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.

Factors associated with lifetime suicide attempts: findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

AIM: To evaluate the risk factors associated with lifetime suicide attempts in bipolar disorder (BD) patients. METHODOLOGY: 773 BD patients with a duration of illness of at least ten years, currently in clinical remission, were evaluated for suicidal attempts in their lifetime. Those with and without lifetime suicide attempt(s) were compared for various demographic and clinical risk factors. RESULTS: 242 (31.3%) patients had a history of at least one lifetime suicide attempt. Compared to those without lifetime suicide attempts, those with suicidal attempts were less educated, were more often females, spent more time in episodes, and had a significantly more number of total episodes (in the lifetime, first five years of illness, and per year of illness), had significantly more number of total depressive episodes (in the lifetime, first five years of illness, and per year of illness), spent more time in depressive episodes, had more severe depressive episodes, more often had depression as the first episode in the lifetime, spent more time in mania/hypomania/mixed episodes, had higher residual depressive and manic symptoms, more often had rapid cycling affective disorder pattern in the lifetime, use of cannabis in dependence pattern, had poorer insight into their illness and had a higher level of disability (especially in three out of the four domains of Indian disability evaluation assessment scale). CONCLUSIONS: About one-third of the patients with BD have at least one-lifetime suicidal attempt, and those with suicide attempts usually have a poorer course of illness.

Cingulum bundle integrity in schizophrenia with auditory verbal hallucinations: A diffusion tensor imaging tractographic study.

Background & objectives: Cingulum bundle (CB) is frequently implicated in schizophrenia; however, its role in specific symptoms of schizophrenia such as auditory verbal hallucinations (AVHs) is less explored. Few studies have reported association between reduced integrity of CB and severity of AVH. Using a symptom-based approach, this diffusion tensor imaging (DTI) tractographic study was aimed to assess and compare the integrity of CB in schizophrenia with AVH, schizophrenia without AVH and healthy controls. Methods: A total of 92 right-handed adult individuals (aged 18-50 yr) were recruited across three study groups. Those with Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of schizophrenia with AVH (group I; n=30) were compared to those with DSM-5 schizophrenia without lifetime AVH (group II; n=32) and healthy controls (group III; n=30; screened using Mini International Neuropsychiatric Interview version-7.0.0. and negative family history). Clinical assessments (groups I and II) included scale for assessment of positive symptoms, scale for assessment of negative symptoms, clinical global impression-schizophrenia and psychotic symptom rating scale. All participants underwent DTI, and quantitative tract-based measurements of fractional anisotropy (FA) were obtained for images using DTI studio version-3.0. Results: All groups were comparable for age, gender, education and severity of illness. Group I had significantly lower FA values in the cingulate gyrus (CG) part of the left CB compared to groups II and III. No significant difference was found between groups II and III. Interpretation & conclusions: The findings of this study suggest that the disruption in the left CB appears to be specific for AVH-positive schizophrenia. The finding is, however, preliminary subject to replication in future studies. Further investigations are needed to understand its relevance in the context of AVH-positive schizophrenia.

Is unipolar mania a distinct entity: findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

AIM: This study aimed to evaluate the prevalence of unipolar mania (UM) in a group of patients of bipolar disorder (BD). Additionally, effort was made to evaluate the demographic, clinical and treatment related factors, which distinguish subjects of UM from BD. METHODOLOGY: Seven hundred and seventy-three patients with BD, of at least 10 years duration, recruited from 14 General Hospital Units of tertiary care centers from India were evaluated for UM. RESULTS: The prevalence of UM, varied from 5.4% to 20.3%, depending on the definition used. With the most stringent definition of ≥4 episodes of mania and at least 5 years of follow-up, the prevalence of UM was 5.4%. Compared to patients of BD, who have episodes other than mania too, those with UM had lower proportion of patients with lifetime history of suicide attempts, spent less time in the episodes in their lifetime and had lower severity of residual depressive and manic symptoms. Further, compared to those with episodes other than mania too, those with UM had higher number of manic episodes per year of illness, had higher proportion of patients who had more than five episodes in the lifetime and had higher proportion of those with at least one episode with psychotic symptoms in the lifetime. CONCLUSION: The present study suggests that a small proportion of patients with BD have UM course and this runs a different clinical course compared to that seen in patients with traditionally recognized as BD.

Effective Written Communication in Consult Letters: A Crucial Yet Overlooked Skill?

The consult letters can be viewed as a window to the entire consultation process. Suitable drafting of consult letters is a useful but often overlooked skill in training years. It is not uncommon to find the consult notes lacking the relevant context or clinical information. Both the style and content should be kept in mind for an effective written communication. It is also important to supervise and give specific feedback to the trainees to make the consult letters succinct and clear.

Assessment for familial pattern and association of polymorphisms in KIAA0319 gene with specific reading disorder in children from North India visiting a tertiary care centre: A case-control study.

Genetic association studies have identified KIAA0319 gene as a possible susceptibility locus for reading disorder; however, very few studies are available from India. The study was planned to investigate the familial pattern and association of KIAA0319 polymorphisms among children with reading disorder visiting a tertiary centre in North India. This is a case-control, familial, and genetic association study on 30 children diagnosed with reading disorder (ICD-10) and 30 matched healthy controls and their families. The Aggregate Neurobehavioral Student Health and Educational Review System was administered on parents of probands and controls for reading problems in their siblings, and Adult Reading Questionnaire was administered for parents of both groups. The blood sample was taken from probands, and DNA was isolated. Four KIAA0319 coding sequence single nucleotide polymorphisms (SNPs; rs4504469, rs6935076, rs2038137, and rs2179515) were genotyped using SNaPshot single nucleotide extension. The incidence of reading problem was significantly higher in families of probands as compared with families of controls. There were no significant differences in both groups regarding the frequency of alleles of four SNPs. The reading disorder showed a significant familial pattern, but KIAA0319 gene did not appear to be a susceptibility factor. Future replications with larger samples and whole genome studies are warranted.

Mental and behavioural emergencies at a tertiary healthcare centre in India: Pattern and profile.

Background: Sparse data are available on service utilization, pattern and profile of mental and behavioural emergencies in India. We explored the pattern and clinical profile of consecutively referred psychiatric emergencies at a premier tertiary healthcare centre in India. Methods: We reviewed the consecutive referrals for acute mental and behavioural problems made by the emergency department and recorded in an emergency psychiatry register between January 2015 and January 2016. Results: Over a 1 3-month period, 666 patients were assessed; of whom 473 (71 %) had no prior/known psychiatric history and 84 (12.6%) had a comorbid medical condition. Nearly one-third of patients had potential legal issues associated with their emergency. The most common reasons for presentation were: an attempt at self-harm (130; 19.5%), aggression/agitation ( 122; 18.3%) and psychoactive substance use-related problems (69; 10.3%). Schizophrenia and other psychotic disorders (89; 13.4%) and mood disorders (87; 1 3.1%) formed the 2 most common diagnostic groups seen in emergency. Most commonly prescribed medications were benzodiazepines (296; 44.4%) followed by antipsychotics (187; 28.1%) and antidepressants (90; 13.5%). Notably, 11% of patients (76) were advised immediate admission under psychiatry, half of whom could be admitted directly from the emergency. Conclusion: Our findings suggest that there is a need to optimize emergency mental healthcare and develop service delivery models for common psychiatric emergencies in India.

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.

Sublingual Atropine Administration for Clozapine-Induced Sialorrhea in Bipolar Disorder: A Case Report Highlighting its Efficacy, Safety Concerns and Challenges.

We discuss a case with off-label sublingual administration of atropine for clozapine-induced sialorrhea (CIS) after failure of two commonly used agents to manage CIS. Atropine had a demonstrable efficacy, as measured by means of sialometry conducted before and after its administration. The salivary rate, initially measured at 0.60 g/min one hour before atropine administration, reduced to 0.23 g/min two hours after administration. Sublingual administration of atropine was found to be an efficacious option for this patient, but safety issues particularly tachycardia and pragmatics such as risk of inadvertent overdose led to its discontinuation after the initial dose. Developing micro-dosing devices for sublingual atropine could enhance administration precision, reduce side effects, and provide a cost-effective solution. The case report also underscores the need to employ sialometry for the objective assessment of treatment outcomes in future research trials for hypersalivation.

Pattern of adult psychiatric emergencies at a tertiary care center before and after the onset of the COVID-19 pandemic.

A gap exists in published data on psychiatric emergencies presenting to Indian centers over the entire pandemic. We assessed 2,048 consecutive adult psychiatric emergencies for the period April 2019-September 2021 to compare 18 months following the onset of the pandemic, with the pre pandemic year as the control. Mean age was 33.8 ± 13.6 years, with 55% females. The proportion with ICD-10 schizophrenia and related psychotic disorders (18.9% vs 15.3%; P = 0.031), mood disorders (21.8% vs 18.1%; P = 0.038), and personality disorders (3.8% vs 2%; P = 0.018) showed a significant increase during a pandemic, while those with no diagnosable illness reduced (28.6% vs 34.3%; P = 0.006). Suicidality was the reason for referral in 43%, comparable to pre pandemic year. Those with stay ≥24 hours increased (14% vs 11%; P = 0.034). Benzodiazepines remained the commonly prescribed medication, but a notable rise was seen in mood stabilizer prescriptions.

Psychometric properties and factor structure of the suicidal narrative inventory in major depression: A multicentric evaluation.

BACKGROUND: The Suicidal Narrative Inventory (SNI) is a 38-item self-report measure developed to assess elements of the suicidal narrative, a subacute, predominantly cognitive, presuicidal construct. Our objectives were to assess the factor structure, validity, and reliability of the SNI-38 among adults with major depressive disorder (MDD). METHODS: Using a cross-sectional design, we administered the Hindi version of the SNI along with other self-report measures to adults with MDD, recruited from 24 tertiary care hospitals across India. Confirmatory factor analysis (CFA) was performed to assess the factor structure of SNI-38. Reliability (internal consistency) was assessed using Cronbach's alpha (α). Convergent, discriminant, and criterion validity of the SNI-38 were tested by comparing it against other appropriate measures. RESULTS: We collected usable responses from 654 Hindi-speaking participants (Mean age = 36.9 ± 11.9 years, 50.2% female). The eight-factor solution of the SNI showed good model fit indices (χ2[637] = 3345.58, p <.001, CFI =.98, and RMSEA =.08). Internal consistencies for the SNI subscale scores were good to excellent, α ranging from .73 to.92. While most subscales significantly converged with other measures, associations were comparatively weaker and inconsistent for the 'thwarted belongingness' and 'goal reengagement' subscales. CONCLUSION: Consistent with prior data, our study confirmed an eight-factor solution and demonstrated adequate psychometric properties for the Hindi version of the SNI-38 in our sample. These findings provide empirical support for the use of SNI to assess the suicidal narrative among Indian adults with MDD.

Elevated choline in dorsolateral prefrontal cortex of lithium responders with bipolar I disorder.

INTRODUCTION: Response to lithium maintenance varies widely across patients with bipolar disorder (BD). The studies on neurochemical correlates of long-term lithium response in BD remain scant. AIM: To assess the neurochemical profile in DLPFC based on lithium response status among subjects with bipolar I disorder (BD-I) using in vivo MRS. MATERIALS AND METHOD: This was an observational study of 40 right-handed, euthymic adult participants with DSM-5 BD-I on long-term lithium maintenance with no psychiatric comorbidities (MINI 7.0). Using Alda Lithium Response Scale (LRS), a cut-off ≥ 7 for excellent lithium response, the sample was grouped into study group I for responders and group II for non-responders. All participants were assessed using NIMH Life Chart Method and IGSLI typical/atypical features scale. 1H-MRS was carried out on a 3 T MR scanner (Achieva, Phillips) using a 32-channel head coil, with a voxel placed at the left DLPFC. LC model was used to measure absolute concentrations of neurochemicals and their ratios in relation to creatine. RESULTS: Group I (n = 20) was comparable to Group II (n = 20) with respect to demographic and illness profile. The GPC/Cr+PCr ratio was significantly higher (p = 0.028) among excellent lithium responders (0.32 ± 0.20 mmol/l) compared to sub-optimal responders (0.25 ± 0.05 mmol/l). Choline-containing compounds reflect alterations in cell membrane synthesis or myelin turnover, and are a marker of overall cell density. No significant alterations were detected in NAA, glutamate, glutamine, myo-inositol and creatine. CONCLUSION: The lithium responders exhibited elevated choline (GPC) in the left DLPFC compared to non-responders.

Pattern of Psychiatric Emergencies in Children and Adolescents at a Tertiary Care Centre After Onset of COVID-19 Pandemic.

OBJECTIVES: To assess changes in profile of psychiatric emergencies in children and adolescents (aged <19 year) during the coronavirus disease 2019 (COVID-19) pandemic compared to pre-pandemic period. METHODS: The psychiatric emergency records were analyzed for the period of April, 2019 - September, 2021 to assess the pattern and profile of mental health emergencies in children and adolescents in the period before and after the onset of the pandemic lockdown (i.e., 23 March, 2020). RESULTS: 379 consecutive child and adolescent psychiatric emergencies were identified, of which 219 were seen after the onset of pandemic. Commonest reason for referral in the pandemic group was attempted self-harm (44.3%). The ICD-10 neurotic, stress-related and somatoform disorders constituted the commonest diagnostic category, similar to pre-pandemic period. A significantly higher proportion (44% vs 28%) of children was prescribed benzodiazepines in the pandemic period, compared to the pre-pandemic period. CONCLUSION: The average monthly psychiatric emergencies in children and adolescents showed no increase during the pandemic period. Self-harm was the commonest cause of psychiatric referral in emergency services mental health crisis in the younger population.

Disability and its correlates among persons with bipolar disorder: Exploratory findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Aim: This study aimed to evaluate the disability and its correlates in persons with Bipolar Disorder during the remission phase. Materials and Methods: As part of the multicentric study, 773 patients with bipolar disorder, currently in clinical remission, were evaluated for disability on the Indian Disability Assessment Evaluation Scale. Results: About one-fifth of the participants had some level of disability in the domain of self-care, one-third had some level of disability in the interpersonal domain, one-fourth had some level of disability in communication and understanding, and a maximum proportion (43.7%) had some disability in the domain of work. Overall, about one-fifth (18.4%) were considered to have a benchmark disability (i.e., disability >40%). In terms of correlates, those with a disability had a short duration of current remission, a higher number of manic and mixed episodes, a higher mean number of total episodes, spent more time in the episodes, had lower severity of the depressive episodes, higher residual depressive and manic symptoms, had overall higher manic affective morbidity, had a higher level of cognitive deficits, and had poorer insight. Conclusion: A significant proportion of patients with bipolar disorder have disability in work domain, and the presence of residual symptoms of either polarity are associated with higher level of disability.

Insight in patients with bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Background: There are limited number of studies evaluating insight among patients with bipolar disorder (BD). Aim: This study aimed to examine insight and its correlates in BD using the data from the multicenter BD course and outcome study from India (BiD-CoIN). The additional aim was to evaluate the insight in patients with BD using different scales and understand the correlates of insight. Materials and Methods: 773 BD patients presently in clinical remission were evaluated on the Insight Scale for Affective Disorders (ISAD), insight items of the Hamilton Depression Rating Scale (HDRS), and the Young Mania Rating Scale (YMRS). Results: The assessment scales influenced the prevalence of poor insight. Poorer insight irrespective of the assessment scale was consistently associated with higher residual depressive and manic symptoms, and a higher level of cognitive impairment and disability. Poor insight as assessed by ISAD was associated with a higher number of episodes in the lifetime, shorter duration of current remission, a higher number of depressive episodes, a higher amount of time spent in depressive episodes, higher depressive affective morbidity, a higher number of manic episodes, and higher residual depressive and manic symptoms. Conclusion: Poor insight in BD is consistently associated with higher residual depressive and manic symptoms and a higher level of cognitive impairment and disability. However, in terms of course variables, the correlates vary depending on the assessment method.

Subjective cognitive deficits and its correlates among patients with bipolar disorder: Findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

Aim: This study aimed to evaluate the prevalence of subjective cognitive complaints and their association with clinical variables, insight, and disability. Methodology: Seven hundred and seventy-three subjects with bipolar disorder (BD), recruited across 14 centers, currently in the euthymic phase were cross-sectionally evaluated on Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA). Results: The mean total COBRA score was 9.79 (SD: 6.99), and 322 (41.7%) of the participants were found to have subjective cognitive complaints when the cut-off of >10 was used. Compared to those without cognitive complaints, those with cognitive complaints more often had depression as the first episode in their lifetime, had a higher prevalence of alcohol dependence, a higher number of depressive episodes (first five years of illness, lifetime, and per year of illness), a higher number of manic episodes in the first five years of illness, more often had depressive or indeterminate predominant polarity, lower prevalence of at least one-lifetime episode with psychotic symptoms, higher severity of residual symptoms, spent more time in the episodes in the lifetime, had poorer insight and higher disability. Conclusion: The present study suggests subjective complaints complaints are associated with more severe illness, higher levels of residual symptoms, poor insight, and higher disability.

Prevalence of mixed features in patients with first-episode depression: An exploratory multicentric study.

Background and Aim: There is limited literature on the prevalence of mixed features in patients with depression, especially from countries in Asia. Our aim was to evaluate the prevalence of "mixed features" in patients with first-episode depression. Materials and Methods: Patients with first-episode depression were evaluated for the presence of mixed features as per the Diagnostic and Statistical Manual (DSM)-5 criteria. They were additionally evaluated on Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Results: About one-sixth (16%) of the patients fulfilled the DSM-5 criteria for the mixed features specifier. The most common manic/hypomanic clinical feature was increased talkativeness or pressure of speech, followed by elevated expansive mood (12.5%), and inflated self-esteem or grandiosity was the least common feature (8.7%). Those with mixed features had higher prevalence of comorbid tobacco dependence and psychotic symptoms. In terms of frequency of depressive symptoms as assessed on HDRS, compared to those without mixed features, those with mixed features had higher frequency of symptoms such as depressed mood, insomnia during early hours of morning, work and activities, agitation, gastrointestinal somatic symptoms, genital symptoms, hypochondriasis, and poorer insight. Conclusion: Mixed features specifier criteria were fulfilled by 16% patients with first-episode depression. This finding suggests that the extension of this specifier to depression can be considered as a useful step in understanding the symptom profile of patients with depression.

Pharmacological treatment of bipolar disorder in pregnancy: An update on safety considerations.

Pregnancy in women with bipolar disorder (BD) can be considered a high-risk pregnancy in view of several clinical and pharmacotherapeutic considerations. Pharmacological treatment during pregnancy requires a careful weighing of psychotropic drug exposure against the risk of BD relapse. An untreated bipolar illness can negatively affect the health of mother as well as unborn child in the event of a relapse. Availability of well balanced, latest information on safety of prophylactic drugs for BD is crucial for making informed decisions. The review provides an evidence-based update (2015-2021) on the drug safety considerations involved in providing care for women with BD who are either pregnant or planning to conceive in near future. Literature review based on systematic reviews, meta-analyses, and data available from studies based on large-scale cohorts and birth registries has been synthesized and presented along with clinically relevant recommendations.