Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine.

Bipolar disorder's core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression-mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine's potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine's demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression.

A multicentric exploratory study of behavioral and psychological symptom characteristics of dementia.

Background: Behavioral and psychological symptoms (BPS) are usually the expected consequences of dementia. BPS increases morbidity and burden, affects the quality of life, and impacts care costs. However, the symptom characteristics, clinical correlations, and symptom-specific clusters aiding the diagnosis are less well studied, especially in the Indian population. Materials and Methods: The present study examined the BPS clusters based on various cognitive and neuropsychiatric profiles in patients with dementia under a multicentric study in India. We did a cross-sectional assessment using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and cognitive functions by Montreal Cognitive Assessment (MoCA), and the severity of dementia using the Clinical Dementia Rating (CDR) scale. In addition, all of the participants were evaluated on a structured Clinical Interview for DSM-5 Research Version for past or current psychiatric disorder(s). Results: We describe the various BPS clusters uniquely associated with the severity of dementia. Further, on linear regression analysis, we predicted three symptom clusters (anxiety, irritability, aberrant motor) in mild, two symptom clusters (disinhibition, agitation/aggression) in moderate and three symptom clusters (delusion, euphoria/elation, disinhibition) in severe dementia. Conclusion: The study provides insights into the various symptom characteristics and inter-relationship of BPS, which may benefit the clinician while assessing patients with dementia.

Clinical Research Center for Neuromodulation in Psychiatry: A Multi-Center Initiative to Advance Interventional Psychiatry in India.

This manuscript introduces a unique program titled "Clinical Research Center (CRC) for Neuromodulation in Psychiatry" supported by the prestigious CRC/Public Health Research Center Grant of the DBT Wellcome Trust India Alliance. This multi-institutional research program will be led by NIMHANS (Bengaluru) in collaboration with the Central Institute of Psychiatry (Ranchi), and Kasturba Medical College (Manipal). The goal of this CRC is in alignment with the editorial titled "Need to Develop "Interventional Psychiatry" as a subspecialty in India" published in the January 2020 issue of the Indian Journal of Psychiatry. The translational research studies and the training programs envisaged through this center will facilitate the development of cost-effective, advanced interventional psychiatry tailored to resource-limited Indian clinical settings and similar other countries as well.

Marital Duration, and Fertility-Related Stress as Predictors of Quality of life: Gender Differences among Primary Infertile Couples.

CONTEXT: Infertility is a global public health issue, and the current data suggest that the problem is growing. Various infertility-related issues are responsible for poorer mental health and well-being in couples with primary infertility. AIM: The present study aimed to understand the gender differences of psychological factors related to infertility in couples with primary infertility. Furthermore, an attempt was also made to understand gender-specific associations that could interact with the fertility-related quality of life (FertiQoL). SETTINGS AND DESIGN: This cross-sectional hospital-based study included 100 married couples with the diagnosis of primary infertility, irrespective of the cause of infertility. The study was conducted at Infertility centers in the Eastern region of India. SUBJECT AND METHODS: One hundred men and women (n = 100 couples) with the diagnosis of primary infertility were recruited in the study. The fertility problem inventory and FertiQoL were used to measure the couples fertility-related stress and FertiQoL, respectively. STATISTICAL ANALYSIS USED: Descriptive statistics, independent t-statistics, Pearson correlation, linear regression, and mediation analysis were conducted. RESULTS: A significantly higher social and sexual concern of infertility and "need for parenthood" were found in women. Men had a significantly better quality of life compared to women. Significant negative predictors of quality of life were noted for both men and women separately. Fertility stress was a significant mediating factor between marital duration and global FertiQoL in men. However, women showed a direct negative association between marital duration and FertiQoL. CONCLUSIONS: The study provides important insights into the couple's experiences with various infertility problems that may potentially be addressed during psychotherapy or during infertility counseling.

Adjuvant High-Definition Transcranial Direct Current Stimulation for Negative Symptoms in Schizophrenia: A Pilot Study.

OBJECTIVE: In schizophrenia, negative symptoms account for a substantial amount of the comorbidity resulting in poor performance in social interaction, interpersonal relationships, economic functioning, and recreational activities. Research has implicated hypofrontality in the pathogenesis of negative symptoms of schizophrenia. Conventional transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex has attracted significant interest as an add-on treatment for negative symptoms in schizophrenia. High-definition tDCS (HD-tDCS), an optimized form of tDCS, has the potential for more focalized neuromodulation. Hence, we aimed to evaluate the efficacy of HD-tDCS over the left dorsolateral prefrontal cortex in the improvement of negative symptoms in schizophrenia. METHODS: Fourteen patients with schizophrenia with predominantly negative symptoms were enrolled for this pilot, randomized, sham-controlled, double-blind trial. Each participant received 10 sessions of HD-tDCS at 2 mA for 20 minutes twice daily over 5 days. Negative symptoms were assessed with the Scale for Assessment of Negative Symptoms and Positive and Negative Syndrome Scale for Schizophrenia. The Calgary Depression Scale for Schizophrenia was used to rule out depressive symptoms. Assessments were carried out at baseline and at 2 weeks. RESULTS: The improvement in negative symptoms in the active group was statistically significant at P value of 0.05 as compared with the sham group. CONCLUSION: These results suggest that HD-tDCS may lead to improvement in negative symptoms of schizophrenia. Its use as an adjunct to pharmacological treatment of negative symptoms may be worth considering.

Cortical source localization during facial emotion recognition in bipolar mania: An ERP study.

Facial emotion recognition has enormous value for humans in social cognition and thereby day to day functioning. Disturbances in the processing of emotional cues are seen in all the three phases of bipolar disorder and have been proposed as an etiology in the development of bipolar disorder. 30 consented patients with bipolar mania with psychotic symptoms and 30 age and sex matched healthy controls were taken for the study. Facial emotion ecognition task containing four basic emotions namely happy, sad, anger and fear were used. Sixty four (64) channel ERP recordings were done for all the subjects. Source localization was done using sLORETA selecting the window for late positive potentials (LPP). Statistically significant and reduced cortical sources were noted in the right insula (p = 0.004) at the peak of LPP during response to anger facial emotions in bipolar mania patients. Hypoactivation of right insular cortex during response to anger emotion may be due to the aberrant activation and possible failure of interoceptive prediction system during acute manic phase are discussed.

Social anhedonia and gamma band abnormalities as a composite/multivariate endophenotype for schizophrenia: a dense array EEG study.

AIM: Social anhedonia and gamma band oscillations are proposed as a promising endophenotype for schizophrenia (SZ). The aim was to assess whether social anhedonia and spontaneous gamma band oscillations could be used as multivariate/composite endophenotypic measures for SZ. METHODS: Sixty consented subjects, of which 20 remitted SZ patients, 20 unaffected siblings of patients with schizophrenia (US) and 20 healthy controls (HC) were recruited for the study. The Revised Social Anhedonia Scale, Temporal Experience of Pleasure Scale and the Schizotypal Personality Questionnaire assessed social anhedonia, temporal experience of pleasure and schizotypal features. All participants underwent awake, resting state 192-channel dense array electroencephalographic recording. Gamma spectral power and coherence were calculated. We performed chi-square test, one-way analysis of variance, Pearsons correlation coefficient and step-by-step linear discriminant functional analysis. RESULTS: Social anhedonia was significantly higher and anticipatory aspects of pleasure were significantly lower in both SZ and US compared with HC. US scored significantly higher than HC in the Schizotypal Personality Questionnaire. Spectral power of high gamma band (>70 Hz) was significantly lower over the right temporo-parietal and midline regions in both SZ and US than HC. We accurately classified (85%) three groups when social anhedonia, high gamma band spectral power of midline, right frontal and right fronto-temporal interhemispheric gamma coherence were considered as composite measures rather than each variable representing independently. CONCLUSION: We propose region-specific high gamma spectral 'power and coherence' and social anhedonia as composite/multivariate measures could be a useful measure in distinguishing schizophrenia patients and unaffected siblings from healthy controls.

Aberrant gamma band cortical sources and functional connectivity in adolescents with psychogenic non-epileptic seizures: A preliminary report.

Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack clinically evident abnormal electrical activity in the brain. We aimed to assess resting gamma spectral power, current source distribution and functional connectivity in adolescents with PNES. Interictal, 32 channels electroencephalographic recording of 15 adolescents with PNES was compared with 10 matched healthy controls. Spectral power, current source distribution and lagged linear coherence were assessed. Statistically significant gamma spectral power, cortical sources and connectivity pattern was found in some brain areas. Region specific aberrant gamma activity and its relationship to psychopathology are discussed.

Inpatient Suicide in a Psychiatric Hospital: A Nested Case-control Study.

OBJECTIVE: Risk factors for inpatient suicide are different from those in the general population. We examined sociodemographic and clinical variables of patients who committed suicide as an inpatient in a psychiatric hospital in India. METHODS: Matched retrospective nested case-control design was adopted. Ten patients who died by suicide as inpatients between 2000 and 2013 were included, along with fifty controls, matched with respect to age, sex, diagnosis, and period of admission. RESULTS: Suicide completers were mostly unskilled in occupation (P = 0.03), had a history of past suicide attempts (P < 0.001), shorter duration of hospital stay (P = 0.001), poorer improvement on psychopathology (P = 0.02), and were having more suicidal ideation (P = 0.02). Significantly more completers were receiving antidepressants (P = 0.04). CONCLUSION: This study adds to the existing sparse literature on inpatient suicides from Asia. Strength of the study was close matching between case and controls and blindedness. Limitations were retrospective design, and variations in prescription behavior and treatment decisions.

Cavum septum pellucidum in a case of schizophrenia presenting with self-mutilating behavior.

Cavum septum pellucidum (CSP) is a neurodevelopmental anomaly, which is commonly reported in schizophrenia patients. Various symptoms of schizophrenia, including thought disturbances have been associated with CSP. We present a rare case of undifferentiated schizophrenia with CSP who presented with self-mutilating behaviors.

Genetics in psychiatry.

Today, psychiatrists are focusing on genetics aspects of various psychiatric disorders not only for a future classification of psychiatric disorders but also a notion that genetics would aid in the development of new medications to treat these disabling illnesses. This review therefore emphasizes on the basics of genetics in psychiatry as well as focuses on the emerging picture of genetics in psychiatry and their future implications.

Acute high dose lithium-induced exacerbation of obsessive compulsive symptoms.

Obsessive compulsive disorder (OCD) is a chronic neuropsychiatric disorder whose pathophysiology is linked to serotonergic dysfunction. More recently, the role of glutamate has also been posited. Lithium is used as an adjunctive for the treatment of OCD which is found to enhance serotonergic transmission. We present a case of OCD who was on stable dose of sertraline developed exacerbation of obsessive compulsive symptoms with acute high dose of lithium but improved after dose reduction.

Juvenile myoclonic epilepsy: Clinical characteristics, standard and quantitative electroencephalography analyses.

OBJECTIVES: Most studies comparing inter-ictal background quantitative electroencephalography (EEG) measures in generalized epilepsies with normal controls do not specifically determine patients with juvenile myoclonic epilepsy (JME) as a separate group. The study aims at comparing absolute spectral power and global field coherence in various frequency bands between patients diagnosed exclusively with JME and 10 healthy controls, and correlating significantly different quantitative EEG measures with various clinical characteristics and standard EEG abnormalities. MATERIALS AND METHODS: Clinical and EEG data were collected from 10 patients with JME and 10 healthy controls. Spectral power and global field spectral coherence were calculated using Welch's averaged periodogram method. The data was analyzed using descriptive statistics, Fisher's exact test and t-test. RESULTS: Statistically significant (or trend level) higher power (global α and θ, frontal α and θ, left temporal θ, right occipital α, δ and γ1, and central δ, θ, α, ß, and γ2) and coherence (global α and γ1) was found in JME patients when compared to controls. Significant correlation of left frontal and central θ-power with presence of absence seizures (negative), central δ-, and θ-power with the presence of psychiatric comorbidity and central θ-power with frequency of myoclonic seizures was found. CONCLUSION: Findings on global-frontal and temporal-occipital power support mild diffuse epileptogenic state and θ-activity as an endophenotype concepts in JME patients, respectively; findings suggest future studies on JME to include psychiatric comorbidity while selecting the sample; some spectral measures (e.g., central θ-power) do relate to progression of JME while some do not.