- Email: [email protected]
Conference proceedings: Biological psychiatry symposium on “Endophenotypes in Psychiatry”
Asian Journal of Psychiatry 2 (2009) 80–81
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Conference
Conference proceedings: Biological psychiatry symposium on ‘‘Endophenotypes in Psychiatry’’ A one-day biological psychiatry symposium on ‘‘Endophenotypes in Psychiatry’’ was organized by the Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India, on the 3rd of January 2009. Dr MS Keshavan, of the Harvard Medical School, Boston, USA, addressed the gathering on the topic ‘‘Schizophrenia: Moving from the phenome to the genome’’. Introducing the concept, Dr Keshavan explained that though research over the last century had enhanced our understanding on the neurobiology of psychiatric disorders, none of the various neuroimaging, neurochemical and neurophysiological alterations described had qualified as definite diagnostic markers. The role of genetic factors in the etiology of schizophrenia, for example, was being increasingly recognized. However, the wide heterogeneity in its phenotypic presentation and the complex gene–environment interactions limited our understanding of the genetic basis of schizophrenia. In this context it was brought out that endophenotypes have emerged as useful tools in enhancing our understanding of psychiatric disorders. Endophenotypes are defined as ‘quantitative traits in the putative pathophysiologic pathway from the genotype to the phenotype’ (Gottesman and Shields, 1973). As per the Gottesman and Gould (2003), criteria, for a marker to qualify as an endophenotype it should: (1) be associated with illness in the relevant population, (2) be state independent, (3) be heritable, (4) co-segregate with the illness within families and (5) be present in unaffected family members more frequently than in the general population. Explaining the utility of endophenotypes, Dr Keshavan highlighted a study (Prasad et al., 2005), which demonstrated association of RGS4 gene polymorphisms with structural alterations of the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. By studying the neurocognitive endophenotype of executive dysfunction and imaging endophenotype of DLPFC alterations, the polymorphism of RGS4 gene could be implicated in the genetic etiology of schizophrenia. Combination of such functionally related endophenotypes termed as ‘extended endophenotypes’ could play an important role in future research and studying these would be more clinically relevant as interventions for these specific phenotypic presentations could be planned. Continuing the discussion on extended endophenotypes, Dr Dawn Thomas K Puthumana, Assistant Professor, Department of Neuroimaging and Interventional Radiology, NIMHANS, Bangalore, India, spoke on ‘‘Functional MR correlates of emotion recognition in subjects at risk for schizophrenia’’. The basic principles and applications of neuroimaging in psychiatric disorders were discussed. Studies demonstrating smaller hippocampal volumes and reduced activation of DLPFC during cognitive tasks, on patients 1876-2018/$ – see front matter doi:10.1016/j.ajp.2009.04.006
and first-degree relatives of schizophrenia were highlighted; alterations in brain structure and function were proposed as potential endophenotypes. A study done by the speaker (Venkatasubramanian et al., 2008) was presented where brain hemodynamic activity during an implicit emotion recognition task was compared between 17 subjects at risk for schizophrenia (SARS) and 16 healthy controls using a novel ecologically valid and culture sensitive tool — Tool for Recognition of Emotions in Neuropsychiatric DisorderS (TRENDS) (Behere et al., 2008). The SARS group was found to have deficient brain activation for fearful expressions in the frontolimbic cortices. This study supported emotion recognition deficits as potential endophenotypes in schizophrenia. In the next session Dr Vikram K Yeragani, Professor of Psychiatry, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, USA and Department of Psychiatry, University of Alberta, Edmonton, Canada, spoke on ‘‘Heritability of autonomic dysfunction in unaffected first-degree relatives of patients suffering from schizophrenia’’. Dr Yeragani discussed the significance of cardiac autonomic dysfunction in schizophrenia and proposed decreased cardiac vagal function as a potential endophenotype. In the study presented heart rate and blood pressure variability, QT variability and baroreflex sensitivity were examined in 27 schizophrenia patients, the NUMBER of unaffected first-degree relatives and 27 healthy controls. The relatives group was found to have decreased vagal modulation of heart rate and decreased baroreflex sensitivity similar to the patient group. The presence of these findings in the high risk group and also the strong heritability of autonomic parameters supported decreased cardiac vagal function as a potential endophenotypic marker of schizophrenia. The clinical significance of this autonomic dysfunction with regards to potential for causing serious cardiovascular events was also discussed. Dr Naren P Rao, Senior Resident, Department of Psychiatry, NIMHANS, Bangalore, India addressed the topic of ‘‘Neurocognitive endophenotypes in psychiatric disorders’’. Dr Rao summarized the concept and utility of endophenotypes in psychiatry research. A study done by the speaker which showed presence of executive dysfunction in a group of remitted patients of obsessive compulsive disorder as compared to healthy controls was presented (Rao et al., 2008). The non-invasive and less expensive nature of assessment and the presence of neurocongnitive deficits in remitted patients and their unaffected relatives in various psychiatric disorders (bipolar disorder, obsessive compulsive disorder and schizophrenia) have deemed these deficits as potential endophenotypes for future research. However, the limitations in terms of sensitivity and reliability of assessments also need to be considered.
Conference / Asian Journal of Psychiatry 2 (2009) 80–81
This symposium addressed the new emerging concept of endophenotypes in psychiatric research. The usefulness of the ‘extended endophenotypes’ and the need to move from the ‘phenome to the genome’ in future studies were highlighted. Endophenotype research would go a long way in enhancing our understanding of the neurobiology of psychiatric disorders.
81
cortex morphometry among first episode schizophrenia patients. Mol. Psychiatry 10 (2), 213–219. Rao, N.P., Reddy, Y.C., Kumar, K.J., Kandavel, T., Chandrashekar, C.R., 2008. Are neuropsychological deficits trait markers in OCD? Prog. Neuropsychopharmacol. Biol. Psychiatry 32 (6), 1574–1579. Venkatasubramanian, G., Gangadhar, B.N., Puthumana, D.T., Jayakumar, P.N., 2008. A functional MRI study of neurohaemodynamic abnormalities during emotion processing in subjects at high risk for schizophrenia (abstract). Indian J. Psychiatry 50 (Suppl. (5)), 5.
References Behere, R.V., Raghunandan, V.N.G.P., Venkatasubramanian, G., Subbakrishna, D.K., Jayakumar, P.N., Gangadhar, B.N., 2008. TRENDS—a Tool for Recognition of Emotions in Neuropsychiatric DisorderS. Indian J. Psychol. Med. 30 (1), 32–38. Gottesman, I.I., Shields, J., 1973. Genetic theorizing and schizophrenia. Br. J. Psychiatry 122 (566), 15–30. Gottesman, I.I., Gould, T.D., 2003. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160 (4), 636–645. Prasad, K.M., Chowdari, K.V., Nimgaonkar, V.L., Talkowski, M.E., Lewis, D.A., Keshavan, M.S., 2005. Genetic polymorphisms of the RGS4 and dorsolateral prefrontal
Rishikesh V. Behere* Department of Psychiatry, National Institute of Mental Health & Neurosciences, Hosur Road, Banglore 560029, India *Tel.: +91 80 26995250; fax: +91 80 26564830 E-mail address: [email protected]
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Conference
Conference proceedings: Biological psychiatry symposium on ‘‘Endophenotypes in Psychiatry’’ A one-day biological psychiatry symposium on ‘‘Endophenotypes in Psychiatry’’ was organized by the Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India, on the 3rd of January 2009. Dr MS Keshavan, of the Harvard Medical School, Boston, USA, addressed the gathering on the topic ‘‘Schizophrenia: Moving from the phenome to the genome’’. Introducing the concept, Dr Keshavan explained that though research over the last century had enhanced our understanding on the neurobiology of psychiatric disorders, none of the various neuroimaging, neurochemical and neurophysiological alterations described had qualified as definite diagnostic markers. The role of genetic factors in the etiology of schizophrenia, for example, was being increasingly recognized. However, the wide heterogeneity in its phenotypic presentation and the complex gene–environment interactions limited our understanding of the genetic basis of schizophrenia. In this context it was brought out that endophenotypes have emerged as useful tools in enhancing our understanding of psychiatric disorders. Endophenotypes are defined as ‘quantitative traits in the putative pathophysiologic pathway from the genotype to the phenotype’ (Gottesman and Shields, 1973). As per the Gottesman and Gould (2003), criteria, for a marker to qualify as an endophenotype it should: (1) be associated with illness in the relevant population, (2) be state independent, (3) be heritable, (4) co-segregate with the illness within families and (5) be present in unaffected family members more frequently than in the general population. Explaining the utility of endophenotypes, Dr Keshavan highlighted a study (Prasad et al., 2005), which demonstrated association of RGS4 gene polymorphisms with structural alterations of the dorsolateral prefrontal cortex (DLPFC) in schizophrenia. By studying the neurocognitive endophenotype of executive dysfunction and imaging endophenotype of DLPFC alterations, the polymorphism of RGS4 gene could be implicated in the genetic etiology of schizophrenia. Combination of such functionally related endophenotypes termed as ‘extended endophenotypes’ could play an important role in future research and studying these would be more clinically relevant as interventions for these specific phenotypic presentations could be planned. Continuing the discussion on extended endophenotypes, Dr Dawn Thomas K Puthumana, Assistant Professor, Department of Neuroimaging and Interventional Radiology, NIMHANS, Bangalore, India, spoke on ‘‘Functional MR correlates of emotion recognition in subjects at risk for schizophrenia’’. The basic principles and applications of neuroimaging in psychiatric disorders were discussed. Studies demonstrating smaller hippocampal volumes and reduced activation of DLPFC during cognitive tasks, on patients 1876-2018/$ – see front matter doi:10.1016/j.ajp.2009.04.006
and first-degree relatives of schizophrenia were highlighted; alterations in brain structure and function were proposed as potential endophenotypes. A study done by the speaker (Venkatasubramanian et al., 2008) was presented where brain hemodynamic activity during an implicit emotion recognition task was compared between 17 subjects at risk for schizophrenia (SARS) and 16 healthy controls using a novel ecologically valid and culture sensitive tool — Tool for Recognition of Emotions in Neuropsychiatric DisorderS (TRENDS) (Behere et al., 2008). The SARS group was found to have deficient brain activation for fearful expressions in the frontolimbic cortices. This study supported emotion recognition deficits as potential endophenotypes in schizophrenia. In the next session Dr Vikram K Yeragani, Professor of Psychiatry, Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, USA and Department of Psychiatry, University of Alberta, Edmonton, Canada, spoke on ‘‘Heritability of autonomic dysfunction in unaffected first-degree relatives of patients suffering from schizophrenia’’. Dr Yeragani discussed the significance of cardiac autonomic dysfunction in schizophrenia and proposed decreased cardiac vagal function as a potential endophenotype. In the study presented heart rate and blood pressure variability, QT variability and baroreflex sensitivity were examined in 27 schizophrenia patients, the NUMBER of unaffected first-degree relatives and 27 healthy controls. The relatives group was found to have decreased vagal modulation of heart rate and decreased baroreflex sensitivity similar to the patient group. The presence of these findings in the high risk group and also the strong heritability of autonomic parameters supported decreased cardiac vagal function as a potential endophenotypic marker of schizophrenia. The clinical significance of this autonomic dysfunction with regards to potential for causing serious cardiovascular events was also discussed. Dr Naren P Rao, Senior Resident, Department of Psychiatry, NIMHANS, Bangalore, India addressed the topic of ‘‘Neurocognitive endophenotypes in psychiatric disorders’’. Dr Rao summarized the concept and utility of endophenotypes in psychiatry research. A study done by the speaker which showed presence of executive dysfunction in a group of remitted patients of obsessive compulsive disorder as compared to healthy controls was presented (Rao et al., 2008). The non-invasive and less expensive nature of assessment and the presence of neurocongnitive deficits in remitted patients and their unaffected relatives in various psychiatric disorders (bipolar disorder, obsessive compulsive disorder and schizophrenia) have deemed these deficits as potential endophenotypes for future research. However, the limitations in terms of sensitivity and reliability of assessments also need to be considered.
Conference / Asian Journal of Psychiatry 2 (2009) 80–81
This symposium addressed the new emerging concept of endophenotypes in psychiatric research. The usefulness of the ‘extended endophenotypes’ and the need to move from the ‘phenome to the genome’ in future studies were highlighted. Endophenotype research would go a long way in enhancing our understanding of the neurobiology of psychiatric disorders.
81
cortex morphometry among first episode schizophrenia patients. Mol. Psychiatry 10 (2), 213–219. Rao, N.P., Reddy, Y.C., Kumar, K.J., Kandavel, T., Chandrashekar, C.R., 2008. Are neuropsychological deficits trait markers in OCD? Prog. Neuropsychopharmacol. Biol. Psychiatry 32 (6), 1574–1579. Venkatasubramanian, G., Gangadhar, B.N., Puthumana, D.T., Jayakumar, P.N., 2008. A functional MRI study of neurohaemodynamic abnormalities during emotion processing in subjects at high risk for schizophrenia (abstract). Indian J. Psychiatry 50 (Suppl. (5)), 5.
References Behere, R.V., Raghunandan, V.N.G.P., Venkatasubramanian, G., Subbakrishna, D.K., Jayakumar, P.N., Gangadhar, B.N., 2008. TRENDS—a Tool for Recognition of Emotions in Neuropsychiatric DisorderS. Indian J. Psychol. Med. 30 (1), 32–38. Gottesman, I.I., Shields, J., 1973. Genetic theorizing and schizophrenia. Br. J. Psychiatry 122 (566), 15–30. Gottesman, I.I., Gould, T.D., 2003. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160 (4), 636–645. Prasad, K.M., Chowdari, K.V., Nimgaonkar, V.L., Talkowski, M.E., Lewis, D.A., Keshavan, M.S., 2005. Genetic polymorphisms of the RGS4 and dorsolateral prefrontal
Rishikesh V. Behere* Department of Psychiatry, National Institute of Mental Health & Neurosciences, Hosur Road, Banglore 560029, India *Tel.: +91 80 26995250; fax: +91 80 26564830 E-mail address: [email protected]