An epidemiological study of psychiatric disorders in Kashmir.

Introduction: Mental disorders are highly prevalent and affect people across all regions of the world. The State of Jammu and Kashmir has been witness to a conflict for about three decades. Little is known about the extent of mental disorders in Kashmir. There was a dire need to estimate the prevalence of mental disorders among the rural population of Kashmir. The study was undertaken to estimate the point prevalence of specific mental disorders in rural population of Kashmir, sociodemographic correlates of mental disorders and to assess the service utilization in individuals with mental disorders. Materials and Methods: Community-based survey carried out in rural districts of Kashmir using a mixed sampling technique. The survey was conducted in six blocks of two districts (Pulwama and Baramulla) of Kashmir. Mini-International Neuropsychiatric Interview (MINI) for psychiatric morbidity was used. Appropriate statistical methods were applied. Results: In total, 11.3% of adult population suffers from mental illness in the valley. As compared to males (8.4%), females had a higher prevalence (12.9%). Depressive disorders (8.4%) were the most common psychiatric disorders, followed by anxiety disorders (5.1%). Only 12.6% of patients suffering from mental disorders had sought treatment for their illnesses. Conclusion: The findings of this study have cleared many doubts and indicated the prevalence of 10 common mental health disorders in the general population as well as among different socioeconomic groups in Kashmir. This study has indicated low levels of treatment sought by people with mental illness.

Highly soluble and stable 'insertion domain' of the capsid penton base protein provides complete protection against infections caused by fowl adenoviruses.

In the current study, we have evaluated the protective efficacy of the 'insertion domain' which is commonly found in the capsid penton base protein of many adenoviruses. Using the 'insertion domain' of the penton base protein of a representative fowl adenovirus, fowl adenovirus serotype 4 (FAdV-4), we find that the 'insertion domain' can readily be expressed in a soluble form in the bacterial system, and can be purified in sufficient quantities through simple chromatographic methods. We demonstrate that the 'insertion domain', when employed as a subunit vaccine candidate, provides complete protection against hydropericardium syndrome, caused by FAdV-4, in chickens. The data presented here indicate that the protein, adjuvanted with Montanide™ ISA71 VG, provides complete protection in chickens against a lethal FAdV-4 challenge after administration of two doses (100 µg of the protein per dose) two weeks apart (the first dose at the 7th day of life and a booster dose at the age of 21 days). Furthermore, the purified protein can be stored at low temperatures without any observable loss in the protein integrity up to one year, tested so far. Due to the conserved nature of the 'insertion domain' across the penton base protein of fowl adenoviruses, it is suggested that homologous insertion domains could be employed as highly stable and cost-effective subunit vaccine candidates against infections caused by respective fowl adenoviruses.

Staphylococcus aureus Does Not Synthesize Arginine from Proline under Physiological Conditions.

The Gram-positive pathogen Staphylococcus aureus is the only bacterium known to synthesize arginine from proline via the arginine-proline interconversion pathway despite having genes for the well-conserved glutamate pathway. Since the proline-arginine interconversion pathway is repressed by CcpA-mediated carbon catabolite repression (CCR), CCR has been attributed to the arginine auxotrophy of S. aureus. Using ribose as a secondary carbon source, here, we demonstrate that S. aureus arginine auxotrophy is not due to CCR but due to the inadequate concentration of proline degradation product. Proline is degraded by proline dehydrogenase (PutA) into pyrroline-5-carboxylate (P5C). Although the PutA expression was fully induced by ribose, the P5C concentration remained insufficient to support arginine synthesis because P5C was constantly consumed by the P5C reductase ProC. When the P5C concentration was artificially increased by either PutA overexpression or proC deletion, S. aureus could synthesize arginine from proline regardless of carbon source. In contrast, when the P5C concentration was reduced by overexpression of proC, it inhibited the growth of the ccpA deletion mutant without arginine. Intriguingly, the ectopic expression of the glutamate pathway enzymes converted S. aureus into arginine prototroph. In an animal experiment, the arginine-proline interconversion pathway was not required for the survival of S. aureus. Based on these results, we concluded that S. aureus does not synthesize arginine from proline under physiological conditions. We also propose that arginine auxotrophy of S. aureus is not due to the CcpA-mediated CCR but due to the inactivity of the conserved glutamate pathway. IMPORTANCE Staphylococcus aureus is a versatile Gram-positive human pathogen infecting various human organs. The bacterium's versatility is partly due to efficient metabolic regulation via the carbon catabolite repression system (CCR). S. aureus is known to interconvert proline and arginine, and CCR represses the synthesis of both amino acids. However, when CCR is released by a nonpreferred carbon source, S. aureus can synthesize proline but not arginine. In this study, we show that, in S. aureus, the intracellular concentration of pyrroline-5-carboxylate (P5C), the degradation product of proline and the substrate of proline synthesis, is too low to synthesize arginine from proline. These results call into question the notion that S. aureus synthesizes arginine from proline.

In silico designed Staphylococcus aureus B-cell multi-epitope vaccine did not elicit antibodies against target antigens suggesting multi-domain approach.

The vaccine development strategies have evolved from using an entire organism as an immunogen to a single antigen and further towards an epitope. Since an epitope is a relatively tiny and immunologically relevant part of an antigen, it has the potential to stimulate more robust and specific immune responses while causing minimal adverse effects. As a result, the recent focus of vaccine development has been to develop multi-epitope vaccines that can target multiple virulence mechanisms. Accordingly, we designed multi-epitope vaccine candidates B (multi-B-cell epitope immunogen) and CTB-B (an adjuvant - cholera toxin subunit B (CTB) - attached to immunogen B) against S. aureus by employing immunoinformatics approaches. The designed vaccines are composed of B-cell epitope segments (20-mer) of the eight well-characterized S. aureus virulence factors, namely ClfB, FnbpA, Hla, IsdA, IsdB, LukE, SdrD, and SdrE connected in series. The designed vaccines were expressed, purified, and administered to C57BL/6 mice with Freund adjuvant to evaluate the immunogenicity and protective efficacy. The results revealed that the immunized mice showed high IgG titers for the immunogen, and the antibody titers increased significantly following the second immunization. However, the generated antibodies did not protect the mice from infection. The interaction of anti-B antibodies with source virulence factors showed that the generated antibodies have no binding affinity with any of the corresponding virulence factors. Our results demonstrate the limitation of the in silico designed B-cell multi-epitope vaccine and suggest that a protein domain carrying both linear and conformational B-cell epitopes might be a better choice for developing an effective multi-epitope vaccine against S. aureus.

Ftsh Sensitizes Methicillin-Resistant Staphylococcus aureus to ß-Lactam Antibiotics by Degrading YpfP, a Lipoteichoic Acid Synthesis Enzyme.

In the Gram-positive pathogen Staphylococcus aureus, FtsH, a membrane-bound metalloprotease, plays a critical role in bacterial virulence and stress resistance. This protease is also known to sensitize methicillin-resistant Staphylococcus aureus (MRSA) to ß-lactam antibiotics; however, the molecular mechanism is not known. Here, by the analysis of FtsH substrate mutants, we found that FtsH sensitizes MRSA specifically to ß-lactams by degrading YpfP, the enzyme synthesizing the anchor molecule for lipoteichoic acid (LTA). Both the overexpression of FtsH and the disruption of ypfP-sensitized MRSA to ß-lactams were observed. The knockout mutation in ftsH and ypfP increased the thickness of the cell wall. The ß-lactam sensitization coincided with the production of aberrantly large LTA molecules. The combination of three mutations in the rpoC, vraB, and SAUSA300_2133 genes blocked the ß-lactam-sensitizing effect of FtsH. Murine infection with the ypfP mutant could be treated by oxacillin, a ß-lactam antibiotic ineffective against MRSA; however, the effective concentration of oxacillin differed depending on the S. aureus strain. Our study demonstrated that the ß-lactam sensitizing effect of FtsH is due to its digestion of YpfP. It also suggests that the larger LTA molecules are responsible for the ß-lactam sensitization phenotype, and YpfP is a viable target for developing novel anti-MRSA drugs.

Identification of potent epitopes on hexon capsid protein and their evaluation as vaccine candidates against infections caused by members of Adenoviridae family.

Adenoviruses cause economically important diseases in vertebrates. Effective vaccines against adenoviral diseases are currently lacking. Here, we report a highly conserved epitopic region on hexon proteins of adenoviruses that generate a strong immune response when used as a virus-like-particle (VLP) vaccine, produced by inserting the epitopic region into the core protein of hepatitis B virus. For evaluation of its protective efficacy, the epitopic region from a representative adenovirus, fowl adenovirus serotype 4 (FAdV-4), was tested as a VLP vaccine which conferred 90% protection against challenge with a virulent FAdV-4 isolate in chickens. Importantly, such a high level of protection is not achieved when the epitopic region is employed as a part of a subunit vaccine. As the sequence and the structure of the epitopic region are highly conserved in hexon proteins of adenoviruses, the epitopic region could be employed as a promising VLP vaccine candidate against adenoviral diseases, in general.

Characterization of the highly immunogenic VP2 protrusion domain as a diagnostic antigen for members of Birnaviridae family.

Birnaviridae is a family of viruses (birnaviruses) which consists of four genera, members of which cause diseases in fish, birds, mollusks, and insects. The genome of birnaviruses encodes the highly immunogenic VP2 capsid protein. In order to demonstrate that the VP2 protein can be exploited as a diagnostic antigen for birnaviruses, we developed a lateral flow assay based on the surface-exposed VP2 protrusion domain of a representative birnavirus, infectious bursal disease virus (IBDV) of serotype 1 which causes the highly devastating infectious bursal disease in chickens. The biophysical characterization of the purified domain reveals that the domain predominantly consists of ß-sheets, exists in a trimeric form, and remains folded at high temperatures, making it suitable for diagnostic purposes. Owing to its highly immunogenic nature and excellent biophysical properties, we employed the VP2 protrusion domain in a gold nanoparticle-based lateral flow assay for rapid detection of anti-IBDV antibodies in serum samples of infected chickens. Our results indicate that the domain binds anti-IBDV antibodies with high specificity during laboratory testing and on-site testing. The lateral flow assay reported here yields comparable results in a qualitative manner as obtained through a commercial enzyme-linked immunosorbent assay (ELISA). As VP2 is a common capsid protein of birnaviruses, the lateral flow assay can be generalized for other birnaviruses, and members of Tetraviridae and Nodaviridae families which contain homologous VP2 capsid proteins.

C-Terminal Domain of the Human Zinc Transporter hZnT8 Is Structurally Indistinguishable from Its Disease Risk Variant (R325W).

The human zinc transporter 8 (hZnT8) plays important roles in the storage of insulin in the secretory vesicles of pancreatic ß cells. hZnT8 consists of a transmembrane domain, with its N- and C-termini protruding into the cytoplasm. Interestingly, the exchange of arginine to tryptophan at position 325 in the C-terminal domain (CTD) increases the risk of developing type 2 diabetes mellitus (T2D). In the present study, the CTDs of hZnT8 (the wild-type (WT) and its disease risk variant (R325W)) were expressed, purified, and characterized in their native forms by biophysical techniques. The data reveal that the CTDs form tetramers which are stabilized by zinc binding, and exhibit negligible differences in their secondary structure content and zinc-binding affinities in solution. These findings provide the basis for conducting further structural studies aimed at unravelling the molecular mechanism underlying the increased susceptibility to develop T2D, which is modulated by the disease risk variant.

In silico epitope prediction and immunogenic analysis for penton base epitope-focused vaccine against hydropericardium syndrome in chicken.

Certain strains of fowl adenovirus serotype 4 (FAdV-4) of the family Adenoviridae are recognized to be the causative agents of Hydropericardium Syndrome (HPS) in broiler chicken. Despite the significantly spiking mortality in broilers due to HPS, not much effort has been made to design an effective vaccine against FAdV-4. The combination of immuno- and bioinformatics tools for immunogenic epitope prediction is the most recent concept of vaccine design. It reduces the time and effort required for hunting a potent vaccine candidate and is economical. Previously, we have reported the penton base protein of FAdV-4 to be a candidate for subunit vaccine against HPS. In the present study, we have computationally pre-screened promising B- and T-cell epitopes of the penton base. Multiple methods were employed for linear B-cell epitope identification; BepiPred and five other methods based on physicochemical properties of the amino acids. The penton base was homology modeled by means of Modeller 9.17 and after refinement of the model (by GalaxyRefine web server) ElliPro web tool was used to predict the discontinuous epitopes. NetMHCcons 1.1 and NetMHCIIpan 3.1 servers were used for the likelihood of peptide binding to Major Histocompatibility Complex (MHC) class I & II molecules respectively for T-cell epitope forecast. As a result, we identified the peptide stretch of 1-225  as the most promiscuous B- and T-cell epitope region in penton base Full Length (FL) protein sequence. Escherichia coli based expression vectors were generated containing cloned peptide stretch 1-225 (penton base1-225) and penton base FL gene sequence. The recombinant penton base1-225 and penton base FL proteins were expressed and purified using Escherichia coli-based expression system. Purification yield of penton base1-225 was 3-fold higher compared to penton base FL. These proteins were injected in chickens to determine their competence in protection against HPS. The results showed equal protection level of the two proteins and the commercial inactivated vaccine against FAdV-4 infection. The results suggest the peptide stretch 1-225 of penton base as a valuable candidate for developing an epitope-driven vaccine to combat HPS.

Brain Correlates of Mental Stress-Induced Myocardial Ischemia.

OBJECTIVE: Coronary artery disease (CAD) is a major cause of morbidity and mortality, and despite important advances in our understanding of this disorder, the underlying mechanisms remain under investigation. Recently, increased attention has been placed on the role of behavioral factors such as emotional stress on CAD risk. Brain areas involved in memory and the stress response, including medial prefrontal cortex, insula, and parietal cortex, also have outputs to the peripheral cardiovascular system. The purpose of this study was to assess the effects of mental stress on brain and cardiac function in patients with CAD. METHODS: CAD patients (N = 170) underwent cardiac imaging with [Tc-99m] sestamibi single-photon emission tomography at rest and during a public speaking mental stress task. On another day, they underwent imaging of the brain with [O-15] water positron emission tomography (PET) during mental stress (arithmetic and public speaking) and control conditions. RESULTS: Patients with mental stress-induced myocardial ischemia showed increased activation with stress in anterior cingulate, inferior frontal gyrus, and parietal cortex (p < .005). This was seen with both arithmetic stress and public speaking stress. Arithmetic stress was additionally associated with left insula activation, and public speaking with right pre/postcentral gyrus and middle temporal gyrus activation (p < .005). CONCLUSIONS: These findings suggest that mental stress-induced myocardial ischemia is associated with activation in brain areas involved in the stress response and autonomic regulation of the cardiovascular system. Altered brain reactivity to stress could possibly represent a mechanism through which stress leads to increased risk of CAD-related morbidity and mortality.

A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder.

OBJECTIVE: Brain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD. METHOD: Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures. RESULTS: Post-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group. CONCLUSION: This study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response.

Overexpression and characterization of the 100K protein of Fowl adenovirus-4 as an antiviral target.

100K is an important scaffolding protein of adenoviruses including fowl adenovirus serotype 4 (FAdV-4) that causes inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) in poultry. 100K carries out the trimerization of the major capsid hexon protein of the virus for the generation of new virions inside the target host cells. Despite its critical role for FAdV-4, no structural study, in particular, has been conducted so far. Here, the overexpression of soluble 100K protein was successfully carried out in E. coli using various expression constructs and purification yield of 3mg per litre culture volume was obtained. Gel filtration chromatography suggested that 100K protein exists in trimeric form. Circular dichroism and Fourier transform infrared spectroscopy clearly reveal that 100K protein folds with a high content of α-helices. The 3-dimentional homology model of the 100K protein, refined with molecular dynamics tools also depicts higher α-helical content within the protein model. Moreover, overexpressed recombinant 100K protein could be used to differentiate vaccinated and FAdV-4 infected chickens on the basis of higher serum anti 100K antibody titres. Our work provides preliminary structural and functional results to study biological role of the 100K protein and for further investigations to develop 100K inhibitors to control IBH-HPS in poultry.

Correction: Activity of the Human Rhinovirus 3C Protease Studied in Various Buffers, Additives and Detergents Solutions for Recombinant Protein Production.

[This corrects the article DOI: 10.1371/journal.pone.0153436.].

Activity of the Human Rhinovirus 3C Protease Studied in Various Buffers, Additives and Detergents Solutions for Recombinant Protein Production.

Proteases are widely used to remove affinity and solubility tags from recombinant proteins to avoid potential interference of these tags with the structure and function of the fusion partner. In recent years, great interest has been seen in use of the human rhinovirus 3C protease owing to its stringent sequence specificity and enhanced activity. Like other proteases, activity of the human rhinovirus 3C protease can be affected in part by the buffer components and additives that are generally employed for purification and stabilization of proteins, hence, necessitate their removal by tedious and time-consuming procedures before proteolysis can occur. To address this issue, we examined the effect of elution buffers used for common affinity based purifications, salt ions, stability/solubility and reducing agents, and detergents on the activity of the human rhinovirus 3C protease using three different fusion proteins at 4°C, a temperature of choice for purification of many proteins. The results show that the human rhinovirus 3C protease performs better at 4°C than the frequently used tobacco etch virus protease and its activity was insensitive to most of the experimental conditions tested. Though number of fusion proteins tested is limited, we expect that these finding will facilitate the use of the human rhinovirus 3C protease in recombinant protein production for pharmaceutical and biotechnological applications.

Seasonal Affective Disorder (SAD): Role of Lamotrigine Augmentation to Anti-Depressant Medication in Winter Depression.

BACKGROUND: Many therapeutic options have been evaluated and tried for seasonal affective disorder (SAD) including bright light therapy (BLT), anti-depressants, beta-blockers and psychotherapy, but the data supporting use of mood-stabilizing agents is just handful in spite of this condition being understood most frequently to be associated with bipolar affective disorder II (BPAD II). So we planned to study role of Lamotrigine (Mood stabilizing agent) in SAD. MATERIALS AND METHODS: 30 patients of SAD who were prescribed lamotrigine in addition to antidepressant medications for a minimum of 8 weeks and were assessed for severity using HAM-D were selected retrospectively from the hospital records for this study. HAM-D scores at 2, 4 and 8 weeks were compared to baseline scores. STATISTICS ANALYSIS: Single tailed t-test was used to study the difference of means to assess the therapeutic response and pre/post analysis of change. Statistical significance was set at P < 0.05. RESULTS: Though no significant difference was seen in HAM-D Scores at 2 weeks of treatment compared to baseline, but results were statistically significant at 4 and 8 weeks of treatment with lamotrigine augmentation of antidepressant medications. CONCLUSION: We conclude that lamotrigine augmentation was found to be effective treatment strategy for managing winter depression phase of Seasonal Affective Disorder.

Systemic Lupus Erythematous Presenting as Catatonia and its Response to Electroconvulie Therapy.

Neuropsychiatric systemic lupus erythematous (SLE) encompasses various psychiatric and neurological manifestations that develop in SLE patients, secondary to involvement of central nervous system. Neuropsychiatric SLE, presenting as catatonia is very uncommon, and treatment of this condition is not well defined. Previously the role of benzodiazepines, immunosuppression, plasma exchange, and electroconvulsive therapy (ECT) has been described in its management. Here we describe a case of neuropsychiatric lupus presenting as catatonia that did not respond to benzodiazepines or immunosuppression. The symptoms of catatonia showed improvement with ECT. Furthermore, we have discussed the pathology of the disorder and the role of ECT in the treatment of cases of catatonia associated with SLE, who do not respond to benzodiazepines.

Role of lamotrigine augmentation in treatment-resistant obsessive compulsive disorder: a retrospective case review from South Asia.

BACKGROUND: Resistance to pharmacotherapy is one of the major challenges in the management of obsessive-compulsive disorder (OCD). OCD being a quite prevalent disorder, this resistance adds to the disability. Different strategies are being employed to counter this resistance, one of them being augmentation with glutamatergic modulators. Lamotrigine is being used for same since the recent past with mixed results. OBJECTIVE: The aim was to study the role of lamotrigine augmentation in serotonin reuptake inhibitor (SRI) resistant OCD patients. METHODOLOGY AND RESULTS: This study was carried by studying the case sheets of SRI resistant cases having already completed the treatment. A total of 22 cases sheets over 2 years met the study criteria with a mean age of mean age of 34.14 years. Over a period of 16 weeks, with a mean lamotrigine dose of 150 mg/day, 20 out of 22 patients had shown a significant response. The mean decrease in Yale-Brown Obsessive Compulsive Scale score was 67.23% with a baseline score of 28.87. There was a similar change on different domains of World Health Organization quality of life (P = 0.00564). CONCLUSION: Lamotrigine augmentation to on-going treatment with SRIs may be an effective move in case of SRI resistant OCD patients.

Prevalence of psychiatric disorders in patients with a diagnosis of polycystic ovary syndrome in kashmir.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the common endocrine disorders and is associated with reproductive, metabolic, and psychological disturbances affecting one in five women of reproductive age group. OBJECTIVE: To investigate the prevalence of psychiatric disorders among women in ambulatory treatment with a diagnosis of PCOS. MATERIALS AND METHODS: One hundred and ten patients of PCOS were evaluated using Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition criteria by means of Mini International Neuropsychiatric Interview, English version 5.0.0. Diagnosis of PCOS was confirmed according to the National Institute of Health/National Institute of Child Health and Human Development, 1990 consensus conference criteria. Forty subjects without PCOS who were matched for age and body mass index were taken as a comparison group. RESULTS: About 23% of cases had major depressive disorder as compared to 7.5% of controls, 1.8% had dysthymia, 15.45% had panic disorder compared to 5% of controls, 6.36% had obsessive compulsive disorder compared to 2.5% of controls, 8% cases had suicidality, 2.72% of cases were bipolar affective disorder, and 15.45% had generalized anxiety disorder (GAD). CONCLUSION: A high prevalence of mental disorders was observed, especially major depression, panic disorder, and GAD in patients with PCOS in our study. The results suggest that screening and appropriate management for psychiatric disorders should be part of the routine evaluation of these patients.

Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia, before and after antipsychotic treatment.

BACKGROUND: Treatment with antipsychotics increases the risk of developing diabetes in patients of schizophrenia but this diabetogenic potential of different antipsychotics seems to be different. Moreover, there may be an independent link between schizophrenia and diabetes. So we plan to study the prevalence of glucose dysregulation in patients of schizophrenia before and after treatment with various antipsychotics. MATERIALS AND METHODS: Fifty patients (32 males and 18 females) diagnosed with schizophrenia were evaluated for glucose dysregulation using oral glucose tolerance test, initially (drug naive) and after antipsychotic treatment. Age- and sex-matched healthy volunteer group of 50 subjects (35 males and 15 females) was taken for comparison. Results were interpreted using American Diabetic Association criteria. RESULTS: Though the glycemic status of the patient group was comparable with healthy controls initially but antipsychotic treatment was associated with glucose dysregulation. For first 6 weeks the antipsychotic (olanzapine, risperidone, haloperidol and aripiprazole)-induced glucose dysregulation was comparable, which was seen to be maximum with the olanzapine-treated group at the end of this study, 14 weeks. CONCLUSION: We conclude that antipsychotic treatment of nondiabetic drug naive schizophrenia patients was associated with adverse effects on glucose regulation. For initial 6 weeks the antipsychotic-induced glucose dysregulation was comparable, which was seen to be maximum with olanzapine at the end of study, i.e. 14 weeks. Keeping this at the back of mind we can stabilize a patient initially with a more effective drug, olanzapine, and later on shift to one with less metabolic side effects.

Rapid Response of Long-Standing, Treatment-Resistant Non-Catatonic Mutism in Paranoid Schizophrenia with Single ECT session.

CONTEXT: Mutism is a common manifestation of catatonia, but mutism due to other forms of psychopathology and neurological disorders have also been described. Although not common, long-standing mutism has also been a feature of non-catatonic schizophrenia and traditionally responds less to conventional therapies. CASE REPORT: We describe a rare case of paranoid schizophrenia presenting with continuous mutism for about 4 years. This 26-year-old male had symptoms of schizophrenia without catatonia. After failed trial of adequate pharmacotherapy and psychological intervention and considering his level of dysfunction, he was started on electroconvulsive therapy (ECT). To our surprise, he improved with a single session of ECT while he was on concurrent pharmacotherapy. We also discuss the possible explanation for this rapid effect of ECT in such clinical presentation. To our knowledge, this is the first case of non-catatonic mutism of schizophrenia of this long duration responding so promptly to ECT, although there are other reports as well in literature, but multiple ECT sessions were applied in those cases. CONCLUSION: Non-catatonic mutism is perhaps presenting as a cultural variant in this part of the world and whenever encountered, ECT should be an option. Further research should be carried out to validate this idea.