The impaired mitochondrial function hypothesis in schizophrenia is based on evidence of altered brain metabolism, morphology, biochemistry and gene expression. Mitochondria have their own genome, which is needed to synthesize some of the subunits of the respiratory chain enzymes. Mitochondrial DNA (mtDNA) is maternally inherited and we observed an excess of maternal transmission of schizophrenia in a set of parent -offspring affected pairs. We therefore hypothesized that mutations in the mtDNA may contribute to the complex genetic basis of schizophrenia. The entire mtDNA of six schizophrenic patients with an apparent maternal transmission of the disease was sequenced and compared to the reference sequence. We have identified 50 variants and among these six have not been previously reported. Three of them were missense variants: MTCO2 7750C4A, MTATP6 8857G4A and MTND4 12096T4A. These were maternally inherited because they were also present in the mtDNA of their respective schizophrenic mothers and none of them were found in 95 control individuals. The MTND4 12096T4A (Leu446His) is a heteroplasmic variant present in five of the six mother -offspring patient pairs that triggers a nonconservative substitution in the ND4 subunit of complex I. Sequence alignment of 110 ND4 peptides from all eukaryotic kingdoms shows that only hydrophobic amino acids are found in this position. Moreover, leucine was conserved or substituted by an isoleucine in all mammalian species. This indicates that the presence of histidine could affect complex I activity in patients with schizophrenia.

No abstract

1. The effects of 'cafeteria feeding' on primiparous Wistar rats during lactation have been studied by measuring circulating levels of glucose, amino acids, lactate, urea and ammonia as well as glycogen levels in liver and muscle.2. No significant changes in glucose levels were observed despite alterations in blood glucose compartmentation. 3.Compared with controls, the dams given the cafeteria diet had higher liver glycogen stores which were more easily mobilized at the peak of lactation.4. Rats given the cafeteria diet showed a lower amino acid utilization than controls and adequately maintained circulating levels, as determined by the lower circulating levels of ammonia and urea.5. No significant differences in body-weight were observed in the period studied despite increasing dam weight after weaning in the cafeteria-fed group.6. The size of pups of cafeteria-fed dams was greater than that of controls, and the differences were marked after weaning, when the metabolic machinery of the cafeteria pup maintained high protein accretion and body build-up using fat as the main energy substrate characteristic of the preweaning stage. The controls, however, changed to greater utilization of amino acids as an energy substrate and adapted to high-protein (lowbiological-quality) diets with a significantly different pattern of circulating nitrogen distribution.Lactation imposes a very severe burden on maternal energy homeostasis because the increased needs of nursing cannot be met by increased food intake alone, at least in the rat (Spray, 1950; Cripps & Williams, 1975). This situation results in diminishing fat and other stores in the mother and a progressive adaptation to lower nitrogen loss despite increased dietary amino acid utilization for energy purposes (Palou et al. 1982).In the pups, the effect of decreasing milk availability with respect to the enormously increasing demands of their own growth results in the initiation of ingestion of solid food from day 12 onwards (Babicky et al. 1975) and complete weaning by days 24-30; this change of diet is reflected at the biochemical level by an adaptation from a high-fat-highquality-protein diet (milk) to a high-carbohydrate-low-quality-protein in the rat chow.The presentation to the experimental animals of a mixed, highly palatable diet containing densely energy-packed high-quality nutrients, known as a 'cafeteria diet ' (Sclafani & Springer, 1976), results in overfeeding (Rothwell & Stock, 1982) and increased energy disposal through thermogenesis and fat accretion (Rothwell & Stock, 1979), leading to increased body-weight. Feeding this diet results in increased food intake and increased foodstuff availability both for body growth and for energetic purposes. In the present study we have intended to obtain a general idea of the handling of circulating glucose and N compounds as well as the glycogen stores by dams and pups subjected to this diet compared with controls. In addition we have determined whether or not the increased energy ingested could counteract the deman...