Ravinder Reddy | University of Pittsburgh (original) (raw)

Papers by Ravinder Reddy

The Journal of Clinical Psychiatry, 2000

Blepharospasm, the forcible closure of eyelids, is an infrequent consequence of neuroleptic treat... more Blepharospasm, the forcible closure of eyelids, is an infrequent consequence of neuroleptic treatment that, when severe, can interfere with the ability to walk, drive, or work. Like tardive dyskinesia, blepharospasm can be disfiguring and aesthetically distressing, contributing to the increased stigmatization of patients. We report 4 patients with DSM-IV schizoaffective disorder, paranoid schizophrenia, or chronic undifferentiated schizophrenia who developed neuroleptic-induced blepharospasm. In all patients, blepharospasm remitted without the reemergence of psychosis within 3 to 5 months of treatment with clozapine, 100-200 mg/day. The results suggest that clozapine may successfully treat neuroleptic-induced blepharospasm without the reemergence of psychosis in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder.

Free Radical Biology and Medicine, 1998

Ccntro dc Mcdicina Avanqda. Address: Rua Martins Fcrrclra. 75. Rio dc Janeiro Bnsil. ZIP: 22271 0... more Ccntro dc Mcdicina Avanqda. Address: Rua Martins Fcrrclra. 75. Rio dc Janeiro Bnsil. ZIP: 22271 010. Fax: (5521) 5i'MWO(1 crwil ccma~u;iis.com.br t%omiurn and vanadium are somewhat involved in carbohydrate mctabohsm: Ihe same is observed with lithium. They are also mvol~ cd in brain mctabolism.Because of this we thought of interest IU stud\ thor content in hair of cases of clinically depressed ruticnts Patients have a range of age between 30-55 years (18 p.~i~nts and 30 conlrols) Analizing the results we could observe lhni values of lithrom arc somewhat stable (patients: 0.035 5 0.09 wd controls. 0.0?4 -i 0.017 ppm) t= 0.5 (not significant) The same !!as obscncd with chromium (patients: 0.222 + 0.49. controls: 0.41 I i 0.2 ppm. t= 1.6. not significant). Nonetbcless. vanadium is signiticantly diminished in these patients \!hen compared with controls (patients: 0.057 + 0.066. controls: 0.2 * 0 I33. t-4.1 p~o.001) WC could not obscwc any significant correlation between lithunkanad~um. and chromium/vanadium. As a matter of fact. usually hair chromium is significantly correlated wrth harr vanadium in normal patients (I= + 0.289. p< 0.115) or diabetic ones (I= + 0.591. p< 0.01). Both chromium and vanadwm are significantly decreased in diabetic patients when compared with controls (chromium. t= 3.2 I% 0.01. vanadium: t= 4.8X. p( 0.00 I)

Psychiatry Research, Dec 27, 2000

Albumin and bilirubin are metal-binding proteins, shown to possess free radical scavenging proper... more Albumin and bilirubin are metal-binding proteins, shown to possess free radical scavenging properties, and may thus be selective antioxidants. In the present study we examined whether individual plasma antioxidants such as albumin and bilirubin, which significantly contribute to total antioxidant status (TAS), are reduced in patients with schizophrenia. We prospectively studied plasma antioxidant proteins, i.e. albumin and bilirubin, in male veteran schizophrenic patients using a within-subject, repeated measures, on-off-on haloperidol treatment design, as well as age- and sex-matched healthy volunteers. Male patients with schizophrenia either during haloperidol treatment (n=46) or in a drug-free condition (n=35) had significantly lower levels of both plasma albumin and bilirubin compared with age- and sex-matched healthy volunteers (n=31). Such reductions of plasma antioxidant proteins in schizophrenic patients appear to be age-related changes, in contrast to those observed in healthy volunteers. On the other hand, levels of plasma albumin and bilirubin were not significantly affected by haloperidol treatment, haloperidol withdrawal, or length of drug-free period. Moreover, plasma TAS was not influenced significantly by cigarette smoking, even though it may selectively decrease plasma bilirubin but not albumin levels. The present findings, taken together with our previous results of reduced plasma TAS and uric acid, as well as an increased Red blood cell superoxide dismutase, lend further support to the hypothesis that a defect in the antioxidant defense system exists in schizophrenia that may lead to oxidative damage.

Prostagland Leuk Essent Fatty, 1996

Research into the role of oxidative stress and fatty acids in neuropsychiatric disorders has been... more Research into the role of oxidative stress and fatty acids in neuropsychiatric disorders has been ongoing for decades and has been written about before. However, this book aims to examine how these seemingly disparate bodies of evidence from the fields of oxidative stress and essential fatty acid metabolism are, in fact, intimately connected to each other. Therefore, for this book the editors invited researchers of oxidative stress (OS) and essential fatty acid (EFA) in neuropsychiatric disorders, exemplified by schizophrenia, mood disorders, Parkinson’s disease and Alzheimer’s disease. Together, the chapters bring a fresh perspective on the relationship between the presence of oxidative stress in the afore-mentioned disorders and the fatty acid deficits that have been identified in these disorders.

Psychiatry research, 1991

Fibroblast cultures were established from skin biopsies of 18 schizophrenic patients (14 on drug ... more Fibroblast cultures were established from skin biopsies of 18 schizophrenic patients (14 on drug and 4 off drug) and 13 normal subjects, and growth parameters (initial growth and rate of growth) and morphology were studied. Fibroblasts from patients took significantly longer to grow than did normal fibroblasts. Cell lines were established within 2 weeks for all normal controls, but for only 6 (33%) of 18 schizophrenic patients. The rate of growth (doubling time) was also significantly longer for fibroblasts from patients than from normals. Neither time to establishment of initial growth nor doubling time was related to age, sex, age at onset, duration of illness, or medication status in the patients. Fibroblasts from normals showed uniform, long (slender), characteristic spindle-like, bipolar appearance, with unidirectional orientation, both while growing from explant as well as after subculturing. By contrast, fibroblasts from patients generally showed random size (shorter and flat...

Prostaglandins, leukotrienes, and essential fatty acids, 2003

There is accumulating evidence of reductions in red blood cell membrane essential fatty acids in ... more There is accumulating evidence of reductions in red blood cell membrane essential fatty acids in patients with schizophrenia. The mechanisms that may underlie these reductions have yet to be determined. It is possible that the observed membrane fatty acid deficits are associated with the development of schizophrenia. Alternatively, the membrane fatty acid deficits may be due to environmental factors, such as smoking and variations in diet, which may not be associated specifically with the pathophysiology of schizophrenia. Patients with schizophrenia smoke cigarettes at very high rates. Cigarette smoke contains many pro-oxidants that contribute directly to oxidative stress. Polyunsaturated fatty acids (PUFAs) are very susceptible to oxidative effects of free radicals. Thus, smoke-induced oxidative stress could plausibly account for reductions in membrane fatty acid in schizophrenia. Recent studies provide conflicting evidence for smoking effects on membrane fatty acid deficits. Likew...

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2011

Introduction: Patients with schizophrenia have significant cognitive deficits, generally resistan... more Introduction: Patients with schizophrenia have significant cognitive deficits, generally resistant to conventional treatment. This preliminary study examined the effects of ethyl-eicosapentanoate (EPA) on an executive function in early course patients. Patients and methods: Patients with schizophrenia were given, after an informed consent, 2 g of an EPA daily for 24 weeks, in an open-label study. The Wisconsin Card Sort Test (WCST) was administered at baseline, weeks 4, 12 and 24. Results: The 27 patients, with a mean duration of illness of 4.2 years, were all receiving atypical antipsychotics; treatment remained unchanged for the study. Perseverative errors -the key measure derived from WCST -were significantly reduced from the baseline mean of 28.2 to 18.4 errors at week 24. Positive symptoms also improved significantly. There were no correlations between EPA levels and any clinical or other neuropsychological measures. Conclusion: These findings suggest that an EPA has procognitive effects for patients with schizophrenia, but controlled trials are required.

Frontiers in Cellular Neuroscience, 2013

Schizophrenia (SZ) is a biochemically complex disorder characterized by widespread defects in mul... more Schizophrenia (SZ) is a biochemically complex disorder characterized by widespread defects in multiple metabolic pathways whose dynamic interactions, until recently, have been difficult to examine. Rather, evidence for these alterations has been collected piecemeal, limiting the potential to inform our understanding of the interactions amongst relevant biochemical pathways. We herein review perturbations in purine and neurotransmitter metabolism observed in early SZ using a metabolomic approach. Purine catabolism is an underappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. We have observed a homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with SZ (FENNS). Precursor and product relationships within purine pathways are tightly correlated. Although some of these correlations persist across disease or medication status, others appear to be lost among FENNS suggesting that steady formation of the antioxidant uric acid (UA) via purine catabolism is altered early in the course of illness. As is the case for within-pathway correlations, there are also significant cross-pathway correlations between respective purine and tryptophan (TRP) pathway metabolites. By contrast, purine metabolites show significant cross-pathway correlation only with tyrosine, and not with its metabolites. Furthermore, several purine metabolites (UA, guanosine, or xanthine) are each significantly correlated with 5-hydroxyindoleacetic acid (5-HIAA) in healthy controls, but not in FENNS at baseline or 4-week after antipsychotic treatment. Taken together, the above findings suggest that purine catabolism strongly associates with the TRP pathways leading to serotonin (5-hydroxytryptamine, 5-HT) and kynurenine metabolites. The lack of a significant correlation between purine metabolites and 5-HIAA, suggests alterations in key 5-HT pathways that may both be modified by and contribute to oxidative stress via purine catabolism in FENNS.

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2004

Studies suggest that the omega-3 fatty acid supplementation may be beneficial in reducing symptom... more Studies suggest that the omega-3 fatty acid supplementation may be beneficial in reducing symptom severity in schizophrenia. The mechanism(s) underlying the clinical effect is not known. Serotonin (5-HT) has been implicated in the pathophysiology of schizophrenia and in the mechanism of some antipsychotic agents. 5-HT receptors are known to be modified by omega-3 fatty acids. We examined whether supplementation with the omega-3 fatty acid eicosapentaenoic acid (EPA)-modified 5-HT amplified ADPinduced platelet aggregation in patients with schizophrenia. Two grams of ethyl-EPA was administered daily for 6 months supplementally to ongoing antipsychotic treatment in 12 patients with chronic schizophrenia, using an open-label design. Red blood cell membrane fatty acids and platelet functions (platelet aggregation and dense granule secretion) were monitored at baseline, 1-, 3-and 6-months. The EPA levels were elevated more than five-fold in RBC membranes of all patients after 3 months supplementation, indicating a high degree of compliance. Consistent with previous reports, there was inhibition of ADP-induced platelet aggregation by EPA supplementation. Moreover, EPA markedly enhanced the 5-HT responsivity as measured by the magnitude of 5-HT amplification on ADP-induced platelet aggregation. Previously, we have demonstrated a significant inverse correlation between 5-HT responsivity and psychosis severity in unmedicated patients with schizophrenia. Taken together, the present data support the notion that EPA may be mediating its therapeutic effects in schizophrenia via modulation of the 5-HT 2 receptor complex.

Schizophrenia Research, 1997

Objective: The purpose of this paper is to review the potential role of free radicals in schizoph... more Objective: The purpose of this paper is to review the potential role of free radicals in schizophrenia, examine existing hypotheses, and propose future research directions. There is accumulating evidence for a role of free radicals in many neuropsychiatric disorders. Free radicals are generated during many biochemical processes, and can produce pathological alterations in critical cellular constituents, including cell membranes, mitochondria, and DNA. Although free radicals are ubiquitous and normally of little threat, damage can occur due to generation of excess free radicals, deficient antioxidant mechanisms or both (oxidative stress).

Current Medicinal Chemistry-Central Nervous System Agents, 2003

... Res., 2000, 42, 7. [14] Horrobin, DF; Manku, MS; Morse-Fisher, N.; Vaddadi, KS; Courtney, P.;... more ... Res., 2000, 42, 7. [14] Horrobin, DF; Manku, MS; Morse-Fisher, N.; Vaddadi, KS; Courtney, P.; Glen, AIM; Glen, E.; Spellman, M.; Bates, C. Biol. Psychiatry, 1989, 25, 562. [15] Vaddadi, KS;Courtney, P.; Gilleard, CJ; Manku, MS; Horrobin, DF Psychiat. Res., 1989, 27, 313. ...

Schizophrenia Research, 2005

Apolipoprotein D (apoD) is a member of the lipocalin superfamily of transporter proteins that bin... more Apolipoprotein D (apoD) is a member of the lipocalin superfamily of transporter proteins that bind small hydrophobic molecules, including arachidonic acid (AA). The ability of apoD to bind AA implicates it in pathways associated with membrane phospholipid signal transduction and metabolism. Recent findings of an increased expression of apoD in the mouse brain after clozapine treatment suggested a role for apoD in the pharmacological action of clozapine. Moreover, clozapine has been shown to increase membrane AA levels in RBC phospholipids from schizophrenic patients. ApoD levels have also been shown to be elevated in the CNS of subjects with chronic schizophrenia, a disorder associated with AA dysfunction. In this study, we examined whether plasma apoD levels are related to red blood cell membrane AA contents in the first-episode neuroleptic-naRve schizophrenic (FENNS) patients. Plasma apoD levels as measured by enzyme-linked immunosorbent assay (ELISA) were not significantly different ( F=0.51, df=2,86, p=0.60) among healthy controls (n=36), FENNS patients (n=33) and patients with other psychiatric disorders (n=19). However, plasma apoD levels were significantly correlated with RBC-AA ( p=0.0022) and docosapentaenoic acid ( p=0.0008) in FENNS patients. There are several known mechanisms that can lead to the type of membrane fatty acid defects that have been identified in schizophrenia. Whether plasma apoD alone is a major determinant of reduced RBC membrane AA levels in FENNS patients remains to be determined, although these preliminary data appear not to support this premise. Taken together with other in vitro studies, however, the present data support the view that an increased expression of apoD such as induced by atypical neuroleptic drug, may facilitate incorporation of AA into membrane phospholipids by its selective binding to AA. D

Schizophrenia Research, 2000

Previous studies in schizophrenia have shown alterations in membrane phospholipids and polyunsatu... more Previous studies in schizophrenia have shown alterations in membrane phospholipids and polyunsaturated fatty acids. However, these studies have primarily examined peripheral (non-neuronal ) cell types. The purpose of the present study was to examine whether the membrane deficits seen in peripheral tissues are also observed in the brain. The caudate was the primary region of interest for this study. Using high-pressure liquid chromatography in conjunction with an evaporative light-scattering detector, we first measured the level of various membrane phospholipids (PL) in schizophrenic (n=11) and control groups with (n=7) and without (n=14) other mental disorders. Polyunsaturated fatty acids (PUFAs) were then determined by capillary gas chromatography. Within groups, there are no significant correlations between membrane PL levels and other collection and demographic parameters including age, postmortem interval, storage time and brain weight. Significantly lower amounts of phosphatidylcholine and phosphatidylethanolamine were found in postmortem brain tissue from schizophrenic patients than in those from control groups, even after accounting for potential confounds. In addition, strong reductions of total PUFAs and saturated fatty acids were found in schizophrenic brains, relative to control brains. Specifically, the reduced PUFAs were largely attributable to decreases in arachidonic acid (AA) and, to a lesser extent, its precursors, linoleic and eicosadienoic acids. There are no significant differences between the control groups with and without other mental disorders. The present findings suggest that deficits identified in peripheral membranes may also be present in the brain from schizophrenic patients. Such a deficit in membrane AA may contribute to the many biological, physiological, and clinical phenomena observed in schizophrenia.

Schizophrenia Research, 2003

Recent findings suggest that free radical-mediated pathological processes may underlie membrane d... more Recent findings suggest that free radical-mediated pathological processes may underlie membrane deficits that have been observed in schizophrenia. We have previously demonstrated that both total antioxidant status (TAS) and individual antioxidants were significantly reduced in plasma of chronic schizophrenic patients, on and off haloperidol. To test whether reductions in plasma antioxidants are independent of treatment or illness progression, levels of plasma antioxidants were evaluated in 43 patients at first-episode of psychosis, 31 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (reconfirmed after 6 months) and 12 patients with primary mood (bipolar or depressive (BP/D)) disorder, at neuroleptic-naive baseline as well as 40 age- and sex-matched normal controls (NC). The major plasma antioxidants albumin, uric acid and bilirubin were all significantly lower in the first-episode schizophrenic, but not in the BP/D patients, than in normal controls. Factors that can affect these antioxidants-age, gender, diet and smoking-were examined. Body mass index (BMI) was significantly lower in patients, but was not correlated with plasma albumin and bilirubin; there was a trend for a correlation with uric acid in schizophrenic patients. Lower antioxidant levels were independent of smoking status of patients. The present data suggest that a defect in the antioxidant defense system (AODS), which may lead to oxidative damage, occurs early in the course of illness and is independent of treatment effects.

Schizophrenia Research, 1990

It has been proposed that obstetric complications (OCs) are more common in patients with nonfamil... more It has been proposed that obstetric complications (OCs) are more common in patients with nonfamilial schizophrenia, and associated with lateral ventricular enlargement in such patients. We examined the relations among OCs, family history of schizophrenia or bipolar mood disorder, and lateral ventricular size and cortical sulcal prominence in 44 schizophrenic patients. A history of OCs was not related to an absence of a family history of schizophrenia, ventricle-brain ratio, or cortical sulcal prominence. None of the CT findings was related to family history.

Schizophrenia Research, 1989