric units, and enrollees were randomly allocated to STEP or usual treatment. Main outcomes included hospital utilization (primary); the ability to work or attend age-appropriate schooling-or to actively seek these opportunities (vocational engagement); and general functioning. Analysis was by modified intent to treat (excluding only three who withdrew consent) for hospitalization; for other outcomes, only data for completers were analyzed. RESULTS After one year, STEP participants had less inpatient utilization compared with those in usual treatment: no psychiatric hospitalizations, 77% versus 56% (risk ratio [RR]=1.38, 95% confidence interval [CI]=1.08-1.58); mean hospitalizations, .33±.70 versus .68±.92 (p=.02); and mean bed-days, 5.34±13.53 versus 11.51±15.04 (p=.05). For every five patients allocated to STEP versus usual treatment, one additional patient avoided hospitalization over the first year (number needed to treat=5; CI=2.7-26.5). STEP participants also demonstrated better vocational engagement (91.7% versus 66.7%; RR=1.40, CI=1.18-1.48) and showed salutary trends in global functioning measures. CONCLUSIONS This trial demonstrated the feasibility and effectiveness of a U.S. public-sector model of early intervention for psychotic illnesses. Such services can also support translational research and are a relevant model for other serious mental illnesses.

Reversible Lithium Neurotoxicity: Review of the Literature

OBJECTIVE Lithium neurotoxicity may be reversible or irreversible. Reversible lithium neurotoxicity has been defined as cases of lithium neurotoxicity in which patients recovered without any permanent neurologic sequelae, even after 2 months of an episode of lithium toxicity. Cases of reversible lithium neurotoxicity differ in clinical presentation from those of irreversible lithium neurotoxicity and have important implications in clinical practice. This review aims to study the clinical presentation of cases of reversible lithium neurotoxicity. DATA SOURCES A comprehensive electronic search was conducted in the following databases: MEDLINE (PubMed), 1950 to November 2010; PsycINFO, 1967 to November 2010; and SCOPUS (EMBASE), 1950 to November 2010. MEDLINE and PsycINFO were searched by using the OvidSP interface. STUDY SELECTION A combination of the following search terms was used: lithium AND adverse effects AND central nervous system OR neurologic manifestation. Publications cited include articles concerned with reversible lithium neurotoxicity. DATA EXTRACTION The age, sex, clinical features, diagnostic categories, lithium doses, serum lithium levels, precipitating factors, and preventive measures of 52 cases of reversible lithium neurotoxicity were extracted. DATA SYNTHESIS Among the 52 cases of reversible lithium neurotoxicity, patients ranged in age from 10 to 80 years and a greater number were female (P = .008). Most patients had affective disorders, schizoaffective disorders, and/or depression (P < .001) and presented mainly with acute organic brain syndrome. In most cases, the therapeutic serum lithium levels were less than or equal to 1.5 mEq/L (P < .001), and dosage regimens were less than 2,000 mg/day. Specific drug combinations with lithium, underlying brain pathology, abnormal tissue levels, specific diagnostic categories, and elderly populations were some of the precipitating factors reported for reversible lithium neurotoxicity. The preventive measures were also described. CONCLUSIONS Reversible lithium neurotoxicity presents with a certain clinical profile and precipitating factors for which there are appropriate preventive measures. This recognition will help in early diagnosis and prompt treatment of lithium neurotoxicity.

Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe): Development and validation

BACKGROUND The use of electroconvulsive therapy (ECT) in treatment of psychiatric disorders is associated with adverse cognitive effects. There is a need to develop a short assessment tool of cognitive functions during the course of ECT. OBJECTIVE This study aimed at developing and validating a short, sensitive battery to assess cognitive deficits associated with ECT in India. METHODS Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe), a brief cognitive battery (20-30 min) to assess verbal, visual, working and autobiographic memory, sustained attention, psychomotor speed and subjective memory impairment, was administered to 30 in-patients receiving bilateral ECT, one day after the 1st, 3rd and 6th ECT. Data was analysed using repeated measures analysis of variance and Pearsons correlation. RESULTS Significant deficits were found in verbal, visual and autobiographic memory, psychomotor speed. Subjective experience of memory loss correlated positively with verbal memory impairment. CONCLUSIONS B4ECT-ReCoDe, a brief, sensitive measure of cognitive impairments associated with ECT can be used in routine clinical practice.

Who Is Paying the Price? Loss of Health Insurance Coverage Early in Psychosis

OBJECTIVE Discontinuities in health insurance coverage may make it difficult for individuals early in psychosis to receive the services that are critical in determining long-term outcome. This study reports on the rates and continuity of insurance coverage among a cohort of early-psychosis patients enrolled in Specialized Treatment Early in Psychosis (STEP) at the Connecticut Mental Health Center. METHODS Insurance status at baseline, six months, and 12 months was collected from 82 participants from a combination of self-reports, clinical chart review, clinician reports, and a database maintained by the state Department of Social Services. RESULTS A total of 34 participants did not know whether they had health insurance or did not appear for follow-up assessments at six and 12 months. Among the remaining 48 participants, at baseline 18 had private insurance, 13 had public insurance, and 16 had no insurance. By the 12-month assessment, 13 (72%) privately insured and five (38%) publicly insured participants had lost coverage; less than one-third of the 48 participants (N=14) maintained continuous coverage. CONCLUSIONS Specialty services for individuals experiencing early psychosis should address the difficulty of maintaining health insurance coverage during a period of illness in which continuity of care is critical to recovery.

Research on Electroconvulsive Therapy in India: An Overview

The contribution of researchers from India in the field of electroconvulsive therapy (ECT) has been substantial. Over 250 papers have been published by authors from India in the past five decades on this issue; about half of these have appeared in the Indian Journal of Psychiatry. This article summarizes the papers on ECT research that have appeared in the Journal. A bulk of these articles has focused on establishing the efficacy in different disorders. Considerable numbers of papers describe refinement in the ECT procedure, including anesthetic modification, ECT machine and EEG monitoring. Papers on neurobiology of ECT and long-term follow-up of ECT-treated patients form a minority. Despite the decline in the use of ECT across the globe, papers on ECT have only increased in the recent decades in the Journal.

Concomitant Anticonvulsants With Bitemporal Electroconvulsive Therapy: A Randomized Controlled Trial With Clinical and Neurobiological Application.

Background Electroconvulsive therapy (ECT) is an effective treatment for major affective disorders. The combined use of ECT and anticonvulsant mood stabilizers is a common clinical scenario. There is dearth of systematic studies on the use of this combination with regard to clinical or cognitive outcomes. Objective/Hypothesis We aimed to compare clinical improvement and cognitive adverse effects between patients who received only ECT versus those who received ECT and anticonvulsants. We hypothesized that improvement would be fastest in patients who received only ECT. Methods We conducted a randomized controlled trial in which patients prescribed ECT while being treated with anticonvulsants were randomized into 3 groups: full-dose (FD), half-dose (HD), and stop anticonvulsant. A blind rater assessed clinical improvement in patients using rating scales [Young’s Mania Rating Scale (YMRS) and Clinical Global Impression] for clinical improvement and cognitive adverse effects (Postgraduate Institute memory scale). Analysis was done using mixed-effects modeling to delineate differences in clinical and cognitive outcomes across the 3 arms of the study over the course of ECT. Results Of the 54 patients recruited, 36 patients went into treatment allocation arms per the initial randomization plan. The main anticonvulsants prescribed were sodium valproate and carbamazepine. Patients in the 3 groups were comparable on clinical features. The most common diagnosis was bipolar affective disorder—with current episode of mania. Overall, there was no difference across the 3 groups in final clinical outcome scores (YMRS and Clinical Global Impression) when analyzed as intention to treat (ITT) or “as treated.” In both analyses, group × time interaction was significant when comparing trend of YMRS scores between the FD anticonvulsant group and the HD group from baseline to last ECT (P = 0.0435 in ITT and P = 0.0055 in as treated). Patients in the FD group improved faster than those in the HD group. There were no differences across the 3 groups with regard to their cognitive adverse effects in the ITT analysis; “as-treated analysis” showed the HD patients to have performed poorly on some domains. Seizure parameters showed no significant difference across the 3 groups. Conclusion This is a preliminary prospective study examining whether coprescription of anticonvulsants with ECT affected clinical or cognitive outcomes. The most important takeaway point from this study is the significant reduction in YMRS scores when ECT was given with FD anticonvulsant compared with halving the dose (HD) of anticonvulsant. This difference was shown in both ITT and as-treated analysis. There is a need for more prospective studies to examine this clinical question.

Maximum Fractal Dimension of Cerebral Seizure Remains Constant Through the Course of Electroconvulsive Therapy

Electroconvulsive therapy (ECT), in which electrical current is used to induce seizures, is an effective treatment in psychiatry. Different methods of analyzing the electroencephalogram (EEG) changes during ECT have been studied for predicting clinical outcome. Analysis of the fractal dimension (FD) is one such method. Mid-seizure and post-seizure FD has been shown to correlate with antidepressant effect. In this study, we examined whether the highest fractal dimension achieved during each ECT session changed over the course of 6 ECTs. The sample for this study came from a randomized controlled trial, comparing the efficacy of bifrontal and bitemporal electrode placements in schizophrenia. EEG was recorded using bilateral frontal pole leads during all ECT sessions. In 40 of the 114 randomized patients, we could obtain artifact-free EEGs for the first 6 ECT sessions. FD was calculated using standardized algorithms. For each session, the average of 5 highest FDs was calculated. The change in this value over a course of 6 ECTs was analyzed using repeated-measures analysis of variance. The average highest FD remained virtually unchanged across the 6 ECT sessions. Means (standard deviations) average maximum FDs over the 6 sessions were 1.57 (0.075), 1.57 (0.064), 1.56 (0.064), 1.57 (0.062), 1.55 (0.07), and 1.56 (0.067); occasion effect, F = 0.5, P = .75. Group effect (F = 0.01, P = .92) and group × occasion interaction effect (F = 1.88, P = .1) were not significant, suggesting no influence of electrode placement on maximum FD. Seizure duration, however, showed significant decline over the course of ECT. Maximum FD of ECT-induced EEG seizure remains fairly constant over frontal poles across the first 6 ECT sessions, which is true irrespective of ECT electrode placements.

Seizure duration decreases over a course of bifrontal and not bitemporal electroconvulsive therapy.

Context: Mechanism of action of electroconvulsive therapy (ECT) is unclear. Anticonvulsant action of ECT has also been one among the hypothesized mechanisms. Anticonvulsant effect may manifest during ECT in at least two ways (a) increased seizure threshold (b) decrease in seizure duration. In depression, increased seizure threshold has been shown to be associated with better antidepressant response. However, relationship between seizure duration and antidepressant activity has been inconsistent. These issues are not investigated in conditions other than depression. Aims: We examined seizure duration over the course of ECT in schizophrenia patients. Settings and Design: Material for this analysis was obtained from a clinical trial examining the differential efficacy of bifrontal ECT (BFECT) versus bitemporal ECT (BTECT) in schizophrenia patients. As a part of study 122 schizophrenia patients who were prescribed ECT were randomized to receive either BFECT or BTECT. Subjects and Methods: Final analysis was conducted on data from 70 patients, as the rest of the data either had artifact or there was a significant change in medication status. Electroencephalogram seizure duration was noted in each session for these patients. Results: Seizure duration declined significantly from second ECT to 6th ECT (repeated measures analysis of variance F = 4.255; P = 0.006). When separate analysis was conducted for BTECT and BFECT patients the decline in seizure duration from 2nd to 6th ECT was significant only with BFECT (F = 3.94; P = 0.014) and not with BTECT (F = 0.966; P = 0.424). Conclusions: Better anticonvulsant effects with BFECT may explain the better therapeutic observed with BFECT in schizophrenia as well as mania in our earlier studies.

Are Advanced Paternal Age and Point Mutation at Chromosome 4 Associated With Schizophrenia

To the Editor: Schizophrenia genes are associated with different chromosomal locations in affected family members, but individual genes have not been recognized. Advanced paternal age has now been considered an independent risk factor for developing schizophrenia in adult offspring.1–3 Schizophrenia is rarely known to co-occur with genetic syndromes of which short stature is also a part.4–6 Like schizophrenia, achondroplasia is also known to occur as a result of sporadic mutation consequent to advanced paternal age.7 Here we describe a case of a combination of schizophrenia and achondroplasia associated with advanced paternal age. Case report. Ms A, a 41-year-old woman with a personal history of dwarfism since birth as well as family history of dwarfism and schizophrenia in her father, who was 44 years old at the time of her birth (her father died 7 years before this presentation due to an accident), presented in 2007 with a 5-year illness, characterized by auditory hallucinations that commented on her actions and gave her commands, delusion of persecution, somatic passivity, and impaired biologic, social, and occupational functioning. Physical examination revealed dextrocardia as well as the classical phenotype of achondroplasia: short stature, rhizomelic shortening of the arms and legs, a disproportionately long trunk, trident hands, midfacial hypoplasia, and prominent forehead. We made a diagnosis of paranoid schizophrenia (DSM-IV criteria) and strongly considered the possibility of achondroplasia. The patient was treated with risperidone (3 mg oral tablets twice per day), and, by the fourth week, the psychotic symptoms had disappeared completely. Since prevalence of schizophrenia in velo-cardio-facial syndrome is about 24%,6 we performed fluorescent in situ hybridization, results of which were negative for deletion of 22q11. Her chromosomal analysis showed 46 XX, which ruled out Turners syndrome. To the best of our knowledge, this is the first reported case of achondroplasia and schizophrenia occurring in the same individual. Achondroplasia is the most common type of short-limbed dwarfism, and 80%–90% of cases are caused by de novo mutations in the gene for fibroblast growth factor receptor 3 (FGFR3) on chromosome 4 (4p16.3).8 Molecular analysis is required for confirmatory diagnosis, but, unfortunately, financial limitations restricted our intentions. Achondroplasia and schizophrenia are genetic conditions known to occur as a result of mutations consequent to advanced paternal age. Considering our patient inherited the mutant gene through an autosomal dominant mechanism, such a mutation may have less likely influenced development of both of these disorders as a coincidence in our patient, despite the fact that the age of her father was 44 years at the time of her birth. Here, a sporadic mutation in a “hot spot” in the FGFR3 gene was responsible for the achondroplasia phenotype in our patients father. We propose that a single de novo sporadic gene mutation was possibly responsible for both phenotypes and transmitted together to the offspring as autosomal dominant disorders. However, schizophrenia has multifactorial etiology, and environmental factors could have influenced the genetic risk in the pathogenesis of schizophrenia. Many scientists are searching the etiology of schizophrenia, but we have not found the definite answer yet. Our case report is a small trial to discern its etiology.