Diagnostic Interview For Genetic Studies Research Articles

Relationship between Polygenic Risk Score and the Hypnotics in Bipolar I Disorder.

Bipolar disorder (BD) is marked by significant change in mood and energy levels with sleep disturbance a common feature, resulting in diminished quality of life and impaired daily functioning. This study assessed the association between BD-polygenic risk scores (PRS) and hypnotics in bipolar I disorder (BD-I) patients. Large-sample data were collected from the genome-wide association study of a multicenter Bipolar Genomic Study, and 1,394 BD-I patients with available medication information were divided into two groups depending on whether they used hypnotics or not. The Diagnostic Interview for Genetic Studies (DIGS) score was used to assess the clinical manifestations and function of the participants and the association between the use of hypnotics and genetic risk was analyzed. Of the 1,394 total participants, 556 (40%) patients received hypnotics, mostly benzodiazepines, administered singly or in combination with other sleeping agents such as, Z-drugs, melatonin-related drugs, and trazodone. The DIGS score was significantly higher for negative categories in the group prescribed hypnotics as was the BD-PRS score, according to the four p value thresholds (p = 0.3, 0.2, 0.1, and 0.05). Logistic regression analysis confirmed a statistically significant association between the BD-PRS and hypnotic use. Our results suggest an association between hypnotic use and genetic susceptibility to BD. Sleep disturbances in participants were based on the prescription status of hypnotics supporting the hypothesis that sleep disturbances may be associated with genetic aspects of BD-I. Further genetic studies on genetic overlaps between BD and specific phenotypes or medication responses are required.

GxE interaction effects of HCRTR2 single nucleotide polymorphism and adverse childhood experiences on methamphetamine use disorder

ABSTRACT Background: Methamphetamine use disorder (MUD) is a worldwide health concern. The hypothalamic orexin system regulates stress response and addictive behaviors. The genetic variation in the hypocretin receptor 2 (HCRTR2), rs2653349, is associated with substance use disorder. Objectives: We explored the gene-environment (GxE) interaction of rs2653349 and adverse childhood experiences (ACEs) associated with MUD susceptibility. Methods: Four hundred and one individuals (336 males, 65 females) with MUD and 348 healthy controls (288 males, 60 females) completed a self-report questionnaire evaluating ACEs, encompassing childhood abuse and household dysfunction categories, and were genotyped for SNP rs2653349. Methamphetamine use variables were collected using the Diagnostic Interview for Genetic Studies. We used regression analyses to assess the GxE effect on MUD risk. Results: The MUD group had a comparable genotypic distribution for rs2653349 to the control group, albeit with a higher prevalence and number of types of ACEs, correlating with an increased MUD risk (p < .05). No significant genetic impact of rs2653349 on MUD risk was found. However, we observed a GxE interaction effect between the minor allele of rs2653349 and the number of childhood abuse or household dysfunction types, correlating with a reduced MUD risk (OR = -0.71, p = .04, Benjamini-Hochberg adjusted p = .08 and OR = -0.59, p = .045, Benjamini-Hochberg adjusted p = .09, respectively). Conclusion: HCRTR2 SNP rs2653349 has no significant impact on MUD risk, but ACEs may increase this risk. GxE results suggest that rs2653349 could offer protection against developing MUD in individuals experiencing multiple types of ACEs.

Preliminary studies on apparent mendelian psychotic disorders in consanguineous families

BackgroundPsychiatric disorders are characterized by alteration in emotions, mood and behavior. Genetics is known to play a significant role in the development of psychiatric disorders. Genome-wide association studies have identified several loci associated with psychiatric illnesses. We hypothesize the existence of rare variants following Mendelian recessive mode of inheritance. These variants can be identified in families with multiple affected individuals born to unaffected consanguineous parents.MethodsWe visited psychiatric outpatient departments of multiple hospitals in Lahore, Pakistan. We focused on psychosis, as it can occur in several DSM disorders such as schizophrenia, dementia and bipolar disorder. After clinical diagnosis by an American trained psychiatrist, detailed clinical assessments using Diagnostic Interview for Genetic Studies (DIGS), Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD), Positive and Negative Syndrome Scale (PANSS), Hamilton Depression and Anxiety Rating Scale (HAM-D; HAM-A) were administered to all willing affected and unaffected participants.ResultsWe identified eight pedigrees with two or more psychotic individuals in each family. Clinical diagnoses determined by their psychiatrists included ten individuals with schizophrenia; four individuals with psychosis and bipolar disorder; and two patients with “unspecified psychosis.” The rating instruments rigorously confirmed the diagnosis of psychosis in the affected patients from the six families as well as the absence of psychotic disorders in unaffected individuals from the six families. We obtained DNA samples from willing members of all eight families for future genetic analyses.ConclusionOur research highlights an alternative approach to discovery of rare recessively inherited genetic variants causing psychiatric disorders that have remained unidentified to date. These findings could illuminate underlying biological mechanisms leading toward development of targeted therapies in future.

Effect of the Type and Number of Adverse Childhood Experiences and the Timing of Adverse Experiences on Clinical Outcomes in Individuals with Bipolar Disorder.

Studies have reported an association between adverse childhood experiences (ACEs) and the clinical outcomes of bipolar disorder (BD). However, these studies have several limitations; therefore, we aimed to clarify the effect of the type and number of ACEs and the timing of adverse experiences on clinical outcomes in patients with BD. We analyzed the data of patients with BD (N = 2675) obtained from the National Institute of Mental Health: Bipolar Disorder Genetic Association Information Network, Translational Genomic Institute-I, and Translational Genomic Institute-II. All patients had been diagnosed using the Diagnostic Interview for Genetic Studies. ACEs were evaluated using the Childhood Life Events Scale (CLES). We analyzed the relationship between childhood trauma and clinical outcome in patients with and without exposure to ACEs. We found that ACEs had a robust negative effect on clinical outcomes, including earlier age at onset, presence of psychotic episodes, suicide attempts, mixed symptoms or episodes, substance misuse comorbidity, and worse life functioning. Specifically, the number of ACEs had the most significant effect on clinical outcomes; however, specific ACEs, such as physical abuse, had a considerable influence. Moreover, post-childhood adverse experiences had a weaker effect on clinical outcomes than ACEs did. There was an association of ACEs with negative clinical outcomes in patients with BD. This indicates the importance of basic and clinical research on ACEs in patients with BD.

A preliminary study to investigate resting state fMRI as a potential group differentiator for schizophrenia.

Schizophrenia (SZ) is found to be associated with dysconnectivity between the various regions of the brain. These aberrant connections in brain networks responsible for various mental processes in schizophrenia. We examined differences in functional connectivity among persons with SZ (n = 30) and an equal number of their unaffected relatives using resting state functional Magnetic Resonance Imaging (rsfMRI). Subjects were interviewed using the Diagnostic Interview for Genetic Studies (DIGS) and Family Interview for Genetic Studies (FIGS). Cognition was assessed using the Computerized Neuropsychological Battery (CNB) and Trail Making Tests A and B. The resting state functional data were acquired using 3.0 T Magnetic Resonance Imaging system and analysed using Statistical Package for the Social Sciences (SPSS) version 21 and FSL version 5.01 (FMRIB's) Software. The persons with SZ performed significantly worse on tasks of cognition and executive functioning. On rsfMRI, a significantly reduced connectivity was noted in the case group in right and left precentral gyri, right post central gyrus, right and left middle temporal gyrus, left paracingulate gyrus, anterior and posterior cingulate, right planum temporale, right pallidum, left cerebellum-6,7b and 8 lobules. Increased connectivity was noted between areas of right temporal pole and left hippocampus, posterior cingulate and the precuneus, right planum polare and right amygdala, right Heschl's gyrus and left posterior supramarginal gyrus, right amygdala with right insular cortex and left cerebellum 6 with bilateral postcentral gyrus in the same group. These differences in connectivity could be utilised as potential group differentiator for schizophrenia.

On the Continuity Between Autistic and Schizoid Personality Disorder Trait Burden: A Prospective Study in Adolescence.

Although widely conceived as distinct conditions, higher-functioning autism spectrum disorder (ASD) and schizoid personality disorder (schizoid PD) share similar clinical symptomatology. This study explored the relationship between the two disorders by collecting extensively validated measures of autistic trait burden (Social Responsive Scale, Second Edition) and schizoid PD affectation (Diagnostic Interview for Genetic Studies) from clinically ascertained verbal males with and without autism ages 12 to 25 years (N = 72) via parent, teacher, and self-report. Although only a small minority of adolescents with ASD met full diagnostic criteria for schizoid PD, participants with ASD endorsed a continuous distribution of schizoid PD traits that reflected a pronounced pathological shift in comparison with those in the control group, with one half of ASD males experiencing three or more Diagnostic and Statistical Manual of Mental Disorders, 4th Edition schizoid PD criterion items "often" or "almost always." Results suggest significant amplification of schizoid PD trait burden in adolescents with ASD. ASD-specific interventions should be considered for patients with schizoid PD with premorbid histories of ASD.

Identifying an accurate self-reported screening tool for alcohol use disorder: evidence from a Swiss, male population-based assessment.

Short screenings for alcohol use disorder (AUD) are crucial for public health purposes, but current self-reported measures have several pitfalls and may be unreliable. The main aim of our study was to provide empirical evidence on the psychometric performance of self-reports currently used. Our research questions were: compared with a gold standard clinical interview, how accurate are (1) self-reported AUD, (2) self-reported alcohol use over time and (3) biomarkers of alcohol use among Swiss men? Finally, we aimed to identify an alternative screening tool. A single-center study with a cross-sectional design and a stratified sample selection. Lausanne University Hospital (Switzerland) from October 2017 to June 2018. We selected participants from the French-speaking participants of the ongoing Cohort Study on Substance Use and Risk Factors (n=233). The sample included young men aged on average 27.0years. We used the Diagnostic Interview for Genetic Studies as the gold standard for DSM-5 AUD. The self-reported measures included 11 criteria for AUD, nine alcohol-related consequences, and previous 12months' alcohol use. We also assessed biomarkers of chronic excessive drinking (ethyl glucuronide and phosphatidylethanol). None of the self-reported measures/biomarkers taken alone displayed both sensitivity and specificity close to 100% with respect to the gold standard (e.g. self-reported AUD: sensitivity=92.3%, specificity=45.8%). The best model combined eight self-reported criteria of AUD and four alcohol-related consequences. Using a cut-off of three, this screening tool yielded acceptable sensitivity (83.3%) and specificity (78.7%). Neither self-reported alcohol use disorder nor heavy alcohol use appear to be adequate to screen for alcohol use disorder among young men from the Swiss population. The best screening alternative for alcohol use disorder among young Swiss men appears to be a combination of eight symptoms of alcohol use disorder and four alcohol-related consequences.

Decreased core symptoms of mania and utilization of lithium/mood stabilizing anticonvulsants in U.S. bipolar I patients of African vs European ancestry

ObjectiveMisdiagnosis is common in bipolar disorder and disproportionally affects racial and ethnic minorities. There is interest in better understanding the contribution of differential symptomatic illness presentation to misdiagnosis. MethodsUtilizing the Genetic Association Information Network (GAIN) public database, this study compared clinical phenomenology between bipolar patients of African vs European ancestry (AA = 415 vs EA = 480). The Diagnostic Interview for Genetic Studies (DIGS) was utilized to evaluate symptom endorsement contributing to diagnostic confirmation of bipolar I disorder (BPI) and lifetime medication use. ResultsElevated/euphoric mood was less endorsed in AA vs EA participants (p = 0.03). During the most severe episode of mania, AA participants, in comparison to EA participants, had a lower sum of manic symptoms (p = 0.006) and a higher rate of hallucinations (p = 0.01). During lifetime psychosis, AA participants, in comparison to EA participants, had a higher lifetime sum of delusions (p = 0.01) and hallucinations (p < 0.0001). AA participants reported lower use of lithium (p < 0.0001) and mood stabilizing anticonvulsants (p = 0.0003). ConclusionsThe differential rate of manic and psychotic symptom endorsement from a semi-structured diagnostic interview may represent differential illness presentation based on biological differences or racial or study biases (e.g. ascertainment). Increased minority recruitment in bipolar research is therefore a necessary future direction. LimitationsRecall and interviewer bias may affect study results, but are likely diminished by the alignment of symptom endorsement and medication use.

Patterns and predictors of family environment among adolescents at high and low risk for familial bipolar disorder

Children's perceptions are important to understanding family environment in the bipolar disorder (BD) high-risk context. Our objectives were to empirically derive patterns of offspring-perceived family environment, and to test the association of family environment with maternal or paternal BD accounting for offspring BD and demographic characteristics. Participants aged 12–21 years (266 offspring of a parent with BD, 175 offspring of a parent with no psychiatric history) were recruited in the US and Australia. We modeled family environment using latent profile analysis based on offspring reports on the Conflict Behavior Questionnaire, Family Adaptability and Cohesion Evaluation Scales, and Home Environment Interview for Children. Parent diagnoses were based on the Diagnostic Interview for Genetic Studies and offspring diagnoses were based on the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Latent class regression was used to test associations of diagnosis and family environment. Two-thirds of all offspring perceived well-functioning family environment, characterized by nurturance, flexibility, and low conflict. Two ‘conflict classes’ perceived family environments low in flexibility and cohesion, with substantial separation based on high conflict with the father (High Paternal Conflict), or very high conflict and rigidity and low warmth with the mother (High Maternal Conflict). Maternal BD was associated with offspring perceiving High Maternal Conflict (OR 2.8, p = 0.025). Clinical care and psychosocial supports for mothers with BD should address family functioning, with attention to offspring perceptions of their wellbeing. More research is needed on the effect of paternal BD on offspring and family dynamics.

Assessment of heavy alcohol drinking among young Swiss men

There is a need of empirical evidence of the relationship between heavy alcohol use and alcohol markers. More precisely, associations of these markers with patterns of alcohol use, such as risky single occasion drinking (i.e., drinking 6 drinks or more on a single occasion) have been scarcely investigated. This study aimed to derive psychometric properties of alcohol markers in comparison with different measures of alcohol use and to test whether it allows detecting excessive alcohol use. Participants ( n = 233, male, around 20 years old) were recruited based on a stratified random selection of the Swiss Cohort Study on Substance Use and Risk Factors. Inclusion criterion was an Audit score ≥ 13. Assessments included a clinical interview based on the Diagnostic Interview for Genetic Studies (DIGS) and self-reported alcohol measures [1] . Hair ( n = 230) and capillary blood ( n = 233) on Hemaxis ® DBS device were collected for ethyl glucuronide (EtG) and phosphatidylethanol (PEth) determination, respectively. EtG was extracted from washed hair by micropulverized extraction and SPE purification. The extracts were submitted to LC-MS/MS analysis (6500 Qtrap Sciex). Chromatographic separation was achieved using a Merck Chromolith ® RP-C18e column (150 × 3 mm). The PEth homologs 16:0/18:1 and 16:0/18:2 concentrations were determined by LC-MS/MS (5000 Qtrap Sciex) according to a validated method [2] . For the interpretation, only the PEth homolog 16:0/18:1 were used. Statistical data treatment (ROC-analysis) was carried out using R software. EtG could be detected in 151 of 230 samples with concentrations ≥ 4.0 pg/mg (LOQ). The maximum measured concentration was 690 pg/mg. Twenty-five percent, 50% (median) and 75% percentiles were 6.8, 15, and 34 pg/mg, respectively. In 53 cases, EtG concentrations were ≥ 30 pg/mg, suggesting excessive alcohol consumption. The area under the ROC curve for EtG ≥ 30 pg/mg vs. PEth was 0.8322. In cases where PEth ≥ 210 ng/mL, more than 75% presented also EtG ≥ 30 pg/mg. PEth 16:0/18:1 detected in 218 of 233 samples with concentrations ≥ 10 ng/mL (LOQ). The maximum measured concentration was 1990 ng/mL. Twenty-five percent, 50% (median) and 75% percentiles were 71, 182, and 360 ng/ml, respectively. In 99 cases, PEth 16:0/18:1 concentrations ≥ 210 ng/mL, suggesting excessive alcohol consumption, were found. Compared to self-reported data (last week total alcohol intake diary), area under the ROC curve for PEth ≥ 210 ng/mL were 0.8174. For detecting a risky single occasion drinking (≥ 5 drinks at one occasion), the area under the ROC curve for PEth were 0.7955. EtG and PEth measurement allowed detecting excessive alcohol consumption with high specificity and sensitivity. Both marker are complementary and do not necessarily provide the same information because of their different detection window and change of consumption during the evaluation period. The results support the statement in the SoHT consensus for the use of alcohol markers: “It is not advisable to use the results of hair testing for alcohol markers in isolation” [3] .

M64 - POLYGENIC RISK FOR ANXIETY SHAPES PATTERNS OF COMORBIDITY IN BIPOLAR DISORDER

Background Anxiety disorders are one of the most common comorbid conditions in people with bipolar disorder and are associated with unfavorable outcomes, including increased recurrence, higher rates of alcohol and substance abuse, and more frequent suicide attempts. However, the causal direction has remained unclear: Does poorer outcome lead to anxiety, or does comorbid anxiety result in poorer outcomes? Methods Here we used a Polygenic Risk Score (PGS) for anxiety to approach this question in a sample of 1754 adults with bipolar I or schizoaffective bipolar disorder previously characterized by the Diagnostic Interview for Genetic Studies (DIGS) and genotyped on Affymetrix 6.0 arrays. Anxiety PGS was calculated on the basis of results from the largest published GWAS meta-analysis of anxiety disorders (Otowa et al., 2016). Markers were LD clumped and the p-value threshold was set at 1. First we examined anxiety disorder comorbidity by creating a categorical ‘anxiety disorders’ variable comprising any DSM anxiety disorder diagnosis. Results Anxiety PGS was significantly associated with anxiety comorbidity (X2=7.756, df=1, p Discussion Taken together, these findings indicate that genetic risk for anxiety contributes to patterns of comorbidity in bipolar disorder, increasing risk for some anxiety disorders and for anorexia. Other common comorbidities and clinical features appear unrelated to genetic risk for anxiety, suggesting distinct etiologies.

SA96 - ASSOCIATION STUDY POLYMORPHISMS OF THE NEUREGULIN 1 (NRG1) GENE WITH SCHIZOPHRENIA

Background The dysfunction of Neuregulin 1 (NRG1) is one of the plausible hypotheses for the pathogenesis of schizophrenia. The Neuregulin 1 (NRG1) is located on chromosome 8p, as suggested by multiple linkage studies. The aim of this study is to clarify the contribution of polymorphisms of the Neuregulin 1 (NRG1) with schizophrenia. Methods After informed consent was obtained, 100 schizophrenia patients and 100 control subjects were enrolled in this study. All subjects were administered the Diagnostic Interview for Genetic Studies (DIGS) (National Institute of Mental Health-Molecular Genetics Initiative, 1992; Nurnberger et al., 1994) by a research assistant with extensive training in this interview. Blood samples were collected in anonymously identified 10-ml Vacutainer tubes (Becton Dickinson). DNA was prepared by a modified SDS/Proteinase K procedure (Gusells et al., 1979). We genotyped polymorphism Neuregulin 1 (NRG1) with the PCR-RFLP methods. The PCR products were digested by restricted enzyme. Results We observed a significant association between the polymorphism neuregulin 1 (NRG1) and the schizophrenia (Chi-Square Test P= 0.0449). Discussion The NRG1 gene was originally identified as a susceptibility gene for schizophrenia by using a combination of a linkage and association approaches based on microsatellite markers and then using SNPs after microsatellite at risk haplotypes were identified. We found there is the frequency of the polymorphism of Neuregulin 1 (NRG1) was significantly increased in schizophrenia patients. This allelic association suggests that the functional polymorphism Neuregulin 1 (NRG1) may play a role in susceptibility to schizophrenia. Further study with larger sample sizes is required.

Relationship between Craving and Early Relapse in Alcohol Dependence: A Short-Term Follow-up Study.

Background:The role of craving in alcohol dependence and its relationship with relapse has been studied widely in the past decade. The present study was undertaken to assess the role of craving in short-term relapse of patients seeking treatment for alcohol dependence and changes in craving score at the end of detoxification and at follow-up.Materials and Methods:A total of 34 male individuals with alcohol dependence (excluding comorbid drug dependence, organic or psychiatric disorder), after detoxification and discharge, consented. No anticraving medicine, aversive or psychotherapy, was advised. They were diagnosed on the International Statistical Classification of Diseases-10 using Diagnostic Interview for Genetic Studies. Severity of Alcohol Dependence Questionnaire (SADQ) and Clinical Institute Withdrawal Assessment Scale–Alcohol-Revised (CIWA-AR) were administered at the time of admission. Penn Alcohol Craving Scale (PACS) was applied at the time of discharge and follow-up to measure craving for alcohol.Results:Out of a total of thirty patients analyzed after dropout, 21 relapsed at the end of 1 month. On comparing PACS scores between relapsed and nonrelapsed patients, the difference was significant at both time points, i.e., at discharge and follow-up (t = 4.15, P < 0.0001 and t = 4.01, P < 0.001, respectively). In the total sample, SADQ and CIWA-AR scores were positively correlated (r = 0.47, P = 0.009). PACS at discharge was compared with PACS at follow-up, of which the correlation was high (r = 0.832, P < 0.0001).Conclusion:Craving seems to be a main factor related to relapse. Its measurement with PACS can be a useful tool to predict subsequent drinking and to identify individual risk for relapse during treatment.

Risk Factors Associated With Antidepressant Exposure and History of Antidepressant-Induced Mania in Bipolar Disorder.

Despite their widespread use in bipolar disorder, there is controversy surrounding the inclusion of antidepressant medications in the disorder's management. We sought to identify which demographic, socioeconomic, and clinical factors are associated with antidepressant exposure in bipolar disorder and which bipolar disorder patients are most likely to report a history of antidepressant-induced mania (AIM) when exposed to antidepressants. Our study included subjects with bipolar I disorder (n = 309), bipolar II disorder (n = 66), and bipolar disorder not otherwise specified (n = 27) and schizoaffective disorder, bipolar type (n = 14), from a longitudinal, community-based study. Subjects were evaluated using the Diagnostic Interview for Genetic Studies, modified for DSM-IV criteria. We applied multivariate logistical regression modeling to investigate which factors contribute to antidepressant exposure in bipolar disorder patients. We also used a logistic regression modeling approach to determine which clinical factors in bipolar disorder patients are associated with a history of AIM. Data were gathered from February 2006 through December 2010. Our results suggest that the risk factors most strongly associated with antidepressant exposure are female sex (OR = 2.73, P = .005), older age (OR = 1.03, P = .04), greater chronicity of illness (OR = 2.29, P = .04), and, to a lesser extent, white race (OR = 0.44, P = .051). Factors associated with reduced antidepressant exposure include history of affective psychosis (OR = 0.36, P = .01) and a greater number of previous manic episodes (OR = 0.98, P = .03). In subjects who reported a history of AIM, regression analysis revealed that the only statistically significant factor associated with AIM history was female sex (OR = 3.74, P = .02). These data suggest that there are certain identifiable factors associated with antidepressant exposure in bipolar disorder patients, and some of these, specifically female sex, are also associated with a history of AIM. These data may be useful in designing prospective trials to identify interventions that can reduce the risk of this adverse outcome.

2040 Symptom endorsement in bipolar patients of African Versus European ancestry

OBJECTIVES/SPECIFIC AIMS: Learning Objectives of this session: Identify possible reasons for misdiagnosis of bipolar patients of African ancestry by reviewing differences in symptom presentation between African American (AA) and European American (EA) bipolar individuals. Introduction: Bipolar disorder is a chronic mental illness with a prevalence rate up to 5.5% of the US population and is associated with substantial personal and economic morbidity/mortality. Misdiagnosis is common in bipolar disorder, which can impact treatment and outcome. Misdiagnosis disproportionally affects racial/ethnic minorities; in particular, AAs are often misdiagnosed with schizophrenia. There is interest in better understanding the contribution of differential illness presentation and/or racial bias to misdiagnosis. METHODS/STUDY POPULATION: Patients and Methods Utilizing the Genetic Association Information Network (GAIN) public database, this study compared clinical phenomenology between bipolar patients of African Versus European ancestry (AA=415 vs. EA=1001). The semi-structured Diagnostic Interview for Genetic Studies (DIGS) was utilized to evaluate individual symptom endorsement contributing to diagnostic confirmation. A χ2 test was used to compare group differences in DIGS harvested mania and psychosis sections, and overview of psychiatric medications. RESULTS/ANTICIPATED RESULTS: Results: The symptom of auditory hallucination was significantly more endorsed in AA bipolar patients than EA bipolar patients (57.9% AA vs. 36.1% EA, p≤0.0001). Conversely, the symptom of elevated or euphoric mood was significantly less endorsed in AA bipolar patients than in EA patients (94.6% AA vs. 97.5% EA, p=0.027). AA, in comparison to EA bipolar patients, had a significantly higher prevalence of lifetime exposure to haloperidol (36.9% AA vs. 29.4% EA, p=0.017) and fluphenazine (12.3% AA vs. 6.7% EA, p=0.004). In contrast, AA, in comparison to EA bipolar patients, had a significantly lower prevalence rate of lifetime exposure to lithium (52.5% AA vs. 74.2% EA, p&lt;0.0001), and lamotrigine (13.7% AA vs. 35.6% EA, p&lt;0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: Conclusion: The higher rate of psychotic symptom endorsement and lower rate of core manic symptom endorsement represent differential illness presentation that may contribute to misdiagnosis in African-American bipolar patients. The higher rate of high potency typical antipsychotic treatment and lower rate of classic mood stabilizing treatment may also contribute poorer bipolar treatment outcome. While structured diagnostic interviews are the gold standard in diagnostic confirmation, this study is limited by lack of knowledge of clinician/expert interviewer interpretation of symptom endorsement which may contribute to symptom misattribution and misdiagnosis. Incorporation of additional African American participants in research is a critical future direction to further delineate symptom presentation and diagnosis to serve as validation for these results.

F89. COGNITIVE IMPAIRMENT WORSENING ACROSS AFFECTIVE TO PSYCHOSIS SPECTRUM: A COHORT STUDY OF UNIPOLAR/BIPOLAR DEPRESSION AND BIPOLAR SCHIZOAFFECTIVE DISORDERS

BackgroundBipolar (BPD), schizoaffective bipolar (SAM) and major depressive disorders (MDD) reveal large heterogeneity in terms of symptom expression, course and treatment response. This heterogeneity could be the source of a large variance of cognitive performance observed in these subjects. The aim of the present analyses was to compare the cognitive performance of patients with BPD, SAM, MDD and medical controls with adjustment for a comprehensive array of potential confounders. To go a step further we will simultaneously test the effects of multiple clinical characteristics including lifetime history and duration of psychotic symptoms, manic/hypomanic and depressive episodes, age of onset of disorder, current GAF score, time since remission of the last episode and presence of a depressive episode at the time of the assessment on the cognitive performance.MethodsData stemmed from the Lausanne-Geneva Family and High-Risk study. Patients with BPD (n=62), SAM (n=22) and MDD (n=51) were interviewed every three years over a mean duration of follow-up of 12 years. All patients were assessed clinically with the semi-structured Diagnostic Interview for Genetic Studies (DIGS). The cognitive assessment was made with the MATRICS and the Victoria Stroop Test.ResultsThe global cognitive index (excluding Stroop result) shows that SAM subgroup had the lowest global score with 40.6 (SD=8.5), BPD 47.4 (SD=7.8) and MDD 49.7 (SD=8.7). A multiple linear regression accounting for several confounders such as comorbid psychiatric disorders and medication confirms that only SAM and BPD are statistically different from controls (p<0.001 and p<0.01 respectively). MDD did not differ from controls (p>0.05). Overall, patients with BPD or SAM but not with MDD showed poorer cognitive performance than controls in terms of the global score and speed of processing, verbal learning, working memory, visual learning, attention/vigilance and inhibition.DiscussionOur data confirm cognitive impairment in patients with BPD or SAM compared to controls after adjustment for a comprehensive array of potential confounder variables. We were able to evaluate the specificity of cognitive performance of psychotic, maniac and depressive dimensions of the major mood disorders within the same sample. Furthermore, these data stress that the presence of the “schizo dimension” concomitant to mania and depression contributes to worsening the cognitive performance in an additive manner.

Changes in resting EEG in Colombian ex-combatants with antisocial personality disorder

IntroductionAlthough the social and economic consequences of Colombian internal conflicts mainly affected the civilian population, they also had other implications. The ex-combatants, the other side of the conflict, have been the subject of many studies that question their personality structures and antisocial features. Results suggest that ex-combatants usually have characteristics of an antisocial personality disorder (ASPD) that is related with their behaviour. MethodsQuantitative EEG (qEEG) was used to evaluate differences in cortical activity patterns between an ex-combatants group and a control group. The Psychopathy Checklist-Revised (PCL-R) was used to assess the presence of ASPD in the ex-combatants group, as well as the Diagnostic Interview for Genetic Studies (DIGS) for other mental disorders classified in the DCI-10. ResultsThere are significant differences in psychopathy levels between groups, as well as in alpha-2 and beta waves, especially in left temporal and frontal areas for alpha-2 waves and left temporal-central regions for beta waves. ConclusionsqEEG measurements allow spectral resting potential to be differentiated between groups that are related with features typically involved in antisocial personality disorder, and to correlate them with patterns in the questionnaires and clinical interview.

T186. ASSOCIATION BETWEEN POLYMORPHISMS OF THE NEUREGULIN 1 (NRG1) GENE AND SCHIZOPHRENIA

BackgroundThe dysfunction of neuregulin 1 (NRG1) is one of the plausible hypotheses for the pathogenesis of schizophrenia. The neuregulin 1 (NRG1) is located on chromosome 8p, as suggested by multiple linkage studies. The aim of this study is to clarify the contribution of polymorphisms of the neuregulin 1 (NRG1) with schizophreniaMethodsAfter informed consent was obtained, 100 schizophrenia patients and 100 control subjects were enrolled in this study. All subjects were administered the Diagnostic Interview for Genetic Studies (DIGS) (National Institute of Mental Health-Molecular Genetics Initiative, 1992; Nurnberger et al., 1994) by a research assistant with extensive training in this interview. Blood samples were collected in anonymously identified 10-ml Vacutainer tubes (Becton Dickinson). DNA was prepared by a modified SDS/Proteinase K procedure (Gusells et al., 1979). We genotyped polymorphism neuregulin 1 (NRG1) with the PCR-RFLP methods. The PCR products were digested by restricted enzyme.ResultsWe observed a significant association between the polymorphism neuregulin 1 (NRG1) and the schizophrenia (Chi-Square Test P= 0.0449).DiscussionThe NRG1gene was originally identified as a susceptibility gene for schizophrenia by using a combination of a linkage and association approaches based on microsatellite markers and then using SNPs after microsatellite at risk haplotypes were identified. We found there is the frequency of the polymorphism of neuregulin 1 (NRG1) was significantly increased in schizophrenia patients. This allelic association suggests that the functional polymorphism neuregulin 1 (NRG1) may play a role in susceptibility to schizophrenia. Further study with larger sample sizes is required.

S189. CARVING A MORE SPECIFIC SUBTYPE OF SCHIZOPHRENIA FOR GENETIC STUDIES: SPORADIC SCHIZOAFFECTIVE BIPOLAR TYPE

BackgroundSchizophrenia is a heterogeneous group of disorders. The familial-sporadic distinction has been considered under a range of genetic models. Research supports a strong association of de novo copy mutations with sporadic schizophrenia. The aim of the study was to determine a more homogenous phenotype for genetic research via comparison of various clinical and socio-demographic variables in familial and sporadic schizophrenia.MethodsA cross-sectional observational design was used. This study included 384 participants with schizophrenia/schizoaffective disorder from an Afrikaner founder population in South Africa that previously participated in genetic research. A comprehensive data capturing sheet was completed from a pre-existing database that contains information obtained from the Diagnostic Interview for Genetic Studies, chronological clinical summary reports and additional sources of information. The study protocol was approved by the Research Ethics Committee from the Faculty of Health Sciences at the University of Pretoria. Logit models were fitted using the backward elimination procedure to investigate relationships where the dependent variable was binary. Odds ratio estimates were calculated for independent variables that were significant in the model. The Kruskal-Wallis test was conducted to compare the means of groups. For cases where there were significant differences a post-hoc test with a Bonferroni correction was done to determine which groups differ significantly.ResultsThere were 214 familial and 170 sporadic subjects. 279 had a diagnosis of schizophrenia, 66 schizoaffective, bipolar type and 39 schizoaffective disorder, depressive type. 242 were male and 142 female. The age at onset of the primary psychiatric diagnosis, season of birth, co-morbid diagnoses, symptomatology, suicidality history and marital status weren’t significantly different when considering the combined schizophrenia/schizoaffective disorder group and its relationship to familiality. Early deviant behaviour was however decreased in the sporadic group. These findings were replicated when analysing schizophrenia independently from schizoaffective disorder. The sporadic schizoaffective disorder, bipolar type did however have a significantly lower age at onset (mean 20.18 versus 25.07 years), 8.8 times more hallucinations, 6.6 times more odd behaviour before the age of 10 and were 2.8 times more likely to be single. The bipolar type also had 2.9 times more suicide attempts as opposed to ideation. This finding wasn’t statistically significant. The sporadic schizoaffective group overall was 2.2 times more likely to abuse substances. The depressive type didn’t differ significantly with regards to age at onset, season of birth, co-morbidities, early deviant behaviour, symptomatology, suicidality or marital status.DiscussionThe combined schizophrenia/schizoaffective group didn’t differ significantly, nor did schizophrenia and schizoaffective disorder depressive type when analysed independently. The sporadic schizoaffective bipolar type differed significantly on multiple important variables that suggest a poorer prognosis and increased disease severity. The sporadic schizoaffective bipolar type forms a more homogenous group, with genetic studies hinting at relatively specific genetic risk factors. Studies elucidating the genetic architecture of this group could prove invaluable in clarifying the aetiology of schizophrenia.

A preliminary study of association of genetic variants with early response to olanzapine in schizophrenia.

Background:Treatment response can be predicted in schizophrenia by DNA information in the drug metabolism pathways. This study aimed to examine clinical characteristics and genetic determinant (s) of early response to olanzapine treatment in schizophrenia using specified drug metabolizing genes.Materials and Methods:Consenting participants (n = 33) suffering from schizophrenia were diagnosed on Diagnostic Interview for Genetic Studies. Oral olanzapine was administered in an incremental dose up to 10 mg (2 weeks) and 20 mg (6 weeks). All participants were tested on Positive and Negative Syndrome Scale, Clinical Global Impressions, and Global Assessment of Functioning at 0, 2, and 6 weeks. Side effects were also evaluated. After 2 weeks, 11 (33.33%) fulfilled criteria for early response, whereas 17 (51.52%) responded at 6 weeks. We investigated the contribution of clinical factors and five polymorphisms (rs2740574, rs2470890, rs762551, rs3892097, and rs1065852) in predicting response to olanzapine at 2 and 6 weeks of treatment with a standard dose.Results:Severity of positive symptoms at baseline was associated with response at 2 weeks (P = 0.01) while higher scores on Scale for the Assessment of Negative Symptoms (SANS) at baseline was associated with response at both 2 (P = 0.04) and 6 weeks (P = 0.03). None of the five single nucleotide polymorphisms (SNPs) selected were significantly associated with response to olanzapine.Conclusions:Olanzapine is an effective and safe drug. Positive and Negative Syndrome Scale positive score and SANS score were variably associated with response at 2 and/or 6 weeks. Replicate studies with bigger sample size are warranted for conclusive results in the Indian population for genetic association.