An Exploratory Case-Control Study for Mitochondrial DNA G10398A in Bipolar I Disorder Patients with a Family History of Affective Disorders.

BACKGROUND: The mitochondrial DNA (mtDNA) G10398A polymorphism has been associated with bipolar disorder (BD). It leads to an amino acid substitution within NADH dehydrogenase subunit, thereby altering the mitochondrial complex I function. This exploratory case-control study assesses the association of mtDNA G10398A with the risk of BD and its relationship to clinical variables in Indian patients. METHODS: Cases met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of BD-I in remission and had a family history of BD or recurrent unipolar disorder in biological relatives. The healthy controls (HC) had no known illness and were screened negative for Family Interview for Genetic Studies. Participants were assessed using Clinical Pro forma, NIMH-Life Chart Method and Alda lithium response scale. The mtDNA G10398A was assessed with real-time polymerase chain reaction using TaqMan assay. RESULTS: A total of 82 participants were recruited across cases and controls, with 42 patients (50% with maternal history) and 40 healthy individuals with similar demographic profiles. The mean age of onset was 25.16 (standard deviation [SD] 7.6) years, with illness for 11.59 years (SD: 7.18). Allele A was found in 50% of cases compared to 32.5% HC (odds ratio = 2.08; 95% confidence interval [CI]: 0.85-5.09). Findings remain non-significant for patients with maternal mood disorders (allele A: 38.9%; 21/42). Cases with allele G had significantly higher body mass index (BMI) (P = 0.008) than those with allele A. CONCLUSION: The study adds information on mtDNA 10398A amongst Indian patient samples and healthy individuals. No significant group difference was found with respect to mtDNA G10398A. The positive association of allele G with higher BMI has potential clinical relevance that can be further investigated in larger samples.

Ultrasonically Determined Thyroid Volume in Individuals with Bipolar Disorder on Lithium Prophylaxis Compared with Healthy Controls.

Introduction: Lithium is a gold-standard agent for bipolar disorder (BD) and can affect the size, structure and/or function of thyroid gland with long-term exposure. Thyroid ultrasound can detect structural thyroid abnormalities, but it is under-reported with few prior studies in lithium users. The study aimed to evaluate thyroid volume and echogenicity in lithium users with BD and healthy participants, and explores its association with clinical variables and thyroid functions. Method: This was an observational study with 102 participants in total. Study group consisted of 52 clinically-stable (HAM-D ≤ 13, YMRS <8) follow-up patients with DSM-5 BD on lithium maintenance. Healthy controls (HC) comprised 50 participants with no illness in self and family. Assessments included NIMH Life-chart, IGLSI typical/atypical scale, lithium response scale (LRS) and CGI-BP. Fasting venous sample was taken for thyroid functions, Anti-TPO antibodies and serum lithium. Thyroid ultrasonography was also conducted. Results: Mean age of cases was 39.42 ± 12.62 years, with 42.3% females, which was comparable to HC. Median duration of illness was 10.5 years (Q1-Q3 = 6-19 years), with median lithium exposure for 4.5 years (Q1-Q3:2.2-7.75), and serum lithium 0.67 mmol/L (SD:0.31). Thyroid volume was significantly higher for cases than HC (10.67 ± 5.46 mL vs 4.30 ± 2.06 mL; p < 0.001). Relative to HC, serum TSH was higher in cases (p = 0.018), while anti-TPO positivity was comparable (14.0% vs 3.85%, p = 0.089). Thyroid nodules were more frequent in male cases (p = 0.013) compared to male controls.Thyroid volume did not show association with serum TSH (p = 0.277) and lithium response (p = 0.36). Conclusion: Findings indicate a uniform enlargement of thyroid gland in lithium users with BD. Thyroid volume did not show association with thyroid functions and lithium response, however prospective studies may give better insight about their trajectories over time.

Serum brain-derived neurotrophic factor level and its relation with cannabis use disorder and schizophrenia: A cross-sectional exploratory study in patients at a tertiary care hospital.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has considerable relevance in neural growth and differentiation. It has been evaluated as a biomarker for individuals with various psychiatric disorders such as substance-related disorders and psychotic disorders. OBJECTIVE: The present study explored differences in the levels of BDNF (in serum) among subjects using cannabis (with and without schizophrenia). METHODS: This cross-sectional observational study compared the serum BDNF level in male subjects aged 18-45 years. Four groups of 20 subjects each were included: individuals with tobacco use disorder only, patients having schizophrenia, patients with cannabis use disorder, and finally patients with comorbid cannabis use disorder and schizophrenia. RESULTS: The BDNF levels were found to be significantly different across the four groups. The BDNF levels in subjects with concurrent schizophrenia and cannabis use disorder were higher than each of the other three groups (cannabis use disorder, schizophrenia, and tobacco use disorder only). CONCLUSION: We find that BDNF may be higher when cannabis use disorder and schizophrenia co-occur, as compared to either of the conditions alone. The findings should be interpreted with caution due to the low sample size and potential confounders.

An efficient LC-QTOF-mass spectrometry method for monitoring nal-trexone compliance in urine of opioid-dependent subjects.

Naltrexone (NTX) is an orally effective opiate antagonist used in maintenance treatment for opiate dependence. Its utility is limited by the patient's noncompliance. The study aimed to develop an efficient method for the detection of NTX in urine by LC-QTOF-mass spectrometry (MS) and its application to NTX compliance in opioid-dependent subjects. Sample preparation included a dilution step and direct injection to LC-QTOF-MS. Chromatographic separation was achieved with a C-18 column using a mixture of mobile phase 0.1 percent formic acid in water and 0.1 percent formic acid in 95 percent methanol. The calibration curve was linear in the range 1-100 ng/mL with a correlation coefficient higher than 0.996. Precision and accuracy were acceptable, and the recovery efficiency range was 80-85 percent. The current LC-QTOF-MS method is simple, precise, sensitive, and can be used for monitoring NTX compliance among opioid-dependent subjects in a clinical setting.

Disability and quality of life in patients with treatment-resistant schizophrenia on long- term clozapine therapy.

Objectives: To assess disability and quality of life (QOL) in treatment resistant schizophrenia (TRS) on long term clozapine therapy and assess their correlation with positive, negative and cognitive symptoms. Methodology: Disability and QOL in forty patients with TRS (as per modified Kane's criteria) were assessed using World Health Organization Disability Assessment Schedule 2.0 and World Health Organization Quality of Life-BREF. Scale for assessment of positive symptoms, scale for assessment of negative symptoms and Addenbrooke's cognitive examination-III were used to assess positive, negative and cognitive symptoms. Medication adherence rating scale assessed medication adherence. Results: Disability and QOL correlated significantly with medication adherence, negative and cognitive symptoms but not with positive symptoms. Subgroup analysis revealed significant difference between medication adherence (good vs poor) and cognitive (impairment vs non-impairment) groups. Conclusion: Negative and cognitive symptoms, and medication adherence correlated with disability and QOL.

Effectiveness of smoking cessation intervention in opioid-dependent male subjects on buprenorphine maintenance treatment: An open-label trial.

Background: High prevalence (more than 80%) rates of tobacco smoking have been found both in, opioid-dependent subjects and among opioid-dependent subjects on opioid substitution treatment (OST) with buprenorphine or methadone. Aim: We aimed to explore the efficacy of combined nicotine replacement therapy (NRT) and individual counseling (IC) when compared to NRT alone in subjects on OST with buprenorphine. Methods: This study was carried out in a tertiary medical care center. It was an open-label randomized clinical trial. A total of 57 buprenorphine maintained smokers were recruited and randomized into two groups. They were assigned nicotine gum for 4 weeks plus either (1) a baseline IC session, and a second IC session after 1 week, or (2) simple advice to quit. In the first group, 31 subjects received NRT with IC and in the second group, 26 subjects received NRT plus simple advice to quit. The primary outcomes of this study were seven days point prevalence abstinence, biochemically confirmed by carbon monoxide (CO) breath analyzer, and reduction in smoking (mean no. of cigarettes or bidis/day). The smoking behavior during the 4 weeks follow-up period was assessed by the timeline follow-back (TLFB) method and confirmed by the CO breath analyzer. Results: The group of subjects who received NRT with IC showed higher rates of smoking cessation at the end of treatment (51%) as compared to the NRT and simple advice group where smoking cessation rates were around 8% (P < 0.001). Conclusion: A multi-component approach (pharmacotherapy and counseling) enhances treatment outcomes and enhances rates of abstinence from smoking.

Serum BDNF Levels Among Patients with Alcohol Dependence, Depression and Alcohol Dependence with Comorbid Depression - A Comparative Study.

The study aimed to assess and compare the serum brain derived neurotrophic factor (BDNF) levels in patients with alcohol dependence, depression and alcohol dependence with comorbid depression. Three groups each of 30 alcohol-dependent, depressive and alcohol-dependent with comorbid depressive patients seeking treatment were included. BDNF levels were estimated, and scales were administered to assess severity of alcohol dependence (using severity of alcohol dependence questionnaire, SADQ) and depressive symptoms (using Hamilton depression rating scale, HDRS). The mean BDNF value in ADS, depression and ADS with comorbid depression group was 16.4 ng/mL, 14.4 ng/mL and 12.29 ng/mL respectively, and the differences were statistically significant. In ADS group and ADS with comorbid depression groups significant negative association existed between BDNF and SADQ scores (r = -0.371, p = .043 and r = -0.0474, p = .008 respectively). There were significant negative association between BDNF and HDRS scores in depression and comorbid ADS and depression group (r = -0.400, p = .029 and r = -0.408, p = .025 respectively). The BDNF level was significantly lower in the ADS with comorbid depression group and was associated with severity of dependence and depression across the groups.

Does ethyl glucuronide in hair correlate with alcohol consumption? A comparative study with other traditional biomarkers among individuals with alcohol dependence syndrome.

AIM: Ethyl glucuronide (EtG) in hair is a direct biomarker proven to be useful for the detection of chronic excessive alcohol use. This study investigated the association of self-reported alcohol consumption with traditional biomarkers: GGT, AST, ALT, CDT, and MCV in blood and a direct biomarker, hair EtG, in a total of 122 patients with alcohol dependence syndrome. The diagnostic accuracy of the biomarkers to differentiate heavy from non-heavy drinkers was also evaluated. METHOD: GGT, AST, and ALT in serum were measured by Automated Chemistry Analyzer, MCV in blood was measured by Haematology Analyzer, serum CDT was analyzed by ELISA, and EtG in hair was evaluated by gas chromatography-mass spectrometry. The association between the biomarkers and the amount of alcohol consumed (self-reported) was determined using Spearman's rank correlation. RESULTS: All participants showed EtG level above the cut-off (0.03 ng/mg). Hair EtG showed a statistically significant linear and positive correlation with the amounts (in grams) of alcohol consumed (r = 0.60; p < 0.001). No correlation was observed among the traditional biomarkers and the quantity of alcohol consumed. Also, EtG showed an excellent receiver operating characteristic (ROC) curve (98%) with good sensitivity (85%) and specificity (60%) to classify heavy drinkers among individuals with alcohol dependence syndrome. CONCLUSION: Hair EtG can be helpful to estimate retrospective alcohol consumption in long-term chronic alcohol consumption cases. Hair EtG also provides a reliable diagnostic test to detect heavy drinkers among individuals with alcohol dependence syndrome.

An efficient method for simultaneous detection of Pheniramine, Pentazocine and cotinine in urine by Gas Chromatography in De-addiction program.

Background: Nonmedical use of prescription drugs for recreational purposes is a major health problem that raises high concerns for public health. Recently, several laboratory studies have reported the misuse of pentazocine, an agonist-antagonist opioid in combination with antihistamines in opioid addicts. Illicit self-administration of prescription drugs has been increasingly reported in India. Urinalysis as an adjunct to self-report plays a key role in providing additional information in the treatment of drug users. This paper aims to discuss a simple, convenient, and rapid capillary column gas-liquid chromatography method for simultaneous detection of pentazocine, pheniramine, and cotinine in urine. Methods: The sample was extracted with chloroform and isopropanol (3:1,v/v) and evaporated to dryness. After reconstitution with methanol, it was directly subjected to gas chromatography analysis. Method performance was evaluated and validated in terms of sensitivity, precision, the limit of detection (LOD), and the limit of quantification (LOQ). Findings: The linearity obtained was in the range of 50-1000 ng/ml with a correlation coefficient (r) above 0.999 for each drug. Good LOQ (50ng/ml) was obtained with each drug. Also, the developed method was effective in analyzing samples from patients with suspected abuse of these drugs. Conclusion: The technique was found to be simple, robust, sensitive, and precise in the simultaneous analysis of drugs (pentazocine, pheniramine, and cotinine). This method was proved to be useful and cost-effective in treating and monitoring patients seeking help for addiction in clinical settings.

Exploring the clinical variables among drug-dependent HIV-Positive patients: Implications for treatment strategies.

This study explored the profile of HIV positive patients seeking treatment at a tertiary care addiction treatment facility. A retrospective study was done to collet detailed information on clinical characteristics: drug use (type, age of initiation, duration), general medical condition and past treatment history. The study included 138 patients with mean (SD) age 30.2 (8.3) years. Opioid dependence with injecting drug use (IDU) was diagnosed in 97% of the patients. The median age of injecting onset was 24.5 years (IQR 20-31 years). The most frequently injected substances were pheniramine (60.1%) and buprenorphine (59.4%). Past treatment seeking was reported by 57% patients and interestingly they were less likely to present any medical condition (2 =69.611, p < 0.001). Variability in the age of onset of drug use indicates the need for broad based approach to prevent IDU and motivation to seek treatment may lead to better health conditions.

Effect of chronic opioid use on the hematological and inflammatory markers: A retrospective study from North India.

Background: Chronic opioid use affects biological functioning implicating the hematopoietic and immune system. It may alter various hematological parameters and inflammatory markers. This study aimed to assess the association of opioid dependence with the hematological parameters and inflammatory markers in the Indian population. Methods: A retrospective chart review was done among opioid dependent (ODS) males and healthy controls (HC) who visited the center's laboratory between Jan 2017 and Dec 2018 for hematological investigations. Clinical records reviewed for opioid use details like type, duration, and route of administration. The hematological profile presented as Mean or median. Mann-Whitney U test was used to compare the hematological parameters between the cases and controls. Results: The study included 191 ODS patients and 123 controls. Among ODS patients, a significant decrease in the levels of hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin and an increase in RBC count and lymphocytes was observed when compared to controls. The inflammatory markers, Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio, were significantly lower among ODS. Longer duration of opioid use leads to increased NLR among ODS patients. Opioid use by injection did not alter any of the hematological parameters compared to non-injection drug use. Conclusion: Chronic opioid use has a significant effect on the hematopoietic cells. Opioid use for longer durations increases the inflammatory markers suggesting underlying infections.

Urinalysis based assessment of compliance and drug use patterns in patients prescribed tramadol: A cross-sectional study from a tertiary care centre.

BACKGROUND: Strict adherence to pharmacological dosage regimens is a prerequisite to the success of most treatments, particularly for patients in drug abuse programs. The compliance of tramadol, an atypical non-scheduled narcotic analgesic, using objective method has not been adequately studied in an Indian setting. AIM: To evaluate the compliance and pattern of drug use among opioid-dependent subjects prescribed tramadol based on urinalysis. METHOD: Fifty male opioid-dependent patients (ICD 10), seeking treatment at a tertiary de-addiction treatment centre of North India on tramadol prescription for atleast past four weeks were included. Self-reported substance use was recorded using semi-structured proforma. Ten ml of urine was collected for the assessment of compliance of tramadol of other substance use (morphine, buprenorphine, dextropropoxyphene, pentazocine, cannabis, benzodiazepines, pheniramine). All these drugs were analyzed using the immunoassay-based Cassette test and Gas Chromatography in human urine. RESULT: Mean age of the participants was 42.8 years and the mean duration of opioid use was 15.9years. The urine specimen of all subjects tested positive for tramadol. Urinalysis revealed benzodiazepines, cannabis, and pheniramine to be the most common substances of use in this population. It was seen that agreement of self-reporting and urine test results was good for morphine (κ = 0.558) and cannabis (κ = 0.312) and was poor for buprenorphine, pentazocine, and pheniramine. CONCLUSION: The study demonstrates the continued use of several illicit or non-prescribed medications in a medication-assisted opioid treatment population. The results affirm the reliability of urinalysis as an adjunct for testing compliance in such a population.

Serum Corticotrophin Releasing Factor (CRF) and its correlation with stress and craving in detoxified opioid-dependent subjects.

Corticotrophin Releasing Factor (CRF) might be suitable as biological measure of stress as it is implicated directly in both central neurological and endocrine stress-response. The study aims to compare serum CRF levels and perceived stress in opioid-dependent subjects (n = 53) with non-using controls (n = 47) and to correlate them with general and instantaneous craving (in cases only). Perceived stress score and serum CRF levels were significantly higher among the users. No significant correlation with craving was found. The significant difference in serum CRF levels indicate feasibility of measuring CRF levels in peripheral fluids and asserts its role as biochemical measure of stress.

Association of Serotonergic Pathway Gene Polymorphisms With Behavioral Parameters in Patients With Opioid Dependence.

Background and aims Opioid dependence is a chronic, relapsing substance use disorder with a multifactorial etiology, including a genetic component. Serotonin pathway gene polymorphisms have been an important focus of research for psychiatric disorders, including substance use disorders. This study aimed to identify the association of serotonin pathway gene polymorphisms with self-harm, depressive symptoms, impulsiveness, and aggression in patients with opioid dependence. Method The study group comprised 366 subjects with opioid dependence and 200 healthy volunteers. Patients were assessed for a history of self-harm, depressive symptoms, impulsiveness, and aggression using standard tools. Genomic DNA was used for genotyping of four polymorphisms - 5-HTTLPR, STin2 VNTR, TPH1 A218C, and TPH2 G703T. Results The short allele of 5-HTTLPR polymorphism showed a significant difference between cases (59.8%) and controls (40.1%) (p=0.001) and revealed an association with age at opioid dependence (p=0.033). There was a borderline significance of the short allele of 5-HTTLPR with the duration of opioid use (p=0.061) and non-plan impulsivity (p=0.076), suggesting a role of 5-HTTLPR in the susceptibility of opioid dependence. The other markers did not differ between cases and controls. However, the STin2A polymorphism revealed a significant association with anger scores, which may indicate its role in aggressive behavior. Conclusions The present study, the first of its kind, suggests an association of 5-HTTLPR polymorphism with opioid dependence and STin2A polymorphism with aggressive behavior among opioid-dependence patients, signifying the role of these markers in our patient population.

Influence of catechol-O-methyltransferase enzyme gene polymorphism on alcohol and tobacco consumption in North Indian treatment seeking population.

BACKGROUND: The co-occurrence of alcohol and tobacco dependence is frequently witnessed in treatment settings. It is a challenge for clinicians to treat such patients due to their powerful biological association. AIM: The study is aimed to assess the relationship of Catechol-O-methyltransferase (COMT) Val158Met polymorphism with substance intake among individuals who are dependent on both alcohol and tobacco. MATERIALS AND METHODS: A cross-sectional study involving patients coming to the outpatient department was planned. Brief information on their sociodemographic and substance use profile was recorded. Genotyping of COMT Val158Met was carried out using established polymerase chain reaction-restriction fragment length polymorphism method. The COMT genotyping was classified based on the presence or absence of Met allele using the dominant model. Descriptive statistics, Chi-square test, Mann-Whitney test, and Binary logistic regression analysis were performed to analyze the data. RESULTS: The study included 104 alcohol and nicotine co-dependent subjects. More than eighty percent of the participants were educated above secondary level, married, and employed. The allele frequencies of met and Val were found to be 0.23 and 0.77, respectively. Forty percent of the participants reported tobacco-related health problems. The odds of consuming alcohol and nicotine were four times high among Met allele carriers. While the Fagerström test for nicotine dependence and heaviness of smoking index scores were up to four and eight times higher among met allele (odds ratio 4.3 and 8.9, respectively). CONCLUSION: Patients carrying Met allele are reported to consume higher amounts of alcohol and tobacco and were likely to score high among measures of nicotine dependence. Thus met allele carriers needs additional attention for a successful treatment outcome.