Rita Christopher

Glutamatergic dysfunction in OCD.

The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-naïve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (μmol/l) level was found to be significantly higher [F(1,31)=6.846, p=0.014] in OCD patients (47.12±4.25) compared to control subjects (41.36±3.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.

Plasma Proteome Database as a resource for proteomics research: 2014 update.

Plasma Proteome Database (PPD; http://www.plasmaproteomedatabase.org/) was initially described in the year 2005 as a part of Human Proteome Organization’s (HUPO’s) pilot initiative on Human Plasma Proteome Project. Since then, improvements in proteomic technologies and increased throughput have led to identification of a large number of novel plasma proteins. To keep up with this increase in data, we have significantly enriched the proteomic information in PPD. This database currently contains information on 10 546 proteins detected in serum/plasma of which 3784 have been reported in two or more studies. The latest version of the database also incorporates mass spectrometry-derived data including experimentally verified proteotypic peptides used for multiple reaction monitoring assays. Other novel features include published plasma/serum concentrations for 1278 proteins along with a separate category of plasma-derived extracellular vesicle proteins. As plasma proteins have become a major thrust in the field of biomarkers, we have enabled a batch-based query designated Plasma Proteome Explorer, which will permit the users in screening a list of proteins or peptides against known plasma proteins to assess novelty of their data set. We believe that PPD will facilitate both clinical and basic research by serving as a comprehensive reference of plasma proteins in humans and accelerate biomarker discovery and translation efforts.

A comprehensive map of the human urinary proteome.

The study of the human urinary proteome has the potential to offer significant insights into normal physiology as well as disease pathology. The information obtained from such studies could be applied to the diagnosis of various diseases. The high sensitivity, resolution, and mass accuracy of the latest generation of mass spectrometers provides an opportunity to accurately catalog the proteins present in human urine, including those present at low levels. To this end, we carried out a comprehensive analysis of human urinary proteome from healthy individuals using high-resolution Fourier transform mass spectrometry. Importantly, we used the Orbitrap for detecting ions in both MS (resolution 60 000) and MS/MS (resolution 15 000) modes. To increase the depth of our analysis, we characterized both unfractionated as well as lectin-enriched proteins in our experiments. In all, we identified 1,823 proteins with less than 1% false discovery rate, of which 671 proteins have not previously been reported as constituents of human urine. This data set should serve as a comprehensive reference list for future studies aimed at identification and characterization of urinary biomarkers for various diseases.

Anti-brain autoantibodies and altered excitatory neurotransmitters in obsessive-compulsive disorder.

Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive–compulsive disorder (OCD), it is unclear whether these antibodies can cross the blood–brain barrier to bind against BG or other components of the OCD circuit. It is also unclear how they might lead to hyperactivity in the OCD circuit. We examined this by investigating the presence of autoantibodies directed against the BG or thalamus in the serum as well as CSF of 23 OCD patients compared with 23 matched psychiatrically normal controls using western blot. We further investigated CSF amino acid (glutamate, GABA, taurine, and glycine) levels and also examined the extent to which these levels were related to the presence of autoantibodies. There was evidence of significantly more binding of CSF autoantibodies to homogenate of BG as well as to homogenate of thalamus among OCD patients compared with controls. There was no significant difference in binding between patient and control sera except for a trend toward more bands to BG and thalamic protein corresponding to 43 kD among OCD patients compared with controls. CSF glutamate and glycine levels were also significantly higher in OCD patients compared with controls, and further multivariate analysis of variance showed that CSF glycine levels were higher in those OCD patients who had autoantibodies compared with those without. The results of our study implicate autoimmune mechanisms in the pathogenesis of OCD and also provide preliminary evidence that autoantibodies against BG and thalamus may cause OCD by modulating excitatory neurotransmission.

Clinical features of adult GM1 gangliosidosis: Report of three Indian patients and review of 40 cases

Deficiency of enzyme acid β‐galactosidase causes GM1 gangliosidosis. Patients with adult GM1 gangliosidosis typically present with generalized dystonia. We describe clinical, bone marrow, and radiological features of adult GM1 gangliosidosis to help improve its recognition. We report 3 Indian patients and review of reports between 1981 and October 2002. The disease frequently is reported in the Japanese literature (75%). Patients are normal at birth and have normal early motor and mental development. Onset is within the first decade with abnormal gait, or worsening of speech is an initial symptom. Dystonia occurs in 97% of patients. Facial dystonia described as “facial grimacing” observed in ∼90% could be an important clinical clue. Dysarthria/anarthria (97%) is frequent, and eye movements are normal. Bone marrow examination may show Gaucher‐like foam cells (39%). Magnetic resonance imaging (MRI) frequently (90.9%) shows bilateral symmetrical putamenal hyperintensities on T2‐weighted and proton density images. Diagnosis is confirmed by demonstrating deficiency of β‐galactosidase. Adult (Type 3) GM1 Gangliosidosis commonly presents with generalized dystonia with prominent facial dystonia, severe speech disturbances, and normal eye movements. Bone marrow frequently shows Gaucher‐like foam cells. MRI shows typical lesions in the putamen. Deficiency of β‐galactosidase in fibroblasts confirms the diagnosis.

Association of the functional KL-VS variant of Klotho gene with early-onset ischemic stroke

Genetic variants of Klotho have been reported to be associated with human longevity and atherosclerotic vascular events and risk factors. However, very few studies have explored their association with ischemic stroke. We hypothesized that the functional KL-VS and the exonic C1818T variants of Klotho gene may be associated with ischemic stroke in Indian population. We enrolled a total of 460 patients with ischemic stroke and 574 age- and gender-matched controls for the study. Genotyping was done by polymerase chain reaction and restriction fragment length polymorphism. Contrary to other Asian reports, KL-VS variant was polymorphic in our population, with a frequency distribution similar to that of Caucasians. The frequency distribution of the C1818T variant was similar to previously reports in Asians. A differential effect of age on association of Klotho KL-VS variant with ischemic stroke was observed. In subjects aged ≤40 years, the KL-VS homozygotes, 352FF and 352VV, had ~1.5-fold (OR=1.57; 95% CI: 1.02-2.40, p=0.038) and ~3-fold (OR=3.29; 95%CI: 1.02-10.56, p=0.046) higher risk of stroke compared to heterozygotes, whereas in the older group (aged >40 years) no significant association was observed. The C1818T variant was not associated with ischemic stroke. We conclude that KL-VS homozygosity could contribute to early-onset stroke in India. Larger studies in other ethnic populations are warranted to determine the role of these gene variants in the etiology of stroke occurring in the young.

Anticardiolipin antibodies in ischemic stroke in the young: Indian experience

Anticardiolipin antibodies (aCL) have been recognised as a marker for an increased risk of thrombosis. The prevalence of these antibodies in young Indian ischemic stroke population is not known. Our study establishes the prevalence of these antibodies and evaluates their clinical significance in 60 patients aged 40 years or less who presented with completed ischemic stroke. Immunoglobulin G and immunoglobulin M class antibodies to anticardiolipin were determined using a standardized enzyme-linked immunosorbent assay. The prevalence of these antibodies in stroke patients was 23% compared to 3.2% in the controls. All patients studied had no overt evidence of systemic lupus erythematosus or related autoimmune disorders. The aCL-positive stroke patients did not differ significantly from aCL-negative stroke patients with regard to demographic characteristics, risk factor profile, and radiological features. Prior transient ischemic attacks, ischemic retinopathy, and asymptomatic infection were more frequent in the aCL-positive group. The role of anticardiolipin antibodies as a disease marker for ischemic stroke is under-recognised in India and warrants further investigation.

Effect of yoga therapy on plasma oxytocin and facial emotion recognition deficits in patients of schizophrenia

Context: Yoga therapy has been demonstrated to be useful in treatment of negative symptoms and improving the socio-occupational functioning and emotion recognition deficits in antipsychotic-stabilized schizophrenia patients. Oxytocin has been recently implicated in social cognition deficits in schizophrenia. The effect of yoga therapy on oxytocin levels in schizophrenia has not been studied. Aims: This study aimed to assess the effect of yoga therapy on symptoms, socio-occupational functioning, facial emotion recognition deficits and plasma oxytocin levels in antipsychotic stabilized schizophrenia patients. Settings and Design: Randomized controlled study on 43 consenting, medication stabilized patients with schizophrenia in a tertiary psychiatric center using yoga intervention and waitlisted groups. Materials and Methods: A total of 43 schizophrenia patients were randomized to yoga group (n=15) or waitlist group (n=28). Patients in the yoga group received training in a specific yoga therapy module for schizophrenia. Patients in both groups were continued on stable antipsychotic medication. Assessments included scale for assessment of positive symptoms, scale for assessment of negative symptoms, socio-occupational functioning scale and tool for recognition of emotions in neuropsychiatric disorders (TRENDS) and plasma oxytocin levels; performed at baseline and at the end of 1 month. Results: A total of 15 patients in the yoga group and 12 in waitlist group completed the study. The yoga therapy group showed a significant improvement in socio-occupational functioning, performance on TRENDS (P<0.001) and plasma increase in oxytocin levels (P=0.01) as compared with the waitlist group. Conclusion: The study supported the role of add-on yoga therapy in management of schizophrenia and demonstrated an improvement in endogenous plasma oxytocin levels in schizophrenia patients receiving yoga therapy.

Screening for inborn errors of metabolism using automated electrospray tandem mass spectrometry: study in high-risk Indian population.

OBJECTIVES Tandem mass spectrometry is a major technological advance in the screening for inborn errors of metabolism. It has the advantage of sensitive and simultaneous multiple disease screening with minimal sample requirement. The diseases detected include aminoacidemias, fatty acid oxidation disorders, and organic acidemias. DESIGN AND METHODS Using automated electrospray tandem mass spectrometry we screened 3550, clinically selected, symptomatic children for inborn errors of metabolism by analyzing amino acids and acylcarnitines in dried blood filter-paper samples. RESULTS Among these, 113 (3.2%) children were identified with a metabolic disorder: 61 (54%) patients had amino acid disorders, 47 (41.6%) had organic acidemias, and 5 (4.4%) children had disorders of fatty acid oxidation. The diagnoses were further confirmed through clinical symptoms, and other biochemical studies. CONCLUSIONS These results show that inherited metabolic disorders are not rare in India, a rapidly developing country with a high birth rate and relatively frequent occurrence of consanguineous marriages.

Cranial MRI in Acute Hyperammonemic Encephalopathy

Cranial magnetic resonance imaging was performed in three cases of acute hyperammonemic encephalopathy with three diverse etiologies: infantile citrullinemia, acute hepatic encephalopathy, and proximal urea cycle disorder. All three patients exhibited diffuse extensive cortical signal changes and swelling. Neurologic outcome was poor in all three cases. Knowledge of the magnetic resonance imaging findings of hyperammonemic encephalopathy may help in early diagnosis and treatment and could influence the neurologic outcome.