Psychotic Symptoms In Bipolar Disorder Research Articles

Clinicodemographic correlates of psychotic features in bipolar disorder – a multicenter study in China

BackgroundPsychotic symptoms are prevalent in patients with bipolar disorder (BD). However, nearly all previous studies on differences in sociodemographic and clinical factors between patients with (BD P +) and without (BD P-) psychotic symptoms were conducted in Western populations, and limited information is known in China.MethodA total of 555 patients with BD from seven centers across China were recruited. A standardized procedure was used to collect patients’ sociodemographic and clinical characteristics. The patients were divided into BD P + or BD P- groups based on the presence of lifetime psychotic symptoms. Mann–Whitney U test or chi-square test was used to analyze differences in sociodemographic and clinical factors between patients with BD P + and BD P-. Multiple logistic regression analysis was conducted to explore factors that were independently correlated with psychotic symptoms in BD. All the above analyses were re-conducted after the patients were divided into BD I and BD II group according to their types of diagnosis.ResultsA total of 35 patients refused to participate, and the remaining 520 patients were included in the analyses. Compared with patients with BD P-, those with BD P + were more likely to be diagnosed with BD I and mania/hypomania/mixed polarity in the first mood episode. Moreover, they were more likely to be misdiagnosed as schizophrenia than major depressive disorder, were hospitalized more often, used antidepressants less frequently, and used more antipsychotics and mood stabilizers. Multivariate analyses revealed that diagnosis of BD I, more frequent misdiagnosis as schizophrenia and other mental disorders, less frequent misdiagnosis as major depressive disorder, more frequent lifetime suicidal behavior, more frequent hospitalizations, less frequent use of antidepressants, more frequent use of antipsychotics and mood stabilizers were independently correlated with psychotic symptoms in BD. After dividing the patients into BD I and BD II groups, we observed notable differences in sociodemographic and clinical factors, as well as clinicodemographic correlates of psychotic features between the two groups.ConclusionsDifferences in clinical factors between patients with BD P + and BD P- showed cross-cultural consistency, but results on the clinicodemographic correlates of psychotic features were not. Notable differences between patients with BD I and BD II were found. Future work exploring the psychotic features of BD needs to take types of diagnosis and cultural differences into consideration.Trial registrationThis study was first registered on the website of the ClinicalTrials.gov (https://clinicaltrials.gov/) on 18/01/2013. Its registration number is NCT01770704.

Psychotic symptoms in bipolar disorder and their impact on the illness: A systematic review.

BACKGROUNDLifetime psychotic symptoms are present in over half of the patients with bipolar disorder (BD) and can have an adverse effect on its course, outcome, and treatment. However, despite a considerable amount of research, the impact of psychotic symptoms on BD remains unclear, and there are very few systematic reviews on the subject.AIMTo examine the extent of psychotic symptoms in BD and their impact on several aspects of the illness.METHODSThe Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. An electronic literature search of six English-language databases and a manual search was undertaken to identify published articles on psychotic symptoms in BD from January 1940 to December 2021. Combinations of the relevant Medical Subject Headings terms were used to search for these studies. Articles were selected after a screening phase, followed by a review of the full texts of the articles. Assessment of the methodological quality of the studies and the risk of bias was conducted using standard tools.RESULTSThis systematic review included 339 studies of patients with BD. Lifetime psychosis was found in more than a half to two-thirds of the patients, while current psychosis was found in a little less than half of them. Delusions were more common than hallucinations in all phases of BD. About a third of the patients reported first-rank symptoms or mood-incongruent psychotic symptoms, particularly during manic episodes. Psychotic symptoms were more frequent in bipolar type I compared to bipolar type II disorder and in mania or mixed episodes compared to bipolar depression. Although psychotic symptoms were not more severe in BD, the severity of the illness in psychotic BD was consistently greater. Psychosis was usually associated with poor insight and a higher frequency of agitation, anxiety, and hostility but not with psychiatric comorbidity. Psychosis was consistently linked with increased rates and the duration of hospitalizations, switching among patients with depression, and poorer outcomes with mood-incongruent symptoms. In contrast, psychosis was less likely to be accompanied by a rapid-cycling course, longer illness duration, and heightened suicidal risk. There was no significant impact of psychosis on the other parameters of course and outcome.CONCLUSIONThough psychotic symptoms are very common in BD, they are not always associated with an adverse impact on BD and its course and outcome.

A miRNome analysis of drug-free manic psychotic bipolar patients versus healthy controls.

The lifetime presence of psychotic symptoms is associated with more clinical severity, poorer outcome and biological changes in patients affected by bipolar disorder (BD). Epigenetic mechanisms have been evoked to explain the onset of psychotic symptoms in BD as well as the associated biological changes. The main objective of the present study was to evaluate the expression profiles of circulating microRNAs (miRNAs) in drug-free manic psychotic bipolar patients versus healthy controls (HC), to identify possible non-invasive molecular markers of the disorder. 15 drug-free manic psychotic bipolar patients and 9 HC were enrolled and 800 miRNAs expression profile was measured by Nanostring nCounter technology on plasma samples and validated through qPCR. Overall, twelve miRNAs showed a significantly altered expression between the two groups (p < 0.05). Functional annotation of predicted miRNAs targets by MultiMIR R tool showed repression in bipolar patients of genes with a role in neurodevelopment and neurogenesis, and upregulation of genes involved in metabolism regulation. We identified a signature of circulating miRNA characteristic of manic psychotic bipolar patients, suggesting a possible role in neurodevelopment and metabolic processes regulation.

Psychotic versus non-psychotic bipolar disorder: Socio-demographic and clinical profiles in an Italian nationwide study

Psychotic versus non-psychotic patients with bipolar disorder have been traditionally associated with different unfavorable clinical features. In this study on bipolar Italian patients, we aimed to compare clinical and demographic differences between psychotic and non-psychotic individuals, exploring clinical factors that may favor early diagnosis and personalized treatment. A total of 1671 patients (males: n = 712 and females: n = 959; bipolar type 1: n = 1038 and bipolar type 2: n = 633) from different psychiatric departments were compared according to the lifetime presence of psychotic symptoms in terms of socio-demographic and clinical variables. Chi-square tests for qualitative variables and Student's t-tests for quantitative variables were performed for group comparison, and a multivariable logistic regression was performed, considering the lifetime psychotic symptoms as dependent variables and socio-demographic/clinical characteristics as independent variables. Psychotic versus non-psychotic bipolar subjects resulted to: be more frequently unemployed (p < 0.01) and never married/partnered (p < 0.01); have an earlier age at onset (p < 0.01); more frequently receive a first diagnosis different from a mood disorder (p < 0.01); have a shorter duration of untreated illness (p < 0.01); have a more frequently hypomanic/manic prevalent polarity (p < 0.01) and a prevalent manic-depressive type of cycling (p < 0.01); present a lower lifetime number of depressive episodes (p < 0.01), but have more manic episodes (p < 0.01); and less insight (p < 0.01) and more hospitalizations in the last year (p < 0.01). Multivariable regression analysis showed that psychotic versus non-psychotic bipolar patients received more frequently a first diagnosis different from bipolar disorder (odds ratio = 0.64, 95% confidence interval = [0.46, 0.90], p = 0.02) or major depressive disorder (odds ratio = 0.66, 95% confidence interval = [0.48, 0.91], p = 0.02), had more frequently a prevalent manic polarity (odds ratio = 1.84, 95% confidence interval = [1.14, 2.98], p < 0.01) and had a higher number of lifetime manic episodes (more than six) (odds ratio = 8.79, 95% confidence interval = [5.93, 13.05], p < 0.01). Lifetime psychotic symptoms in bipolar disorder are associated with unfavorable socio-demographic and clinical features as well as with a more frequent initial misdiagnosis.

The metabolic basis of psychosis in bipolar disorder: A positron emission tomography study.

Psychotic symptoms are a common feature in bipolar disorder (BD), especially during manic phases, and are associated with a more severe course of illness. However, not all bipolar subjects experience psychosis during the course of their illness, and this difference often guides assessment and pharmacological treatment. The aim of the present study is to elucidate, for the first time, the FDG uptake dysfunctions associated with psychosis in BD patients with and without a history of past psychotic symptoms, through a positron emission tomography (PET) approach. Fifty BD patients with lifetime psychotic symptoms, 40 BD patients without lifetime psychotic symptoms and 27 healthy controls (HC) were recruited and underwent an 18F-FDG-PET session. Compared to HC, BD subjects shared common FDG uptake deficits in several brain areas, including insula, inferior temporal gyrus and middle occipital gyrus. Moreover, we found that BD patients with a history of past psychotic symptoms had a unique FDG uptake alteration in the right fusiform gyrus compared to both BD patients without lifetime psychotic symptoms and HC (all P<0.01, cFWE corrected). Overall, our results suggest that FDG uptake alterations in brain regions involved in emotion regulation are a key feature of BD, regardless the presence of past psychosis. Finally, we demonstrated that the FDG uptake reduction in fusiform gyrus is associated with the presence of past psychotic symptoms in BD, ultimately leading towards the idea that the fusiform gyrus might be considered a putative biomarker of psychosis.

A data-driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome-wide significant genetic loci.

The etiologies of bipolar disorder (BD) and schizophrenia include a large number of common risk alleles, many of which are shared across the disorders. BD is clinically heterogeneous and it has been postulated that the pattern of symptoms is in part determined by the particular risk alleles carried, and in particular, that risk alleles also confer liability to schizophrenia influence psychotic symptoms in those with BD. To investigate links between psychotic symptoms in BD and schizophrenia risk alleles we employed a data‐driven approach in a genotyped and deeply phenotyped sample of subjects with BD. We used sparse canonical correlation analysis (sCCA) (Witten, Tibshirani, & Hastie, 2009) to analyze 30 psychotic symptoms, assessed with the OPerational CRITeria checklist, and 82 independent genome‐wide significant single nucleotide polymorphisms (SNPs) identified by the Schizophrenia Working group of the Psychiatric Genomics Consortium for which we had data in our BD sample (3,903 subjects). As a secondary analysis, we applied sCCA to larger groups of SNPs, and also to groups of symptoms defined according to a published factor analyses of schizophrenia. sCCA analysis based on individual psychotic symptoms revealed a significant association (p = .033), with the largest weights attributed to a variant on chromosome 3 (rs11411529), chr3:180594593, build 37) and delusions of influence, bizarre behavior and grandiose delusions. sCCA analysis using the same set of SNPs supported association with the same SNP and the group of symptoms defined “factor 3” (p = .012). A significant association was also observed to the “factor 3” phenotype group when we included a greater number of SNPs that were less stringently associated with schizophrenia; although other SNPs contributed to the significant multivariate association result, the greatest weight remained assigned to rs11411529. Our results suggest that the canonical correlation is a useful tool to explore phenotype–genotype relationships. To the best of our knowledge, this is the first study to apply this approach to complex, polygenic psychiatric traits. The sparse canonical correlation approach offers the potential to include a larger number of fine‐grained systematic descriptors, and to include genetic markers associated with other disorders that are genetically correlated with BD.

Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder

Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes and mechanisms. To investigate the association between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRSs), and psychotic presentations of BD. This case-control study in the United Kingdom used multinomial logistic regression to estimate differential PRS associations across categories of cases and controls. Participants included in the final analyses were 4436 cases of BD from the Bipolar Disorder Research Network. These cases were compared with the genotypic data for 4976 cases of schizophrenia and 9012 controls from the Type 1 Diabetes Genetics Consortium study and the Generation Scotland study. Data were collected between January 1, 2000, and December 31, 2013. Data analysis was conducted from March 1, 2016, to February 28, 2017. Standardized PRSs, calculated using alleles with an association threshold of P < .05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, were adjusted for the first 10 population principal components and genotyping platforms. Multinomial logit models estimated PRS associations with BD stratified by Research Diagnostic Criteria subtypes of BD, by lifetime occurrence of psychosis, and by lifetime mood-incongruent psychotic features. Ordinal logistic regression examined PRS associations across levels of mood incongruence. Ratings were derived from the Schedules for Clinical Assessment in Neuropsychiatry interview and the Bipolar Affective Disorder Dimension Scale. Of the 4436 cases of BD, 2966 (67%) were female patients, and the mean (SD) age at interview was 46 [12] years. Across clinical phenotypes, there was an exposure-response gradient, with the strongest PRS association for schizophrenia (risk ratio [RR] = 1.94; 95% CI, 1.86-2.01), followed by schizoaffective BD (RR = 1.37; 95% CI, 1.22-1.54), bipolar I disorder subtype (RR = 1.30; 95% CI, 1.24-1.36), and bipolar II disorder subtype (RR = 1.04; 95% CI, 0.97-1.11). Within BD cases, there was an effect gradient, indexed by the nature of psychosis. Prominent mood-incongruent psychotic features had the strongest association (RR = 1.46; 95% CI, 1.36-1.57), followed by mood-congruent psychosis (RR = 1.24; 95% CI, 1.17-1.33) and BD with no history of psychosis (RR = 1.09; 95% CI, 1.04-1.15). For the first time to date, a study shows a polygenic-risk gradient across schizophrenia and BD, indexed by the occurrence and level of mood-incongruent psychotic symptoms.

Psychotic symptoms in bipolar disorder: Two years’ retrospective study

Background: Psychosis in bipolar disorder is common but still not well understood. There is paucity of literature from our country and none from this institute which serves the eastern part of Nepal.Objective: To describe the hallucinations and delusions in bipolar disorders in our place.Methods: Patients-record files of bipolar disorders with psychosis discharged in two years’ time from 2012 to 2014 were analysed. Patients with unipolar depression, recurrent depressive disorder, serious organic illness, and primary substance use disorders were excluded. Information was collected in a structured performa. Association of delusion and hallucination was observed.Results: During the study period, ninety-five patients with bipolardisorder had psychosis. Hallucination was present in 29 (30.5%) cases, and out of these 23 (79.3%) were cases of mania. In 26 (89.7%) patients, the hallucinations were mood congruent. The median duration of appearance of hallucination was 10 days and appeared early in mania. Among hallucinations, auditory verbal hallucinations were present in all 29 patients. Delusions were present in 77 (81.1%) of patients, and grandiose delusions were the most common. Grandiose delusions tended to occur even in the absence of hallucinations. Conclusion: Psychosis is common in bipolar disorder. Grandiose delusions are the most common delusion and are relatively independent of hallucination. The auditory verbal hallucinations are the most common type of hallucination. Hallucinations in mania tend to manifest earlier than in bipolar depression and mixed episode, and most of the hallucinations in bipolar disorder are mood congruent. Health Renaissance 2015;13 (1): 49-57

Lifetime presence of psychotic symptoms in bipolar disorder is associated with less favorable socio-demographic and certain clinical features

BackgroundThe presence of psychotic symptoms in bipolar disorder (BD) is considered a feature of higher severity of illness and, in particular, of manic episodes in bipolar I disorder (BD I). However, the possibility to apply the “with psychotic features” specifier to major depressive episodes in either bipolar II disorder (BD II) or BD I highlights the need for additional research in this area. MethodsThe present study assessed the lifetime presence of psychotic symptoms and related socio-demographic and clinical features in a large sample of BD patients (N=360), with (BDPs, N=207) and without a lifetime history of psychosis (BDNPs, N=153). ResultsAn overall less favorable socio-demographic profile was observed in BDPs vs BDNPs. In terms of clinical variables, BDPs vs BDNPs had: earlier age at onset (27.7±10.5 vs 30.1±12.3years; p=0.02), higher rates of BD I diagnosis (95.7% vs 45.8%; p<0.001), more elevated (manic/hypomanic/mixed) polarity of first (55.2% vs 24.4%; p<0.001) and most recent episode (69.8% vs 35.6%; p<0.001), more comorbid alcohol/substance use disorder (38.1% vs 21.9%; p=0.002), more lifetime hospitalizations (3.8±6.1 vs 2±3; p=0.002) and involuntary commitments (1±1.9 vs 0.1±0.4; p<0.001), more history of psychosocial rehabilitation (17.9% vs 5.7%; p=0.001), more current antipsychotic use (90.1% vs 70.9%; p<0.001), and lower GAF (62.3±14.2 vs 69.3±12.5; p<0.001), but shorter duration of most recent episode (34.1±45.4 vs 50.3±65.7days; p=0.04), lower rates of comorbid anxiety disorders (23.9% vs 38.2%; p=0.005), and antidepressant use (19.4% vs 56.6%; p<0.001). ConclusionsThe present findings indicate an overall worse profile of socio-demographic and certain clinical characteristics associated with the lifetime presence of psychotic symptoms in bipolar patients.

The use of polygenic risk scores to inform aetiology of mood and psychotic disorders

IntroductionPolygenic risk scores (PRS) incorporate many small genetic markers that are associated with conditions. This technique was first used to investigate mental illnesses in 2009. Since then, it has been widely used.ObjectivesWe wanted to explore how PRS have been used to the study the aetiology of psychosis, schizophrenia, bipolar disorder and depression.AimsWe aimed to conduct a systematic review, identifying studies that have examined associations between PRS for bipolar disorder, schizophrenia/psychosis and depression and psychopathology-related outcome measures.MethodsWe searched EMBASE, Medline and PsychInfo from 06/08/2009 to 14/03/2016. We hand-searched the reference lists of related papers.ResultsAfter removing duplicates, the search yielded 1043 publications. When irrelevant articles were excluded, 33 articles remained. We found 24 studies using schizophrenia PRS, three using bipolar PRS and nine using depression PRS. Many studies successfully used PRS to predict case/control status. Some studies showed associations between PRS and diagnostic sub-categories. A range of clinical phenotypes and symptoms has been explored. For example, specific PRS are associated with cognitive performance in schizophrenia, psychotic symptoms in bipolar disorder, and frequency of episodes of depression. PRS have also demonstrated genetic overlap between mental illnesses. It was difficult to assess the quality of some studies as not all reported sufficient methodological detail.ConclusionsPRS have enabled us to explore the polygenic architecture of mental illness and demonstrate a genetic basis for some observed features. However, they have yet to give insights into the biology, which underpin mental illnesses.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Assessment of psychotic symptoms in bipolar disorder

IntroductionBipolar disorder is a disabling condition characterized by the presence of manic, depressive, hypomanic or mixed episodes, affective symptoms that may coexist with several types of psychotic features.ObjectivesThe purpose is to evaluate the frequency of psychotic symptoms among bipolar disorder.MethodThe study included 55 bipolar patients admitted in the Psychiatry Clinical Hospital from January 2012 until May 2013. Inclusion criteria were represented by diagnosis of bipolar disorder, manic or depressive episode, according to DSM-IV-TR and ICD 10 criteria. Clinical instruments used to assess the severity of the current affective episode were Young Mania Rating Scale (YMRS) for manic patients and Hamilton Depression Rating Scale-17 items – (HDRS) for the depressive ones. Psychotic symptoms were evaluated with the Brief Psychiatric Rating Scale-18 items – (BPRS).ResultsOut of the 55 patients, 32 had psychotic symptoms upon admission to the hospital. BPRS results showed delusions of guilt, inutility, hypochondriac and nihilistic delusions for the depressed patients. Delusions of grandiosity and megalomania accounted for most of psychotic symptoms in manic patients. A smaller number of patients showed delusions of invention and reform. Perception disturbances such as auditory hallucinations were present in both diagnosis categories but in a higher percentage in depressive bipolar patients.ConclusionsEven if less frequently than in schizophrenia or schizoaffective disorder, psychotic symptoms are present in bipolar disorder. They influence the general functioning and the outcome of patients diagnosed with this illness.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Revisiting the association between childhood trauma and psychosis in bipolar disorder: A quasi-dimensional path-analysis

BackgroundChildhood trauma has been associated with a more severe clinical expression of bipolar disorder (BD). However, the results that specifically associated traumatic events and psychotic features in BD have been inconsistent, possibly due to the low resolution of the phenotypes being used. Methods270 normothymic patients with BD completed the Childhood Trauma Questionnaire (CTQ) and the Peters Delusion Inventory (PDI) that assessed 21 delusional beliefs. Patients were characterized for the lifetime presence of psychotic features during episodes and cannabis misuse in accordance with DSM-IV. We performed a series of path analyses to investigate the links from three types of childhood abuse (physical, sexual and emotional) directly to delusional beliefs and psychotic features, and indirectly through cannabis misuse. ResultsA first path analysis showed no link between any of the childhood abuse types and psychotic features when only a categorical definition of psychosis was used. When incorporating the quasi-dimensional measure of delusional beliefs in a second path analysis, we found that emotional and physical abuse and cannabis misuse were each directly associated with PDI score. PDI score and psychotic features were strongly correlated. Childhood abuse did not operate through cannabis misuse to increase delusional beliefs. Including type of BD in the model did not alter the results. ConclusionEmotional and physical abuse, but also cannabis misuse, increased delusional beliefs in patients with BD. Using a quasi-dimensional measure of psychotic symptoms in BD provided higher resolution of the psychosis phenotype and helped reconcile ambiguous findings from previous studies.

C-29 * Intellectual Ability and Functional Outcome in Bipolar Disorder and Schizophrenia

Objective: Deficits in intellectual ability and functional outcome are consistently found in schizophrenia (SZ). Recently, there has been a growing interest in the role of psychotic symptoms in bipolar disorder (BP) as markers for impairment typically associated with SZ. This study examined intellectual ability and functional outcome in BP with psychotic features (BP+), BP without psychotic features (BP-), SZ, and normal controls (NC). Method: Individuals (71 SZ, 60 BP + , 68 BP-, 51 NC) were assessed using the UCSD Performance Based Skills Assessment (UPSA), which assesses everyday functioning in five domains (comprehension, finance, transportation, and household skills). Additionally, subtests from the Wechsler Adult Intelligence Scale-III were used to estimate IQ. Results: Results indicated that the SZ group performed worse on all domains of the UPSA and had a lower estimated IQ compared to the BP + , BP-, and NC groups (p < .05). Only performance on the transportation scale of the UPSA differentiated BP + , BP- and NC groups, with the BP+ group performing significantly lower (p < .05). Estimated IQ did not differ between the BP + , BP-, and NC groups and was correlated with all UPSA domains. Conclusion(s): Consistent with previous findings, results indicate impaired intellectual functioning and deficits across functional domains in SZ. This study extends findings to BP, indicating that the transportation scale of the UPSA may be sensitive to psychotic symptoms. Given that intellectual abilities did not differ between BP+ and BP-, further research should investigate cognitive processes underlying this impairment as a potential therapeutic target relevant for improving everyday functioning in the disorder.

The impact of a history of psychotic symptoms on cognitive function in euthymic bipolar patients: a comparison with schizophrenic patients and healthy controls

About two-thirds of patients with bipolar disorder (BD) have a lifetime history of at least one psychotic symptom. To compare the neurocognitive performance of four groups: BD patients with and without a history of psychotic symptoms (BD HPS+ and BD HPS-, respectively); patients with schizophrenia (SZ); and healthy control (HC) subjects. In this cross-sectional study, 35 stabilized patients with SZ, 79 euthymic (44 HPS+ and 35 HPS-) patients with BD, and 50 HC were administered a comprehensive battery of neuropsychological tests. There was worse neurocognitive functioning in both BD and SZ patients compared to HC. Overall, data from both groups of BD patients did not differ on sociodemographic, clinical, or neurocognitive variables. However, BD HPS+ patients had significantly more negative symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS), and showed a trend toward worse performance on executive functions compared to BD HPS- patients. Moreover, both BD groups had better performance on all neurocognitive tests compared to SZ group. Neurocognitive dysfunction may be more marked in SZ than in BD, yet qualitatively similar. A history of past psychotic symptoms in BD was not associated with more severe cognitive impairment during euthymia. Therefore, BD with psychotic symptoms does not appear to be a distinct neurocognitive phenotype.

Erratum to “Genome‐wide association analysis of age at onset and psychotic symptoms in bipolar disorder”, American Journal of Medical Genetics Part B: Neuropsychiatric Genetics”, April 1; 156(3):370–378

Erratum to “Genome‐wide association analysis of age at onset and psychotic symptoms in bipolar disorder”, American Journal of Medical Genetics Part B: Neuropsychiatric Genetics”, April 1; 156(3):370–378

Neocortical levels of lithium are increased in bipolar disorder

Salts of lithium, present in the human diet at trace levels,1 are used to manage depressive, manic and psychotic symptoms in bipolar disorder and related conditions.2, 3 Although a neurological function for lithium was first proposed over 60 years ago based on its anti-manic properties,2 surprisingly, a significant pool of lithium has never been identified in the brain.4, 5 In this study, with quadrupole inductively coupled plasma-mass spectroscopy, lithium is identified as a physiological trace element in the human neocortex. Moreover, cortical levels of lithium are found to be elevated in bipolar subjects with no past history of lithium pharmacotherapy.

The impact of glycogen synthase kinase 3β gene on psychotic mania in bipolar disorder patients

The aim of this study was to examine the relationships between glycogen synthase 3β gene polymorphisms and bipolar I disorder, manic in a Korean sample. Patients with bipolar disorder (n=118) and a control group (n=158) were assessed by genotyping for GSK3β single nucleotide polymorphisms (SNPs) -1727A/T and -50C/T. The patients were divided into two groups according to the presence of psychotic symptoms (psychotic mania, n=92; non-psychotic mania, n=26) and also divided based on gender and age of onset. The severity of symptoms was measured using the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). There were no significant differences in the genotype distributions or allelic frequencies of GSK3β polymorphisms and gender between patients with bipolar disorder and a normal control group. According to haplotype analysis, there was no association between these two groups. However, analysis of the age of onset of bipolar disorder revealed significant differences in genotype and allele distributions among the patients. Patients who were homozygous for the wild-type variant (TT) had an older age of onset than carriers of the mutant allele (A/A: 27.4±9.1; A/T: 30.1±11.8; T/T: 42.3±19.9; p=0.034). We detected differences in allele frequencies of the GSK3β -1727A/T polymorphism between the psychotic mania group and the non-psychotic mania group. This study suggests that GSK3β polymorphisms are not associated with bipolar disorder. However, the GSK3β SNP -1727A/T is associated with age of onset and presence of psychotic symptoms in bipolar disorder.

P01-239 - The effects of childhood trauma on psychotic symptoms in bipolar disorder

IntroductionAlthough history of childhood trauma is present in nearly 50% of bipolar patients, the effects of childhood trauma on the course of bipolar disorder are rarely investigated. Thus, we aimed to investigate the effects of childhood trauma on psychotic symptoms seen in patients with bipolar disorder.MethodsOne-hundred DSM-IV-TR diagnosed bipolar patients who were either manic or depressive were recruited from inpatient units of Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery. Patients were initially evaluated by Young Mania Rating Scale (YMRS), Montgomery-Asperg Depression Rating Scale (MADRS), Scales for Assessment of Positive Symptoms. Patients were also evaluated by Childhood Trauma Questionnaire (CTQ) and Dissociative Experiences Scale in euthymia which was defined by scores of &lt; 7 in YMRS, &lt; 4 in MADRASResultsThere were no differences between the patients with and without a history of psychotic episode in terms of age at onset, duration of illness and episode characteristics. Patients with a history of psychotic episode were hospitalized more. CTQ physical abuse scores were higher in male comparing to female. CTQ sexual abuse scores were higher in female comparing to male. CTQ emotional abuse, physical neglect, physical abuse and total scores were higher in patients who had at least one psychotic episode in lifetime than in patients without a history of psychotic episode.ConclusionThe history of childhood trauma should be investigated and therapeutic interventions for childhood trauma should be added to the standard treatment plan of bipolar patients.

Genome‐wide association analysis of age at onset and psychotic symptoms in bipolar disorder

Genome-wide association studies (GWAS) have identified several susceptibility loci for bipolar disorder (BP), most notably ANK3. However, most of the inherited risk for BP remains unexplained. One reason for the limited success may be the genetic heterogeneity of BP. Clinical sub-phenotypes of BP may identify more etiologically homogeneous subsets of patients, which can be studied with increased power to detect genetic variation. Here, we report on a mega-analysis of two widely studied sub-phenotypes of BP, age at onset and psychotic symptoms, which are familial and clinically significant. We combined data from three GWAS: NIMH Bipolar Disorder Genetic Association Information Network (GAIN-BP), NIMH Bipolar Disorder Genome Study (BiGS), and a German sample. The combined sample consisted of 2,836 BP cases with information on sub-phenotypes and 2,744 controls. Imputation was performed, resulting in 2.3 million SNPs available for analysis. No SNP reached genome-wide significance for either sub-phenotype. In addition, no SNP reached genome-wide significance in a meta-analysis with an independent replication sample. We had 80% power to detect associations with a common SNP at an OR of 1.6 for psychotic symptoms and a mean difference of 1.8 years in age at onset. Age at onset and psychotic symptoms in BP may be influenced by many genes of smaller effect sizes or other variants not measured well by SNP arrays, such as rare alleles.

Influence of the serotonin transporter gene polymorphism, cannabis and childhood sexual abuse on phenotype of bipolar disorder: A preliminary study

Objective The gene coding for the 5-HT transporter ( 5-HTT) is considered as a candidate gene for bipolar disorder, either as a “vulnerability” or as a “modifying the phenotype” gene. Psychotic symptoms occur at least once in one bipolar patient out of two, the relevant risk factors being insufficiently understood. The gene × environment interaction approach offers the opportunity to disentangle the latter, including childhood sexual abuse and cannabis abuse. Methods We investigated the 5-HTTLPR of the 5-HTT gene (G) and the presence of childhood sexual abuse and cannabis comorbidity (E) in 137 bipolar patients with (versus without) lifetime psychotic symptoms. Results The short allele and cannabis abuse were significantly more frequent among patients with psychotic symptoms than in those without ( p = 0.01 and p = 0.004, respectively), while childhood sexual abuse was not. Complex interactions were found between presence of the short allele, cannabis abuse or dependence and childhood sexual abuse. Conclusions The short allele of the 5-HTTLPR polymorphism of the 5-HTT gene was a risk factor for psychotic symptoms in bipolar disorder in the present sample, directly but also indirectly, through the presence of cannabis abuse or dependence, as an exacerbating factor heightening psychotic symptoms.