Perinatal Depression and the Role of Synaptic Plasticity in Its Pathogenesis and Treatment.

Emerging evidence indicates that synaptic plasticity is significantly involved in the pathophysiology and treatment of perinatal depression. Animal models have demonstrated the effects of overstimulated or weakened synapses in various circuits of the brain in causing affective disturbances. GABAergic theory of depression, stress, and the neuroplasticity model of depression indicate the role of synaptic plasticity in the pathogenesis of depression. Multiple factors related to perinatal depression like hormonal shifts, newer antidepressants, mood stabilizers, monoamine systems, biomarkers, neurotrophins, cytokines, psychotherapy and electroconvulsive therapy have demonstrated direct and indirect effects on synaptic plasticity. In this review, we discuss and summarize the various patho-physiology-related effects of synaptic plasticity in depression. We also discuss the association of treatment-related aspects related to psychotropics, electroconvulsive therapy, neuromodulation, psychotherapy, physical exercise and yoga with synaptic plasticity in perinatal depression. Future insights into newer methods of treatment directed towards the modulation of neuroplasticity for perinatal depression will be discussed.

Perspectives of patients and healthcare professionals on metabolic monitoring of adult prescribed second-generation antipsychotics for severe mental illness: A meta-synthesis.

OBJECTIVES: We conducted a meta-synthesis of qualitative studies to synthesize the views of psychiatric patients on second-generation antipsychotics (SGAs) and the healthcare providers about the metabolic monitoring of adult-prescribed SGAs. METHODS: A systematic search was conducted in four databases through SCOPUS, PubMed, EMBASE, and CINAHL to identify qualitative studies of patients' and healthcare professionals' perspectives on the metabolic monitoring of SGAs. Initially, titles and abstracts were screened to exclude articles that were not relevant followed by full-text reading. Study quality was assessed by using Critical Appraisal Skills Program (CASP) criteria. Themes were synthesized and presented as per the Interpretive data synthesis process (Evans D, 2002). RESULTS: A total of 15 studies met the inclusion criteria and were analyzed in meta-synthesis. Four themes were identified: 1. Barriers to metabolic monitoring; 2. Patient related concerns to metabolic monitoring; 3. Support system by mental health services to promote metabolic monitoring; and 4. Integrating physical health with mental health services. From the participants' perspectives, barriers to metabolic monitoring were accessibility of services, lack of education and awareness, time/resource constraints, financial hardship, lack of interest on metabolic monitoring, patient capacity and motivation to maintain physical health and role confusion and impact on communication. Education and training on monitoring practices as well as integrated mental health services for metabolic monitoring to promote quality and safe use of SGAs are the most likely approaches to promote adherence to best practices and minimize treatment-related metabolic syndrome in this highly vulnerable cohort. CONCLUSION: This meta-synthesis highlights key barriers from the perspectives of patients and healthcare professionals regarding the metabolic monitoring of SGAs. These barriers and suggested remedial strategies are important to pilot in the clinical setting and to assess the impact of the implementation of such strategies as a component of pharmacovigilance to promote the quality use of SGAs as well as to prevent and/or manage SGAs-induced metabolic syndrome in severe and complex mental health disorders.

Are remote psychotherapy/remediation efforts accessible and feasible in patients with schizophrenia? A narrative review.

Background: Cognitive remediation (CR) therapy provides an effective way to improve cognitive impairments in schizophrenia. With the advent of telehealth services, especially during COVID 19 pandemic, a suitable alternative can be found in computer and cell phone-based mental health interventions. Previous studies have proven that remote mental health interventions have by and large been successful. Remote psychotherapy/CR services can now be accessed through smartphone apps, iPads, laptops and wearable devices. This has the advantage of reaching a wider population in resource-limited settings. The lack of access to technology, difficulty in using these online interventions and lack of privacy provide impediments to the delivery of care through these online platforms. Further, as some previous studies have shown, there may be a high rate of dropout in people using remote mental health resources. We aim to look at the factors, which influence the accessibility of remote mental health interventions in schizophrenia. Additionally, we test the feasibility of these interventions and look at how they compare and the potential they hold for implementation in future clinical settings. Results: We found remote cognitive remediation to be both accessible and feasible. Concerning features, however, are the high attrition rates and the concentration of the studies in Western populations. Conclusions: Remote interventions are a viable alternative to in-person psychotherapy when in-person resources may not always be present. They are efficacious in improving health outcomes among patients with schizophrenia. Further research into the widespread implementation of remote CR will be beneficial in informing clinical decision-making.

Clinical efficacy and neurobiological correlates of electroconvulsive therapy in patients with clozapine-resistant/intolerant schizophrenia: study protocol of multi-site parallel arm double-blind randomized sham-controlled study.

Background: A substantial proportion of patients with treatment resistant schizophrenia do not respond well or partially to clozapine, with a subset that does not tolerate an adequate trial of clozapine. Electroconvulsive therapy (ECT) is regarded as one of the augmenting options, but there is a lack of high-quality evidence for this practice. This protocol describes a double-blind randomised sham-controlled modified-ECT trial to evaluate its efficacy in patients with clozapine resistant/intolerant schizophrenia. The study also involves multimodal investigations to identify the response predictors and the mechanistic basis of modified ECT in this population. Methods: One hundred consenting schizophrenia patients with resistance/intolerance to clozapine referred by clinicians for ECT would be randomly assigned to receive true ECT or sham ECT at three study centers. Sham ECT would mimic all the procedures of modified ECT including anaesthesia and muscle relaxation, except the electrical stimulation. After a blinded course, non-responders to sham ECT would be offered open-label true ECT. Clinical assessments, neurocognitive assessments and multimodal investigations (magnetic resonance imaging [MRI], electroencephalography, heart rate variability, investigative transcranial magnetic stimulation-transcranial direct current stimulation, gene polymorphism) would be conducted at baseline and repeated after the end of the trial, as well as open-label ECT course. The trial would evaluate the improvement in positive symptoms (scale for assessment of positive symptoms) of schizophrenia as the primary outcome measure with prediction of this change by resting-state functional-MRI based brain-connectivity as the second primary objective. Registration: Clinical Trial Registry of India (Reg no: CTRI/2021/05/033775) on 24 th May 2021.

Facial emotion recognition and its association with quality of life and socio-occupational functioning in patients with bipolar disorder and their first-degree relatives.

INTRODUCTION: Facial emotion recognition deficits (FERD) are common even in the remitted phase of bipolar disorder (BD). Research regarding FERD in first-degree relatives is inconclusive. This study aimed to assess the facial emotion recognition in remitted patients of bipolar disorder and first-degree relatives(FDR) in comparison with healthy controls. Correlation between FERD and quality of life and socio-occupational functioning was also assessed. METHODS: It was an observational, cross-sectional study done at a tertiary hospital in India. Study population (n = 75) included remitted patients of bipolar disorder (n = 27), first-degree relatives of BD patients (FDR) (n = 20) and healthy controls (HC) (n = 28). Facial emotion recognition, social and occupational functioning, and quality of life (QoL) was measured using Tool for Recognition of Emotions in Neuropsychiatric Disorders, Social & Occupational Functioning Assessment Scale and World Health Organization Quality of Life-Bref, respectively, in all the participants. RESULTS: The BD group did significantly worse in facial emotion recognition in comparison to FDR and HC groups (p < 0.001). Emotion recognition of fear, anger, surprise, and happy were most affected. FDR did not vary significantly from HC in facial emotion recognition. Lower scores on facial emotion recognition were associated with lower QoL in the social domain(p = 0.006) and poorer socio- occupational functioning scores (p = 0.01), but it was not significant within the BD group. CONCLUSION: FERD is seen in remitted patients of bipolar disorder but not in the first -degree relatives. FERD affects social quality of life and functioning. Poorer social functioning in remitted patients of bipolar disorder might be multifactorial and cannot be attributed solely to FERD.

High-dose thiamine strategy in Wernicke-Korsakoff syndrome and related thiamine deficiency conditions associated with alcohol use disorder.

Thiamine is essential for the activity of several enzymes associated with energy metabolism in humans. Chronic alcohol use is associated with deficiency of thiamine along with other vitamins through several mechanisms. Several neuropsychiatric syndromes have been associated with thiamine deficiency in the context of alcohol use disorder including Wernicke-Korsakoff syndrome, alcoholic cerebellar syndrome, alcoholic peripheral neuropathy, and possibly, Marchiafava-Bignami syndrome. High-dose thiamine replacement is suggested for these neuropsychiatric syndromes.

Effect of oral magnesium supplementation on measures of airway resistance and subjective assessment of asthma control and quality of life in men and women with mild to moderate asthma: a randomized placebo controlled trial.

BACKGROUND: Epidemiological data shows low dietary magnesium(Mg) may be related to incidence and progression of asthma. OBJECTIVE: To determine if long term(6.5 month) treatment with oral Mg would improve asthma control and increase serum measures of Mg status in men and women with mild-to-moderate asthma. SUBJECTS: 55 males and females aged 21 to 55 years with mild to moderate asthma according to the 2002 National Heart, Lung, and Blood Institute(NHLBI) and Asthma Education and Prevention Program(NAEPP) guidelines and who used only beta-agonists or inhaled corticosteroids(ICS) as asthma medications were enrolled. DESIGN: Subjects were randomly assigned to consume 340 mg(170 mg twice a day) of Mg or a placebo for 6.5 months. MEASUREMENTS: Multiple measures of Mg status including serum, erythrocyte, urine, dietary, ionized and IV Mg were measured. OBJECTIVE: markers of asthma control were: methacholine challenge test(MCCT) and pulmonary function test(PFT) results. Subjective validated questionnaires on asthma quality of life(AQLQ) and control(ACQ) were completed by participants. Markers of inflammation, including c-reactive protein(CRP) and exhaled nitric oxide(eNO) were determined. RESULTS: The concentration of methacholine required to cause a 20% drop in forced expiratory volume in in minute(FEV(1)) increased significantly from baseline to month 6 within the Mg group. Peak expiratory flow rate(PEFR) showed a 5.8% predicted improvement over time(P = 0.03) in those consuming the Mg. There was significant improvement in AQLQ mean score units(P < 0.01) and in overall ACQ score only in the Mg group(P = 0.05) after 6.5 months of supplementation. Despite these improvements, there were no significant changes in any of the markers of Mg status. CONCLUSION: Adults who received oral Mg supplements showed improvement in objective measures of bronchial reactivity to methacholine and PEFR and in subjective measures of asthma control and quality of life.

The use of a commercial vegetable juice as a practical means to increase vegetable intake: a randomized controlled trial.

BACKGROUND: Recommendations for daily dietary vegetable intake were increased in the 2005 USDA Dietary Guidelines as consumption of a diet rich in vegetables has been associated with lower risk of certain chronic health disorders including cardiovascular disease. However, vegetable consumption in the United States has declined over the past decade; consequently, the gap between dietary recommendations and vegetable intake is widening. The primary aim of this study is to determine if drinking vegetable juice is a practical way to help meet daily dietary recommendations for vegetable intake consistent with the 2005 Dietary Guidelines and the Dietary Approaches to Stop Hypertension (DASH) diet. The secondary aim is to assess the effect of a vegetable juice on measures of cardiovascular health. METHODS: We conducted a 12-week, randomized, controlled, parallel-arm study consisting of 3 groups of free-living, healthy volunteers who participated in study visits at the Ragle Human Nutrition Research Center at the University of California, Davis. All subjects received education on the DASH diet and 0, 8 or 16 fluid ounces of vegetable juice daily. Assessments were completed of daily vegetable servings before and after incorporation of vegetable juice and cardiovascular health parameters including blood pressure. RESULTS: Without the juice, vegetable intake in all groups was lower than the 2005 Dietary Guidelines and DASH diet recommendations. The consumption of the vegetable juice helped participants reach recommended intake. In general, parameters associated with cardiovascular health did not change over time. However, in the vegetable juice intervention groups, subjects who were pre-hypertensive at the start of the study showed a significant decrease in blood pressure during the 12-week intervention period. CONCLUSION: Including 1-2 cups of vegetable juice daily was an effective and acceptable way for healthy adults to close the dietary vegetable gap. Increase in daily vegetable intake was associated with a reduction in blood pressure in subjects who were pre-hypertensive at the start of the trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT01161706.

Weight loss in individuals with metabolic syndrome given DASH diet counseling when provided a low sodium vegetable juice: a randomized controlled trial.

BACKGROUND: Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from diets rich in vegetables and fruits in helping individuals reach and achieve healthy weights. OBJECTIVE: To evaluate the effects of a ready to serve vegetable juice as part of a calorie-appropriate Dietary Approaches to Stop Hypertension (DASH) diet in an ethnically diverse population of people with Metabolic Syndrome on weight loss and their ability to meet vegetable intake recommendations, and on their clinical characteristics of metabolic syndrome (waist circumference, triglycerides, HDL, fasting blood glucose and blood pressure).A secondary goal was to examine the impact of the vegetable juice on associated parameters, including leptin, vascular adhesion markers, and markers of the oxidative defense system and of oxidative stress. METHODS: A prospective 12 week, 3 group (0, 8, or 16 fluid ounces of low sodium vegetable juice) parallel arm randomized controlled trial. Participants were requested to limit their calorie intake to 1600 kcals for women and 1800 kcals for men and were educated on the DASH diet. A total of 81 (22 men & 59 women) participants with Metabolic Syndrome were enrolled into the study. Dietary nutrient and vegetable intake, weight, height, leptin, metabolic syndrome clinical characteristics and related markers of endothelial and cardiovascular health were measured at baseline, 6-, and 12-weeks. RESULTS: There were significant group by time interactions when aggregating both groups consuming vegetable juice (8 or 16 fluid ounces daily). Those consuming juice lost more weight, consumed more Vitamin C, potassium, and dietary vegetables than individuals who were in the group that only received diet counseling (p < 0.05). CONCLUSION: The incorporation of vegetable juice into the daily diet can be a simple and effective way to increase the number of daily vegetable servings. Data from this study also suggest the potential of using a low sodium vegetable juice in conjunction with a calorie restricted diet to aid in weight loss in overweight individuals with metabolic syndrome.

Frequency, reasons, and factors associated with antipsychotic polypharmacy in Schizophrenia: A retrospective chart review in a tertiary hospital in India.

The practice of antipsychotic polypharmacy in schizophrenia appears to be common although evidence-based guidelines do not routinely recommend it. The reasons for polypharmacy are however unclear. The objective of the study was to assess the frequency of polypharmacy, reasons for initiation and the factors associated with it. A retrospective chart review of case records of all the patients diagnosed with schizophrenia at the department of psychiatry from January 2011 to December 2018 was done. Frequency of antipsychotic polypharmacy, reasons influencing it and factors associated with polypharmacy were extracted using a proforma. Of 529 patients diagnosed with schizophrenia, 232 patients (43.9 %) were receiving antipsychotic polypharmacy. Common reasons for polypharmacy included the usage of depot along with oral antipsychotic for a prolonged period (37.7 %), augmentation of response with the second antipsychotic (17.7 %) and treatment of a different symptom domain like negative symptoms (9.5 %). In comparison to monopharmacy, antipsychotic polypharmacy was more commonly associated with side effects and extrapyramidal symptoms. Patients on polypharmacy had a higher number of hospitalizations too. As the trend of antipsychotic polypharmacy is on the rise, it is important to assess for reasons influencing polypharmacy to avoid undesirable side effects. The side effect burden of polypharmacy is significantly more than those receiving single antipsychotics. Oral antipsychotics should ideally be discontinued after the depot antipsychotic reaches steady-state levels. Irrational usage of second antipsychotic to augment the response of first antipsychotic agent needs to be avoided.

Identification of risk factors and metabolic monitoring practices in patients on antipsychotic drugs in South India.

The objectives of this study were to identify the risk factors for metabolic syndrome in patients on antipsychotics and to compare the frequency of metabolic monitoring with evidence-based guidelines. We conducted a retrospective cohort study in a tertiary care health institution of South India. The study included patients with schizophrenia, bipolar disorder, and schizoaffective disorders prescribed with antipsychotic drugs. Data was collected from the medical records department. American Diabetic Association/American Psychiatric Association (ADA/APA) guidelines were used as a reference standard to assess the monitoring for metabolic parameters. Diagnosis of metabolic syndrome was done according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) guidelines. Risk factors for metabolic syndrome and frequency of metabolic monitoring were analyzed. A total of 668 patients were included for clinical audit. About 16.5 % of the patients were diagnosed with metabolic syndrome. Age >50 years (Odds Ratio (OR) 2.00; p value <0.001) and duration of antipsychotic treatment>5 years (OR 1.55; p value< 0.05) were recognized as the independent risk factors for metabolic syndrome using multiple logistic regression. Blood pressure (BP) and fasting blood sugar (FBS) levels were documented in 99.7 % and 47 % of cases at baseline respectively, however, subsequent annual data on BP and FBS monitoring was reduced to 72.7 % and 46 % respectively. Weight was documented in 60 % of the cases at baseline, whereas the subsequent data on four times the annual assessment of weight was reduced to 9.8 %. The extent of documentation of metabolic monitoring parameters was inadequate.

Tolerance of transcranial direct current stimulation in psychiatric disorders: An analysis of 2000+ sessions.

Transcranial direct current stimulation (tDCS), a non-invasive, neuromodulatory technique, is being increasingly applied to several psychiatric disorders. In this study, we describe the side-effect profile of repeated tDCS sessions (N = 2005) that were administered to 171 patients (156 adults and 15 adolescents) with different psychiatric disorders [schizophrenia [N = 109], obsessive-compulsive disorder [N = 28], alcohol dependence syndrome [N = 13], mild cognitive impairment [N = 10], depression [N = 6], dementia [N = 2] and other disorders [N = 3]]. tDCS was administered at a constant current strength of 2 mA with additional ramp-up and ramp-down phase of 20 s each at the beginning and end of the session, respectively. Other tDCS protocol parameters were: schizophrenia and obsessive-compulsive disorder: 5-days of twice-daily 20-min sessions with an inter-session interval of 3-h; Mild cognitive impairment/dementia and alcohol dependence syndrome: at least 5-days of once-daily 20-min session; Depression: 10-days of once-daily 30 min session. At the end of each tDCS session, any adverse event observed by the administrator and/or reported by the patient was systematically assessed using a comprehensive questionnaire. The commonly reported adverse events during tDCS included burning sensations (16.2%), skin redness (12.3%), scalp pain (10.1%), itching (6.7%), and tingling (6.3%). Most of the adverse events were noted to be mild, transient and well-tolerated. In summary, our observations suggest that tDCS is a safe mode for therapeutic non-invasive neuromodulation in psychiatric disorders in adults as well as the adolescent population.

Parenting in mothers with schizophrenia and its relation to facial emotion recognition deficits- a case control study.

BACKGROUND: Difficulties in parenting and Facial Emotion Recognition deficits (FERD) in persons with schizophrenia have been demonstrated independently. However, the relationship between parenting deficits and FERD in mothers with schizophrenia is yet to be explored. AIMS AND OBJECTIVES: The aims of the study were to assess parenting in mothers with schizophrenia, to examine the clinical correlates of parenting and to examine if facial emotion recognition deficits had an association with parenting. METHODS: Fifty mothers with schizophrenia and 50 age matched healthy mothers were assessed for parenting and FERD. Parenting was assessed using Arnold's parenting scale and Parent Interview Schedule. Kiddie TRENDS, a modified Tool for Recognition of Emotions in Neuropsychiatric Disorders (TRENDS) was administered to assess facial emotion recognition. RESULTS: Among mothers with schizophrenia, FERD were noted in emotions of sadness, disgust, anger and surprise. Laxness in parenting was associated with negative symptoms of schizophrenia and also facial emotion recognition deficits. CONCLUSION: Parenting difficulties are commonly noticed in mothers with schizophrenia. Laxness style of parenting was found more often in mothers with schizophrenia, especially in mothers with blunt affect. Mothers with schizophrenia had difficulties in recognizing emotions of sadness, anger, disgust and surprise and this was associated with laxness style of parenting.

Efficacy of fronto-temporal transcranial direct current stimulation for refractory auditory verbal hallucinations in schizophrenia: A randomized, double-blind, sham-controlled study.

Persistent auditory verbal hallucinations (AVH) that are refractory to antipsychotic medications are reported in about 20-30% of schizophrenia patients. Transcranial Direct Current Stimulation (tDCS), a non-invasive and safe neuromodulatory technique, has attracted significant interest as an add-on treatment for refractory AVH in schizophrenia. Studies examining the efficacy of tDCS for refractory AVH in schizophrenia have reported inconsistent findings. In this study, using a randomized, double-blind, sham-controlled design (RCT), we sought to examine the effect of add-on tDCS [anode corresponding to left dorsolateral prefrontal cortex and cathode to left temporo-parietal junction; 2-mA, twice-daily sessions for 5-days] to treat refractory AVH in schizophrenia patients (N=25); following this RCT phase, patients that had <30% reduction in AVH severity were offered an open-label extension (OLE) active stimulation to evaluate the effect of cross-over to verum tDCS. In the RCT phase, repeated measures ANOVA with tDCS type [verum (N=12) vs. sham (N=13)] as between subjects factor demonstrated a significant tDCS-type X time-point interaction [F=21.5, p<0.001, partial-η2=0.48] with significantly greater reduction of AVH score in verum tDCS group as compared to sham group. In the OLE phase, sham-to-verum crossed over patients (N=13) showed significantly greater reduction in AVH severity than their corresponding change during RCT phase (t=2.9; p=0.01). Together, these observations add further support to the beneficial effects of add-on tDCS to treat refractory AVH schizophrenia.