Psychotic Bipolar Patients Research Articles

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.

Visual memory uniquely predicts anhedonia in schizophrenia but not bipolar disorder

Deficits in memory have been suggested as an influential mechanism of anhedonia, because while pleasant experiences may be enjoyed in-the-moment, the cognitive processes involved in reporting anticipated or remembered enjoyable experiences is thought to be impaired. This study will determine whether any aspects of memory, including visual memory, verbal memory or working memory, are significantly predictive of anhedonia in a sample of schizophrenia, psychotic bipolar disorder and healthy controls. The study included 38 individuals with schizophrenia, 19 individuals with bipolar disorder with psychosis, and 43 age-matched healthy controls. All participants completed a self-report social and physical anhedonia questionnaire along with a cognitive screening battery, which assessed the domains of attention/vigilance, working memory, verbal learning, visual learning, and reasoning and problem-solving. Anhedonia scores were regressed onto domain scores to determine which areas of cognition uniquely predicted level of anhedonia in each group. For the schizophrenia group, physical anhedonia was significantly predicted by worse visual memory performance. The regression models did not find significant cognitive predictors of physical or social anhedonia in the bipolar disorder or control groups. This study found a significant relationship between visual memory and physical anhedonia in schizophrenia patients that was not present in a sample of psychotic bipolar patients or healthy controls, adding to an accumulating body of evidence that visual memory is related to anhedonia in schizophrenia. This relationship may be explained by underlying abnormalities in the orbitofrontal cortex in schizophrenia.

Behavioral and neural correlates of self-referential processing deficits in bipolar disorder.

Self-referential processing is a core component of social cognition. However, few studies have focused on whether self-referential processing deficits present in bipolar disorder. The current study combined a high-time-resolution event-related potential (ERP) technique with the self-referential memory (SRM) task to evaluate self-referential processing in 23 bipolar patients and 27 healthy controls. All subjects showed a reliable SRM effect, but the bipolar group had poorer recognition scores for the self- and other-referential conditions. The bipolar group presented with smaller voltages in both the self- and other-referential conditions for the N1 (150–220 ms) and the P2 components (130–320 ms) but larger voltages in the positive slow wave (600–1600 ms) component. Larger P3 amplitudes were elicited in the self-referential condition compared with the other-referential condition in controls but not in bipolar patients. Additionally, non-psychotic bipolar patients had a comparative normal SRM effect which was abolished in psychotic bipolar patients; non-psychotic bipolar patients had larger amplitudes of the positive slow wave than the normal controls, whereas it was not differed between psychotic bipolar patients and the healthy subjects. The present study suggests that self- and other-referential processing is impaired in bipolar patients and the deficits may be more pronounced in psychotic bipolar patients.

Neurocognitive and functional performance in psychotic and non-psychotic bipolar patients and schizophrenia patients

IntroductionIt has been suggested that psychotic bipolar patients have more severe cognitive deficits and lower functioning that non-psychotic bipolar patients.ObjectivesTo evaluate neurocognitive and functional performance in stabilized psychotic bipolar patients (BP+), non-psychotic bipolar patients (BP−) and schizophrenia patients (SZ).AimsTo examine whether BP+ might be defined as a more homogenous subtype of bipolar disorder with more severe cognitive deficit and more severe functional impairment.MethodsFifty TB+, 50 TB−, 50 SZ and 51 controls were evaluated with a comprehensive neurocognitive battery (WCST, FAS, TMT-A and B, Stroop Test, Digits span, letters and numbers – WMS-III−, CVLT, ROCFT, CPT-DS). Moreover, patients were evaluated with clinical scales (PANSS, MADRS, YMRS) and functionality scales (WHOs Disability Assessment Scales, QLS and GAF). IBM SPSS Statistics (version 19.0) was used to the data analysis.ResultsNo significant differences were found between three patients’ samples (P &lt; 0.0001). No significant differences in neurocognitive measures were found between BP+ and BP−. Significant differences were found between both groups of bipolar patients and schizophrenia in working memory measures (P &lt; 0.0001). BP+ and BP− showed significant higher functionality than SZ (P &lt; 0.0001), without significant differences in functionality between BP+ and BP−.ConclusionsThe pattern of neurocognitive and functional deficit is similar in BP+ and BP−. The neurocognitive deficit is very similar in both groups of bipolar patients groups in comparison to SZ; functionality is better in both bipolar groups than in schizophrenia patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Association between anti-Toxoplasma gondii antibodies and schizophrenia and psychotic bipolar in patients hospitalized in the psychiatric ward

Background Toxoplasmosis is caused by an intracellular parasite and is a worldwide disease. In laboratory, the parasites that cause the disease increases levels of dopamine in the brain tissue of treated mice. The evidence showed that dopamine releasing in the nucleus accumbens by activating the retro hippocampal region can disrupt the fornix section of brain as evolve to develop a psychosis in human. Methods This retrospective case-control study was conducted in patients with schizophrenia and psychotic bipolar referred to psychiatric clinic in Amir Kabir hospital, Arak. After psychiatric diagnosis of patients with schizophrenia and bipolar disorder, 2ml of blood samples were acquired from 76 patients and 75 controls without any psychotic illness or bipolar disorder and other mental illnesses with safety issues. The serum of samples was separated in laboratory and was kept until the time of testing at -20 degrees C. After collecting all the samples; Anti-Toxoplasma IgG on the case and control samples were analysed by ELISA. Results were analysed by SPSS software version 16 and were calculated by chi 2 tests. Results 55.26 per cent of patients (42 persons) were infected with Toxoplasma gondii and in the control group 36 per cent (27 patients) were infected, that the different between them was significant (p<0/05). Toxoplasmosis in psychotic men was more than psychotic women significantly (p<0/05). Toxoplasma gondii infection in patients with schizophrenia with psychotic bipolar patients showed no significant difference. Conclusion Patients with schizophrenia and bipolar disorder showed significantly higher rate than healthy people against Toxoplasma gondii infection. Whether prevention of infection with these parasites is effective in reducing the risk of psychosis requires further investigation.

P.2.d.007 Misdiagnosis and role of duration of untreated illness (DUI)/untreated psychosis (DUP) in psychotic bipolar patients

P.2.d.007 Misdiagnosis and role of duration of untreated illness (DUI)/untreated psychosis (DUP) in psychotic bipolar patients

Neuropsychological cognitive dysfunctions in psychotic bipolar disorders

Objectives The aim of this study was to determine neuropsychological cognitive dysfunctions in psychotic bipolar disorders and compare the results with a control group. Participants and methods The sample included two groups: group I included 20 psychotic bipolar patients recruited from psychiatric outpatient clinics of Zagazig University Hospitals. Group II included 20 participants selected randomly from Zagazig University Hospitals visitors. Patients were subjected to a semistructured psychiatric interview using the DSM-IV criteria for psychotic bipolar diagnosis, detection of mania by Young mania rating scale for the study group, and detection of neuropsychological cognitive function, where executive functions were assessed using the Wisconsin card sorting tests and memory was assessed using the Wechsler memory scale. Results The results of the current study indicated a highly significant difference between psychotic bipolar patients and the control group in executive functions, logic memory, digit span forward, digit span backward, associative learning, and total memory, and a reversible highly significant correlation between the number of hospitalizations and cognitive functions in psychotic bipolar patients for block design. Conclusion The current study concluded that neuropsychological cognitive dysfunctions are highly prevalent in psychotic bipolar disorders and it is strongly inter-related with sociodemographic and clinical characteristics.

Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders.

Resting State Electroencephalogram Oscillatory Abnormalities in Schizophrenia and Psychotic Bipolar Patients and Their Relatives from the Bipolar and Schizophrenia Network on Intermediate Phenotypes Study

Abnormal resting state electroencephalogram (EEG) oscillations are reported in schizophrenia (SZ) and bipolar disorder, illnesses with overlapping symptoms and genetic risk. However, less evidence exists on whether similar EEG spectral abnormalities are present in individuals with both disorders or whether these abnormalities are present in first-degree relatives, possibly representing genetic predisposition for these disorders. Investigators examined 64-channel resting state EEGs of 225 SZ probands and 201 first-degree relatives (SZR), 234 psychotic bipolar (PBP) probands and 231 first-degree relatives (PBPR), and 200 healthy control subjects. Eight independent resting state EEG spectral components and associated spatial weights were derived using group independent component analysis. Analysis of covariance was conducted on spatial weights to evaluate group differences. Relative risk estimates and familiality were evaluated on abnormal spectral profiles in probands and relatives. Both SZ and PBP probands exhibited increased delta, theta, and slow and fast alpha activity. Post-hoc pair-wise comparison revealed increased frontocentral slow beta activity in SZ and PBP probands as well as SZR and PBPR. Augmented frontal delta activity was exhibited by SZ probands and SZR, whereas PBP probands and PBPR showed augmented fast alpha activity. Both SZ and PBP probands demonstrated aberrant low-frequency activity. Slow beta activity was abnormal in SZ and PBP probands as well as SZR and PBPR perhaps indicating a common endophenotype for both disorders. Delta and fast alpha activity were unique endophenotypes for SZ and PBP probands, respectively. The EEG spectral activity exhibited moderate relative risk and heritability estimates, serving as intermediate phenotypes in future genetic studies for examining biological mechanisms underlying the pathogenesis of the two disorders.

Sensorimotor Transformation Deficits for Smooth Pursuit in First-Episode Affective Psychoses and Schizophrenia

Smooth pursuit deficits are an intermediate phenotype for schizophrenia that may result from disturbances in visual motion perception, sensorimotor transformation, predictive mechanisms, or alterations in basic oculomotor control. Which of these components are the primary causes of smooth pursuit impairments and whether they are impaired similarly across psychotic disorders remain to be established. First-episode psychotic patients with bipolar disorder (n = 34), unipolar depression (n = 24), or schizophrenia (n = 77) and matched healthy participants (n = 130) performed three smooth pursuit tasks designed to evaluate different components of pursuit tracking. On ramp tasks, maintenance pursuit velocity was reduced in all three patients groups with psychotic bipolar patients exhibiting the most severe impairments. Open loop pursuit velocity was reduced in psychotic bipolar and schizophrenia patients. Motion perception during pursuit initiation, as indicated by the accuracy of saccades to moving targets, was not impaired in any patient group. Analyses in 138 participants followed for 6 weeks, during which patients were treated and psychotic symptom severity decreased, and no significant change in performance in any group was revealed. Sensorimotor transformation deficits in all patient groups suggest a common alteration in frontostriatal networks that dynamically regulate gain control of pursuit responses using sensory input and feedback about performance. Predictive mechanisms appear to be sufficiently intact to compensate for this deficit across psychotic disorders. The absence of significant changes after acute treatment and symptom reduction suggests that these deficits appear to be stable over time.

Are auditory P300 and duration MMN heritable and putative endophenotypes of psychotic bipolar disorder? A Maudsley Bipolar Twin and Family Study

Impaired P300 auditory response has been reported in patients with psychotic bipolar disorder (BPD) and unaffected relatives of psychotic bipolar patients. Deficits in mismatch negativity (MMN), however, have not been observed in bipolar patients. To our knowledge, no family study of MMN in BPD has been reported. The current study combined the Maudsley twin and bipolar family samples using genetic model fitting analyses to: (1) assess the relationship between BPD and MMN, (2) substantiate the association between psychotic BPD and P300 variables, (3) verify the genetic overlap of BPD with P300 amplitude previously reported in the twin sample, and (4) examine the shared genetic influences between BPD and bilateral temporal scalp locations of P300 components. A total of 301 subjects were included in this study, including 94 twin pairs, 31 bipolar families, and 39 unrelated healthy controls. Statistical analyses were based on structural equation modelling. Both P300 and MMN are heritable, with heritability estimates of 0.58 for MMN, 0.68-0.80 for P300 amplitude, and 0.21-0.56 for P300 latency. The bipolar patients and their relatives showed normal MMN. No significant association, either genetic or environmental, was found with BPD. BPD was significantly associated with reduced P300 amplitude and prolonged latency on midline and bilateral temporal-posterior scalp areas. Shared genetic factors were the main source of these associations. The results confirm that MMN is not an endophenotype for psychotic BPD whereas P300 amplitude and latency components are valid endophenotypes for psychotic BPD.

Biological Correlates of the Congruence and Incongruence of Psychotic Symptoms in Patients with Type 1 Bipolar Disorder

We examined the catechol-O-methyl transferase (COMT) Val108/158Met genotype in 160 type 1 bipolar patients. We also analyzed the plasma concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethylenglycol (MHPG) and 3,4-dihydroxyphenylacetic acid in 60 of those patients who had been without mood stabilizers or neuroleptic treatment for at least 8 days. Results: Patients with congruent psychotic symptoms presented a higher plasma concentration of HVA than mood incongruent psychotic patients. The Val/Val genotype was associated with higher plasma concentrations of HVA and MHPG. We detected a larger proportion of patients with psychotic symptoms in the Val/Val genotype group, although this did not reach statistical significance. It was found that the distribution of the COMT genotype was not influenced by the congruent/incongruent nature of the psychotic symptoms. Limitations: The proportion of patients without psychotic symptoms in our sample was low. This fact limits the value of some comparisons. Conclusions: Congruent and incongruent psychotic patients can be distinguished in terms of the concentration of plasma HVA. Based on the presence or absence of mood incongruent symptoms, the Val108/158Met polymorphism of the COMT gene alone does not appear to be a crucial determinant in the division of psychotic bipolar patients. Nevertheless, COMT polymorphisms may influence some of the characteristics of the patients by their effect on monoamine metabolism.

Further evidence for shared genetic effects between psychotic bipolar disorder and P50 suppression: A combined twin and family study

P50 suppression deficit has been reported in patients with psychotic bipolar disorder. In our previous report on twin pairs concordant and discordant for bipolar disorder, we found significant genetic overlap between bipolar disorder and P50 sensory gating. However, the sample size in that study was relatively small. A separate study, the Maudsley Bipolar Family Study, reported diminished P50 gating in unaffected relatives of psychotic bipolar patients. However, genetic and environmental influences are confounded in family studies due to lack of monozygotic (MZ) twin pairs. The current study combines the twin sample and the family sample in order to improve statistical power and study design, with the aims of: (1) substantiating the association between psychotic bipolar disorder and diminished P50 suppression and (2) verifying the genetic overlap between the two traits reported in the twin sample. We also assessed the relationship between bipolar disorder and an alternative suppression index, the P50 Condition-Testing (C-T) amplitude difference. A total of 309 subjects was included in this study, comprising 91 twin pairs, 31 bipolar families, and 45 unrelated healthy controls. Statistical analyses were based on structural equation modeling. Bipolar disorder was significantly associated with a diminished P50 suppression ratio and decreased C-T amplitude difference. Shared genetic factors were the main source of these associations. Suppression impairment was due to larger, poorly gated, T amplitude responses. The results provide further evidence that impaired P50 suppressions are promising endophenotypes for psychotic bipolar disorder. The non-specificity of impaired P50 suppression may reflect the impact of shared psychosis susceptibility genes.

The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients

Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients. The study participants were 40 euthymic psychotic, 25 non-psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory. Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non-psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. 'Number of Wisconsin Card Sorting Test (WCST) categories' achieved was the only measure on which psychotic patients performed significantly worse compared to non-psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease. Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.

Assaultive trauma and illness course in psychotic bipolar disorder: findings from the suffolk county mental health project

Little is known about the relationship of assaultive trauma to clinical and functional outcome in patients with bipolar disorder. We assessed trauma histories in a cohort of 109 first-admission bipolar patients with psychosis using structured interviews and medical records. Assaultive trauma included rape, physical attacks, and physical threats. Outcome was assessed using standardized ratings. Forty percent reported a history of assaultive trauma, mostly in childhood (< or =16 years). Exposed patients were more symptomatic at each follow-up than unexposed. Sixteen percent of exposed patients remitted after one episode compared with 38.5% of the non-exposed. Patients exposed as adults were the most symptomatic at 6 months, while patients exposed in childhood were the most symptomatic at 24 months. Our findings supported the salient role of trauma history as a risk factor for poor course in severe bipolar disorder. Given the high prevalence of such exposure, clinical awareness in first-admission psychotic bipolar patients is critical.

Blood groups and affective disorders.

Frequencies of ABO, Rh, MNSs, P, Kell, Lewis and Duffy blood groups were studied in a total of 219 patients with affective disorders. The patients were classified into four groups: (1) bipolar (manic-depressive) psychosis; (2) unipolar recurrent depressive psychosis; (3) nonpsychotic 'reactive' depression, and (4) 'unclassifiable'. The following statistically significant results were found: an increased frequency of the blood group factor B among psychotic (bipolar and unipolar) patients compared to nonpsychotic patients, a decreased frequency of the SS phenotype in the unclassifiable group and an increased frequency of the K(+) phenotype among the nonpsychotic patients. Previous results concerning differences between bipolar and unipolar patients with respect to the A and O blood types were not confirmed in this investigation.