Efficacy of adjunctive D-Cycloserine for the treatment of schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

D-Cycloserine is a partial agonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor. Results have been inconsistent in trials on the efficacy of D-Cycloserine in patients with schizophrenia. We examined the efficacy of D-Cycloserine against negative and cognitive symptoms (primary and co-primary outcomes). Secondary outcomes were efficacy of D-Cycloserine against positive symptoms and the examination of early treatment outcomes. A systematic literature search was carried out using following selection criteria: Population = Patients with Schizophrenia; Intervention = Trials using D-Cycloserine either as monotherapy or adjuvant therapy; Comparison = Placebo or active comparator; Outcome = Change in negative symptoms, cognitive symptoms and positive symptoms; Study design = Randomized controlled trials with parallel design. We used the Cochrane Collaboration tool for risk of bias for study quality appraisal. Effect sizes for trials were calculated separately for negative, positive and cognitive symptom dimensions using the DerSimonian-Laird random effects model. Seven studies (pooled N = 413) provided data for meta-analysis. The pooled Standardized Mean Difference (SMD) for negative, cognitive, and positive symptom change scores were - 0.32 (95% CI, - 0.75 to 0.11), - 0.05 (95% CI, - 0.91 to 0.81), and - 0.08 (95% CI, - 0.37 to 0.20), respectively. No significant improvement was noted with regard to early outcome. I2 values for heterogeneity were 61%, 67%, and 0% for studies assessing negative, cognitive, and positive symptom ratings, respectively. D-Cycloserine did not exhibit significant efficacy in treating negative, cognitive, or positive symptoms of schizophrenia at either study-defined endpoint (4-36 weeks) or at four weeks (early outcome).

Frequency and correlates of mother-infant bonding disorders among postpartum women in India.

PURPOSE: Disorders of mother-infant bonding have been described since early 20th Century. Previous studies have looked at the prevalence of bonding disorders among mothers with postpartum psychiatric disorders. However, its frequency among healthy postpartum mothers is less studied. METHODS: Two hundred and fifty mother-infant dyads were studied using the Mini International Neuropsychiatric Interview (MINI), the Stafford Interview, Bangalore Maternal Behaviour Scale (BMBS) and Tamil versions of the Edinburgh Postnatal Depression Scale (EPDS) and the Postpartum Bonding Questionnaire (PBQ). The mothers were interviewed between 4 weeks to six months postpartum. In addition, thirty one mothers with a lifetime history of psychiatric disorders were interviewed using the above scales. RESULTS: The frequency of bonding disorders was found to be 24% among healthy postpartum mothers as against 45.2% in mothers with psychiatric disorder. However, the frequency of mild disorders of bonding was relatively lower at 5.6% among healthy mothers and 6.5% among mothers with psychiatric disorders. We found that mothers in India had a clinging / over-involved subtype of anxiety that prevented them from leaving their baby under care of another competent adult. While infant-related anxiety was seen in 10% of healthy mothers, about 20% of mothers with psychiatric diagnoses had anxiety. The presence of bonding disorders was not correlated with any maternal or infant related factors except difficulty in breastfeeding. CONCLUSIONS: Disorders of mother infant bonding are seen in healthy postpartum mothers. The frequency of mild disorders of bonding appears to be similar across countries and this condition warrants further attention.

Anti-NMDA receptor antibody positivity in acute psychotic states: An exploratory study.

The glutamatergic theory of schizophrenia postulates N-methyl-D-aspartate receptor (NMDA-R) dysfunction. Anti-NMDA receptor antibodies may be present in some patients with psychosis. Fifteen patients presenting with acute psychotic states having one additional clinical feature suggestive of autoimmune etiology were recruited. Serum antibodies against NMDA-receptor were tested at baseline and at follow-up using Indirect Immunofluorescence Technique. None of the 15 patients had positive anti-NMDA antibody at baseline or at follow-up. The study failed to detect anti-NMDA antibodies in patients with acute psychotic states with clinical suspicion of autoimmunity. This does not rule out other mechanisms of NMDA receptor dysfunction in these patients. The glutamatergic theory of schizophrenia postulates N-methyl-D-aspartate receptor (NMDA-R) dysfunction. Anti-NMDA receptor antibodies may be present in some patients with psychosis. Fifteen patients presenting with acute psychotic states having one additional clinical feature suggestive of autoimmune etiology were recruited. Serum antibodies against NMDA-receptor were tested at baseline and at follow-up using Indirect Immunofluorescence Technique. None of the 15 patients had positive anti-NMDA antibody at baseline or at follow-up. The study failed to detect anti-NMDA antibodies in patients with acute psychotic states with clinical suspicion of autoimmunity. This does not rule out other mechanisms of NMDA receptor dysfunction in these patients.

Cytokine alterations in first-onset postpartum psychosis-clues for underlying immune dysregulation.

BACKGROUND: Emerging evidence suggests a possible role for immune system dysregulation in the pathogenesis of postpartum psychosis (PP) but the evidence is limited. The current study sought to determine the serum cytokines/ chemokine changes associated with first-onset PP. METHODS: Women with first onset PP were recruited as cases and the cytokines/ chemokine changes were compared against healthy postpartum (HP) and healthy non-postpartum (HNP) women.There were 20 subjects in each of the three groups. Levels of serum cytokines and Monocyte Chemoattractant Protein-1 (MCP-1) were estimated with a cytometric beadarray assay. RESULTS: HP group showed significantly elevated levels of interleukin (IL)-6 as compared to HNP group. Whereas, the first onset PP group showed significantly elevated levels of both IL-6 and IL-8 as compared to HNP group. CONCLUSION: Postpartum period appears to be a state of altered immune functioning considering the elevated level of IL-6 in both HP and PP group. Additionally, IL-8 appears to play a role in the manifestation of PP. Our study highlights the immune alterations associated with first-onset PP.

Role of Yoga and Mindfulness in Severe Mental Illnesses: A Narrative Review.

BACKGROUND: Yoga has its origin from the ancient times. It is an integration of mind, body, and soul. Besides, mindfulness emphasizes focused awareness and accepting the internal experiences without being judgemental. These techniques offer a trending new dimension of treatment in various psychiatric disorders. AIMS: We aimed to review the studies on the efficacy of yoga and mindfulness as a treatment modality in severe mental illnesses (SMIs). SMI includes schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD). METHODS: We conducted a literature search using PubMed, Google Scholar, and Cochrane Library with the search terms "yoga," "meditation," "breathing exercises," "mindfulness," "schizophrenia spectrum and other psychotic disorders," "depressive disorder," and "bipolar disorder" for the last 10-year period. We also included relevant articles from the cross-references. RESULTS: We found that asanas and pranayama are the most commonly studied forms of yoga for schizophrenia. These studies found a reduction in general psychopathology ratings and an improvement in cognition and functioning. Some studies also found modest benefits in negative and positive symptoms. Mindfulness has not been extensively tried, but the available evidence has shown benefits in improving psychotic symptoms, improving level of functioning, and affect regulation. In MDD, both yoga and mindfulness have demonstrated significant benefit in reducing the severity of depressive symptoms. There is very sparse data with respect to BD. CONCLUSION: Both yoga and mindfulness interventions appear to be useful as an adjunct in the treatment of SMI. Studies have shown improvement in the psychopathology, anxiety, cognition, and functioning of patients with schizophrenia. Similarly, both the techniques have been established as an effective adjuvant in MDD. However, more rigorously designed and larger trials may be necessary, specifically for BD.

Is menstrual Psychosis a Forgotten Entity?

The connection between menstruation and psychosis has been recognized since the 18th Century. However, there are few case reports available in modern times describing about 30 patients with this condition. The psychosis may occur in the premenstrual phase in some patients and in others it begins with the onset of menses. Polymorphic psychosis is the commonly described clinical picture in these patients with an admixture of mood symptoms and psychotic symptoms. We describe a 42-year old lady who developed psychotic symptoms with the onset of her menses. The patient had irritability and aggression, persecutory ideas, hallucinatory behavior, increased religiosity, formal thought disorder, disorganized behavior and poor self-care lasting for about 20 days after which she will spontaneously remit for about 10 days till the onset of her next menses. These symptoms began about 13 years after her last childbirth and were present in this cyclical manner for the last seven years. She was admitted in view of gross disorganization and was treated with 4 mg per day of risperidone. She did not develop symptoms with onset of her next menstrual period and was discharged. She maintained well on the prophylaxis for a period of three months. After that, she discontinued medications and had a relapse of symptoms lasting the first two weeks of her menstrual cycle and remained well for about two weeks thereafter. Hormonal assays did not reveal abnormal levels of gonadal hormones. We discuss the association between menstrual cycles and the potential association of psychosis with estrogen levels. Various conditions that lead to fluctuation in estrogen levels, such as menopause, postpartum period as well as post-oopherectomy period have been described to lead to a risk for psychotic symptoms. Similarly, the cyclical changes in estrogen levels during the course of a menstrual cycle leads to psychosis in some women.

Age at onset of first suicide attempt: Exploring the utility of a potential candidate variable to subgroup attempters.

PURPOSE: Our objective was to explore the utility of age at first suicide attempt in identifying subgroups of suicide attempters. METHODS: In a retrospective study design, we collected information from the clinical charts of 895 patients assessed over a seven-year period. Admixture analysis was used to determine the best fitting theoretical model for distribution of age at first attempt that divided the sample. Subsequently, multivariate analysis was performed to identify variables that distinguished the subgroups identified. RESULTS: The theoretical solution that best explained the observed distribution of age at first suicide attempt was a mixture of two Gaussian distributions with a cut-off of 31 years for the two subgroups. In logistic regression analysis, male gender (Odds ratios [OR] 3.047, 95% Confidence Interval (CI) 1.818-5.106), fewer years of formal schooling (OR 3.384, 95% CI 1.701-6.734) and being married (OR 23.36, 95% CI 10.753-50.000), were more commonly associated with the late onset subgroup (age at first attempt >31 years). Further, the late onset subgroup had poorer global functioning (OR 0.980, 95% CI 0.962 to 0.998). CONCLUSION: Age at onset of first suicide attempt is a useful candidate marker to delineate an early and late onset subgroup among suicide attempters. These results are likely to inform customization of suicide prevention strategies.

Immune system aberrations in postpartum psychosis: An immunophenotyping study from a tertiary care neuropsychiatric hospital in India.

Postpartum psychosis (PP) is associated with significant morbidity to both mother and infant. Immune system dysregulation during PP is reported in recent studies. This study attempted to determine immune signatures associated with first-onset PP by flow cytometry. Peripheral blood showed decreased naive CD4 and CD8 T cells, while activated CD8 and memory regulatory T cells (Tregs) were increased in women with PP as against healthy controls. The CD14-CD16+non-classical monocytes, CD11c+myeloid DCs and cytotoxic CD56dimCD16+ were reduced, while CD56brtCD16+/-regulatory NK cells were elevated in women with PP. The variations in immune cell subsets highlight the generalized immune dysregulation in PP.

Antipsychotic dose in maintenance treatment of schizophrenia: A retrospective study.

The dose of antipsychotic required for acute phase treatment of schizophrenia is well established, but there is no consensus on dose required for maintenance phase. Current guidelines do not provide definitive recommendations on the dose of antipsychotics needed in the maintenance treatment of schizophrenia, possibly due to limited research. In this retrospective study, minimum antipsychotic dose prescribed in maintenance treatment of schizophrenia in a real life situation was examined. Schizophrenia patients having Clinical Global Impression - Severity (CGI-S)≤3 for at-least six months during the maintenance phase treatment were included (n=163). The medical records of these patients were reviewed and the antipsychotic dose prescribed for acute and maintenance phase treatment was recorded. The mean antipsychotic dose used during maintenance treatment was approximately 30% lower than the dose used during acute phase. Importantly, about 40% of the subjects maintained well with a dose lesser than the recommended therapeutic range. Earlier age at onset and longer duration of illness were associated with higher antipsychotic dose requirement during the maintenance phase treatment. These findings could have important clinical implications if replicated in systematic prospective studies.