BACKGROUND:Despite massive research on weight gain and metabolic complications in schizophrenia there are few studies on energy expenditure and no current data on physical capacity.AIM:To determine oxygen uptake capacity, respiratory quotient (RQ) and energy expenditure during a submaximal exercise test in patients with schizophrenia and healthy controls.METHOD:Ten male patients and 10 controls were included. RQ and energy expenditure were investigated with indirect calorimetry during a cycle ergometer test. The submaximal work level was defined by heart rate and perceived exhaustion. Physical capacity was determined from predicted maximal oxygen uptake capacity (VO(2-max)).RESULTS:The patients exhibited significantly higher RQ on submaximal workloads and lower physical capacity. A significant lower calculated VO(2-max) remained after correction for body weight and fat free mass (FFM). Energy expenditure did not differ on fixed workloads.CONCLUSION:RQ was rapidly increasing in the patients during exercise indicating a faster transition to carbohydrate oxidation and anaerobic metabolism that also implies a performance closer to maximal oxygen uptake even at submaximal loads. This may restrict the capacity for everyday activity and exercise and thus contribute to the risk for weight gain. Physical capacity was consequently significantly lower in the patients.

Aberrant tyrosine transport is a repeated finding in fibroblasts from schizophrenic patients. The transport aberration could lead to disturbances in the dopaminergic and noradrenergic neurotransmitter systems. Tyrosine and tryptophan are the precursors of the neurotransmitters dopamine and serotonin. Disturbed dopaminergic, noradrenergic and serotoninergic systems are implicated as causes of bipolar disorder. Hence, the aim of this study was to explore whether patients with bipolar disorder have an aberrant transport of tyrosine and/or tryptophan. Fibroblast cell lines from patients with bipolar type-1 disorder (n = 10) and healthy controls (n = 10) were included in this study. All patients fulfilled the DSM-IV diagnostic criteria. The transport of amino acids across the cell membranes was measured by the cluster tray method. The kinetic parameters, maximal transport velocity (Vmax) and affinity constant (Km) were determined. A significantly lower Vmax for tyrosine (p = 0.027) was found in patients with bipolar type-1 disorder in comparison to healthy controls. No significant differences in Km for tyrosine and in the kinetic parameters of tryptophan between patients with bipolar type-1 disorder and healthy controls were observed. The decreased tyrosine transport (low Vmax) found in this study may indicate less access of dopamine in the brain, resulting in disturbed dopaminergic and/or noradrenergic neurotransmission, that secondarily could lead to disturbances in other central neurotransmitter systems, such as the serotoninergic system. However, as sample size was small in this study and an age difference between patients and controls existed, the present findings should be considered as pilot data. Further studies with larger sample number are needed to elucidate the transport aberration and the significance of these findings.

Tyrosine transport through LAT1 transport system in fibroblasts of schizophrenic patients and healthy controls

Schizophrenia is a complex disorder and the view that schizophrenia is caused by hyperdopaminergic activity is an oversimplification. In fact, there are clinical evidence in accordance with a hypod ...

Patients with schizophrenia have in different studies shown reduced niacin sensitivity and lower electrodermal activity (EDA) after auditory stimulation. Peripheral mediation of prostaglandins may have a physiological role in both responses. This motivates study of both niacin response and electrodermal responding in the same patients with schizophrenia. Thirty patients with schizophrenia and 17 controls were investigated with EDA and thereafter given 200mg niacin orally with continuous assessment of skin temperature. The patients showed a delayed temperature increase after niacin ingestion (P=0.002) and a higher frequency of electrodermal non-responding (P<0.05). Response/non-response for niacin correlated with EDA response/non-response in the patient group (P=0.009). The niacin test revealed a slower vasodilation reaction in the patients. The association between response patterns for the niacin test and EDA suggests that a common aberration in skin physiology may be of importance for both reactions in schizophrenia.

OBJECTIVE:A lowered energy metabolism in schizophrenia was reported already in the 1920s. However, these early investigations were case studies without control groups or statistical analysis. In this study the resting energy expenditure (REE) and relevant body composition variables were measured in patients with schizophrenia and healthy controls.METHOD:REE was determined in 30 patients and 17 controls. The difference between the measured and the expected level for each individual was calculated as DeltaREE. Body composition was assessed with bioelectrical impedance and calliper measurements.RESULTS:DeltaREE was significantly lower in the patients than in the controls. A decrease was also seen in the non-medicated patients. The patients showed significantly lower percentages of water in fat free-mass and intracellular water.CONCLUSION:The lowering of REE and body water fractions may suggest a homeostatic aberration in schizophrenia that may be of importance for the understanding of metabolic disturbances observed in the disease.

The plasma concentrations of the MAO-inhibitor moclobemide (Ro 11-1163) were determined in six healthy male subjects after oral (tablets) administration. Effects on MAO activity in platelets and excretion of monoamine metabolites in urine were investigated. The design of the study was a double-blind cross-over study with single oral doses of placebo, 50, 100 and 200 mg of moclobemide. The elimination profile of the drug showed that the half life of the unchanged drug ranged between 1 and 2 h except in one subject with a half-life of about 4 h. The mean bioavailability calculated using flow model concepts was F=0.43 after 50 mg, F=0.47 after 100 mg and F=0.59 after 200 mg. The outlier with a t1/2 of 4 h was found to have a bioavailability of more than 0.80 after all 3 doses. The slightly increasing bioavailability with higher doses was interpreted as evidence of saturable hepatic first-pass elimination of the drug. MAO activity in platelets was measured before and 2, 6 and 24 h after drug administration. No inhibition of platelet MAO was obtained at any point in time or dose level, as to be expected since moclobemide preferentially inhibits MAO A. Urine excretion of the monoamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxy-phenylglycol (MOPEG) and 5-hydroxyindoleacetic acid (5-HIAA) was followed during 48 h after placebo, 50 and 200 mg of moclobemide. Time but not dose contributed significantly to the variability in excretion of the monoamine metabolites. An apparent reduction of HVA and DOPAC levels was obtained in the early phase after the administration of 200 mg of moclobemide. In 1 subject with a mild drug reaction a pronounced decrease in the levels of all the metabolites was obtained. In the other 5 subjects, the compound was very well tolerated with a few reported side-effects like increased activity, somnolence or sweatings. There was a slight but significant increase in blood pressure following 50 and 100 mg but not 200 mg of moclobemide.

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The monoamines have been extensively studied in relation to the mechanism of action of antipsychotics and the pathophysiology of schizophrenia. Dopamine was first thought to play only a precursor role in norepinephrine synthesis, but was later suggested to have an independent function in the brain when it was discovered that the distribution of norepinephrine and dopamine differed (Bertler and Rosengren 1959; Ehringer and Hornykiewicz 1960). In 1963, Carlsson and Lindqvist suggested that antipsychotic drugs block postsynaptic catecholamine receptors and thereby induce a compensatory activation of the presynaptic neurons. Later it was demonstrated that most antipsychotic drugs preferentially accelerated the synthesis and turnover of dopamine (Nyback and Sedvall 1968, 1970). The dopamine hypothesis in schizophrenia was initially based on findings demonstrating that neuroleptics antagonized dopamine transmission probably by a blockade of its receptors and that compounds which increased the dopaminergic transmission were psychotomimetic. In humans it was demonstrated that the major dopamine metabolite homovanillic acid increased in the spinal fluid of patients treated with neuroleptics, a finding in line with the proposed negative feedback mechanism regulating activity of dopamine neurons (Carlsson and Lindqvist 1963; Sedvall et al. 1975). However, untreated patients with schizophrenia did not have increased HVA levels in the spinal fluid which would be expected if schizophrenia were to be caused by an increased dopaminergic transmission (Bjerkenstedt et al. 1985).

The journal aims to publish papers which bring together clinical observations, psychological and behavioural abnormalities and genetic data. All papers are fully refereed. Psychiatric Genetics is also a forum for reporting new approaches to genetic research in psychiatry and neurology utilizing novel techniques or methodologies. Psychiatric Genetics publishes original Research Reports dealing with inherited factors involved in psychiatric and neurological disorders. This encompasses gene localization and chromosome markers, changes in neuronal gene expression related to psychiatric disease, linkage genetics analyses, family, twin and adoption studies, and genetically based animal models of neuropsychiatric disease. The journal covers areas such as molecular neurobiology and molecular genetics relevant to mental illness. Reviews of the literature and Commentaries in areas of current interest will be considered for publication. Reviews and Commentaries in areas outside psychiatric genetics, but of interest and importance to Psychiatric Genetics, will also be considered. Psychiatric Genetics also publishes Book Reviews, Brief Reports and Conference Reports.