Resting state and activated brain glutamate-glutamine, brain lactate, cognition, and psychopathology among males with schizophrenia: A 3 Tesla proton magnetic resonance spectroscopic (1H-MRS) study.

Background: Research on glutamate (Glu) in schizophrenia has so far been inconclusive. Based on preclinical studies on Glu lactate interaction, researchers have now focused on brain lactate level as a sign of major pathology, including cognitive dysfunctions in the brain. Our study aimed to examine changes at resting and activated states in brain lactate and Glu-glutamine (Glx) at the anterior cingulate cortex (ACC) in schizophrenia. Methods: A hospital-based prospective study was conducted with twenty-two male cases of schizophrenia and matched healthy controls (HCs). Positive and Negative Syndrome Scale (PANSS), Montreal Cognitive Assessment (MoCA), and Stroop tasks were administered among patients. Brain lactate and Glx at ACC were measured at resting state and during the Stroop test with proton magnetic resonance spectroscopy (1H-MRS) both at baseline and at remission and once among HC. Result: Though MoCA scores improved significantly (P < 0.001) at remission from baseline among cases, repeated-measures analysis of variance (RM-ANOVA) did not find a significant time effect for Glx (P = 0.82) and lactate (P = 0.30) among cases from baseline to remission. Glx and lactate changed differently from baseline to remission. Conclusion: Our study did not find significant differences in Glx and lactate between schizophrenia patients and HC. No significant time effect on Glx and lactate was observed from baseline to remission among schizophrenia cases. Different changes observed in Glx and lactate from baseline to remission require replication in future studies with larger sample size, longer follow-up period, and multivoxel MR assessment.

Pathways to care for substance use treatment among tribal patients at a psychiatric hospital: A comparative study.

Objectives: According to the national mental health survey, substance use disorders (SUDs) are prevalent in 22.4% of the population above 18 years, whereas the same is 26% among the tribal population. The treatment gap is also high in substance-addictive disorders. Our study aimed to compare the severity of substance use, pathways to psychiatric care, and treatment-seeking behavior among the tribal and non-tribal populations. Materials and Methods: The study was conducted at a tertiary psychiatric teaching institute in India. It was a cross-sectional comparative study. Patients fulfilling the International Classification of Disease 10 diagnostic criteria of mental and behavioral disorders due to substance use, with active dependence, were taken without comorbidity. Forty patients in tribal and non-tribal groups were recruited with consecutive sampling. The samples were assessed with a semi-structured interview schedule, addiction severity index, attitudes toward help-seeking, and pathways-to-care. Results: Excessive substance use median was for 7.00 (± 5.00) years in tribal and 6.00 (± 4.00) years in non-tribal; in tribal, substance intake was younger than non-tribal (P = 0.167), and general health-care system more distance than the non-tribal (P < 0.001). Around 65% of the persons with SUD never consulted their general practitioner and primary health-care facilities. Alcohol severity was higher in the tribal population than in the non-tribal population. The cannabis and opioid severity was high in the non-tribal population. Help-seeking behavior was deficient in both groups. Conclusion: Most of the substance abuse tribal and non-tribal populations reach healthcare very late and do not consider it as a health issue initially. The major reason for the delayed pathway is a lack of awareness about mental health care facilities and stigma in both populations. The stigma is high in non-tribal communities compared to the tribal community. There is a need to improve the identification and treatment of alcohol morbidity in primary care.

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.

Adjunctive neuronavigated accelerated continuous theta-burst stimulation in obsessive-compulsive disorder: a randomized sham-controlled study.

BACKGROUND: Approximately 40% of patients treated for obsessive-compulsive disorder (OCD) do not respond to standard and second-line augmentation treatments leading to the exploration of alternate biological treatments. Continuous theta burst stimulation (cTBS) is a form of repetitive transcranial magnetic stimulation inducing more rapid and longer-lasting effects on synaptic plasticity than the latter. To the best of our knowledge, only one recent study and a case report investigated the effect of cTBS at the supplementary motor area (SMA) in OCD. OBJECTIVE: This study aimed to examine the effect of accelerated robotized neuronavigated cTBS over SMA in patients with OCD. METHODS: A total of 32 patients with OCD were enrolled and randomized into active and sham cTBS groups. For active cTBS stimulation, an accelerated protocol was used. Bursts of three stimuli at 50 Hz, at 80% of MT, repeated at 5 Hz were used. Daily 2 sessions of 900 pulses each, for a total of 30 sessions over 3 wk (weekly 10 sessions), were given. Yale-Brown Obsessive-Compulsive Rating Scale (YBOCS), Clinical Global Impressions scale (CGI), Hamilton Depression Rating Scale (HAM-D), and Hamilton Anxiety Rating Scale (HAM-A) were administered at baseline and at end of weeks 3 and 8. RESULTS: A total of 26 patients completed the study. Active cTBS group showed significant group × time effect in YBOCS obsession (P < .001, η2 = 0.288), compulsion (P = .004, η2 = 0.207), YBOCS total (P < .001, η2 = 0.288), CGI-S (P = .010, η2 = 0.248), CGI-C (P = .010, η2 = 0.248), HAM-D (P = .014, η2 = 0.224) than sham cTBS group. CONCLUSIONS: Findings from our study suggest that adjunctive accelerated cTBS significantly improves psychopathology, severity of illness, and depression among patients with OCD. Future studies with larger sample sizes will add to our knowledge.

Adjunctive High-Definition Transcranial Direct Current Stimulation in Brain Glutamate-Glutamine and γ-Aminobutyric Acid, Withdrawal and Craving During Early Abstinence Among Patients With Opioid Use Disorder on Buprenorphine-Naloxone: A Proton Magnetic Resonance Spectroscopy-Based Pilot Study.

OBJECTIVE: Our study aimed to (1) examine the effect of adjunctive high-definition transcranial direct current stimulation (HD-tDCS) in craving and withdrawal among patients with opioid use disorder on buprenorphine-naloxone, and (2) examine effect of HD-tDCS changes in glutamate-glutamine and γ-aminobutyric acid (GABA) at the left dorsolateral prefrontal cortex (DLPFC) among patients with opioid use disorder on buprenorphine-naloxone. METHODS: This was a pilot randomized double-blind, sham-controlled parallel-group study. A total of 28 patients on buprenorphine-naloxone (6/1.5 mg/d) were randomly allocated into 2 groups for active and sham HD-tDCS stimulation. High-definition transcranial direct current stimulation was administered twice daily for consecutive 5 days, from days 2 to 6. The Clinical Opiate Withdrawal Scale (COWS), the Desire for Drug Questionnaire (DDQ), the Obsessive-Compulsive Drug Use Scale (OCDUS), and glutamate-glutamine and GABA at DLPFC via proton magnetic resonance spectroscopy were measured at baseline and on day 7. RESULTS: Both active and sham groups had comparable changes in DDQ, OCDUS (except 2 subcomponents), COWS, and glutamate-glutamine and GABA at DLPFC. In the active HD-tDCS group, statistically significant reductions were observed in DDQ, OCDUS, and COWS but not in glutamate-glutamine and GABA. CONCLUSIONS: The adjunctive active HD-tDCS group showed comparable changes in craving and withdrawal, and glutamate-glutamine and GABA at DLPFC compared with sham HD-tDCS. Craving and withdrawal but not glutamate-glutamine and GABA at DLPFC decreased significantly with adjunctive HD-tDCS. Future studies with larger sample size and online assessment of glutamate-glutamine and GABA would enhance our knowledge.

Serum Lipids among Drug Naïve or Drug-Free Patients with Obsessive Compulsive Disorder and their Association with Impulsivity: A Comparative Study.

BACKGROUND: The derangement of serum lipids is well documented in psychiatric disorders like schizophrenia, mania, and depression but not in obsessive compulsive disorder (OCD), where it has been inadequately examined. Also, serum lipid abnormalities are increasingly found in "impulsivity," an important sub-construct of OCD. Our study aimed to examine serum lipid profile among patients with OCD and its association with clinical profile and impulsivity among them. METHODS: Forty drug naïve or drug-free (four weeks for oral and eight weeks for any depot psychotropics) patients with OCD according to International Classification of Disease -10th version (ICD-10): Diagnostic Criteria for Research (DCR) by the World Health Organization (WHO), from outpatient and inpatient departments of a tertiary care psychiatric hospital were recruited. Measures like Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamliton Rating Scale for Depression (HAM-D), Barratt's Impulsivity Scale (BIS-11), and Hamilton Rating Scale for Anxiety (HAM-A) were administered. Forty age and sex-matched healthy controls (HC) were recruited after screening with General Health Questionnaire 12 (GHQ-12). Serum lipids were assessed in both the groups. RESULTS: Serum high density lipoproteins (HDL) (P < 0.001; partial η2 = 0.176) and apolipoprotein B (P < 0.001; partial η2 = 0.531) were significantly higher in OCD group than age- and sex-matched HC. A trend toward lower serum HDL (P = 0.06; partial η2 = 0.060) was observed among patients of OCD with high impulsivity. Serum HDL was negatively correlated with BIS attention (rs =-0.32; p = 0.03), BIS motor (rs = 0.40; P = 0.01), BIS non-planning (rs = - 0.36; P = 0.02), and BIS total (rs = - 0.36; P = 0.01) scores. Serum triglycerides (TG) (rs = 0.34; P = 0.03) and apolipoprotein B (rs = -0.32; P = 0.04) were negatively correlated with Y-BOCS compulsion score. Serum TG (rs = -0.45, P < 0.01) and serum very low density lipoprotein (VLDL) was negatively (rs = -0.39; P = 0.01) correlated with Y-BOCS total scores. Serum VLDL was positively (rs = 0.34; P = 0.03) correlated with BIS motor scores. CONCLUSIONS: Serum lipid fractions are deranged among patients with OCD. Different lipid fractions have different associations with clinical profiles of OCD. Impulsivity among patients with OCD may have a specific association with serum lipids. A small sample size, use of self-report measure without adaptation for impulsivity, a lack of metabolic profile assessment among participants, and a lack of assessment of impulsivity among HC were the limitations of our tudy.

Absconding During Inpatient Care from a Tertiary Psychiatric Hospital: A Comparative Study.

BACKGROUND: Absconding from psychiatric hospitals is of great concern for patients and caregivers. Absconding affects not only the treatment and safety of these patients but also patient's caregivers and the community. Further investigation is needed to examine the pattern of this event and the characteristics of patients who abscond. Hence, our study was aimed to examine the sociodemographic and clinical profiles of inpatients who absconded from a psychiatric hospital in five years and to compare them with matched controls. METHODS: A retrospective chart review of inpatients who absconded and matched control inpatients during the specified period of five years from January 2014 to December 2018 was done at a psychiatric hospital. Each control was matched with a corresponding absconding case on the following order: (a) admission ward, (b) admission period, (c) diagnosis, and (d) age. Results: Among 20,052 adult admissions during the specified period, 38 patients absconded, with a rate of 1.8 per 1,000 admissions. Most of them were male, from a younger age group, diagnosed with schizophrenia or mood disorder, and having comorbid substance use disorder, irritable affect, impaired judgment, and absent insight. Most of the events occurred within the first two weeks of admission. About 11% of them had a history of prior absconding from the hospital. CONCLUSION: Knowledge about the associated sociodemographic and clinical profile would help clinicians and mental health care professionals to prevent absconding. Further risk assessment using a patient's profile would help to reduce absconding events from psychiatric hospitals in the future.

Postinjection Delirium/Sedation Syndrome After 31st Long-Acting Olanzapine Depot Injection.

OBJECTIVE: Long-acting depot preparations of antipsychotics are the mainstay of treatment for patients with schizophrenia who show nonadherence to their medications. Olanzapine pamoate is one of the recently approved long-acting depot psychotropic preparations that have shown its efficacy both in clinical trials and in clinical uses against the illness. However, emerging literature indicates toward a cluster of adverse effects known as postinjection delirium/sedation syndrome (PDSS). METHODS: We here present a case of PDSS in a woman with paranoid schizophrenia. After maintaining well for almost 1½ years, she developed PDSS at her 31st scheduled long-acting olanzapine injection. RESULTS: Several features of PDSS including its mechanism and course have been discussed. CONCLUSIONS: More research is necessary to understand the syndrome and the association between PDSS and long-acting olanzapine injection. Clinicians should keep in mind that PDSS may worsen compliance in an index patient and affect the course of the illness.

Early Marked Behavioral Symptoms in Bilateral Posterior Cerebral Artery Stroke: A Disguised Presentation.

Clinical signs and symptoms of posterior cerebral artery (PCA) stroke are varied and can be challenging to diagnose at early stage. A case of bilateral PCA infarct presenting with marked behavioral symptoms and minimal neurological symptoms is presented here. A 34 years old female had presented with marked behavioral symptoms, blurring of vision and tingling sensation in left half of body. Though the latter complaints resolved following day, her behavioral complaints persisted. Magnetic Resonance Imaging (MRI) of brain revealed acute non-hemorrhagic infarct in bilateral PCA territory. Psychotropics were beneficial for her behavioral symptoms. Isolated behavioral symptoms in PCA stroke led to speculate anatomical substrate for those symptoms. We discussed possible anatomical substrates for behavioral symptoms. Our case adds to the existing literature on a range of disguising presentations in PCA stroke and also emphasizes those distinctions between 'neurological' or 'psychological' or 'psychiatric' disorders are often sketchy.