Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy.

OBJECTIVES: Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. METHODS: One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. RESULTS: There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. CONCLUSIONS: Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia.

Plasma biomarkers of decreased vesicular storage distinguish Parkinson disease with orthostatic hypotension from the parkinsonian form of multiple system atrophy.

BACKGROUND: Parkinson disease with orthostatic hypotension (PD + OH) and the parkinsonian form of multiple system atrophy (MSA-P) can be difficult to distinguish clinically. Recent studies indicate that PD entails a vesicular storage defect in catecholaminergic neurons. Although cardiac sympathetic neuroimaging by (18)F-dopamine positron emission tomography can identify decreased vesicular storage, this testing is not generally available. We assessed whether plasma biomarkers of a vesicular storage defect can separate PD + OH from MSA-P. METHODS: We conceptualized that after F-dopamine injection, augmented production of F-dihydroxyphenylacetic acid (F-DOPAC) indicates decreased vesicular storage, and we therefore predicted that arterial plasma F-DOPAC would be elevated in PD + OH but not in MSA-P. We measured arterial plasma F-DOPAC after (18)F-dopamine administration (infused i.v. over 3 min) in patients with PD + OH (N = 12) or MSA-P (N = 21) and in healthy control subjects (N = 26). Peak F-DOPAC:dihydroxyphenylglycol (DHPG) was also calculated to adjust for effects of denervation on F-DOPAC production. RESULTS: Plasma F-DOPAC accumulated rapidly after initiation of (18)F-dopamine infusion. Peak F-DOPAC (5-10 min) in PD + OH averaged three times that in MSA-P (P < 0.0001). Among MSA-P patients, none had peak F-DOPAC > 300 nCi-kg/cc-mCi, in contrast with 7 of 12 PD + OH patients (χ(2) = 16.6, P < 0.0001). DHPG was lower in PD + OH (3.83 ± 0.36 nmol/L) than in MSA-P (5.20 ± 0.29 nmol/L, P = 0.007). All MSA-P patients had peak F-DOPAC:DHPG < 60, in contrast with 9 of 12 PD + OH patients (χ(2) = 17.5, P < 0.0001). Adjustment of peak F-DOPAC for DHPG increased test sensitivity from 58 to 81% at similar high specificity. INTERPRETATION: After F-dopamine injection, plasma F-DOPAC and F-DOPAC:DHPG distinguish PD + OH from MSA-P.

Tityus zulianus venom induces massive catecholamine release from PC12 cells and in a mouse envenomation model.

Scorpion envenomation is a public health problem in Venezuela, mainly produced by Tityus discrepans (TD) and Tityus zulianus (TZ). Accidents by these two species differ clinically. Thus, TZ envenomation is associated with high mortality in children due to cardiopulmonary disorders, as a result of, excessive amounts of plasma catecholamines (Epinephrine) release from adrenal medulla, probably via the voltage-gated sodium-channel activated by specific scorpion toxins. This Epi release is, in part responsible, for some of the envenomation clinical consequences, resembling those described for patients presenting catecholamine-releasing tumors (pheochromocytoma). In this work, BALB/c mice and rat pheochromocytoma-derived PC12 cells were used to provide in vivo and in vitro models, respectively, on which the basis for the TZ-mediated catecholamine release mechanism could be elucidated. In mice, TZ venom increased, at 1h post-injection, the Epi plasma levels in 4000%, which remained elevated for 24h. A significant rise in plasma levels of the catecholamine catabolite 3-Methoxy-4-Hydroxy-Phenyl-Glycol (MHPG) was also observed. In [(3)H]dopamine-loaded PC12 cells, TZ venom potentiated the carbamylcholine (CC)-mediated release of [(3)H]dopamine, as shown by the leftward shift in the CC-dose-response curves. Moreover, TZ venom also displayed the maximal [(3)H]dopamine releasing activity compared to TD venom, with significant reduction of the EC50 for CC. The nicotinic-acetylcholine receptor (nAChR) blocker hexamethonium induced a significant inhibition of the [(3)H]dopamine release produced by CC in PC12 cells but the TZ-elicited release of [(3)H]dopamine was 70% hexamethonium-insensitive, suggesting unidentified TZ toxins affecting other regulatory mechanisms of catecholamine secretion.

Plasma levels of metabolites of catecholamine in nicotine-dependent patients treated with varenicline.

INTRODUCTION: Our hypothesis is that varenicline decreases the plasma levels of catecholamine metabolites; such a decrease is associated with the main mechanisms of smoking cessation and leads to a depressive state. To confirm the hypothesis, we investigated the association of plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with nicotine dependence in comparison with nonsmokers. METHODS: To confirm the hypothesis, we investigated the association of plasma HVA and MHPG levels in patients with nicotine dependence in comparison with nonsmokers. In addition, we also examined the plasma HVA and MHPG levels before (T0) and 8 weeks after the varenicline treatment (T8). RESULTS: Seventeen of 20 smokers (85.0%) stopped smoking during the 12 weeks of treatment. Plasma HVA levels and MHPG levels in the patients at T0 (HVA 5.1 ± 2.1 ng/ml, MHPG 2.2 ± 0.6 ng/ml) were significantly higher than those of the control group (HVA 3.0 ± 1.0 ng/ml, MHPG 1.6 ± 1.4 ng/ml; HVA p = .0012, MHPG p = .0069). In this study, the plasma HVA and MHPG levels were not changed after treatment with varenicline, although the smokers had already quit. CONCLUSIONS: These results suggest that varenicline sustains higher catecholamine levels. The findings that the treatment with varenicline did not decrease the plasma levels of catecholamine metabolites can explain why none of the smokers had become depressed after the varenicline treatment.

Co-involvement of psychological and neurological abnormalities in infertility with polycystic ovarian syndrome.

OBJECTIVE: To investigate psychological distress, serum levels of monoamine neurotransmitters and their metabolites, as well as their correlation with polycystic ovarian syndrome (PCOS). METHODS: Thirty infertility patients with PCOS were assigned as the experimental group and 30 infertility patients without PCOS were assigned as the control group. Psychological distress was self-evaluated in all patients with Symptom Checklist 90 (SCL-90). Serum concentrations of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA) and its metabolites homovanillic acid (HVA) and dihydroxy-phenyl acetic acid (DOPAC) were measured by high-performance liquid chromatography. RESULTS: The anxious and depressive subscales of SCL-90 were significantly higher in infertility patients with PCOS than those without PCOS (p < 0.05). The serum concentrations of 5-HT, 5-HIAA and HVA were significantly lower in infertility patients with PCOS than those without PCOS (p < 0.05). Importantly, the phobia subscale scores of SCL-90 positively correlated with serum MHPG level (p < 0.05), while the hostility subscale's scores negatively correlated with serum DOPAC level (p < 0.05). CONCLUSION: Psychological and neurological factors play a crucial role in PCOS.

Abrupt termination of an ethanol regimen provokes ventricular arrhythmia and enhances susceptibility to the arrhythmogenic effects of epinephrine in rats.

BACKGROUND: Pathologists examining victims of sudden unexpected death encounter alcoholics more often than expected; alcohol may play a role in sudden arrhythmic death. Here we determine whether a pattern of alcohol consumption, chronic ethanol intake, and withdrawal increases the incidence of malignant ventricular arrhythmia and modulates susceptibility to the arrhythmogenic potential of sympathetic stimulation from an epinephrine test in rats. METHODS: Male Wistar rats were treated with a continuous ethanol liquid diet for 7 weeks, and then subjected to 1-day withdrawal or 21-day abstinence. Ventricular ectopy was evaluated by 24-hour electrocardiographic telemetry recording; whole-body sympathetic activation, cardiac sympathovagal balance, and susceptibility to ventricular arrhythmia induced by sympathetic stimulation were evaluated based on blood noradrenalin metabolite concentrations, heart rate variability, and a 3-step epinephrine test. RESULTS: Ventricular arrhythmia and related death were observed only in rats at 1 day of withdrawal, but not in nonalcoholic, continuous ethanol intake or 21-day abstinence rats. One-day withdrawal after a 7-week continuous ethanol regimen elevated circulating noradrenalin metabolite levels and induced cardiac sympathovagal imbalance. Deaths related to the epinephrine test and ventricular arrhythmia induced by low doses of epinephrine were observed only in 1-day withdrawal rats. However, all anomalies were normalized by 21-day abstinence. CONCLUSIONS: Abrupt termination of a 7-week continuous ethanol regimen is sufficient to enhance the whole-body sympathetic activation and cardiac sympathovagal imbalance that contribute to ventricular arrhythmia and sudden death in alcoholic rats. Those providing medical care for alcoholics, including in cases of legal imprisonment, should be aware of the possibility of enhanced susceptibility to sudden arrhythmic death due to the abrupt termination of a chronic ethanol regimen.

Reduced monoamine oxidase A activity in pregnant smokers and in their newborns.

BACKGROUND: Tobacco smoking is associated with reduced monoamine oxidase A (MAOA) activity. Smoking-associated low MAOA activities in pregnancy and in newborns may have negative perinatal and postnatal consequences. We aimed to compare, in everyday clinical conditions, biomarkers of MAOA activity in smoking (SPW) and lifetime nonsmoking pregnant women (NSPW) and in cord blood and to assess the newborns' behavior during the first 48 hours of life. METHODS: Thirty SPW and 29 NSPW in their second trimester of pregnancy were included. Plasma MAOA dependent metabolites of norepinephrine: dihydroxyphenylglycol; dopamine: homovanillic and dihydroxyphenylacetic acid; and serotonin: 5-hydroxy-indol acetic acid were measured at the end of the second trimester, at delivery, and in arterial cord blood along with plasma cotinine. The newborns' discomfort was evaluated every 8 hours by a standardized questionnaire. RESULTS: The SPW smoked, on average, 73 cigarettes per week at the end of second trimester and 80 cigarettes per week at delivery. Mean plasma cotinine was 84 ng/mL, 105 ng/mL, and 95 ng/mL at the end of second trimester, at delivery, and in cord blood, respectively (NSPW < 10 ng/mL). Plasma markers of MAOA activity, in particular those reflecting dopamine's catabolism, were significantly lower in SPW and in the arterial cord blood of their newborns than in NSPW and their newborns. Newborns of SPW showed significantly more facial discomfort than those of NSPW. CONCLUSIONS: Smoking is associated with MAOA inhibition in pregnant women and in their newborns at birth. Further studies are needed to estimate the behavioral significance of these findings.

Neonatal diagnosis and treatment of Menkes disease.

BACKGROUND: Menkes disease is a fatal neurodegenerative disorder of infancy caused by diverse mutations in a copper-transport gene, ATP7A. Early treatment with copper injections may prevent death and illness, but presymptomatic detection is hindered by the inadequate sensitivity and specificity of diagnostic tests. Exploiting the deficiency of a copper enzyme, dopamine-beta-hydroxylase, we prospectively evaluated the diagnostic usefulness of plasma neurochemical levels, assessed the clinical effect of early detection, and investigated the molecular bases for treatment outcomes. METHODS: Between May 1997 and July 2005, we measured plasma dopamine, norepinephrine, dihydroxyphenylacetic acid, and dihydroxyphenylglycol in 81 infants at risk. In 12 newborns who met the eligibility criteria and began copper-replacement therapy within 22 days after birth, we tracked survival and neurodevelopment longitudinally for 1.5 to 8 years. We characterized ATP7A mutations using yeast complementation, reverse-transcriptase-polymerase-chain-reaction analysis, and immunohistochemical analysis. RESULTS: Of 81 infants at risk, 46 had abnormal neurochemical findings indicating low dopamine-beta-hydroxylase activity. On the basis of longitudinal follow-up, patients were classified as affected or unaffected by Menkes disease, and the neurochemical profiles were shown to have high sensitivity and specificity for detecting disease. Among 12 newborns with positive screening tests who were treated early with copper, survival at a median follow-up of 4.6 years was 92%, as compared with 13% at a median follow-up of 1.8 years for a historical control group of 15 late-diagnosis and late-treatment patients. Two of the 12 patients had normal neurodevelopment and brain myelination; 1 of these patients had a mutation that complemented a Saccharomyces cerevisiae copper-transport mutation, indicating partial ATPase activity, and the other had a mutation that allowed some correct ATP7A splicing. CONCLUSIONS: Neonatal diagnosis of Menkes disease by plasma neurochemical measurements and early treatment with copper may improve clinical outcomes. Affected newborns who have mutations that do not completely abrogate ATP7A function may be especially responsive to early copper treatment. (ClinicalTrials.gov number, NCT00001262.)

Stress at work alters serum brain-derived neurotrophic factor (BDNF) levels and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in healthy volunteers: BDNF and MHPG as possible biological markers of mental stress?

There is growing evidence that blood levels of brain-derived neurotrophic factor (BDNF) and catecholamine, and cytokines are related to not only to depressive, suicidal, and anxious states but also to depression-associated personality traits. Psychological job stress is well known to lead to symptoms of depression and anxiety. In the present study, we examined effects of psychological job stress on serum levels of BDNF and plasma levels of catecholamine metabolites, and cytokines in healthy volunteers (n=106, male/female=42/64, age=36+/-12 yr) working in a hospital setting. The values (mean+/-SD) of scores for stress items in the Stress and Arousal Check List (s-SACL), plasma MHPG levels, and, serum BDNF levels in all participants were 7.2+/-3.3, 5.2+/-3.4 ng/mL, and 23.3+/-14.7 ng/mL, respectively. A negative correlation was found between scores for s-SACL and serum BDNF levels (rho=-0.211, p=0.022). A positive correlation was also found between scores on the s-SACL and plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) (rho=0.416, p=0.01), but not homovanillic acid (HVA). No relationship was found between s-SACL scores and plasma levels of interleukin-6 (IL-6) or tumor necrosis factor alpha (TNFalpha). These results suggest that serum BDNF levels and plasma MHPG levels might be biological markers reflective of psychological job stress in hospital employees.

Effects of acute paroxetine treatment on the consumption of cigarette smoking and caffeine in depressed patients.

In the present study, we examined the effects of acute treatment with paroxetine on the consumption of cigarette smoking and caffeine in 65 patients who met the DSM-IV criteria for major depressive disorder (M/F: 28/37, age: 48 +/- 15 years). Plasma levels of cotinine or caffeine were analysed using high-performance liquid chromatography (HPLC). The amount of cigarette smoking and plasma levels of cotinine, but not caffeine, decreased 4 weeks after paroxetine treatment. There was no difference between smokers and nonsmokers with respect to their response to paroxetine treatment. In addition, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in responders to paroxetine treatment was higher than those in nonresponders, and there was a negative correlation between the changes in plasma MHPG levels and the changes in Hamilton rating scale for depression (Ham-D) scores before and 4 weeks after paroxetine administration. These results suggest that paroxetine has the potential to reduce the amount of cigarette smoking in depressed smokers, and we reconfirmed our previous results that depressed patients with higher plasma MHPG levels had better response to paroxetine treatment than those with lower plasma MHPG levels using larger depressed samples.

Effects of olanzapine on plasma levels of catecholamine metabolites, cytokines, and brain-derived neurotrophic factor in schizophrenic patients.

In the present study, we examined the effects of olanzapine on plasma levels of catecholamine metabolites, brain-derived neurotrophic factor, and cytokines (interleukin-2, interleukin-6 and tumor necrosis factor-alpha) using 32 olanzapine-treated schizophrenic patients and age and sex-matched 55 healthy individuals. Treatment with olanzapine for 8 weeks improved both positive and negative symptoms of schizophrenia. It also increased the plasma 3-methoxy-4-hydroxyphenylglycol levels, which were associated with the changes in the total scores of negative symptoms measured on the Positive and Negative Symptom Scale, and decreased the plasma homovanillic acid levels. In addition, treatment with olanzapine for 8 weeks reduced the plasma interleukin-2 levels. In contrast, olanzapine did not alter the plasma levels of brain-derived neurotrophic factor, interleukin-6, or tumor necrosis factor-alpha. These results suggest that olanzapine influences the dynamics of catecholamine and interleukin-2, which might be associated with its clinical efficacy.

Prediction of response to risperidone treatment with respect to plasma concencentrations of risperidone, catecholamine metabolites, and polymorphism of cytochrome P450 2D6.

In the present study, we examined the relationships between plasma concentrations of risperidone and clinical responses, extrapyramidal symptoms, plasma levels of cotinine and caffeine, or cytochrome (cyp)2D6 genotypes. In addition, we also investigated the relationships between plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) or homovanillic (HVA) acid and clinical responses to risperidone. One hundred and 36 patients (male/female: 58/78, age 37+/-13 years) who met DSM-IV criteria for schizophrenia, schizoaffective disorder, delusional disorder and brief psychotic disorder, and who were being treated with risperidone alone, were evaluated regarding their clinical improvement and extrapyramidal symptoms using the Positive and Negative Syndrome Scale (PANSS) and Simpson and Angus (SAS), respectively, and plasma levels of cotinine, caffeine, MHPG and HVA were analysed by high-performance liquid chromatography. The cyp2D6*5 and *10 alleles were identified using the polymerase chain reaction. There was a positive correlation between plasma levels of risperidone plus 9-hydroxyrisperidone (active moiety) and SAS scores, but not the PANSS. Pretreatment HVA levels in responders were higher than those in nonresponders. In addition, there was a negative correlation between changes in HVA levels and improvement in PANSS scores. There was no association between plasma levels of risperidone and plasma levels of cotinine or caffeine. Furthermore, there were no differences in the risperidone/9-hydroxyrisperidone ratio, clinical improvements and extrapyramidal symptoms among cyp2D6 genotypes. These results indicate that pretreatment HVA levels and plasma concentrations of active moiety might play a part in predicting the clinical response and occurrence of extrapyramidal symptoms, respectively, when treating patients with risperidone.

Estrogen raises the sweating threshold in postmenopausal women with hot flashes.

OBJECTIVE: To determine if estrogen ameliorates hot flashes by raising the core body temperature sweating threshold, by reducing core body temperature fluctuations, and/or by reducing sympathetic activation (as measured by plasma 3-methoxy-4-hydroxyphenylglycol). DESIGN: Laboratory physiological study. SETTING: University medical center. PATIENT(S): Twenty-four healthy postmenopausal women reporting frequent hot flashes. INTERVENTION(S): Participants were randomly assigned, in double-blind fashion, to receive 1 mg/d 17beta-estradiol orally or placebo for 90 days. MAIN OUTCOME MEASURE(S): Core body temperature, core body temperature fluctuations, mean skin temperature, sternal sweat rate, laboratory hot flash counts (sternal skin conductance), plasma 3-methoxy-4-hydroxyphenylglycol. RESULT(S): The E(2) group had significant increases in plasma E(2) (8 +/- 2 vs. 132 +/- 22 pg/mL) and core body temperature sweating threshold (37.98 +/- 0.09 vs. 38.14 +/- 0.09 degrees C) and decreases in plasma FSH (58.8 +/- 8.9 vs. 40.1 +/- 7.6 mIU/mL) and hot flashes (1.4 +/- 0.5 vs. 0.6 +/- 0.6). These changes did not occur in the placebo group. There were no significant changes in any other measure. CONCLUSION(S): E(2) ameliorates hot flashes by raising the core body temperature sweating threshold, but does not affect core temperature fluctuations or plasma 3-methoxy-4-hydroxyphenylglycol.

Association of plasma free-3-methoxy-4-hydroxyphenyl (ethylene)glycol, natural killer cell activity and delirium in postoperative patients.

We measured and compared levels of plasma free 3-methoxy-4-hydroxyphenyl (ethylene)glycol (pMHPG), a major metabolite of noradrenaline, and natural killer (NK) cell activity in 26 patients prior to their undergoing an operation for cardiovascular diseases; 11 of whom expressed delirium and 15 who did not. In conclusion, we found that pMHPG levels before an operation were higher in patients with postoperative delirium than in the patients without, while NK cell activity showed no difference between the two groups. It is possible that hyperactivity of noradrenargic neurons is connected with the development of postoperative delirium. Furthermore, we considered that measurement of pMHPG level before operation might be a useful tool to predict the occurrence of postoperative delirium.

Endocrine and immunologic parameters indicative of 6-month prognosis after the onset of low back pain or neck/shoulder pain.

STUDY DESIGN: Prospective study. OBJECTIVES: To evaluate the prognosis of spine disease by investigating biologic parameters reflecting different physiologic or psychophysiological systems in men and women with acute onset of low back or neck/shoulder complaints. SUMMARY OF BACKGROUND DATA: Psychosocial factors may be of importance to the etiology and prognosis of musculoskeletal disorders. The possible mechanisms, however, remain unclear. Stress-induced long-lasting energy mobilization resulting in inhibited anabolism has been discussed. Using a theoretical framework within stress physiology, such psychophysiological processes were recorded by measures of substances representing the anabolic, catabolic, immunologic, and opioid systems. METHODS: The study comprised 67 working men and women 21 to 59 years of age seeking care by any caregiver for acute low back and/or neck/shoulder pain. Blood samples were taken and analyzed for 3 methyl 5hydroxy phenylethylene glycol (MHPG, reflecting sympathoadrenomedullary activity), DHEA-s (anabolism), immunoglobulin E, interleukin 6 (immune activity), and beta-endorphin (pain regulation). The participants were followed up for 6 months after the blood samples had been drawn. RESULTS: In women, low MHPG, low DHEA-s, and low beta-endorphin predicted persistent disability due to low back complaints. Few significant findings were made for self-reported pain, for neck/shoulder complaints, and for men. CONCLUSION: Disturbances of the regulation of certain biologic parameters might be indicators of a prolonged course of low back disease in women. Prospective studies are necessary to enable causal conclusions.

Antenatal and early postnatal dexamethasone treatment decreases cortisol secretion in preterm infants.

Glucocorticoids are used antenatally to accelerate the maturation of fetal respiratory and cardiovascular systems when a threat of preterm delivery exists. Postnatally, they are used to prevent and treat respiratory distress syndrome. This study investigates the effects of antenatal (ACT) and early postnatal corticosteroid treatment (PCT) on serum cortisol and plasma catecholamine and adenosine 3',5'-cyclic monophosphate (cAMP) concentrations in preterm neonates. The infants in the ACT group had a significantly lower cortisol concentration than the infants in the non-ACT group on the first day of life. After birth, the infants were further divided into non-PCT and PCT groups. PCT suppressed cortisol levels significantly after 2 days, and the cortisol levels were still lower 2 days after discontinuation of PCT. No effect of PCT on plasma cAMP or catecholamine concentrations was observed. The results indicate that both ACT and a short PCT can significantly suppress basal cortisol levels in preterm infants.

Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels.

BACKGROUND: Many complaints of Gulf War veterans are compatible with a neurologic illness involving the basal ganglia. METHODS: In 12 veterans with Haley Gulf War syndrome 2 and in 15 healthy control veterans of similar age, sex, and educational level, we assessed functioning neuronal mass in both basal ganglia by measuring the ratio of N-acetyl-aspartate to creatine with proton magnetic resonance spectroscopy. Central dopamine activity was assessed by measuring the ratio of plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenlyglycol (MHPG). RESULTS: The logarithm of the age-standardized HVA/MHPG ratio was inversely associated with functioning neuronal mass in the left basal ganglia (R(2) = 0.56; F(1,27) = 33.82; P<.001) but not with that in the right (R(2) = 0. 04; F(1,26) = 1.09; P =.30). Controlling for age, renal clearances of creatinine and weak organic anions, handedness, and smoking did not substantially alter the associations. CONCLUSIONS: The reduction in functioning neuronal mass in the left basal ganglia of these veterans with Gulf War syndrome seems to have altered central dopamine production in a lateralized pattern. This finding supports the theory that Gulf War syndrome is a neurologic illness, in part related to injury to dopaminergic neurons in the basal ganglia.

Bupropion slow-release response in depression: diagnosis and biochemistry.

BACKGROUND: Bupropion has been previously shown to be particularly beneficial in bipolar and atypical depression. Previous research has supported a possible association of response to plasma levels and to changes in plasma homovanillic acid (HVA). These findings were here extended to bupropion slow-release (SR), a formulation with slower release kinetics. METHODS: Forty-one patients with major depressive disorder (DSM-III-R) completed 8 weeks of a fixed dose of 300 mg/day in two doses/day. Clinical outcome measures were the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). Biological parameters included plasma HVA and 3-methoxy-4-hydroxyphenyl-glycol (MHPG), as well as a final measurement of plasma bupropion and its metabolites. RESULTS: Response to bupropion SR differed among the three groups: results for change in HDRS and in BDI were greater in the bipolar and atypical than in the "typical" depressed patients. Mean change in HDRS was, respectively, of 15.6, 17.1, and 7.6 (F = 5.57, p < .01); mean change in the BDI, 21.1, 16.9, and 7.3 (F = 3.32, p < .05). Threobupropion levels correlated with HDRS scores (r = .47, p = .02, n = 23); plasma HVA and MHPG increased significantly (t = 2.31, p = .03; t = 2.15, p = .04, n = 17). Bipolar depressed patients' improvement in HDRS was related to increases in MHPG (r = .87, p = .01) and in HVA (r = .70, p = .08). CONCLUSIONS: This fixed-dose study indicates that there may be specific benefits for bupropion SR in atypical and bipolar depression, and that these benefits may be related also to plasma levels and biochemical changes in catecholamines. Due to the small sample size, replication is of key importance.

What determines primary breast cancer patients' hope to recover.

The main purpose was to offer evidence for the hypothesis that the stronger an acute real life stressor, namely, hearing from the physician that one has breast cancer and that one has to undergo mastectomy, the greater the induced noradrenaline (NA) depletion in the central nervous system (CNS) and the more the patient loses hope to recover. The data were derived from answers to interviews, questionnaires, and analyses of blood samples obtained from the patients on the day of admission to the hospital for a biopsy and 24 hours after the surgeon communicated the results of the biopsy to the patients. Analysis showed that a decline in 3-Methoxy 4-Hydroxy Methoxy 4-Hydroxy Phenylethylene Glycol (MHPG) concentration in blood plasma samples after being informed of the diagnosis is associated with less hope of recovery. MHPG is the main metabolite of CNS noradrenaline.

Antenatal dexamethasone treatment decreases plasma catecholamine levels in preterm infants.

Antenatal corticosteroid therapy (ACT) has many beneficial effects on preterm infants. The cellular mechanisms of action of ACT include beta-adrenergic receptor-mediated cAMP generation. This study investigated the effects of ACT on sympathoadrenal mechanisms during immediate postnatal adaptation of preterm infants. Plasma epinephrine, norepinephrine, 3,4-dihydroxyphenylglycol, and cAMP were measured within 12 h after birth in 103 preterm infants (gestational age 24-36 wk), who were divided into two groups (non-ACT and ACT group) according to whether the mother had received dexamethasone treatment. Infants in the ACT group had significantly lower concentrations of plasma catecholamines than infants in the non-ACT group; plasma epinephrine was 38% lower, and plasma norepinephrine was 20-40% lower in the ACT group, depending on gestational age (r = -0.37 in the non-ACT group and r = -0.28 in the ACT group, p < 0.05). Plasma cAMP concentrations were similar in the two groups. Antihypertensive treatment of the mother was associated with low plasma cAMP (p < 0.001), whereas tocolytic treatment was associated with high plasma cAMP (p = 0.001) of the infant. The results indicate that ACT attenuates the birth-related increase in plasma catecholamines. Still, plasma cAMP levels remain high, which suggests enhanced beta-adrenoceptor signaling after ACT.