Om Prakash Singh

Effects of lithium therapy on Na+–K+-ATPase activity and lipid peroxidation in bipolar disorder

OBJECTIVES Oxidative stress induced lipid peroxidation along with a reduced Na(+)-K(+)-ATPase activity has been implicated in the pathophysiology of bipolar disorders (BPD). Although, lithium therapy results in significant improvement in the symptoms of the disease, studies regarding its effect on the altered sodium pump activity and lipid peroxidation status have come out with conflicting results. The present study was undertaken to evaluate the status of lipid peroxidation and analyze the role of lithium and Na(+)-K(+)-ATPase activity in its regulation in BPD patients in our region. METHOD We measured RBC membrane Na(+)-K(+)-ATPase activity and serum thiobarbituric acid reacting substances (TBARS) level in 73 BPD patients and serum lithium, in addition, in 48 patients receiving lithium therapy among them. RESULTS Na(+)-K(+)-ATPase activity and serum TBARS level were significantly decreased and increased respectively in all BPD patients compared to age and sex matched healthy controls. Same trend was observed in the BPD patients stabilized on lithium therapy compared to the lithium naive ones. Although, the enzyme activity showed a reciprocal relationship with TBARS in all patients of BPD, a significant positive correlation and dependence of the enzyme activity was evident with serum lithium level only in the lithium stabilized BPD group. CONCLUSIONS BPD patients showed significantly compromised Na(+)-K(+)-ATPase activity and increased lipid peroxidation. Lithium induced improvement in the enzyme activity was associated with significant reduction in lipid peroxidation. Enhancement of the Na(+)-K(+)-ATPase activity by optimum dosage of lithium may be a potential contributing factor for reducing oxidative stress in BPD patients.

Correlation between lipid peroxidation-induced TBARS level and disease severity in obsessive–compulsive disorder

Oxidative stress is thought to play an important role in several neuropsychiatric diseases including obsessive-compulsive disorder (OCD). Thiobarbituric acid reacting substances (TBARS) are products formed as a result of free radical induced lipid peroxidation in the human body. Our study investigated the correlation between TBARS and the clinical severity of OCD as indicated by the Yale Brown Obsessive Compulsive Scale (YBOCS). Serum TBARS was estimated in thirty nine newly diagnosed drug free OCD patients and thirty three disease free control subjects. Mean values for serum TBARS were found to be significantly higher (P < 0.001) in cases than in controls (5.85 nmol/ml and 3.90 nmol/ml with an SD of 0.56 and 0.81 respectively). A strong positive correlation (rs = 0.757, p < 0.01) between the lipid peroxidation marker TBARS and the disease severity indicator YBOCS was found among cases. Significant positive correlation was also found between TBARS and the obsessive and compulsive subscales of YBOCS. These findings were in tune with previous studies, which suggested oxidative stress induced increased free radical generation in the OCD patients. Our findings may help in understanding the development and progress of OCD and the treatment of patients of OCD in future.

A comparative study of oxidative stress and interrelationship of important antioxidants in haloperidol and olanzapine treated patients suffering from schizophrenia

Context: Oxidative stress induced lipid peroxidation has been a significant contributing factor for schizophrenia. Older antipsychotics, like haloperidol , were found to increase lipid peroxidation, whereas, the newer atypical antipsychotics, like olanzapine, did not generate free radicals as metabolic end products. Aims: The interrelationship of the antioxidant vitamins and antioxidant enzymes, and their overall effect on regulation of oxidative stress induced by haloperidol as compared to olanzapine were analyzed in present study. Setting and Design: It was an open randomized cross sectional study that consisted of two groups of fifty schizophrenic patients treated by haloperidol and olanzapine, respectively for at least six months. Materials and Methods: Serum thiobarbituric acid reacting substances (TBARS) was selected as marker of lipid peroxidation, whereas, serum tocopherols, plasma ascorbate and plasma superoxide dismutase (SOD) activity, were selected to assess the antioxidant vitamin and antioxidant enzyme status, respectively. All measurements were done by standard photometric methods. Statistical Analysis Used: Statistical analysis was performed to find out the significance for the differences of means between two groups. Bivariate and partial correlation coefficients for assessing the interrelationship between different parameters were done by using statistical package for social sciences (SPSS) software. Results: Results showed significantly higher serum TBARS and lower antioxidant values in the haloperidol treated patients. Significant positive correlations among the individual antioxidant parameters and significant negative correlation between all of the antioxidant parameters and serum TBARS were found only in haloperidol treated patients. Plasma SOD activity correlated to plasma ascorbate in both groups. Partial correlation results revealed that the serum tocopherol decreased linearly with an increase in serum TBARS significantly in olanzapine treated patients when effect of plasma ascorbate was controlled. Conclusions: Haloperidol caused more oxidative stress along with a significant reduction of important antioxidant parameters. Plasma ascorbate was found to be the chief antioxidant on which the activity of both plasma SOD and alpha tocopherol were dependent under oxidative stressful conditions.

Insulin resistance and metabolic profile in antipsychotic naïve schizophrenia patients

OBJECTIVES Several studies have suggested insulin resistance related to dyslipidemia and body weight in drug treated schizophrenia patients. Although, insulin resistance or impaired glucose tolerance is also reported in antipsychotic naïve schizophrenia patients, their relationship with dyslipidemic changes and body weight is not well established. The present study was undertaken to examine insulin resistance in antipsychotic naïve schizophrenia patients of this region and to evaluate any association between lipid parameters and body weight with their insulin resistance, if any. METHOD Plasma glucose, total serum cholesterol and its LDL, HDL fractions, and serum insulin levels were measured from fasting blood samples of newly diagnosed, antipsychotic naïve schizophrenia patients (n=30) and matched control group (n=25) in a hospital based case control study. Homoeostatic model assessment (HOMA) was done to evaluate insulin resistance. RESULTS Means of plasma glucose, total serum cholesterol and its LDL, HDL fractions did not vary significantly (p>0.05) between cases and control. Insulin resistance was significantly increased (p<0.05) in drug naïve cases. Multiple linear regression analyses did not show any association (p>0.05) between insulin resistance and lipid parameters. CONCLUSIONS Newly diagnosed schizophrenia patients were more prone to insulin resistance in our study population. This was not associated with any dyslipidemic changes as the lipid parameters were not elevated in them compared to the healthy controls. It was not dyslipidemia, but some other common genetic or risk factors that might be responsible for the increased insulin resistance in antipsychotic naïve schizophrenia patients in our study population.

Role of antiparasitic therapy for seizures and resolution of lesions in neurocysticercosis patients: An 8 year randomised study

Neurocysticercosis is a common cause of acquired seizure disorder in developing countries, including India. The role of antiparasitic (albendazole) therapy for seizure control and resolution of lesions is still controversial due to a lack of adequately controlled studies. The objective of the present study was to evaluate the role of albendazole therapy for neurocysticercosis patients with two or more lesions to achieve seizure-free status and resolution of lesions. This was a randomised controlled study in which patients suffering from neurocysticercosis were prospectively followed up for more than 5 years (from January 1997 to January 2005). Patients were divided into two groups: patients in group A (n=150) were treated with a combination of tapered doses of dexamethasone and albendazole, plus antiepileptic drugs; patients in group B (n=150) were treated with antiepileptic drugs plus a placebo control. Patients were followed up every month for the first 6 months and then at 3-month intervals thereafter up to 5 years. Variables of interest were (i) recurrence of seizures; (ii) encephalopathy (headache/vomiting/altered sensorium); (iii) need for subsequent hospital admission; (iv) death; (v) resolution of lesions on follow-up CT. During the first 6 months and at intervals thereafter, increased seizure frequency and hospital readmissions, and increased incidence of encephalopathy were observed in group A (p=0.01), and two patients in this group died with intractable seizures and encephalopathy. A greater proportion of lesions completely resolved in group B (p=0.05), whereas a greater proportion of lesions calcified in group A (p=0.05). Albendazole plus antiepileptic drugs did not have greater beneficial effects than antiepileptic drugs alone, but may have an adverse effect with respect to seizure control, encephalopathy, recurrent hospital admissions, calcification of lesions and cost of treatment.

Rapid response with ketamine on suicidal cognition in resistant depression

Context: Suicidal ideation in depressed patients is a serious and emergent condition that requires urgent intervention. Intravenous ketamine, an N-methyl-D-aspartate (NMDA) antagonist, has shown rapid antidepressant effects, making it a potentially attractive candidate for depressed patients with suicidal risk. Aims: In India few studies have corroborated such findings; the present study aimed to assess the effectiveness and sustainability of antisuicidal effects of ketamine in subjects with resistant depression. Settings and Design: Single-center, prospective, 4 weeks, open-label, single-arm pilot study. Materials and Methods: Twenty-seven subjects with DSM-IV major depression (treatment resistant) were recruited. The subjects were assessed on Scale for Suicidal Ideation (SSI), 17-item Hamilton Depression Rating Scale (HDRS). After a 2-week drug-free period, subjects were given a single intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and were rated at baseline and at 40, 80, 120, and 230 minutes and 1 and 2 days postinfusion. Results: The ketamine infusion was effective in reducing the SSI and HDRS scores, the change remained significant from minute 40 to 230 at each time point. Conclusions: The real strength of this study rests in documenting the rapid albeit short-lasting effect of ketamine on suicidal ideation in depressed patients.

Prevalence of depression in patients with type ii diabetes mellitus and its impact on quality of life

Background: Diabetes mellitus (DM) is a frequently encountered chronic metabolic disease with various complications throughout its course, which causes severe restriction and disability in an individuals life. It has been well documented that the incidence of depression is higher in diabetic patients and co-morbid depression causes further deterioration in the quality of life in diabetic patients. Aims: To study the prevalence of depression and its impact on quality of life in patients with type II DM. Settings and Design: Single centre, cross-sectional, single interview. Materials and Methods: Total 195 type II DM patients are included in this study. To diagnose Depressive Episode Structured Clinical Interview for DSM IV Axis-1 Disorders, Research Version patient edition was applied. All patients were evaluated with a semi-structured socio-demographic proforma to assess socio-demographic characteristics, Hamilton Rating Scale for Depression (HAM-D) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES–Q) SF (Short Form) to measure the quality of life. Results: Among them, 46.15% (N=90; males: 41, females: 49) met the DSM-IV diagnostic criteria for major depressive episodes. Among the depressed group, majority were (36.7%) moderately depressed. QLESQ-SF total and each item scores were significantly lower in the depressed group than in the non-depressed group. Both the HAM-D scores and HbA1c level have significant negative correlations with QLESQ-SF total scores. Conclusion: Our study demonstrates that the presence of depression in type II DM further deteriorates the quality of life of the patients. Therefore, treating depression would have a beneficial effect on the quality of life.

Study of oxidative stress in obsessive compulsive disorder in response to treatment with Fluoxetine

Oxidative stress has been found to play important role in several neuropsychiatric diseases including Obsessive Compulsive Disorder. A longitudinal case control study was conducted to evaluate the oxidative stress in 30 newly diagnosed obsessive compulsive disorder patients and same number of control patients. Serum thiobarbituric acid reacting substances, plasma ascorbate were assessed to evaluate oxidative stress and Yale Brown obsessive compulsive scale for disease severity before and after treatment with Fluoxetine at the average dosage of 40 mg/day. Improvement in Yale Brown obsessive compulsive scale score by about 43% after 12 weeks treatment was associated with significantly decreased thiobarbituric acid reacting substances and increased plasma ascorbate values (p < 0.05). The newly diagnosed obsessive compulsive disorder patients had higher serum thiobarbituric acid reacting substances as well as a lower plasma ascorbate levels than the control population. Thus, the present study suggested a significant role of oxidative stress in obsessive compulsive disorder and showed that a successful treatment with Fluoxetine not only improves the clinical scenario but also reduces the oxidative stress that may further improve the prognosis of the disease.

Rapid Antidepressant Response with Ketamine: Is it the Solution to Resistant Depression?

Background: Treatment-resistant depression (TRD) is a relatively common condition, challenging the clinician. There is an urgent need to develop pharmacological treatments for TRD that exert rapid and sustained antidepressant effects. Ketamine induces a rapid antidepressant effect. Aims: In India, very few studies have corroborated such findings, and the present study aimed to assess the effectiveness and sustainability of antidepressant effects of ketamine in subjects with TRD. Materials and Methods: The present study was a single-center, prospective, 4-week, open-label, single-arm pilot study. Twenty-two subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depression (treatment resistant) were recruited. After a 2-week drug-free period, subjects were given a single intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and were rated at baseline and at 40, 80, 110, and 230 min and 1, 2, 3, 4, 7, and 14 days postinfusion. The main outcome measure was changes in scores on the 17-item Hamilton Depression Rating Scale (HDRS). Data were analyzed by using Freidmans analysis of variance and a post hoc test. Results: The ketamine infusion was effective in reducing the HDRS scores, and the change remained significant from minute 80 to day 3 postinfusion at each time point. The change was not significant at any time after day 3. Conclusion: The real strength of this study rests in documenting the rapid, albeit short-lived, antidepressant effect of ketamine in TRD.

A study on socio-demographic characteristics of alcoholics attending the de-addiction center at Burdwan medical college and hospital in West Bengal

Prevalence of alcohol use in India is reported to be 21.4% and there is increasing alcohol intake among the young people. The present study was undertaken to study the socio-demographic characteristics of patients having alcohol-related disorders attending the de-addiction center at Burdwan Medical College in West Bengal and to find out some factors responsible for that. A clinic-based descriptive cross-sectional study was conducted among 187 patients with the help of pre-tested pre-designed schedule after obtaining informed consent. Data analysis was carried out with the help of Epi info software version 6. Majority of the patients were male, in productive age group and married. Age of initiation and amount of alcohol intake were significantly associated with positive family history of alcoholism. Children having family history of alcoholism should be counseled to prevent development of alcoholism.