Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms.GPT2 | intellectual and developmental disability | mitochondria | metabolomics | spastic paraplegia

Background Cognitive behavior therapy (CBT) is an evidence based therapy and is now recommended by national organizations in many high income countries. CBT is underpinned by the European values and therefore for it to be effective in other cultures it needs to be adapted. Aims This paper describes an evidence based approach to culturally adapt CBT in Asian context, areas of focus for such adaptation and lessons learned. Methods An environmental scan of the literature, description of local CBT associations and perspectives from these organizations. Results Cultural adaptation of CBT focuses on three main areas; 1 awareness of culture and related issues, 2 assessment and 3 adjustment in therapy techniques. Conclusions The last decade has seen an increase in culturally adapted CBT in Asia, however, more work needs to be done to improve access to CBT in Asia.

Introduction:Early psychosis is not a discrete disorder; rather it is mixed-up state .Different states like depression, anxiety, psychosis, obsession manifest during this period. 20% to 40% of BLIPS positive subjects eventually make transition to psychosis. Large proportion of remaining patients develops anxiety or mood disorders. During early psychosis unitary psychosis, manifest itself in forms of different psychiatric disorders.Method:An electronic search was made at data based websites including pub med and Blackwell synergy using key words, unitary psychosis, prodrom, early psychosis .This was followed by manual and internet study of relevant articles .Results:Cognitive deficits and defects of facial recognition were present in both schizophrenic and bipolar prodrom .In 24.2% schizo-obsessive patients reduced size of the left hippocampus was found. 84% subjects reported depressive symptoms before transition to psychosis, 73% of patient of schizophrenia starts with non-specific affective and negative symptoms. In presence of depression, probability of transition to psychosis increased from 4% to 21.7%. In 47.3% of patients, OCD occur before onset of frank psychosis.Discussion:High prevalence of comorbidities during prodromal phase indicates that shared common factor is involved. Anxiety, depression and attenuated psychosis are integral components of early psychosis. Overlapping of bipolar and schizophrenic prodrms depicts commonality of origin of two disorders.OCD is associated with schizo-obsessive subgroup. Strong interactive relationship among different disorders could be explained on basis of unitary psychosis.Conclusion:Presence of unitary psychosis is realized in the studies of early psychosis.

Background:Premature ejaculation (PME) is the most prevalent sexual disorder. It affects more than 30% of male population. Thus far SSRI,s clomipramine, local anesthetic along with psychological therapies are the mainstay in the treatment of PME. However, not all the cases are amenable to these treatments. Attempts are underway to find out better remedies for this problem. Gabapentine an anticonvulsant drug is being tested for treatment of PME.Method:Electronic search was made at database websites, using key words gabapentine, premature ejaculation. It was followed by manual research to find out possible mechanism by which gabapentine could delay orgasm.Results:Search could not provide concert mode of action which explain inhibitory action on premature ejaculation by gabapentine; except for its anti anxiety effect mediated by gabanergic properties.Discussion:Gabanergic action explains its anti anxiety, muscle relaxant and CNS depressant properties which could be beneficial, for premature ejaculation. Gabapentine has anti glutamate properties as well. This action further imparts anti excitatory effect which is helpful for PME. Excellent efficacy on neuralgic pains and neuropathies indicates that gabapentine desensitize the receptors which are oversensitive as are found in erogenous zones of premature ejaculators. Orgasm and partial seizure share many common features. Hence anti antiepileptic properties increase threshold of physiological seizure that is orgasm.Conclusion:Gabapentine can be considered as medicine which works on PME with a mode of action different from SSRI,s.