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Poster #122 CORRELATIONS BETWEEN CLINICAL SYMPTOMS AND LEVEL OF SERUM ANTIBODIES TO HERPES GROUP VIRUSES IN PARANOID SCHIZOPHRENIA
Abstracts of the 3rd Biennial Schizophrenia International Research Conference / Schizophrenia Research 136, Supplement 1 (2012) S1–S375
source utilization costs and outcome measures were analyzed over time and compared between remission groups using mixed models for repeated measures or generalized estimating equations after adjusting for age, gender, race, site, illness duration, insurance, schizoaffective disorder diagnosis, substance use, personality disorder diagnosis, retardation, prior 1-year hospitalization, and site by remission interaction. Sensitivity analyses were conducted on total costs with/without multiple imputation to account for the missing data. Results: The sample was comprised primarily of male, Caucasian subjects with a mean age of 42 years. At enrollment, most (1684 of 2282, or 74%) did not meet remission criteria. Non-remitters had significantly higher PANSS total scores at baseline (76.4 vs. 53.2) than remitters, were younger at illness onset, less likely to be Caucasian, and more likely to have been hospitalized in the previous year and have a personality disorder (each comparison, p<0.05). Total mental health costs were higher for non-remitted than remitted subjects over the three year study (p=0.001). Sensitivity analysis using multiple imputation of the missing data confirmed the primary conclusion on total costs. The initial difference between groups was $5400 for the 6 months prior to enrollment and ranged from $2000 to $3000 at each 6-month assessment. The majority of the cost difference was due to psychiatric hospitalizations. Non-remitters were significantly more likely to be victims of crime, to exhibit violent behavior and be arrested, require emergency services and psychiatric hospitalization, and lack paid employment (all p<0.05). The groups did not significantly differ in likelihood of living independently. At enrollment, remitters had a 20 point higher total score on the Quality of Life Scale; this difference between groups was maintained at each 6 month assessment (p<0.001). Mean Global Assessment of Functioning scores significantly differed between groups over the 3 years; remitters’ scores were approximately 10 points higher at each assessment. For most measures, relative differences between remitters and non-remitters at enrollment were maintained over the three year period. Discussion: In this post-hoc analysis of a 3-year prospective observational study, the failure to achieve symptomatic remission at enrollment was associated with higher subsequent healthcare costs and worse functional outcomes. Further examination of outcomes for non-remitted subjects at baseline by their subsequent clinical status is warranted.
Poster #121 PROTEIN PROFILING OF PATIENTS WITH ACUTE PSYCHOSIS VS PSYCHIATRIC CONTROLS: A PROTEOMIC APPROACH. Valentina Mantua, Ginevra Orsolini, Laura Giusti, Mauro Mauri, Antonio Lucacchini Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, Pisa, Italy Background: Psychotic disorders such as schizophrenia and bipolar disorder are complex neuropsychiatric conditions of multifactorial etiology whose diagnosis is currently made solely on interview-based methodology. Therefore, biological markers which could improve the current classification and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. We describe here the preliminary data on the application of a protein profiling investigation for the identification of serum protein biomarkers in lymphocytes of patients with acute phase psychotic disorder compared with psychiatric controls. Methods: Patients were sampled and evaluated by means of SCID-I, PANSS, YMRS, HAM-A, HAM-D. Lymphocytes have been separeted and Two-dimensional electrophoresis (2-DE) was carried out on protein extracts. Analysis was performed using Progenesis Same Spot software and statistical univariate (ANOVA) and multivariate (PCA) analysis have been performed. Results: In this pilot study we recruited 9 patients with acute psychosis (4 had a diagnosis of Bipolar Disorder, 2 of Major Depression with psychotic symptoms, 2 of Schizoaffective Disorder, 1 of Schizophrenia) and 8 patients with mild to moderate Major Depression and no personal or family history of psychosis. Patients were all minimally medicated at time of blood sampling. Statistically significant difference have been reported between the two groups in PANSS total mean scores (p<0.001) and in YMRS total mean score (p=0.001). 2-DE showed significant differences between the two groups; in particular some protein spots are up regulated in a statistically
S229
significant manner and are under identification by mass spectrometry. PCA underlies a clear separation between the two groups, with a t1 value for the first component of 54%. Discussion: Preliminary analysis oN a small sample shows significant differences in protein expression. Though these proteins are currently still under identification, the results may suggest that patients with acute psychosis may carry a “ peripheral molecular fingerprint” that can be used to distinguish them regardless of diagnosis.
Poster #122 CORRELATIONS BETWEEN CLINICAL SYMPTOMS AND LEVEL OF SERUM ANTIBODIES TO HERPES GROUP VIRUSES IN PARANOID SCHIZOPHRENIA Irina I. Mikhailova 1 , Vera A. Orlova 1 , Vitalij L. Minutko 2 National Mental Health Research Center, National Academy of Medical Sciences, Moscow, Russia; 2 Clinic “Mental Health”, Moscow, Russia
1
Background: Last studies revealed a lot of findings in favor of the virus theory for Schizophrenia. However, the data are often conflicting. Methods: To study correlations between clinical symptoms and level of serum IgM and nuclear IgG to herpes group viruses in paranoid schizophrenia (ICD-10) 48 patients were examined: 16 patients with episodic type of flow and tendency to continuous one (1-st group), 16 – with episodic type of flow (2-nd group), and 16 – with remittent one (3-d group). All the patients were examined in hospital in acute paranoid state. There were used BPRS rating, the method of enzyme-linked immunosorbent assay (ELISA). Connections between different data were detected by correlation analysis. Results: In the 1-st group connections between IgM and IgG to Cytomegalovirus levels (r=0,6; p=0,004), between levels of IgG to Cytomegalovirus and to Herpes simplex virus 2 (r=0,; p=0,015) and between levels of IgM to Herpes simplex viruses 1 and 2 (r=0,54; p =0,032) have been discovered. There were found the connections between IgM to Herpes simplex virus 1 level and such BPRS parameters as the “Guilt” (r=0,5; p=0,05), “Unusual thought content” (r=0,52; p=0,04) an “Excitement” (r=-0,5; p=0,04). The last parameter also correlated with IgG to Herpes simplex virus 2 level (r=0,55; p=0,03). IgM to Herpes simplex virus 2 level was connected with “Motor retardation” (r=0,5; p=0,03) and “Excitement” parameters (r=-0,73; p=0,001), and IgM to Cytomegalovirus level– with “Hallucinations” (r=0,5; p=0,001) and “Unusual thought content” parameters (r=0,5; p=0,016). IgM to Epstein-Barr virus level correlated with “Depression” (r=0,58; p=0,04) and “Grandiosity” (r=-0,56; p=0,05) parameters. In the 2-nd group connections between levels of IgG to Herpes simplex virus 1 and IgM to the same virus (r=0,6; p=0,004), levels of IgG and IgM to Herpes simplex virus 2 (r=0,5; p=0,02 and r=0,53; p=0,036) and IgM to Herpes simplex viruses 1 and 2 (r=0,87; p=0,000) and between levels of IgM to Cytomegalovirus and Epstein-Barr virus (r=-0,6; p=0,011) have been revealed. Correlations of IgM to Cytomegalovirus level with “Tension” parameter (r=0,56; p=0,025), IgM to Epstein-Barr virus level with “Tension” (r=-0,6; p=0,008) and “Suspiciousness” parameters (r=-0,5; p=0,036) have been found. In the 3-rd group intervirus interactions have been found only between levels of IgM to Herpes symplex virus 2 and IgG to Cytomegalovirus (r=-0,54; p=0,03). Correlations of IgM to Herpes symplex virus 2 level with “Somatic concern” (r=0,7; p=0,001) and “Guilt” (r=0,59; p=0,017) parameters and also IgM to Epstein-Barr virus level with “Hostility” (r=0,6; p=0,01) parameter have been revealed. Discussion: The results confirm the significance of herpes group viruses in schizophrenia pathogenesis. For various paranoid schizophrenia course types spectrum of viruses, intervirus interactions and correlation between different viruses and clinic symptoms are different. In the most adverse forms of episodic type that tends to become continuous the biggest amount of virus agents, their prolonged persistence and connection with most psychopathological symptoms are being revealed. In episodic and remitting forms of paranoid schizophrenia pathogenetic participation of herpes group viruses is more partial. Clearly more research needs to be done on samples of bigger volume.
source utilization costs and outcome measures were analyzed over time and compared between remission groups using mixed models for repeated measures or generalized estimating equations after adjusting for age, gender, race, site, illness duration, insurance, schizoaffective disorder diagnosis, substance use, personality disorder diagnosis, retardation, prior 1-year hospitalization, and site by remission interaction. Sensitivity analyses were conducted on total costs with/without multiple imputation to account for the missing data. Results: The sample was comprised primarily of male, Caucasian subjects with a mean age of 42 years. At enrollment, most (1684 of 2282, or 74%) did not meet remission criteria. Non-remitters had significantly higher PANSS total scores at baseline (76.4 vs. 53.2) than remitters, were younger at illness onset, less likely to be Caucasian, and more likely to have been hospitalized in the previous year and have a personality disorder (each comparison, p<0.05). Total mental health costs were higher for non-remitted than remitted subjects over the three year study (p=0.001). Sensitivity analysis using multiple imputation of the missing data confirmed the primary conclusion on total costs. The initial difference between groups was $5400 for the 6 months prior to enrollment and ranged from $2000 to $3000 at each 6-month assessment. The majority of the cost difference was due to psychiatric hospitalizations. Non-remitters were significantly more likely to be victims of crime, to exhibit violent behavior and be arrested, require emergency services and psychiatric hospitalization, and lack paid employment (all p<0.05). The groups did not significantly differ in likelihood of living independently. At enrollment, remitters had a 20 point higher total score on the Quality of Life Scale; this difference between groups was maintained at each 6 month assessment (p<0.001). Mean Global Assessment of Functioning scores significantly differed between groups over the 3 years; remitters’ scores were approximately 10 points higher at each assessment. For most measures, relative differences between remitters and non-remitters at enrollment were maintained over the three year period. Discussion: In this post-hoc analysis of a 3-year prospective observational study, the failure to achieve symptomatic remission at enrollment was associated with higher subsequent healthcare costs and worse functional outcomes. Further examination of outcomes for non-remitted subjects at baseline by their subsequent clinical status is warranted.
Poster #121 PROTEIN PROFILING OF PATIENTS WITH ACUTE PSYCHOSIS VS PSYCHIATRIC CONTROLS: A PROTEOMIC APPROACH. Valentina Mantua, Ginevra Orsolini, Laura Giusti, Mauro Mauri, Antonio Lucacchini Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, Pisa, Italy Background: Psychotic disorders such as schizophrenia and bipolar disorder are complex neuropsychiatric conditions of multifactorial etiology whose diagnosis is currently made solely on interview-based methodology. Therefore, biological markers which could improve the current classification and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. We describe here the preliminary data on the application of a protein profiling investigation for the identification of serum protein biomarkers in lymphocytes of patients with acute phase psychotic disorder compared with psychiatric controls. Methods: Patients were sampled and evaluated by means of SCID-I, PANSS, YMRS, HAM-A, HAM-D. Lymphocytes have been separeted and Two-dimensional electrophoresis (2-DE) was carried out on protein extracts. Analysis was performed using Progenesis Same Spot software and statistical univariate (ANOVA) and multivariate (PCA) analysis have been performed. Results: In this pilot study we recruited 9 patients with acute psychosis (4 had a diagnosis of Bipolar Disorder, 2 of Major Depression with psychotic symptoms, 2 of Schizoaffective Disorder, 1 of Schizophrenia) and 8 patients with mild to moderate Major Depression and no personal or family history of psychosis. Patients were all minimally medicated at time of blood sampling. Statistically significant difference have been reported between the two groups in PANSS total mean scores (p<0.001) and in YMRS total mean score (p=0.001). 2-DE showed significant differences between the two groups; in particular some protein spots are up regulated in a statistically
S229
significant manner and are under identification by mass spectrometry. PCA underlies a clear separation between the two groups, with a t1 value for the first component of 54%. Discussion: Preliminary analysis oN a small sample shows significant differences in protein expression. Though these proteins are currently still under identification, the results may suggest that patients with acute psychosis may carry a “ peripheral molecular fingerprint” that can be used to distinguish them regardless of diagnosis.
Poster #122 CORRELATIONS BETWEEN CLINICAL SYMPTOMS AND LEVEL OF SERUM ANTIBODIES TO HERPES GROUP VIRUSES IN PARANOID SCHIZOPHRENIA Irina I. Mikhailova 1 , Vera A. Orlova 1 , Vitalij L. Minutko 2 National Mental Health Research Center, National Academy of Medical Sciences, Moscow, Russia; 2 Clinic “Mental Health”, Moscow, Russia
1
Background: Last studies revealed a lot of findings in favor of the virus theory for Schizophrenia. However, the data are often conflicting. Methods: To study correlations between clinical symptoms and level of serum IgM and nuclear IgG to herpes group viruses in paranoid schizophrenia (ICD-10) 48 patients were examined: 16 patients with episodic type of flow and tendency to continuous one (1-st group), 16 – with episodic type of flow (2-nd group), and 16 – with remittent one (3-d group). All the patients were examined in hospital in acute paranoid state. There were used BPRS rating, the method of enzyme-linked immunosorbent assay (ELISA). Connections between different data were detected by correlation analysis. Results: In the 1-st group connections between IgM and IgG to Cytomegalovirus levels (r=0,6; p=0,004), between levels of IgG to Cytomegalovirus and to Herpes simplex virus 2 (r=0,; p=0,015) and between levels of IgM to Herpes simplex viruses 1 and 2 (r=0,54; p =0,032) have been discovered. There were found the connections between IgM to Herpes simplex virus 1 level and such BPRS parameters as the “Guilt” (r=0,5; p=0,05), “Unusual thought content” (r=0,52; p=0,04) an “Excitement” (r=-0,5; p=0,04). The last parameter also correlated with IgG to Herpes simplex virus 2 level (r=0,55; p=0,03). IgM to Herpes simplex virus 2 level was connected with “Motor retardation” (r=0,5; p=0,03) and “Excitement” parameters (r=-0,73; p=0,001), and IgM to Cytomegalovirus level– with “Hallucinations” (r=0,5; p=0,001) and “Unusual thought content” parameters (r=0,5; p=0,016). IgM to Epstein-Barr virus level correlated with “Depression” (r=0,58; p=0,04) and “Grandiosity” (r=-0,56; p=0,05) parameters. In the 2-nd group connections between levels of IgG to Herpes simplex virus 1 and IgM to the same virus (r=0,6; p=0,004), levels of IgG and IgM to Herpes simplex virus 2 (r=0,5; p=0,02 and r=0,53; p=0,036) and IgM to Herpes simplex viruses 1 and 2 (r=0,87; p=0,000) and between levels of IgM to Cytomegalovirus and Epstein-Barr virus (r=-0,6; p=0,011) have been revealed. Correlations of IgM to Cytomegalovirus level with “Tension” parameter (r=0,56; p=0,025), IgM to Epstein-Barr virus level with “Tension” (r=-0,6; p=0,008) and “Suspiciousness” parameters (r=-0,5; p=0,036) have been found. In the 3-rd group intervirus interactions have been found only between levels of IgM to Herpes symplex virus 2 and IgG to Cytomegalovirus (r=-0,54; p=0,03). Correlations of IgM to Herpes symplex virus 2 level with “Somatic concern” (r=0,7; p=0,001) and “Guilt” (r=0,59; p=0,017) parameters and also IgM to Epstein-Barr virus level with “Hostility” (r=0,6; p=0,01) parameter have been revealed. Discussion: The results confirm the significance of herpes group viruses in schizophrenia pathogenesis. For various paranoid schizophrenia course types spectrum of viruses, intervirus interactions and correlation between different viruses and clinic symptoms are different. In the most adverse forms of episodic type that tends to become continuous the biggest amount of virus agents, their prolonged persistence and connection with most psychopathological symptoms are being revealed. In episodic and remitting forms of paranoid schizophrenia pathogenetic participation of herpes group viruses is more partial. Clearly more research needs to be done on samples of bigger volume.