- Email: [email protected]
Fronto-parietal connectivity and its relation to frontal glutamate in patients suffering from schizophrenia
Abstracts of the ENCP Workshop for Junior Scientists in Europe, 2018
Posters P.3.001 Depression is associated with increased insulin resistance: a meta-analysis E. Salagre Muñozn,1, A. McGuiness2, F. Jacka3, E. Vieta1, I. Grande1, A.F. Carvalho4, M. Berk3, B.S. Fernandes3 1
Hospital Clinic- Institute of Neurosciences- University of Barcelona- IDIBAPS- CIBERSAM, Bipolar Unit, Barcelona, Spain 2 Federal University of Rio Grande do Sul, Laboratory of Calcium Binding Proteins in the Central Nervous SystemDepartment of Biochemistry, Porto Alegre, Brazil 3 Deakin University- School of Medicine- and Barwon Health, IMPACT Strategic Research Centre, Geelong, Australia 4 Faculty of Medicine- Federal University of Ceará, Translational Psychiatry Research Group and Department of Clinical Medicine, Fortaleza, Brazil Background: Depression has been linked to an increased incidence of clinical comorbidity, such as diabetes mellitus (DM) [1]. Moreover, a bidirectional relationship between depression and DM has been described, with depressive symptoms being predictive of poor glycemic control in type 2 DM and DM increasing the incidence of depression [2]. To date, increased levels of insulin, indicating metabolic alterations, have been described in schizophrenia and bipolar disorder [3,4]. However, the presence of increased levels of insulin in depression remains unclear. The aim of this study is to verify if peripheral insulin levels are altered in acute or remitted depression compared to healthy controls. We also seek to determine whether there are changes on insulin levels after clinical resolution of an index depressive episode following antidepressant treatment. Methods: A systematic search for all eligible peerreviewed articles was conducted using Medline, the Cochrane Library and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA Statement). No language, year or country restrictions were used. The last search was performed in August of 2016. We included studies assessing serum or plasma fasting insulin in adults with depression alongside a control group of healthy volunteers. Two reviewers performed the study selection and data extraction. We identified 8,769 studies, of which thirty-eight fulfilled inclusion criteria. We carried out three between-group meta-analyses examining differences in serum or plasma insulin levels between healthy controls and: a) adult subjects with acute depression with psychiatric medication, b) adult subjects with acute depression without psychiatric medication and c) adult subjects with remitted depression with psychiatric medications. We also conducted a within-group meta-analysis comparing changes on insulin levels before and after treatment of an index depressive episode with antidepressants. Standardized mean difference estimates in insulin levels were calculated for all meta-analyses. Sensitivity analyses and meta-regressions according to mood state and psychiatric medication status were also performed. As the analyses showed that the studies were heterogeneous,
S61
effect size results from different studies were pooled according to the inverse variance method accounting for random effects. Results: Thirty-eight studies were included, providing data on 31,763 participants. Of all the participants, 7,142 were subjects with depression and 24,623 were healthy controls. Insulin levels were moderately increased in subjects with acute depression compared with healthy controls, both in patients treated with psychiatric medication (g = 0.38, 95% CI 0.17 to 0.59, po0.001, n= 5,038) and in drug-free patients (g =0.45, 95% CI 0.08 to 0.83, p= 0.018, n= 18,673). There were no differences on insulin levels between subjects with remitted depression and healthy controls (g = 0.11, 95% CI -0.13 to 0.36, p=0.351, n= 8,054). In sensitive analyses considering only studies paired by age, gender, or BMI, the results remained unchanged. There were no changes on insulin levels (g = 0.07, 95% CI -0.43 to 0.29, p= 0.699, n =117) following treatment with antidepressants. Conclusions: Our findings show that insulin levels are increased in acute depression and normal in remission. These results highlight a potential use of insulin as a biomarker of disease activity in depression. Further studies are warranted.
Disclosure statement BSF is supported by a postdoctoral research fellowship from Deakin University, Australia, and by a research grant MCTI/ CNPQ/Universal 14/2014461833/2014-0 from CNPq, Brazil. MB is supported by a NHMRC Senior Principal Research Fellowship 1059660. IG is supported by a Juan Rodés Contract (JR15/00012) and grant Proyecto de Investigación en Salud PI16/00187 from Instituto de Salud Carlos III, Spanish Ministry of Economy and Competiveness, Spain, and has served as a consultant for Ferrer and as a speaker for AstraZeneca, Ferrer and Janssen-Cilag. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, Actavis, Allergan, AstraZeneca, Bristol-Myers Squibb, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, Telefónica, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM),the Seventh European Framework Programme (ENBREC), and the Stanley Medical Research Institute.
References [1] Lang, U.E., Borgwardt, S. 2013. Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies. Cellular Physiology and Biochemistry 31(6): 761-77. [2] Stuart, M.J., Baune, B.T. 2012. Depression and type 2 diabetes: inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neuroscience and Biobehavioral Reviews 36(1): 658-676. [3] Pillinger, T., Beck, K., Gobjila, C., Donocik, J. G., Jauhar, S., Howes, O.D. 2017. Impaired Glucose Homeostasis in First-Episode Schizophrenia A Systematic Review and Meta-analysis. JAMA Psychiatry 74(3): 261-269.
S62 [4] Prathama Guha, P., Bhowmick, K., Mazumder, P., Ghosal, M., Chakraborty, I., Burman, P. 2014. Assessment of Insulin Resistance and Metabolic Syndrome in Drug Naive Patients of Bipolar Disorder. Ind J Clin Biochem 29(1): 51–56. http://dx.doi.org/10.1016/j.euroneuro.2017.12.091
P.3.002 Stigmatic attitudes towards mentally ill patients in Hungary between 2001 and 2015: results of a time-trend analysis T. Buchman-Wildbaumn,1,2, B. Paksi3, E. Sebestyén1,2, B. Kun2, K. Felvinczi2, A. Schmelowszky2, M.D. Griffiths4, Z. Demetrovics2, R. Urbán2 1
Doctoral School of Psychology, Eötvös Loránd University, Budapest, Hungary 2 Institute of Psychology, Eötvös Loránd University, Budapest, Hungary 3 Institute of Education, Eötvös Loránd University, Budapest, Hungary 4 Psychology Department, Nottingham Trent University, Nottingham, United Kingdom Background: Stigmatic attitudes towards people with the diagnosis of mental illness are widespread in the general public [1] and are the major obstacle for successful treatment, rehabilitation and reintegration of patients into the society [2]. Given the magnitude of this issue, and in the effort to develop effective anti stigma intervention programs, trend analysis studies were conducted, examining the changes in attitudes over the years [3]. The construct of social distance, which involves the desire to avoid contact with a particular group of people was commonly used to assess stigma. These studies have consistently reported that despite the improvement in mental health literacy of the public, social distance preferences concerning mentally ill patients have not changed over the last 20 years, and in some cases have even increased [3]. However, the number of studies using trend analysis is scarce and mainly limited to wealthier countries because such studies are both costly and time intensive. Consequently, most studies to date have been carried out in North Western Europe whereas data from Central and Eastern European countries, especially from former communist countries, is lacking [4,5]. Objective: In the face of underfinanced mental health system and the lack of any national anti-stigma programs or research, the aim of this study is to shed light into mental illness stigma in Hungary. More specifically, this study aimed to explore for the first time, potential changes concerning attitudes of the Hungarian population towards mentally ill patients. Method: National representative surveys (N =7605) of adults aged 18-53 years were carried out in Hungary in 2001, 2003, 2007 and 2015. An interview was conducted, asking for socio-demographic information and participants' desire for social distance from mentally ill patients, measured by Bogardus social distance scale. In order to put into context the stigmatic attitudes towards mentally ill patients, participants were also asked to report on their
social distance preferences towards other minorities in the Hungarian society. Trend analysis was performed to examine the trends of social distance. Results: Time-trend analysis indicated a significant (positive) trend in public preferences for social distance towards more accepting attitudes during the years of 2001-2015. However, closer examination reveals that the effect size is very small (0.05) and the 2015 rejection level is still high (57%) compared to over 60% in both 2001 and 2003. Moreover, during a period of 15 years, mentally ill patients are among the three most rejected groups in the society (with only alcoholics and drug users being more rejected). Conclusions: As was found in other countries around the world, in Hungary as well, stigmatic attitudes towards mentally ill patients are highly prevalent, and have not changed over the last decade. While stressing a worrisome reality in Hungary, where no efforts to tackle mental illness stigma were done, this study also verifies the enormity of the stigma phenomenon. It is evident, maybe more than anything, that much effort is needed in Hungary, but also worldwide, in order to understand and defeat mental illness stigma.
References [1] Angermeyer, M.C., Dietrich, S., 2006. Public beliefs about and attitudes towards people with mental illness: a review of population studies. Acta Psychiatr Scand 113, 163–179. [2] Hansson, L., Jormfeldt, H., Svedberg, P., Svensson, B., 2013. Mental health professionals’ attitudes towards people with mental illness: do they differ from attitudes held by people with mental illness? Int J Soc Psychiatry 59, 48–54. [3] Schomerus, G., Schwahn, C., Holzinger, A., Corrigan, P. W., Grabe, H.J., Carta, M.G., et al., 2012. Evolution of public attitudes about mental illness: a systematic review and meta-analysis. Acta Psychiatr Scand 125, 440–452. [4] Clarke, A., Gatineau, M., Grimaud, O., Royer-Devaux, S., Wyn-Roberts, N., Le Bis, I., et al., 2007. A bibliometric overview of public health research in Europe. Eur J Public Health 17, 43–49. [5] Evans-Lacko, S., Courtin, E., Fiorillo, A., Knapp, M., Luciano, M., Park, A.L., et al., 2014. The state of the art in European research on reducing social exclusion and stigma related to mental health: a systematic mapping of the literature. Eur Psychiatry 29, 381–389. http://dx.doi.org/10.1016/j.euroneuro.2017.12.092
P.3.003 Pleiotropic genes in psychiatry: calcium channels and the stress-related FKBP5 gene in antidepressant resistance F. Corponin,1, C. Fabbri1, D. Albani2, I. Raimondi2, G. Forloni2, K. Schruers3, S. Kasper4, A. Kautzky4, J. Zohar5, D. Souery6, S. Montgomery7, C.P. Cristalli8, V. Mantovani8, J. Mendlewicz9, A. Serretti1 1
University of Bologna, Department of Biomedical and NeuroMotor Sciences, Bologna, Italy
Posters P.3.001 Depression is associated with increased insulin resistance: a meta-analysis E. Salagre Muñozn,1, A. McGuiness2, F. Jacka3, E. Vieta1, I. Grande1, A.F. Carvalho4, M. Berk3, B.S. Fernandes3 1
Hospital Clinic- Institute of Neurosciences- University of Barcelona- IDIBAPS- CIBERSAM, Bipolar Unit, Barcelona, Spain 2 Federal University of Rio Grande do Sul, Laboratory of Calcium Binding Proteins in the Central Nervous SystemDepartment of Biochemistry, Porto Alegre, Brazil 3 Deakin University- School of Medicine- and Barwon Health, IMPACT Strategic Research Centre, Geelong, Australia 4 Faculty of Medicine- Federal University of Ceará, Translational Psychiatry Research Group and Department of Clinical Medicine, Fortaleza, Brazil Background: Depression has been linked to an increased incidence of clinical comorbidity, such as diabetes mellitus (DM) [1]. Moreover, a bidirectional relationship between depression and DM has been described, with depressive symptoms being predictive of poor glycemic control in type 2 DM and DM increasing the incidence of depression [2]. To date, increased levels of insulin, indicating metabolic alterations, have been described in schizophrenia and bipolar disorder [3,4]. However, the presence of increased levels of insulin in depression remains unclear. The aim of this study is to verify if peripheral insulin levels are altered in acute or remitted depression compared to healthy controls. We also seek to determine whether there are changes on insulin levels after clinical resolution of an index depressive episode following antidepressant treatment. Methods: A systematic search for all eligible peerreviewed articles was conducted using Medline, the Cochrane Library and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA Statement). No language, year or country restrictions were used. The last search was performed in August of 2016. We included studies assessing serum or plasma fasting insulin in adults with depression alongside a control group of healthy volunteers. Two reviewers performed the study selection and data extraction. We identified 8,769 studies, of which thirty-eight fulfilled inclusion criteria. We carried out three between-group meta-analyses examining differences in serum or plasma insulin levels between healthy controls and: a) adult subjects with acute depression with psychiatric medication, b) adult subjects with acute depression without psychiatric medication and c) adult subjects with remitted depression with psychiatric medications. We also conducted a within-group meta-analysis comparing changes on insulin levels before and after treatment of an index depressive episode with antidepressants. Standardized mean difference estimates in insulin levels were calculated for all meta-analyses. Sensitivity analyses and meta-regressions according to mood state and psychiatric medication status were also performed. As the analyses showed that the studies were heterogeneous,
S61
effect size results from different studies were pooled according to the inverse variance method accounting for random effects. Results: Thirty-eight studies were included, providing data on 31,763 participants. Of all the participants, 7,142 were subjects with depression and 24,623 were healthy controls. Insulin levels were moderately increased in subjects with acute depression compared with healthy controls, both in patients treated with psychiatric medication (g = 0.38, 95% CI 0.17 to 0.59, po0.001, n= 5,038) and in drug-free patients (g =0.45, 95% CI 0.08 to 0.83, p= 0.018, n= 18,673). There were no differences on insulin levels between subjects with remitted depression and healthy controls (g = 0.11, 95% CI -0.13 to 0.36, p=0.351, n= 8,054). In sensitive analyses considering only studies paired by age, gender, or BMI, the results remained unchanged. There were no changes on insulin levels (g = 0.07, 95% CI -0.43 to 0.29, p= 0.699, n =117) following treatment with antidepressants. Conclusions: Our findings show that insulin levels are increased in acute depression and normal in remission. These results highlight a potential use of insulin as a biomarker of disease activity in depression. Further studies are warranted.
Disclosure statement BSF is supported by a postdoctoral research fellowship from Deakin University, Australia, and by a research grant MCTI/ CNPQ/Universal 14/2014461833/2014-0 from CNPq, Brazil. MB is supported by a NHMRC Senior Principal Research Fellowship 1059660. IG is supported by a Juan Rodés Contract (JR15/00012) and grant Proyecto de Investigación en Salud PI16/00187 from Instituto de Salud Carlos III, Spanish Ministry of Economy and Competiveness, Spain, and has served as a consultant for Ferrer and as a speaker for AstraZeneca, Ferrer and Janssen-Cilag. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, Actavis, Allergan, AstraZeneca, Bristol-Myers Squibb, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, Telefónica, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM),the Seventh European Framework Programme (ENBREC), and the Stanley Medical Research Institute.
References [1] Lang, U.E., Borgwardt, S. 2013. Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies. Cellular Physiology and Biochemistry 31(6): 761-77. [2] Stuart, M.J., Baune, B.T. 2012. Depression and type 2 diabetes: inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neuroscience and Biobehavioral Reviews 36(1): 658-676. [3] Pillinger, T., Beck, K., Gobjila, C., Donocik, J. G., Jauhar, S., Howes, O.D. 2017. Impaired Glucose Homeostasis in First-Episode Schizophrenia A Systematic Review and Meta-analysis. JAMA Psychiatry 74(3): 261-269.
S62 [4] Prathama Guha, P., Bhowmick, K., Mazumder, P., Ghosal, M., Chakraborty, I., Burman, P. 2014. Assessment of Insulin Resistance and Metabolic Syndrome in Drug Naive Patients of Bipolar Disorder. Ind J Clin Biochem 29(1): 51–56. http://dx.doi.org/10.1016/j.euroneuro.2017.12.091
P.3.002 Stigmatic attitudes towards mentally ill patients in Hungary between 2001 and 2015: results of a time-trend analysis T. Buchman-Wildbaumn,1,2, B. Paksi3, E. Sebestyén1,2, B. Kun2, K. Felvinczi2, A. Schmelowszky2, M.D. Griffiths4, Z. Demetrovics2, R. Urbán2 1
Doctoral School of Psychology, Eötvös Loránd University, Budapest, Hungary 2 Institute of Psychology, Eötvös Loránd University, Budapest, Hungary 3 Institute of Education, Eötvös Loránd University, Budapest, Hungary 4 Psychology Department, Nottingham Trent University, Nottingham, United Kingdom Background: Stigmatic attitudes towards people with the diagnosis of mental illness are widespread in the general public [1] and are the major obstacle for successful treatment, rehabilitation and reintegration of patients into the society [2]. Given the magnitude of this issue, and in the effort to develop effective anti stigma intervention programs, trend analysis studies were conducted, examining the changes in attitudes over the years [3]. The construct of social distance, which involves the desire to avoid contact with a particular group of people was commonly used to assess stigma. These studies have consistently reported that despite the improvement in mental health literacy of the public, social distance preferences concerning mentally ill patients have not changed over the last 20 years, and in some cases have even increased [3]. However, the number of studies using trend analysis is scarce and mainly limited to wealthier countries because such studies are both costly and time intensive. Consequently, most studies to date have been carried out in North Western Europe whereas data from Central and Eastern European countries, especially from former communist countries, is lacking [4,5]. Objective: In the face of underfinanced mental health system and the lack of any national anti-stigma programs or research, the aim of this study is to shed light into mental illness stigma in Hungary. More specifically, this study aimed to explore for the first time, potential changes concerning attitudes of the Hungarian population towards mentally ill patients. Method: National representative surveys (N =7605) of adults aged 18-53 years were carried out in Hungary in 2001, 2003, 2007 and 2015. An interview was conducted, asking for socio-demographic information and participants' desire for social distance from mentally ill patients, measured by Bogardus social distance scale. In order to put into context the stigmatic attitudes towards mentally ill patients, participants were also asked to report on their
social distance preferences towards other minorities in the Hungarian society. Trend analysis was performed to examine the trends of social distance. Results: Time-trend analysis indicated a significant (positive) trend in public preferences for social distance towards more accepting attitudes during the years of 2001-2015. However, closer examination reveals that the effect size is very small (0.05) and the 2015 rejection level is still high (57%) compared to over 60% in both 2001 and 2003. Moreover, during a period of 15 years, mentally ill patients are among the three most rejected groups in the society (with only alcoholics and drug users being more rejected). Conclusions: As was found in other countries around the world, in Hungary as well, stigmatic attitudes towards mentally ill patients are highly prevalent, and have not changed over the last decade. While stressing a worrisome reality in Hungary, where no efforts to tackle mental illness stigma were done, this study also verifies the enormity of the stigma phenomenon. It is evident, maybe more than anything, that much effort is needed in Hungary, but also worldwide, in order to understand and defeat mental illness stigma.
References [1] Angermeyer, M.C., Dietrich, S., 2006. Public beliefs about and attitudes towards people with mental illness: a review of population studies. Acta Psychiatr Scand 113, 163–179. [2] Hansson, L., Jormfeldt, H., Svedberg, P., Svensson, B., 2013. Mental health professionals’ attitudes towards people with mental illness: do they differ from attitudes held by people with mental illness? Int J Soc Psychiatry 59, 48–54. [3] Schomerus, G., Schwahn, C., Holzinger, A., Corrigan, P. W., Grabe, H.J., Carta, M.G., et al., 2012. Evolution of public attitudes about mental illness: a systematic review and meta-analysis. Acta Psychiatr Scand 125, 440–452. [4] Clarke, A., Gatineau, M., Grimaud, O., Royer-Devaux, S., Wyn-Roberts, N., Le Bis, I., et al., 2007. A bibliometric overview of public health research in Europe. Eur J Public Health 17, 43–49. [5] Evans-Lacko, S., Courtin, E., Fiorillo, A., Knapp, M., Luciano, M., Park, A.L., et al., 2014. The state of the art in European research on reducing social exclusion and stigma related to mental health: a systematic mapping of the literature. Eur Psychiatry 29, 381–389. http://dx.doi.org/10.1016/j.euroneuro.2017.12.092
P.3.003 Pleiotropic genes in psychiatry: calcium channels and the stress-related FKBP5 gene in antidepressant resistance F. Corponin,1, C. Fabbri1, D. Albani2, I. Raimondi2, G. Forloni2, K. Schruers3, S. Kasper4, A. Kautzky4, J. Zohar5, D. Souery6, S. Montgomery7, C.P. Cristalli8, V. Mantovani8, J. Mendlewicz9, A. Serretti1 1
University of Bologna, Department of Biomedical and NeuroMotor Sciences, Bologna, Italy