Interdisciplinary study of telomere length, polymorphism of genes of renin-angiotensin (ACE) and serotonin (5HTR2A and 5HTTPR) systems in population of aged and old inhabitants of the North-West of Russia was conducted, in their relations to data from clinical and geriatric anamnesis, and psychological functioning. Regular link between telomere length and respondent's age was demonstrated in subgroups of old respondents and long-livers, by method of factor analysis.
Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
A number of recent clinical and molecular observations in major psychosis indicate that epigenetic factors may be operational in the origin of major mental illness. This article further develops the idea that epigenetic factors may play an etiopathogenic role in schizophrenia and bipolar affective disorder. The putative role of epigenetic factors is shown by the epigenetic interpretation of genetic association studies of the genes for serotonin 2A (HTR2A) and the dopamine D3 (DRD3) receptors in schizophrenia.
The serotonin-2A (HTR2A) receptor is a molecule of particular interest in biological psychiatry, as it is an important target for psychotropic drugs, and altered HTR2A expression has been found in several neuropsychiatric conditions, including depression and schizophrenia. Genetic association has been reported between a synonymous 102T/C polymorphism in the gene encoding HTR2A and a number of clinical phenotypes, including schizophrenia, clozapine response, psychotic symptoms in Alzheimer's disease and certain features of depression.
Progress in Neuro-Psychopharmacology & Biological Psychiatry
5-HT2A receptor density in prefrontal cortex was associated with depression and suicide. 5-HT2A receptor gene polymorphism rs6313 was associated with 5-HT2A receptor binding potential, with the ability of individuals to use environmental support in order to prevent depression, and with sleep improvement after antidepressant treatment with mirtazapine. Studies on response to antidepressant drugs gave inconsistent results.
INTRODUCTION: HTR2A gene has been the subject of numerous studies in psychiatric genetics because LSD, which resembles serotonin causes psychosis and atypical antipsychotic drugs target the HTR2A receptor. However, evidence for the role of HTR2A polymorphism(s) in schizophrenia (SCZ) and bipolar disorder (BD) has been elusive. We hypothesized that epigenetic dysregulation of HTR2A may be involved in psycho-pathogenesis and analyzed promoter DNA methylome and expression of HTR2A in SCZ, BD and control subjects.
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics
Several lines of evidence indicate that dysfunction of serotonin signaling and HTR2A receptor are involved in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BD). DNA methylation of HTR2A at T102C polymorphic site influences HTR2A expression and aberrant DNA methylation of HTR2A promoter was reported in postmortem brain of patients with SCZ and BD.
Histone deacetylases (HDACs) compact chromatin structure and repress gene transcription. In schizophrenia, clinical studies demonstrate that HDAC inhibitors are efficacious when given in combination with atypical antipsychotics. However, the molecular mechanism that integrates a better response to antipsychotics with changes in chromatin structure remains unknown.
Proceedings of the National Academy of Sciences of the United States of America
Punishment of free-riding has been implicated in the evolution of cooperation in humans, and yet mechanisms for punishment avoidance remain largely uninvestigated. Individual variation in these mechanisms may stem from variation in the serotonergic system, which modulates processing of aversive stimuli. Functional serotonin gene variants have been associated with variation in the processing of aversive stimuli and widely studied as risk factors for psychiatric disorders.
The serotonin receptor 5-HT2A (encoded by HTR2A) is an important regulator of fetal brain development and adult cognitive function. Environmental signals that induce epigenetic changes of serotonin response genes, including HTR2A, have been implicated in adverse mental health outcomes. The objective of this perspective article is to address the medical implications of HTR2A epigenetic regulation, which has been associated with both infant neurobehavioral outcomes and adult mental health.
The past two decades have witnessed a rise in the 'NMDA receptor hypofunction' hypothesis for schizophrenia, a devastating disorder that affects around 1% of the population worldwide. A variety of presynaptic, postsynaptic, and regulatory proteins involved in glutamatergic signaling have thus been proposed as potential therapeutic targets.