Bexarotene as add-on to antipsychotic treatment in schizophrenia patients: a pilot open-label trial.

Objectives: Bexarotene is a synthetic retinoid used for treatment of neoplastic or dermatologic disorders. Based on the retinoid dysregulation hypothesis, it was hypothesized that bexarotene augmentation would have a beneficial effect in the antipsychotic treatment of schizophrenia patients. This study is the first to investigate the safety and efficacy of add-on oral bexarotene to ongoing antipsychotic treatment in chronic schizophrenia patients who were stabilized on regular antipsychotic treatment.

Association of the gene encoding neurogranin with schizophrenia in males.

The neurogranin (NRGN) gene produces a postsynaptic brain-specific protein that regulates calmodulin-Ca(2+) availability in neurons. Acting downstream of the NMDA receptor and upstream of calcineurin and other proteins implicated in schizophrenia, NRGN is a good candidate for association studies in schizophrenia. NRGN expression is regulated during development and is modulated by thyroid hormones and retinoids, molecules essential for the proper development of the central nervous system.

Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease.

Vitamin A (retinoid) is required in the adult brain to enable cognition, learning, and memory. While brain levels of retinoid diminish over the course of normal ageing, retinoid deficit is greater in late onset Alzheimer disease (LOAD) brains than in normal-aged controls. This paper reviews recent evidence supporting these statements and further suggests that genes necessary for the synthesis, transport and function of retinoid to and within the ageing brain are appropriate targets for treatment of LOAD.

Transthyretin: no association between serum levels or gene variants and schizophrenia.

It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP).

Thyroid hormones and retinoids: a possible link between genes and environment in schizophrenia.

Phenotypic discordance for schizophrenia in monozygotic twins clearly indicates involvement of environmental factors as key determinants in disease development. Positive findings from genome scans, linkage and association studies apply in only a minority of those affected, while post-mortem brain investigations reveal altered expression of genes and proteins involved in numerous neurodevelopmental, metabolic and neurotransmitter pathways. Such altered expressions could result, on the one hand, from mutations in coding regions or polymorphisms in the promoter and regulatory regions in genes within those areas identified by gene searches or, on the other hand, from inadequate amounts of modulators, transporters and synthesizers of transcription factors necessary for regulation of the putative genes.

Evidence for defective retinoid transport and function in late onset Alzheimer's disease.

The hypothesis of this article is that late onset Alzheimer's disease (AD) is influenced by the availability in brain of retinoic acid (RA), the final product of the vitamin A (retinoid) metabolic cascade. Genetic, metabolic, and environmental/dietary evidence is cited supporting this hypothesis. Significant genetic linkages to AD are demonstrated for markers close to four of the six RA receptors, RA receptor G at 12q13, retinoid X receptor B at 6p21.