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Rudolf Uher - One of the best experts on this subject based on the ideXlab platform.

  • functional polymorphism in the brain derived neurotrophic factor gene interacts with stressful life events but not childhood maltreatment in the Etiology of Depression
    Depression and Anxiety, 2014
    Co-Authors: George W Brown, Rudolf Uher, K Thomas J M D Craig, D Tirril H C O Harris, M Joe B Herbert, Karen Hodgson, Katherine E Tansey
    Abstract:

    BACKGROUND: We test the hypothesis that the functional Val66Met polymorphism of BDNF interacts with recent life events to produce onset of new depressive episodes. We also explore the possibility that the Met allele of this polymorphism interacts with childhood maltreatment to increase the risk of chronic Depression. METHODS: In a risk-enriched combined sample of unrelated women, childhood maltreatment and current life events were measured with the Childhood Experience of Care and Abuse, and Life Events and Difficulties Schedule interviews. Chronic episodes of Depression (12 months or longer) during adulthood and onset of a major depressive episode during a 12-month follow-up were established with the Schedules for Clinical Assessment in Neuropsychiatry interview. RESULTS: Met alleles of BDNF moderated the relationship between recent life events and adult onsets of Depression in a significant gene-environment interaction (interaction risk difference 0.216, 95% CI 0.090-0.342; P =.0008). BDNF did not significantly influence the effect of childhood maltreatment on chronic Depression in the present sample. CONCLUSIONS: The Met allele of BDNF increases the risk of a new depressive episode following a severe life event. The BDNF and the serotonin transporter gene length polymorphism (5-HTTLPR) and BDNF may contribute to Depression through distinct mechanisms involving interactions with childhood and adulthood adversity respectively, which may, in combination, be responsible for a substantial proportion of Depression burden in the general population.

  • the moderation by the serotonin transporter gene of environmental adversity in the Etiology of Depression 2009 update
    Molecular Psychiatry, 2010
    Co-Authors: Rudolf Uher, Peter Mcguffin
    Abstract:

    An updated review of 34 human observational studies indicates that the length polymorphism of the serotonin transporter gene moderates the effect of environmental adversity in the development of Depression. This finding depends on the use of contextual or objective methods to assess environmental adversity and is attenuated when self-report instruments are used. Inconsistent findings in male adolescents suggest a developmental stage and sex-specific protective mechanism. These systematic relationships between method and results should be followed up to specify causal mechanisms leading to Depression.

Charles B Nemeroff - One of the best experts on this subject based on the ideXlab platform.

  • Etiology of Depression genetic and environmental factors
    Psychiatric Clinics of North America, 2012
    Co-Authors: Radu V Saveanu, Charles B Nemeroff
    Abstract:

    In summary, depressed patients with a history of childhood trauma may have a distinct Depression endophenotype characterized by a specific neurobiology and risk genotype that may be responsive to different treatment strategies than depressed patients without childhood adversity. Based on current findings, treatment strategies should be multimodal and include the following: 1. Psychotherapy that addresses a number of domains, such as emotional regulation, cognitive reframing, careful exploration of past traumatic events, attachment, and interpersonal relationships in a safe and trusting therapeutic environment. 2. The therapy should likely be longer term in order to effectively impact those domains. 3. Pharmacotherapy that will be effective in quieting the body’s hyperresponsiveness to stress and reverse epigenetic modifications induced by trauma and stress. 4. Environmental interventions that provide a support network (maternal care, a positive family environment, the support of a close friend) have all been shown to attenuate the impact of childhood abuse. In addition, there is great potential in the identification of genomic biomarkers to help guide us in the identification of traumatized individuals who are susceptible to Depression. These indices may also help identify those for whom the immediate provision of treatment may have a preventive effect and may someday guide us in the development of novel pharmacologic approaches.

  • the interaction of serotonin transporter gene polymorphisms and early adverse life events on vulnerability for major Depression
    Current Psychiatry Reports, 2006
    Co-Authors: Derick E Vergne, Charles B Nemeroff
    Abstract:

    Considerable literature supports the hypothesis of dysfunction in central nervous system serotonergic circuits in the pathophysiology of mood disorders, specifically major Depression. Since the development of the selective serotonin (5-HT) reuptake inhibitors, a putative role for the 5-HT transporter (SERT) in the Etiology of Depression has been explored. The discovery of a functional SERT polymorphism has provided a novel tool to further scrutinize the role of serotonergic neurons in Depression. This article reviews the burgeoning evidence of an interaction between early life stress and an SERT polymorphism on vulnerability to Depression.

  • the role of early adverse life events in the Etiology of Depression and posttraumatic stress disorder
    Annals of the New York Academy of Sciences, 1997
    Co-Authors: Christine Heim, Michael J Owens, Paul M Plotsky, Charles B Nemeroff
    Abstract:

    The remarkable progress in neurobiological research techniques has now been applied to investigate the pathogenesis of psychiatric disorders. A large body of literature has confirmed an important biological basis for a majority of severe psychiatric disorders, such as affective and anxiety disorders, including posttraumatic stress disorder (PTSD).' At the beginning of this century, Sigmund Freud's psychoanalytical theory was the major etiological approach for the explanation of psychopathology. According to this theory, conflicts in early life constitute a causal factor for the development of psychological disorders.* In addition to convincing evidence for a genetic contribution in the development of mood and anxiety disorder^,^" evidence for a preeminent role of psychosocial stressors in the pathogenesis of these disorders has also been obtained. For example, episodes of major Depression are often preceded by stressful life events6 or are mutually related to episodes of stress.' In a study of identical twins by Kendler et a1.,* lifetime stressors, including childhood abuse and neglect as well as stressful life events in adulthood, were identified as predictors of major Depression. In the case of PTSD, a stressful life event outside the range of usual human experiences is required for a diagnosis of the disorder according to DSM-IV criteria.' The inclusion of a stressful event as an etiological factor in the DSM-IV differentiates PTSD from other psychiatric disorders. However, less than one quarter of traumatized individuals subsequently develop syndromal PTSD, suggesting that the disorder does not merely represent a normative reaction to extreme stress.'' Increasing evidence indicates that the Occurrence and persistence of PTSD in response to trauma depends on many factors including other stressful life events"-" as well as minor psychosocial stressors and daily stressors14 before or after the onset of the traumatic event. Furthermore, recent studies suggest a strong relation between early adverse life events, that is,

Roberto Maniglio - One of the best experts on this subject based on the ideXlab platform.

  • child sexual abuse in the Etiology of Depression a systematic review of reviews
    Depression and Anxiety, 2010
    Co-Authors: Roberto Maniglio
    Abstract:

    BACKGROUND: Despite a large amount of research, there is considerable controversy about the role that child sexual abuse plays in the Etiology of Depression. To prevent interpretative difficulties, mistaken beliefs, or confusion among professionals who turn to this literature for guidance, this article addresses the best available scientific evidence on the topic, by providing a systematic review of the several reviews that have investigated the literature on the issue. METHODS: Seven databases were searched, supplemented with hand search of reference lists from retrieved papers. The author and a psychiatrist independently evaluated the eligibility of all studies identified, abstracted data, and assessed study quality. Disagreements were resolved by consensus. RESULTS: Four reviews, including about 60,000 subjects from 160 studies and having no limitations that could invalidate their results, were analyzed. There is evidence that child sexual abuse is a significant, although general and nonspecific, risk factor for Depression. The relationship ranges from small-to-medium in magnitude and is moderated by sample source. Additional variables may either act independently to promote Depression in people with a history of sexual abuse or interact with such traumatic experience to increase the likelihood of Depression in child abuse survivors. CONCLUSIONS: For all victims of abuse, programs should focus not only on treating symptoms, but also on reducing additional risk factors. Depressed adults who seek psychiatric treatment should be enquired about early abuse within admission procedures.

  • Child sexual abuse in the Etiology of Depression: A systematic review of reviews.
    Depression and anxiety, 2010
    Co-Authors: Roberto Maniglio
    Abstract:

    Background: Despite a large amount of research, there is considerable controversy about the role that child sexual abuse plays in the Etiology of Depression. To prevent interpretative difficulties, mistaken beliefs, or confusion among professionals who turn to this literature for guidance, this article addresses the best available scientific evidence on the topic, by providing a systematic review of the several reviews that have investigated the literature on the issue. Methods: Seven databases were searched, supplemented with hand search of reference lists from retrieved papers. The author and a psychiatrist independently evaluated the eligibility of all studies identified, abstracted data, and assessed study quality. Disagreements were resolved by consensus. Results: Four reviews, including about 60,000 subjects from 160 studies and having no limitations that could invalidate their results, were analyzed. There is evidence that child sexual abuse is a significant, although general and nonspecific, risk factor for Depression. The relationship ranges from small-to-medium in magnitude and is moderated by sample source. Additional variables may either act independently to promote Depression in people with a history of sexual abuse or interact with such traumatic experience to increase the likelihood of Depression in child abuse survivors. Conclusions: For all victims of abuse, programs should focus not only on treating symptoms, but also on reducing additional risk factors. Depressed adults who seek psychiatric treatment should be enquired about early abuse within admission procedures. Depression and Anxiety 27:631–642, 2010. r 2010 Wiley-Liss, Inc.

Karestan C Koenen - One of the best experts on this subject based on the ideXlab platform.

Laszlo Mayer - One of the best experts on this subject based on the ideXlab platform.

  • tagging snp association study of the il 1β gene il1b and childhood onset mood disorders
    American Journal of Medical Genetics, 2009
    Co-Authors: Virginia L Misener, Lissette Gomez, Karen Wigg, Nicole King, Enikő Kiss, Gabriella Daroczi, Krisztina Kapornai, Zsuzsanna Tamas, Laszlo Mayer, Julia Gadoros
    Abstract:

    Given substantial evidence for IL-1β involvement in the Etiology of Depression, the IL1B gene is a strong candidate for involvement in susceptibility to depressive disorders. However, association studies investigating this, to date, have been limited to just two polymorphisms (rs1143627[−31T/C] and rs16944[−511C/T]) that constitute only a fraction of the genetic variation that is actually present across this gene in the population. Here, in a family-based association study of childhood-onset mood disorders (COMD), characterized by onset of Depression before the age of 15, we have used a gene-wide approach, employing a panel of five tagging SNPs spanning the entire gene. Based on TDT analyses of both individual alleles and haplotypes, in a study sample of 646 families (with 782 affected children), none of the SNPs, including those implicated in transcriptional regulation of the gene, showed evidence for association with COMD. This is the largest and most comprehensive study of IL1B in relation to mood disorders that has been carried out, to date. The results do not support the involvement of IL1B as a major factor in genetic risk for early-onset mood disorders. © 2008 Wiley-Liss, Inc.

  • cytokine genes tnf il1a il1b il6 il1rn and il10 and childhood onset mood disorders
    Neuropsychobiology, 2008
    Co-Authors: Virginia L Misener, Lissette Gomez, Karen Wigg, P Luca, Nicole King, Enikő Kiss, Gabriella Daroczi, Krisztina Kapornai, Zsuzsanna Tamas, Laszlo Mayer
    Abstract:

    Background/Aims: Inflammatory cytokines induce a behavioral syndrome, known as sickness behavior, that strongly resembles symptoms typically seen in Depression. This resemblance has led to the theory that an imbalance of inflammatory cytokine activity may be a contributing factor in depressive disorders. Support for this is found in multiple lines of evidence, such as the effects of cytokines on the activities of the hypothalamic-pituitary-adrenal axis, serotonin and brain-derived neurotrophic factor, and hippocampal function, all of which are implicated in the Etiology of Depression. In addition, associations between inflammatory activity and depressive symptomology have been documented in a number of studies, and the depressogenic effects of cytokine therapy are well known. Accordingly, given that Depression has a substantial genetic basis, genes involved in the regulation of inflammatory cytokine activity are strong candidates for involvement in genetic susceptibility to depressive disorders. Here, we have tested 6 key genes of this type, TNF, IL1A, IL1B, IL6, IL1RN and IL10, as candidates for involvement in childhood-onset mood disorders. Methods: In this study of 384 families, each ascertained through a child with Depression diagnosed before the age of 15 years, 11 polymorphisms of known or likely functional significance (coding and regulatory variants) were analyzed. Results: Testing for biased transmission of alleles from parents to their affected offspring, we found no evidence for an association between childhood-onset mood disorders and any of the polymorphisms, either individually or as haplotypes. Conclusion: The present study does not support the involvement of the TNF, IL1A, IL1B, IL6, IL1RN and IL10 variants as major genetic risk factors contributing to early-onset mood disorders.