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S.15.02 Childhood maltreatment and the course of depression: the role of inflammation
S.15. Immunogenetics and psychiatric disorders Therefore, we performed several studies investigating the effects of a single dose of modafinil on different aspects of impulsivity and their neural correlates in alcohol dependent subjects using task-related and resting-state fMRI. Results showed that modafinil had differential behavioral and neurobiological effects on different aspects of impulsivity. With regard to motor impulsivity, baselinedependent effects of modafinil were observed on stop signal task performance and underlying brain activation and connectivity of the supplemental motor area and the thalamus. In contrast, beneficial effects of modafinil on impulsive decision making was found in all subjects, which was accompanied by changes in activation in and connectivity between frontoparietal and striatal brain regions. These findings stress the important differences between different aspects of impulsivity. Furthermore, modafinil modulated the functional coupling between resting-state networks including the default mode network, salience network and central executive network, which was associated with modafinil-induced improvement in Stroop task performance, indicating that modafinil exerts its effects by targeting important intrinsic large-scale networks of the brain. The current work provides additional information on modafinil’s mechanisms of action and provides some evidence that modafinil could be a potential treatment option for alcohol dependence. However, caution is warranted with the prescription of modafinil to nonselected samples, since detrimental effects were also observed in subjects with low levels of motor impulsivity.
S.15. Immunogenetics and psychiatric disorders S.15.01 Immunogenetics: a molecular approach to the modulation of emotion and cognitive processes B. Baune1 ° 1 University of Adelaide, Department of Psychiatry, Adelaide, Australia The immune system has been involved in the pathogenesis of psychiatric disorders. Early studies identified potential systemic immunological blood biomarkers associated with depression, schizophrenia and cognitive decline. More recently, it was suggested that an immunological imprint obtained through maltreatment during childhood might underpin the adult onset of depression. Research on the immunogenetic background of emotion and cognitive processes has only emerged recently based on animal models and translational human research. Transgenic mouse models have shown that cytokines play a physiological role in normal cognitive function during neurodevelopment. Specifically, it was shown that the absence of tumor necrosis factor alpha (TNF) in genetically modified mice is detrimental of cognitive function during neurodevelopment. In translational research, it was demonstrated that genetic variants of cytokines such as TNF were associated with cognitive speed performance during aging [1]. Furthermore, first studies suggest that genetic variants of IL-6 and TNF are predictive of hippocampal volumes in adults [2]. Genetic variants of IL-1b are associated with functional brain activity, such as emotion processing in the amygdala, as well as with anti-depressant treatment response in depression. Taken together, immune genes are relevant since these cytokines interact with molecular mechanisms of memory, learning and
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neuroplasticity in the hippocampus and the amygdala in particular [3], both of which are highly relevant to emotion and cognitive processing. Immunogenetics is a promising area for characterising the predisposition to psychiatric disorders, for identifying biomarkers of brain morphology and function, disease and treatment biomarkers and developing novel interventions. References [1] Baune B.T., et al. (2008). Association between genetic variants of IL-1beta, IL-6 and TNF-alpha cytokines and cognitive performance in the elderly general population of the MEMO-study. Psychoneuroendocrinology 33(1), 68−76. [2] Baune B.T., et al. (2012). Tumor necrosis factor gene variation predicts hippocampus volume in healthy individuals. Biol Psychiatry 72(8), 655−62. [3] Eyre H., Baune, B.T., (2012). Neuroplastic changes in depression: a role for the immune system. Psychoneuroendocrinology 37(9), 1397– 416.
S.15.02 Childhood maltreatment and the course of depression: the role of inflammation A. Danese1 ° 1 MRC Social Genetic and Developmental Psychiatry Centre, Department of Child & Adolescent Psychiatry, London, United Kingdom Depression is a common and impairing psychiatric disorder associated with large health burden. Evidence that depression has 12month prevalence of 7% and lifetime prevalence of 16% emphasises that most depressive episodes cluster in the same individuals, who develop recurrent and persistent illness. In order to prevent a large fraction of the health burden linked to depression, it is therefore important to identify risk factors for recurrent and persistent depressive episodes, and to investigate the mechanisms through which risk factors confer liability for this subtype of depression. In a meta-analytical study, we have described that individuals with a history of childhood maltreatment are at high risk of developing recurrent and persistent depressive episodes, and to show poor response to treatment [1]. Furthermore, in a series of longitudinal-prospective investigations based on the New Zealand Dunedin Multidisciplinary Health and Development Study and the UK Environmental-Risk (E-Risk) Longitudinal Twin Study, we have observed that depressed individuals with a history of childhood maltreatment have high circulating inflammation levels, both in childhood and in adult life [2,3]. Therefore, inflammation might contribute to the liability for recurrent and persistent depressive episodes, and for poor treatment outcomes. These findings are consistent with data from epidemiological studies linking recurrent depression to high inflammation levels, and data from clinical trials suggesting that high inflammation levels predict poor response to antidepressants and that anti-inflammatory medications may be effective in some cases of treatment-resistant depression. References [1] Nanni V, Uher R, Danese A, 2012. Childhood maltreatment predicts unfavourable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry 169(2): 141−51. [2] Danese A, Moffitt TE, Pariante C, Ambler A, Poulton R, Caspi A, 2008. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry, 65(4), 409–415. [3] Danese A, Caspi A, Williams B, Ambler A, Sugden K, Mika J, Werts H, Freeman J, Pariante CM, Moffitt TE, Arseneault L, 2011. Biological embedding of stress through inflammation processes in childhood. Mol Psychiatry 16(3): 244−6.
S.15. Immunogenetics and psychiatric disorders S.15.01 Immunogenetics: a molecular approach to the modulation of emotion and cognitive processes B. Baune1 ° 1 University of Adelaide, Department of Psychiatry, Adelaide, Australia The immune system has been involved in the pathogenesis of psychiatric disorders. Early studies identified potential systemic immunological blood biomarkers associated with depression, schizophrenia and cognitive decline. More recently, it was suggested that an immunological imprint obtained through maltreatment during childhood might underpin the adult onset of depression. Research on the immunogenetic background of emotion and cognitive processes has only emerged recently based on animal models and translational human research. Transgenic mouse models have shown that cytokines play a physiological role in normal cognitive function during neurodevelopment. Specifically, it was shown that the absence of tumor necrosis factor alpha (TNF) in genetically modified mice is detrimental of cognitive function during neurodevelopment. In translational research, it was demonstrated that genetic variants of cytokines such as TNF were associated with cognitive speed performance during aging [1]. Furthermore, first studies suggest that genetic variants of IL-6 and TNF are predictive of hippocampal volumes in adults [2]. Genetic variants of IL-1b are associated with functional brain activity, such as emotion processing in the amygdala, as well as with anti-depressant treatment response in depression. Taken together, immune genes are relevant since these cytokines interact with molecular mechanisms of memory, learning and
S135
neuroplasticity in the hippocampus and the amygdala in particular [3], both of which are highly relevant to emotion and cognitive processing. Immunogenetics is a promising area for characterising the predisposition to psychiatric disorders, for identifying biomarkers of brain morphology and function, disease and treatment biomarkers and developing novel interventions. References [1] Baune B.T., et al. (2008). Association between genetic variants of IL-1beta, IL-6 and TNF-alpha cytokines and cognitive performance in the elderly general population of the MEMO-study. Psychoneuroendocrinology 33(1), 68−76. [2] Baune B.T., et al. (2012). Tumor necrosis factor gene variation predicts hippocampus volume in healthy individuals. Biol Psychiatry 72(8), 655−62. [3] Eyre H., Baune, B.T., (2012). Neuroplastic changes in depression: a role for the immune system. Psychoneuroendocrinology 37(9), 1397– 416.
S.15.02 Childhood maltreatment and the course of depression: the role of inflammation A. Danese1 ° 1 MRC Social Genetic and Developmental Psychiatry Centre, Department of Child & Adolescent Psychiatry, London, United Kingdom Depression is a common and impairing psychiatric disorder associated with large health burden. Evidence that depression has 12month prevalence of 7% and lifetime prevalence of 16% emphasises that most depressive episodes cluster in the same individuals, who develop recurrent and persistent illness. In order to prevent a large fraction of the health burden linked to depression, it is therefore important to identify risk factors for recurrent and persistent depressive episodes, and to investigate the mechanisms through which risk factors confer liability for this subtype of depression. In a meta-analytical study, we have described that individuals with a history of childhood maltreatment are at high risk of developing recurrent and persistent depressive episodes, and to show poor response to treatment [1]. Furthermore, in a series of longitudinal-prospective investigations based on the New Zealand Dunedin Multidisciplinary Health and Development Study and the UK Environmental-Risk (E-Risk) Longitudinal Twin Study, we have observed that depressed individuals with a history of childhood maltreatment have high circulating inflammation levels, both in childhood and in adult life [2,3]. Therefore, inflammation might contribute to the liability for recurrent and persistent depressive episodes, and for poor treatment outcomes. These findings are consistent with data from epidemiological studies linking recurrent depression to high inflammation levels, and data from clinical trials suggesting that high inflammation levels predict poor response to antidepressants and that anti-inflammatory medications may be effective in some cases of treatment-resistant depression. References [1] Nanni V, Uher R, Danese A, 2012. Childhood maltreatment predicts unfavourable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry 169(2): 141−51. [2] Danese A, Moffitt TE, Pariante C, Ambler A, Poulton R, Caspi A, 2008. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry, 65(4), 409–415. [3] Danese A, Caspi A, Williams B, Ambler A, Sugden K, Mika J, Werts H, Freeman J, Pariante CM, Moffitt TE, Arseneault L, 2011. Biological embedding of stress through inflammation processes in childhood. Mol Psychiatry 16(3): 244−6.