Brain-derived neurotrophic factor and suicide pathogenesis.
ABSTRACT Abstract Suicide is a major public health concern. The etiology and pathogenic mechanisms associated with suicidal behavior are poorly understood. Recent research on the biological perspective of suicide has gained momentum and appears to provide a promising approach for identifying potential risk factors associated with this disorder. One of the areas that have gained the most attention in suicide research is the role of brain-derived neurotrophic factor (BDNF), which participates in many physiological functions in the brain, including synaptic and structural plasticity. Several studies consistently show that expression of BDNF is reduced in blood cells of suicidal patients and in brains of subjects who committed suicide. Recent studies also demonstrate abnormalities in the functioning of BDNF, because its cognate receptors (tropomycin receptor kinase B and pan75 neurotrophin receptor) are abnormally active and/or expressed in the post-mortem brains of suicide subjects. There is further evidence of the role of BDNF in suicide as numerous studies show a strong association of suicidal behavior with BDNF functional polymorphism. Overall, it appears that abnormalities in BDNF signaling may serve as an important biological risk factor in the etiology and pathogenesis of suicide.
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ABSTRACT: In this study we investigated whether single nucleotide polymorphisms (SNP) in the genes coding for BDNF (Val66Met) and VEGF (C2578A) may be associated with maladaptive strategies among suicide attempt patients. We found that BDNF Val66Met gene polymorphism probably affect avoidant coping strategies.Psychiatry Research 07/2014; · 2.68 Impact Factor
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ABSTRACT: Adaptation to stress leads to the activation of several biological systems that maintain homeostasis and enable effective coping with challenges. These adaptive processes have been designated as 'allostasis'. However, overactivation or aberrant performance of allostatic mechanisms due to chronic stress exposure may exert systemic deleterious effects. This condition has been called 'allostatic load' (AL). The AL concept is a useful framework allowing to understand the mulitisystem physiological dysregulation due to cumulative stressful demands over the lifespan. In the recent years, the AL paradigm has emerged as a novel concept explaining the morbidity and mortality with respect to several mental disorders. In this article, we suggest that AL provides a useful framework to describe schizophrenia-its etiology, course, outcome and comorbidities. Schizophrenia is a severe mental illness that is characterized by multidimensional psychopathology including positive and negative symptoms, affective symptoms and cognitive impairment with several known risk factors and accompanying pathophysiological correlates. However, there is a great need to refine and integrate the plethora of findings reported from various research perspectives. We propose that AL is a meaningful concept integrating findings on pathophysiological underpinnings, factors influencing course of the disorder and the development co-occurring physical health impairments as well as substance use disorders in schizophrenia. Furthermore, there is an urgent necessity to investigate AL and its correlates in schizophrenia as no studies in this field have been performed so far.Neuroscience & Biobehavioral Reviews 06/2014; · 10.28 Impact Factor
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ABSTRACT: Patients with psychiatric disorders exhibit sev-eral neurobehavioral and neuropsychological alterations compared to healthy controls. However, signature endpoints of these behav-ioral manifestations have not yet been translat-ed into clinical tests for diagnosis and follow-up measures. Recently, neuroproteomic approaches have been utilized to identify unique signature markers indicative of these disorders. Develop -ment of reliable biomarkers has the potential to revolutionize the diagnosis, classification, and monitoring of clinical responses in psychiatric diseases. However, the lack of biological gold standards, the evolving nosology of psychiatric disorders, and the complexity of the nervous system are among the major challenges that have hindered efforts to develop reliable bio-markers in the field of neuropsychiatry and drug abuse. While biomarkers currently have a limited role in the area of neuropsychiatry, sev-eral promising biomarkers have been proposed in conditions such as dementia, schizophrenia, depression, suicide, and addiction. One of the primary objectives of this review is to discuss the role of proteomics in the development of bio-markers specific to neuropsychiatry. We discuss and evaluate currently available biomarkers as well as those that are under research for clinical use in the future. (Journal of Psychiatric Practice 2015;21:37–48) A biomarker broadly refers to any measurable bio-logical characteristic that reflects the presence, absence, and/or severity of a disease. In specific terms, a biomarker is a " characteristic that is objec-tively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic interven-tion. " 1 Biomarkers represent important diagnostic tools for the sensitive identification and selection of patients with a particular disease. They act as moni-tors of disease progression, prognosis, and classifica-tion. They provide information to help guide decisions about dosing of medications and strategies to minimize interindividual variation. They also enhance the evaluation of the benefits and risks of specific therapeutic interventions, are helpful in pre-dicting and monitoring clinical response to interven-tions in the follow-up of patients with a specific disease, constitute a basis for the design of clinical trials, and serve as starting points for drug discovery and development. Biomarkers have revolutionized medical research, and several biomarkers are currently widely used in clinical medicine. Examples of such diagnostic bio-markers include prostate specific antigen (PSA) for prostate cancer, troponin and creatine phosphoki-nase MB (CPK-MB) for myocardial infarction, aspartate aminotransferase (AST)/alanine amino-transferase (ALT) for liver pathologies, and the 14-3-3 protein for Creutzfeldt-Jakob disease (CJD). 2 However, efforts to establish and develop sensitive and specific biomarkers in the field of psychiatryJournal of Psychiatric Practice 01/2015; 21(1). · 1.35 Impact Factor