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Biomedical subjects

J Levine

Publications and source records attributed to J Levine.

At least 37 records · Page 2Linked to original sources

Brain metabolic effects of acute nicotine.

(-)Nicotine acetylcholine receptors are located on both nerve cell bodies and synaptic terminals, are permeable to calcium, and function perhaps predominantly by facilitating the release of neurotransmitters and neuropeptides. The behavioral rewards from (-)nicotine and perhaps addiction appear to be related to dopamine release. 31P NMR analysis reveals subcutaneously administered (-)nicotine produces acute alterations in brain membrane phospholipid and high-energy phosphate metabolism of Fischer 344 rats. These metabolic responses to (-)nicotine could contribute to nicotine's behavioral effects.

Animals↗

Illness characteristics and their association with prescription patterns for bipolar I disorder.

INTRODUCTION: The present study explores the relationships among psychotropic medications, illness-related parameters, patient demography, suicidality, and levels of functioning in a voluntary bipolar case registry. METHODS: Four hundred and fifty-seven subjects with bipolar I disorder were selected from a voluntary registry for subjects with bipolar illness. Demographic characteristics, psychotropic medications, age at onset of illness, duration of illness, number of hospitalizations, the ability to live independently, employment and driving status as well as the history of suicidal attempts were obtained through a structured phone interview. RESULTS: Subjects treated with antidepressants had a shorter duration of illness, while patients treated with antipsychotic drugs had an earlier onset of illness. The number of hospitalizations for mania was fewer among patients taking a combination of lithium and carbamazepine as compared to patients not receiving them, while subjects taking neuroleptics had more hospitalizations as compared to subjects not receiving them. The number of psychotropic agents prescribed correlated positively with the number of hospitalizations for depressive episodes. Curiously, no correlations were found between the types of psychotropic agents prescribed and the levels of functioning or a history of suicidal attempts. Interestingly, our results suggest that more than half of the subjects were unable to live independently or to work due to their illness. Also, more than 50% of the subjects had at least one suicidal attempt, the majority occurred during depressive episodes. CONCLUSIONS: Our results suggest that subjects with bipolar I disorder have high rate of suicidal attempts and may have serious functional impairments.

Adolescent↗

A short course of induction chemotherapy followed by two cycles of high-dose chemotherapy with stem cell rescue for chemotherapy naive metastatic breast cancer.

A single cycle of high-dose chemotherapy with stem cell support (HDC) in women with responsive metastatic breast cancer (BC) consistently achieves over 50% complete and near complete response (CR/nCR). This significant cytoreduction results in a median event-free survival (EFS) of 8 months, and approximately 20% 3-year and 16% 5-year EFS in selected patients. To improve long-term outcomes, new strategies to treat minimal residual tumor burden are needed. Increased total dose delivered can be achieved with two cycles of HDC. Critical design issues include shortening induction chemotherapy to avoid development of drug resistance and the use of different agents for each HDC cycle. We have determined the maximum tolerated dose (MTD) for paclitaxel combined with high-dose melphalan in the context of a double transplant and explored the impact of a short induction phase. Between June 1994 and August 1996, we enrolled 32 women with metastatic BC on to this phase I double transplant trial. Induction consisted of doxorubicin 30 mg/m2/day days 1-3 given for 2 cycles every 14 days with G-CSF 5 microg/kg s.c. days 4-12. Stem cell collection was performed by leukapheresis in each cycle when the WBC recovered to above 1000/microl. Patients with stable disease or better response to induction were eligible to proceed with HDC. HDC regimen I (TxM) included paclitaxel with dose escalation from 0 to 300 mg/m2 given on day 1 and melphalan 180 mg/m2 in two divided doses given on day 3. HDC regimen II was CTCb (cyclophosphamide 6 g/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 total doses) delivered by 96-h continuous infusion. At the first dose level of 150 mg/m2 paclitaxel by 3 h infusion, four of five patients developed dose-limiting toxicity consisting of diffuse skin erythema and capillary leak syndrome. Only two of these five completed the second transplant. Subsequently, paclitaxel was delivered by 24-h continuous infusion together with 96 h of dexamethasone and histamine receptor blockade. This particular toxicity was not observed again. No toxic deaths occurred and dose-limiting toxicity was not encountered. Three patients were removed from study prior to transplant: one for insurance refusal and two for disease progression. All others completed both cycles of transplant. Complete and near complete response (CR/nCR) after completion of therapy was achieved in 23 (72%) of 32 patients. The median EFS is 26 months. The median overall survival has not yet been reached. At a median follow-up of 58 months, EFS and overall survival are 41% and 53%, respectively. This double transplant approach is feasible, safe, and tolerable. Treatment duration is only 14 weeks and eliminates lengthy induction chemotherapy. The observed event-free and overall survivals are promising and are better than expected following a single transplant. Whilst selection biases may in part contribute to this effect, a much larger phase II double transplant trial is warranted in preparation for a potential randomized comparison of standard therapy vs single vs double transplant.

Adult↗

A short course of induction chemotherapy followed by two cycles of high-dose chemotherapy with stem cell rescue for chemotherapy naive metastatic breast cancer: sequential phase I/II studies.

Two cycles of high-dose chemotherapy with stem cell support (HDC) may increase the total dose delivered and dose intensity. A brief induction phase and different non-cross-resistant agents for each HDC cycle were used to avoid drug resistance. Twenty-six women with metastatic BC had induction and stem cell mobilization with two cycles of doxorubicin/G-CSF given every 14 days. Patients with stable disease or better after induction received HD CTCb followed by HD melphalan and dose-escalated paclitaxel. At 475 mg/m(2) of paclitaxel by 24-h infusion, dose-limiting transient peripheral sensory neuropathy was encountered. No toxic deaths occurred. Complete and near complete response after completion of therapy was achieved in 22 (85%) of 26 patients. The median EFS was 38 months. The median OS has not yet been reached. At a median follow-up of 33 (25-43) months, actuarial EFS and OS were 54% (95% confidence interval (CI), 39-69%) and 69% (95% CI, 56-79%), respectively. This double transplant approach lasts only 14 weeks and is feasible, safe, and tolerable. Whilst selection biases may in part contribute to favorable EFS and OS, a randomized comparison of standard therapy vs double transplant in both metastatic and locally advanced breast cancer is warranted.

Adult↗

Working with victims of persecution: lessons from Holocaust survivors.

It is estimated that 25 to 30 million people are forced to leave their homes because of human rights violations or threats to their lives. Such massive dislocations at the international level result in significant numbers of diverse, persecuted populations seeking asylum in the United States. It is estimated that as many as 400,000 victims of torture now reside in the United States, with many survivors suffering in silence. The challenge for social workers is to discover this often hidden, vulnerable population and to serve them. Among all the populations experiencing the trauma and stress of persecution, most is know about Holocaust survivors. Through examining the long-term effects of massive psychic trauma gleaned from research on Holocaust survivors and their children, this article addresses the skills, techniques, and insights about current refugee populations that can be incorporated into social work practice and training.

Adaptation, Psychological↗

Obesity and medical illnesses in psychiatric patients admitted to a long-term psychiatric facility.

Obesity and associated medical conditions may have an impact on morbidity and even mortality in patients with psychiatric disorders. The authors present the results of a survey of the prevalence of obesity and selected medical conditions among 420 consecutively admitted psychiatric inpatients at a long-stay facility and compare these data with those reported in the literature. Female psychiatric subjects had considerably higher rates of being either overweight or obese (69%) as compared to women in the general U.S. population (51%). Male psychiatric subjects did not differ significantly from their counterparts in the general population in being overweight or obese (nearly 55%). The majority of psychiatric subjects with essential hypertension, diabetes mellitus, dyslipidemias, cardiovascular disease, or sleep apnea were either overweight or obese (72%-87%). In this cross-sectional study, no associations could be deduced between psychotropic drug classes and specific medical conditions. No specific psychiatric diagnostic category was associated with a significantly greater prevalence of any specific medical condition, except that subjects with schizoaffective disorder appeared to have a higher prevalence of type II diabetes mellitus (11.6%). Subjects with predominant substance or alcohol abuse or dependence disorders had a lower prevalence of obesity and associated medical conditions.Obesity-either independently or additively along with a sedentary lifestyle, unhealthy dietary habits, and nicotine dependence-may have a serious impact on coexisting medical comorbidity in psychiatric patients. Judicious monitoring for obesity and rapid pharmacological and nonpharmacological intervention, where appropriate, by concerned clinicians may improve several coexisting medical conditions in psychiatric patients and thereby improve patients' overall quality of life.

Journal Article↗

The association of the dopamine D4 receptor gene (DRD4) and the serotonin transporter promoter gene (5-HTTLPR) with temperament in 12-month-old infants.

This study examined the association between two common polymorphisms, the dopamine D4 receptor (DRD4) gene and the serotonin transporter promoter (5-HTTLPR) gene and temperament in 61 infants aged 12 months. Twenty-two infants had a least one copy of the 6-8 repeat DRD4 alleles (L-DRD4) and 39 had two copies of the 2-5 repeat allele (S-DRD4). Twenty infants were homozygous for the short form (s/s) of 5-HTTLPR while 41 were either heterozygous for the short and the long form (l/s) or were homozygous for the long form (l/l). The infants were observed in a series of standard temperament episodes that elicited fear, anger, pleasure, interest, and activity. L-DRD4 infants showed less interest in a structured block play situation and more activity in a free play situation. They also displayed less anger in an episode of mild physical restraint. Infants with s/s 5-HTTLPR showed less fearful distress to stranger approach and less pleasure in a structured play situation than infants with l/l or l/s 5-HTTLPR. Duration of looking during block play was affected by a significant interaction between DRD4 and 5-HTTLPR. Shortest duration of looking was associated with the L-DRD4 and s/s 5-HTTLPR genotypes. The implications and limitations of these findings are discussed.

Anger↗

The IBD1 locus for susceptibility to Crohn's disease has a greater impact in Ashkenazi Jews with early onset disease.

OBJECTIVE: Recent studies have suggested that a susceptibility gene located on chromosome 16 and designated IBD1 may contribute to the development of Crohn's disease (CD). However, these findings were observed in predominantly non-Jewish populations; in the three studies where Ashkenazi Jews were included for analysis, the results have been widely divergent. Because Ashkenazi Jews are known to have a higher incidence of the disease than non-Jews, we sought to determine whether this previously reported linkage could be extended to the Ashkenazi population. In addition, we examined whether Ashkenazi Jewish patients with an early age of onset (< or = 21 yr) showed greater evidence of linkage to this locus. METHODS: Linkage analysis for the IBD1 region was performed on 123 Ashkenazi Jewish CD patients distributed among 53 families. Only patients with four Jewish grandparents were considered to be Jewish. Of the 123 Ashkenazi Jewish patients, 75 (61%) had an age of onset < or = 21 yr. RESULTS: Ashkenazi Jews showed only modest evidence of linkage (nonparametric linkage 1.63, p = 0.05) to the IBD1 locus. However, when the Ashkenazi population was subdivided on the basis of age of onset, there was a striking increase in linkage in families where affected individuals had an age of onset < or = 21 yr (nonparametric linkage 3.02, p = 0.002). In contrast, there was no evidence of linkage in the Jewish families where all affected individuals had an age of onset > 21 yr. CONCLUSIONS: The IBD1 gene plays a greater role in conferring susceptibility to CD in Jews with early onset disease than in Jews with late onset disease.

Adult↗

T(3) increases mitochondrial ATP production in oxidative muscle despite increased expression of UCP2 and -3.

Triiodothyronine (T(3)) increases O(2) and nutrient flux through mitochondria (Mito) of many tissues, but it is unclear whether ATP synthesis is increased, particularly in different types of skeletal muscle, because variable changes in uncoupling proteins (UCP) and enzymes have been reported. Thus Mito ATP production was measured in oxidative and glycolytic muscles, as well as in liver and heart, in rats administered T(3) for 14 days. Relative to saline-treated controls, T(3) rats had 80, 168, and 62% higher ATP production in soleus muscle, liver, and heart, respectively, as well as higher activities of citrate synthase (CS; 63, 90, 25%) and cytochrome c oxidase (COX; 119, 225, 52%) in the same tissues (all P < 0.01). In plantaris muscle of T(3) rats, CS was only slightly higher (17%, P < 0.05) than in controls, and ATP production and COX were unaffected. mRNA levels of COX I and III were 33 and 47% higher in soleus of T(3) rats (P < 0.01), but there were no differences in plantaris. In contrast, UCP2 and -3 mRNAs were 2.5- to 14-fold higher, and protein levels were 3- to 10-fold higher in both plantaris and soleus of the T(3) group. We conclude that T(3) increases oxidative enzymes and Mito ATP production and Mito-encoded transcripts in oxidative but not glycolytic rodent tissues. Despite large increases in UCP expression, ATP production was enhanced in oxidative tissues and maintained in glycolytic muscle of hyperthyroid rats.

Adenosine Triphosphate↗

Measurement of the components of nonexercise activity thermogenesis.

Nonexercise activity thermogenesis (NEAT) accounts for the vast majority of nonresting metabolic rate and changes in NEAT-predicted susceptibility to fat gain with overfeeding. Measuring physical activity and its components in free-living humans has been a long-standing challenge. In this study, we combine information about lightweight sensors that capture data on body position and motion with laboratory measures of energy expenditure to calculate nonfidgeting NEAT. This measurement of nonfidgeting NEAT was compared with total NEAT measured in a room calorimeter in 11 healthy subjects. The measurement of nonfidgeting NEAT accounted for 85 +/- 9% of total NEAT measured in the room calorimeter. The intraclass correlation coefficient for the two methods was 0.86 (95% confidence interval 0.56, 0.96; P < 0.05). This suggests that 86% of the variance is attributable to between-subject variance and 14% to between-method disagreement. These instruments are applicable to free-living subjects; they are stand-alone, are lightweight, and allow normal daily activities. This novel technology has potential application for not only assessing NEAT but also tracking physical activity in free-living humans.

Adult↗

Adipose tissue metabolism in benign symmetric lipomatosis.

Type 2 benign symmetric lipomatosis (BSL) is characterized by abnormal growth of adipose tissue in the upper back, deltoid region, upper arms, hips, and upper thigh region. Studies of lipomatous tissue in vitro have suggested that defective lipolysis may account for excess fat accumulation; however, in vivo adipose tissue metabolism has not been evaluated. We measured systemic adipose tissue lipolysis and regional adipose tissue fatty acid uptake in a patient with type 2 BSL scheduled for elective brachioplasty. We found increased, rather than decreased, rates of systemic free fatty acid release coupled with normal fatty acid oxidation. The uptake of fatty acids was 19% greater in deltoid region lipomatous tissue than in abdominal sc fat, whereas in control studies the relative uptake of fatty acids in deltoid fat averaged 29% less than that in abdominal fat. Adipocyte size was smaller than expected in lipomatous tissue. These results suggest that type 2 BSL is a hyperplastic adipose tissue abnormality that does not impair systemic lipolysis. The pathophysiology appears similar to what has been termed hyperplastic obesity. A better understanding of this condition could lead to insights into the mechanisms of hyperplastic obesity.

Adipose Tissue↗

Inositol treatment has no effect on the dexamethasone suppression test.

The dexamethasone suppression test (DST) is a widely studied state marker for endogenous depression. Several drugs cause false positives or negatives in this test. Since inositol is a new treatment for depression it is important to determine if it causes artifacts in the DST. Five patients with major depression diagnosed according to DSM-IV underwent a dexamethasone suppression test before and after one and two weeks of 12 grams daily inositol treatment. Three normal subjects underwent the same procedure before and after one week of inositol treatment. Four depressed patients and all three normal subjects demonstrated pretreatment dexamethasone suppression of plasma cortisol. One or two weeks of inositol treatment had no effect on post-dexamethasone cortisol plasma levels in patients or subjects. One depressed patient was a non-suppressor before treatment and continued to show elevated post dexamethasone cortisol levels after one week of inositol treatment. However, after two weeks on inositol, when substantial clinical improvement was noted, he converted to a normal DST. Chronic inositol treatment does not seem to induce false positive DST results.

Adult↗

Bupropion sustained release as a smoking cessation treatment in remitted depressed patients maintained on treatment with selective serotonin reuptake inhibitor antidepressants.

BACKGROUND: Patients with depressive disorders smoke tobacco more often than the population at large and find quitting more difficult. Furthermore, when they quit smoking, they are more likely to suffer a relapse of depression. We evaluated the addition of bupropion sustained release (SR) for smoking cessation among patients with a history of depressive disorders being maintained in a euthymic state with selective serotonin reuptake inhibitor (SSRI) antidepressants. METHOD: Twenty-five adults with DSM-IV major depressive disorder or depressive disorder NOS currently receiving SSRI maintenance treatment and smoking > or = 15 cigarettes per day participated in the 9-week study. Bupropion SR, 150 mg/day, was added to SSRI treatment and increased to 300 mg/day. Subjects were counseled on smoking cessation measures and chose a target quit date 2 or 4 weeks after the initiation of bupropion SR. Self-reported smoking status, expired carbon monoxide (CO) measurements, Hamilton Rating Scales for Depression and Anxiety scores, and weight were measured at each visit. Subjects were abstinent if they reported not smoking during the prior 7 days, confirmed with an expired-air CO value of < or = 10 ppm. RESULTS: Eight (32%) of 25 subjects were abstinent after 9 weeks. At 3-month follow-up, 3 subjects remained abstinent, 3 relapsed, and 2 were lost to follow-up. Eleven subjects (44%) were nonresponders, and 6 (24%) dropped out prior to 3 weeks of treatment due to side effects (N = 3) or were lost to follow-up (N = 3). Mean weight gain was approximately 0.5 lb (0.2 kg) for those completing 9 weeks of bupropion SR treatment. During the 9-week study and the 3-month follow-up, there was no evidence of emergent depression in any subject. Four subjects (16%) spontaneously reported an improvement in SSRI-associated sexual dysfunction. CONCLUSION: These open data suggest modest effectiveness for and the safety of bupropion SR as a smoking cessation agent in individuals with depression maintained on treatment with SSRIs. Minimal weight gain, lack of emergent depressive episodes, and improvement of SSRI-associated sexual dysfunction are added advantages.

Adolescent↗

Rituximab and ifosfamide, mitoxantrone, etoposide (RIME) with Neupogen support for B-cell non-Hodgkin's lymphoma prior to high-dose chemotherapy with autologous haematopoietic transplant.

A phase I/II study was performed to analyse the ability of ifosfamide-based chemotherapy with rituximab to produce a turmour-free graft as well as the safety of retuximab prior to stem cell harvest and post high-dose chemotherapy. Twenty-two patients with B-cell non-Hodgkin's lymphoma were enrolled either having aggressive large-cell disease in relapse or at high/high-intermediate risk of relapse, or refractory lymphoma or mantle cell lymphoma, or indolent lymphoma. Chemotherapy consisted of ifosfamide 2 g/m2, days 1-3 with mesna, etoposide 100 mg/m2, days 1-3, and mitoxantrone 8 mg/m2 day 1, with figrastim. Rituximab was given at 375 mg/m2 for 4 doses. An encouraging overall response rate of 90%, including 11 CRs was achieved. CD34+ cells were successfully mobilized in 18 or 19 patients analysed so far with a median number of 3.4 x 10(6) cells/kg. The combination of ifosfamide-based chemotherapy with rituximab significantly reduced the number of contaminating B-cells in the stem cell product and so far there has only been a single relapse post high-dose chemotherapy with autologous haematopoietic transplant. The RIME regimen was generally well tolerated with minimal non-haematological toxicity and most of the treatment was done completely on an outpatient basis. Haematological toxicity was manageable with filgrastim, there were some infectious complications.

Adult↗

Effects of chronic lithium administration on rat brain phosphatidylinositol cycle constituents, membrane phospholipids and amino acids.

OBJECTIVE: There is evidence linking affective disorders and their treatment to alterations in membrane phospholipid metabolism, the phosphatidylinositol (PtdIns) second messenger cycle and brain excitatory and inhibitory amino acids. This study examines lithium effects on rat brain metabolites associated with the above systems and their reversal by myo-inositol. METHODS: Thirty rats were treated for 14 days with i.p. lithium, saline or lithium plus myo-inositol. 1H, 31P and 7Li NMR were used to measure brain metabolites. RESULTS: Lithium, administered alone or with myo-inositol, resulted in brain lithium concentrations of approximately 0.6 microM/gram brain tissue. Brain myo-inositol was unchanged when lithium was co-administered with myo-inositol. Lithium increased brain inositol-1-phosphate (I1P) by 98% compared with saline and this effect was not attenuated by the addition of myo-inositol. Lithium treatment decreased phosphatidylserine (PtdSer) and PtdIns by 3% and 8%, respectively. Lithium also decreased taurine levels by 8% and increased aspartate levels by 9%. The above effects of lithium on PtdSer, PtdIns and taurine were attenuated or abolished by the co-administration of myo-inositol. CONCLUSIONS: Lithium alters levels of key membrane phospholipids and appears to affect the balance between inhibitory and excitatory amino acids in rat brain. Co-administration of myo-inositol attenuates some of these lithium effects on brain metabolites.

Amino Acids↗

The evolving role of topiramate among other mood stabilizers in the management of bipolar disorder.

OBJECTIVES: Topiramate, a structurally novel anticonvulsant, is being evaluated for other neurological conditions such as migraine, neuropathic pain, and essential tremor, and also for psychiatric conditions such as bipolar disorder, bulimia, post-traumatic stress disorder, and schizoaffective disorder, in addition to obesity. This article will focus on the use of topiramate for bipolar disorder. METHODS: The pharmacological profile of topiramate is compared to other established and putative mood stabilizers, and a rationale for its use in bipolar disorder is presented. Data from open clinical trials of topiramate for depression, mania, and rapid-cycling bipolar disorder are summarized. Preliminary data from one pilot dose-finding, double-blind, random-assignment, placebo-controlled, 3-week parallel group study of two doses of topiramate for acute bipolar I mania is reported. Safety data regarding topiramate was reviewed. Finally, the potential place of this agent in bipolar illness is considered. RESULTS: The pharmacological advantages for topiramate are low protein binding, minimal hepatic metabolism and mainly unchanged renal excretion, a 24-h half-life, and minimal drug interactions. Open clinical studies suggest a 50-65% response for refractory bipolar mania, and a 40-56% response for refractory bipolar depression in mainly add-on treatment. Open clinical studies of topiramate for rapid-cycling subjects and those for comorbid bulimia, substance abuse, post-traumatic stress, migraine, and obesity report effectiveness. The primary efficacy endpoint data (change from baseline Y-MRS total scores) of the placebo-controlled, random assignment parallel group phase II dose-finding study were not statistically significant. However, once the antidepressant-associated manias (28 of the sample, of 97 subjects) were excluded from the controlled study, the post-hoc analyses indicated the higher dose (512 mg/day) topiramate treatment group showed a statistically significant reduction in endpoint Y-MRS change scores as compared to placebo (p < 0.03). Adverse effects of topiramate in bipolar subjects include attention, concentration and memory problems, fatigue, sedation, transient paraesthesias, nausea, and anorexia. Some subjects experience word-finding difficulty. Weight loss may be seen in several topiramate-treated subjects with bipolar disorder. CONCLUSIONS: Topiramate appears to show promise as an addition to the agents available to treat bipolar disorder. More definitive controlled data on the efficacy of topiramate in the acute and continuation phases as well as for the prophylaxis either as monotherapy or as combination treatment of bipolar disorder are ongoing, and the results are awaited.

Acetates↗

Anti-CD20 chimeric monoclonal antibody treatment of refractory immune-mediated thrombocytopenia in a patient with chronic graft-versus-host disease.

BACKGROUND: Autoimmune thrombocytopenia in chronic graft-versus-host disease may represent an instance of B-cell dysregulation leading to clinical disease. OBJECTIVE: To attempt to treat refractory immune-mediated thrombocytopenia in a patient with chronic graft-versus-host disease by using anti-CD20 chimeric monoclonal antibody. DESIGN: Case report. SETTING: Academic medical center. PATIENT: A patient with chronic graft-versus-host disease after allogeneic peripheral blood stem-cell transplantation who had severe refractory immune-mediated thrombocytopenia. INTERVENTION: Weekly infusion of rituximab, 375 mg/m2, for 4 weeks. MEASUREMENTS: Platelet count, CD3+ cell count, and CD19+ cell count. RESULTS: Rituximab therapy resulted in marked depletion of B cells in the peripheral blood and decreased levels of platelet-associated antibody. The increase in platelet count persisted despite tapering and discontinuation of immunosuppressive therapy for chronic graft-versus-host disease. CONCLUSION: The efficacy of rituximab for the treatment of immune-mediated thrombocytopenia suggests that this drug may have activity in other autoimmune diseases or chronic graft-versus-host disease.

Adult↗

Increased cerebrospinal fluid glutamine levels in depressed patients.

BACKGROUND: There is increasing evidence for an association between alterations of brain glutamatergic neurotransmission and the pathophysiology of affective disorders. METHODS: We studied the association between cerebrospinal fluid (CSF) metabolites, including glutamine, in unipolar and bipolar depressed patients versus control subjects using a proton magnetic resonance spectroscopy technique. Cerebrospinal fluid samples were obtained from 18 hospitalized patients with acute unmedicated severe depression without medical problems and compared with those of 22 control subjects. RESULTS: Compared with the control group, the depressed patient group had significantly higher CSF glutamine concentrations, which correlated positively with CSF magnesium levels. CONCLUSIONS: These findings suggest an abnormality of the brain glial-neuronal glutamine/glutamate cycle associated with N-methyl-D-aspartate receptor systems in patients with depression.

Adolescent↗