Bipolar Disorder Subjects Research Articles

24.4 PROBING THE ACUTE NEUROPHYSIOLOGY OF AEROBIC EXERCISE IN ADOLESCENTS WITH BIPOLAR DISORDER

Contrasting widespread beliefs and speculations regarding putative mechanisms underlying the salutary effects of exercise in bipolar disorder (BD), supporting evidence is sparse thus far. This presentation provides an overview of a series of studies, integrating prior published data with new data, seeking to illuminate the acute neurophysiological effects of aerobic exercise in adolescents with BD versus healthy control (HC) subjects.

41.2 NEURAL MARKERS AND CLINICAL RISK CALCULATION FOR PREDICTING BIPOLAR DISORDER

Family history is a potent risk factor for bipolar spectrum disorder (BPSD), although most offspring of parents with bipolar disorder will not develop BPSD. Neuroimaging studies assessing the differences between offspring of parents with bipolar disorder (OBP) and healthy control (HC) subjects have identified intrinsic functional connectivity (iFC) of the left inferior frontal gyrus (IFG) to be decreased in OBP. We recently developed a risk calculator (RC) in the Pittsburgh Bipolar Offspring Study (BIOS), a longitudinal cohort that includes OBP and HC parents, that accurately discriminates between OBP who will develop BPSD and those who do not (AUC = 0.76). Here, we present recent findings correlating risk score and mood lability (an important predictor of future BPSD onset) with IFG iFC.

Transcriptomic abnormalities in peripheral blood in bipolar disorder, and discrimination of the major psychoses

We performed a transcriptome-wide meta-analysis and gene co-expression network analysis to identify genes and gene networks dysregulated in the peripheral blood of bipolar disorder (BD) cases relative to unaffected comparison subjects, and determined the specificity of the transcriptomic signatures of BD and schizophrenia (SZ). Nineteen genes and 4 gene modules were significantly differentially expressed in BD cases. Thirteen gene modules were shown to be differentially expressed in a combined case-group of BD and SZ subjects called “major psychosis”, including genes biologically linked to apoptosis, reactive oxygen, chromatin remodeling, and immune signaling. No modules were differentially expressed between BD and SZ cases. Machine-learning classifiers trained to separate diagnostic classes based solely on gene expression profiles could distinguish BD cases from unaffected comparison subjects with an area under the curve (AUC) of 0.724, as well as BD cases from SZ cases with AUC = 0.677 in withheld test samples. We introduced a novel and straightforward method called “polytranscript risk scoring” that could distinguish BD cases from unaffected subjects (AUC = 0.672) and SZ cases (AUC = 0.607) significantly better than expected by chance. Taken together, our results highlighted gene expression alterations common to BD and SZ that involve biological processes of inflammation, oxidative stress, apoptosis, and chromatin regulation, and highlight disorder-specific changes in gene expression that discriminate the major psychoses.

Differentially methylated regions in bipolar disorder and suicide.

The addition of a methyl group to, typically, a cytosine-guanine dinucleotide (CpG) creates distinct DNA methylation patterns across the genome that can regulate gene expression. Aberrant DNA methylation of CpG sites has been associated with many psychiatric disorders including bipolar disorder (BD) and suicide. Using the SureSelectXT system, Methyl-Seq, we investigated the DNA methylation status of CpG sites throughout the genome in 50 BD individuals (23 subjects who died by suicide and 27 subjects who died from other causes) and 31 nonpsychiatric controls. We identified differentially methylated regions (DMRs) from three analyses: (a) BD subjects compared to nonpsychiatric controls (BD-NC), (b) BD subjects who died by suicide compared to nonpsychiatric controls (BDS-NC), and (c) BDS subjects compared to BD subjects who died from other causes (BDS-BDNS). One DMR from the BDS-NC analysis, located in ARHGEF38, was significantly hypomethylated (23.4%) in BDS subjects. This finding remained significant after multiple testing (PBootstrapped = 9.0 × 10-3 ), was validated using pyrosequencing, and was more significant in males. A secondary analysis utilized Ingenuity Pathway Analysis to identify enrichment in nominally significant DMRs. This identified an association with several pathways including axonal guidance signaling, calcium signaling, β-adrenergic signaling, and opioid signaling. Our comprehensive study provides further support that DNA methylation alterations influence the risk for BD and suicide. However, further investigation is required to confirm these associations and identify their functional consequences.

Suicide Risk in Bipolar Disorder: A Brief Review.

Bipolar disorders (BDs) are prevalent mental health illnesses that affect about 1–5% of the total population, have a chronic course and are associated with a markedly elevated premature mortality. One of the contributors for the decreased life expectancy in BD is suicide. Accordingly, the rate of suicide among BD patients is approximately 10–30 times higher than the corresponding rate in the general population. Extant research found that up to 20% of (mostly untreated) BD subjects end their life by suicide, and 20–60% of them attempt suicide at least one in their lifetime. In our paper we briefly recapitulate the current knowledge on the epidemiological aspects of suicide in BD as well as factors associated with suicidal risk in BD. Furthermore, we also discuss concisely the possible means of suicide prevention in BD.

Cerebral bioenergetic differences measured by phosphorus-31 magnetic resonance spectroscopy between bipolar disorder and healthy subjects living in two different regions suggesting possible effects of altitude.

AimIncreased oxidative stress in cerebral mitochondria may follow exposure to the systemic hypobaric hypoxia associated with residing at higher altitudes. Because mitochondrial dysfunction is implicated in bipolar disorder (BD) pathophysiology, this may impact the cerebral bioenergetics in BD. In this study, we evaluated the cerebral bioenergetics of BD and healthy control (HC) subjects at two sites, located at sea level and at moderate altitude.MethodsForty‐three veterans with BD and 33 HC veterans were recruited in Boston (n = 22) and Salt Lake City (SLC; n = 54). Levels of phosphocreatine, β nucleoside triphosphate (βNTP), inorganic phosphate, and pH over total phosphate (TP) were measured using phosphorus‐31 magnetic resonance spectroscopy in the following brain regions: anterior cingulate cortex and posterior occipital cortex, as well as bilateral prefrontal and occipitoparietal (OP) white matter (WM).ResultsA significant main effect of site was found in βNTP/TP (Boston > SLC) and phosphocreatine/TP (Boston < SLC) in most cortical and WM regions, and inorganic phosphate/TP (Boston < SLC) in OP regions. A main effect analysis of BD diagnosis demonstrated a lower pH in posterior occipital cortex and right OP WM and a lower βNTP/TP in right prefrontal WM in BD subjects, compared to HC subjects.ConclusionThe study showed that there were cerebral bioenergetic differences in both BD and HC veteran participants at two different sites, which may be partly explained by altitude difference. Future studies are needed to replicate these results in order to elucidate the dysfunctional mitochondrial changes that occur in response to hypobaric hypoxia.

Serum level of cathelicidin LL-37 is increased in euthymic patients with bipolar disorder irrespective of their cardio-metabolic status

Abstract Background Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in patients with bipolar disorder. Objectives The aim of this study is to re-evaluate serum LL-37 levels in patients with euthymic bipolar disorder and in healthy controls, matched for anthropometric and body composition parameters. Methods 36 adult patients with euthymic bipolar disorder and 68 non-depressed adults were included into the study. Concentration of LL-37 in serum was assessed using ELISA method. Detailed anthropometric measurements, body composition and biochemical analyses were performed. Results There was a statistically significant difference (p = 0.01) in serum LL-37 level between patients with bipolar disorder (4.97 ± 7.98 ng/mL) and control subjects (1.78 ± 2.69 ng/mL). Discussion Results of this study indicate that LL-37 serum level is increased in euthymic bipolar disorder patients. We found that this increase could not be attributed to analyzed anthropometric or body composition parameters.

Characterizing the gut microbiota in adults with bipolar disorder: a pilot study

ABSTRACT Background: Convergent evidence implicates gut microbiota in human health and disease. Hitherto, relatively few studies have evaluated the gut microbiota profile in individuals with bipolar disorder (BD) relative to healthy controls (HC). Methods: Fecal samples were collected from subjects (aged 18–65) meeting DSM-5-defined criteria for BD and age- and sex-matched HC without current or past history of mental or major medical disorders. Samples were sequenced using Illumina sequencing and association of specific taxa and co-occurrence of taxa with sample groups including the effect of diet was assessed using cluster analysis and analysis of communities of microorganisms (ANCOM). Nutritional composition was evaluated using the Dietary Questionnaire for Epidemiological Studies (DQES v2) Food Frequency Questionnaire. Results: Forty-six subjects were enrolled (n=23 BD, n=23 HC). Cluster analyses did not identify any significant differences between BD and HC (p=0.38). Lower microbiota diversity was observed among BD subjects relative to HC (p=0.04). A greater abundance of a Clostridiaceae OTU was observed among BD subjects when compared to HC and of Collinsella among BD-II subjects relative to BD-I. Cluster analysis revealed that neither diagnosis (p=0.38) nor diet (p=0.43) had a significant effect on overall gut microbiota composition. Limitations: This study has a small sample size and insufficient control for some potential moderating factors (e.g. psychotropic medication and smoking). Conclusion: This study suggests that individuals with BD may have a distinct gut microbiota profile compared to healthy controls, with a greater abundance of Clostridiaceae and Collinsella. These findings need to be replicated in future studies with larger sample sizes.

Convergent neural substrates of inattention in bipolar disorder patients and dopamine transporter-deficient mice using the 5-choice CPT.

Bipolar disorder (BD) is a debilitating psychiatric illness affecting 2%-5% of the population. Although mania is the cardinal feature of BD, inattention and related cognitive dysfunction are observed across all stages. Since cognitive dysfunction confers poor functional outcome in patients, understanding the relevant neural mechanisms remains key to developing novel-targeted therapeutics. The 5-choice continuous performance test (5C-CPT) is a mouse and fMRI-compatible human attentional task, requiring responding to target stimuli while inhibiting responding to nontarget stimuli, as in clinical CPTs. This task was used to delineate systems-level neural deficits in BD contributing to inattentive performance in human subjects with BD as well as mouse models with either parietal cortex (PC) lesions or reduced dopamine transporter (DAT) expression. Mania BD participants exhibited severe 5C-CPT impairment. Euthymic BD patients exhibited modestly impaired 5C-CPT. High impulsivity BD subjects exhibited reduced PC activation during target and nontarget responding compared with healthy participants. In mice, bilateral PC lesions impaired both target and nontarget responding. In the DAT knockdown mouse model of BD mania, knockdown mice exhibited severely impaired 5C-CPT performance versus wildtype littermates. These data support the role of the PC in inattention in BD-specifically regarding identifying the appropriate response to target vs nontarget stimuli. Moreover, the findings indicate that severely reduced DAT function/hyperdopaminergia recreates the attentional deficits observed in BD mania patients. Determining the contribution of DAT in the PC to attention may provide a future target for treatment development.

Sex-based dimorphisms in expression of BDNF and BACE1 in bipolar patients

Bipolar disorder (BD) is a chronic, serious mental disorder distinguished by repeated episodes of mania and depression. Previous studies have demonstrated dysregulation of a number of transcripts in brain tissue or peripheral blood of BD patients. In the present study, we compared expression of two protein coding genes (brain-derived neurotrophic factor (BDNF) and beta-secretase 1 (BACE1)) and their natural occurring anti-sense (AS) RNAs (BDNF-AS and BACE1-AS) in peripheral blood of 50 BD patients (mean age ± standard deviation (SD) = 36.5 ± 9.32) and 50 healthy subjects (mean age ± SD = 33.62 ± 8.59). BDNF and BACE1 were significantly up-regulated in peripheral blood of total BD patients compared with total healthy subjects (Expression ratio = 2.2, P value = 0.003; Expression ratio = 2.2, P value = 0.002 respectively). However, comparison of their levels in sex-based subgroups showed their up-regulations only in male patients compared with male health subjects (Expression ratio = 2.48, P value = 0.006; Expression ratio = 2.1, P value = 0.01). No significant differences were found in expressions of BDNF-AS and BACE1-AS between BD and health subjects. We detected a significant correlation between BDNF expression and age at disease onset in BD group after adjustment of the effects of sex (R = 0.26, P value = 0.03). Moreover, there were trends toward correlations between BDNF expression and disease duration in BD group and between BDNF expression and age in health subjects (P values = 0.05). Combination of BDNF, BDNF-AS and BACE1 expression levels could differentiate BD patients from healthy subjects with 68% sensitivity and 82% specificity (area under curve = 0.72, P value = 0.0001). The current study suggests a sex-based dimorphic pattern in expression of BDNF and BACE1. Moreover, our results imply that expression pattern of these genes could be diagnostic markers in BD. Future studies are needed to assess this speculation in larger patient samples.

SUBJECTIVELY AND OBJECTIVELY RATED MIXED AFFECTIVE STATES IN A MIXED-AGE SAMPLE OF ADULTS WITH BIPOLAR DISORDER: ASSOCIATIONS WITH AGE, SUICIDALITY, SYMPTOM SEVERITY, COGNITION AND INFLAMMATION

SUBJECTIVELY AND OBJECTIVELY RATED MIXED AFFECTIVE STATES IN A MIXED-AGE SAMPLE OF ADULTS WITH BIPOLAR DISORDER: ASSOCIATIONS WITH AGE, SUICIDALITY, SYMPTOM SEVERITY, COGNITION AND INFLAMMATION

Early maladaptive schemas in patients with obsessive-compulsive disorder, bipolar disorder, and schizophrenia: A comparative study

This study aimed to compare early maladaptive schemas (EMSs) among patients suffering from obsessive-compulsive disorder (OCD, n = 120), bipolar disorder (BD, n = 100), schizophrenia (n = 82), and healthy subjects (n = 60). To collect data, the Young Schema Questionnaire-Short Form (YSQ-SF), the Beck Depression Inventory-II (BDI-II), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Young Mania Rating Scale (YMRS), and the Positive and Negative Syndrome Scale (PANSS) were used. The results showed that patients with OCD, BD, and schizophrenia had higher scores on all EMSs than healthy subjects. Patients with OCD had higher scores on all EMSs except for entitlement, insufficient self-control, and mistrust/abuse than individuals with schizophrenia and/or BD. The entitlement and insufficient self-control schemas were higher in BD patients than patients with OCD and schizophrenia. Patients with schizophrenia scored higher on the mistrust/abuse schema than OCD and BD patients. Similar findings were also reported in subgroups with low and high depression. The findings show that some of the EMSs are specific to OCD, BD, and schizophrenia. Also, patients with OCD, BD, and schizophrenia have the highest numbers of EMSs respectively. In addition, increased depression may activate EMSs in patients with OCD, BD, and schizophrenia.

Peripheral and central levels of kynurenic acid in bipolar disorder subjects and healthy controls

Metabolites of the kynurenine pathway of tryptophan degradation, in particular, the N-Methyl-d-aspartic acid receptor antagonist kynurenic acid (KYNA), are increasingly recognized as primary pathophysiological promoters in several psychiatric diseases. Studies analyzing central KYNA levels from subjects with psychotic disorders have reported increased levels. However, sample sizes are limited and in contrast many larger studies examining this compound in blood from psychotic patients commonly report a decrease. A major question is to what extent peripheral KYNA levels reflect brain KYNA levels under physiological as well as pathophysiological conditions. Here we measured KYNA in plasma from a total of 277 subjects with detailed phenotypic data, including 163 BD subjects and 114 matched healthy controls (HCs), using an HPLC system. Among them, 94 BD subjects and 113 HCs also had CSF KYNA concentrations analyzed. We observe a selective increase of CSF KYNA in BD subjects with previous psychotic episodes although this group did not display altered plasma KYNA levels. In contrast, BD subjects with ongoing depressive symptoms displayed a tendency to decreased plasma KYNA concentrations but unchanged CSF KYNA levels. Sex and age displayed specific effects on KYNA concentrations depending on if measured centrally or in the periphery. These findings implicate brain-specific regulation of KYNA under physiological as well as under pathophysiological conditions and strengthen our previous observation of CSF KYNA as a biomarker in BD. In summary, biomarker and drug discovery studies should include central KYNA measurements for a more reliable estimation of brain KYNA levels.

Evidence for perturbed metabolic patterns in bipolar disorder subjects associated with lithium responsiveness

Bipolar disorder (BD) is multifactorial mood disorder characterized by alternating episodes of hyperactive mania and severe depression. Lithium is one of the most preferred drug used as mood stabilizer in treating BD. In this study, we examined the changes in plasma metabolome in BD subjects in the context of lithium responsiveness. Plasma samples from clinically defined, age and gender matched unrelated healthy controls and BD subjects (lithium responders and non-responders) were obtained and processed in positive and negative mode using untargeted liquid chromatography/mass spectrometry analysis. We identified significant alterations in plasma levels of dopamine along with its precursors (tyrosine and phenylalanine), branched chain amino acid such as valine and excitatory neurotransmitter glutamate between healthy control and BD subjects. Lipid molecules such as, eicosenoic acid and retinyl ester also showed distinguished patterns between control and BD individuals. Lithium responsiveness was markedly associated with significant differences in proline, L-gamma-glutamyl-isoleucine, dopamine, palmitic acid methyl ester, cholesterol sulfate, androsterone sulfate and 9S,12S,13S-triHOME levels. Altered metabolites enriched with key biochemical pathways associated with neuropsychiatry disorders. We hypothesize that BD pathogenesis and lithium responsiveness is associated with impaired homeostasis of amino acid and lipid metabolism.

M23 - GENETIC ASSOCIATION AND FUNCTIONAL CHARACTERIZATION OF A VARIANT IN THE MCPH1 GENE IN BIPOLAR DISORDER AND SCHIZOPHRENIA

Background Both Schizophrenia (SCZ) and Bipolar Disorder (BPD) disorder are serious psychiatric conditions that can give rise to debilitating symptoms that can severely impact the life of the affected individual, and their families. We have previously reported that the MCPH1 gene variant rs61749465 A>G (p.Asp61Gly) showed suggestive evidence for association with schizophrenia (SCZ; Leonenko et al. 2017). The MCPH1 gene has multiple roles in cellular functions including, DNA damage/repair pathways; centrosomal localization; E2F transcription factor 1-mediated apoptosis; transcriptional activation of cell cycle checkpoint, DNA stability; and telomere structure. A second MCPH1 point mutation (rs199422124 C>G; p.Thr27Arg) is an autosomal recessive cause of microcephaly. Methods The schizophrenia associated MCPH1 variant rs61749465 was tested for association in 2,300 Bipolar Disorder (BPD) subjects, and 1,820 normal comparison subjects. We also analysed the microcephaly causing mutation rs199422124 in the BPD and control subjects and in our SCZ cohort of 1,930 subjects. Next, we conducted analysis of the in vitro effects of the rs6174965 and rs199422124 variants on cell survival/proliferation using cell counts, and the MTT assay; their effect on DNA damage using the comet assay; their effect on mRNA stability using a combination of Actinomycin D treatment followed by Q-PCR; and their effect on gene expression using RNA-Seq analysis combined with pathway analysis and gene network analyses. Results After genotyping we report evidence for association with BPD (P=0.0009). Notably the variant allele of rs61749465 was absent in the 1,820 comparison subjects tested. rs61749465 is located in the N-terminal of the BRCT1 domain of MCPH1. Bioinformatic analysis predicted the Asp61Gly substitution to be damaging to MCPH1 protein function. rs199422124 was not detected in any of the participants. We sought to characterize the functional effects of these variants on MCPH1 function. Cell viability and cell count assays indicated that the variant allele of rs199422124 had a larger impact on cell survival compared to the variant allele of rs61749465, however neither of the variant alleles significantly altered DNA damage or mRNA stability. Gene expression analysis for rs61749465 using RNA-seq shows that the expression of a number of heat shock protein have been affected. Gene network and pathway analysis indicated that the variant alleles may impact cellular aging and protein translation. Discussion Further in vitro and in vivo characterization of the rs61749465 variant in MCPH1 may provide insight into the molecular pathogenesis of psychosis.

Bipolar disorder and 1513A>C P2RX7 polymorphism frequency

Although the etiology of Bipolar Disorder (BD) remains unknown, a strong genetic component to the pathogenesis and risk for this disorder has been widely hypothesized. Several risk genes for BD have been identified; of these, the purinergic P2 × 7 receptor (P2 × 7R) constitutes a pro-inflammatory receptor and a potential risk gene candidate. The purpose of the present study was to assess the frequency of the 1513 A > C P2RX7 polymorphism (rs3751143; Glu496Ala), which leads to receptor loss-of-function, in 154 BD patients versus 184 control subjects. The existence of a differential modulation of P2 × 7R was also analyzed in 22 euthymic BD patients, in comparison to 18 healthy controls. Our data show a decrease in 1513C allele frequency (p = 0.045) and a potential increase in 1513 A A/AC (p = 0.055) genotype frequency in BD patients, compared to controls, indicating an enhanced function of the pro-inflammatory P2 × 7 receptor in BD subjects. Interestingly, no differences in P2RX7 gene and protein expression were found between euthymic BD patients and matched healthy controls. In conclusion, our results suggest that P2 × 7R might play a role in the pathophysiology of BD and add new information regarding this receptor as a potential biomarker for the prediction and diagnosis of the disorder.

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.

The complement C4 structural diversity in bipolar disorder and schizophrenia

Background Genetic and clinical overlaps between Schizophrenia (SZ) and Bipolar disorder (BD) are remarkable with at least immune dysfunction as a common thread. Belonging to the innate arm of immune responses, the complement system encodes important molecules for: (i) immune surveillance and (ii) physiological synaptic pruning processes during childhood [1,2]. Recently, strong correlations between C4 copy number variations (CNVs) and SZ risk through complex gene rearrangements likely influencing the synaptic pruning were demonstrated [3]. The C4 component corresponds to the C4A and C4B protein isoforms encoded by loci differing only by five nucleotides and by distinct functions. The C4 genetic diversity, mainly represented by CNVs and structural size variations (long/short forms according to presence/absence of HERV-K), was demonstrated to influences the C4 protein expression [4]. Objective: We took advantage of phenotypically well-defined cohorts of BD and SZ patients to analyze the distribution of C4 structural variants as compared to healthy controls (HC). We also examined the presence of potential relationships between the C4 structural diversity and clinico-biological parameters. Methods: A total of 190 BD subjects, 97 SZ subjects and 132 HC were included in the study at Henri Mondor Hospital, Creteil, France. Digital Droplet PCR was used to determine the C4A, C4B, C4L and C4S CNVs as well as the exact C4AL, C4AS, C4BL and C4BS CNV types. The circulating serum levels of 44 cytokines and chemokines were quantified using electro-chemiluminescence. Results: We identified 44 different structural forms of C4 gene among which three were more represented: AL-AL-BL-BS (21.5 %), AL-AL-BL-BL (11.4 %) and AL-AL-BS-BS a (10.9 %). The C4 haplotypic analysis showed that the AL-AL-BL-BS haplotype was less frequent in SZ patients as compared to HC (p=0.017). We also observed in SZ patients that (i) high copy number of some C4 structural forms are correlated with a high level of some circulating cytokines (p

Attention deficit-hyperactivity disorder in adult bipolar disorder patients

BackgroundIt has long been recognized that bipolar disorder (BD) and attention deficit-hyperactivity disorder (ADHD) co-occur in an uncertain proportion of patients, recognized commonly in juvenile years. There is growing suspicion that such co-occurrence is associated with several clinically unfavorable characteristics. Accordingly, we compared 703 type I or II BD subjects with vs. without a lifetime diagnosis of ADHD. MethodsWe compared 173 BD patients with vs. 530 without co-occurring ADHD for selected demographic and clinical factors, using standard initial bivariate comparisons followed by multivariable logistic regression modeling. ResultsADHD was found in 25% of BD subjects, more among men and with type I BD. Those with ADHD had higher scores at the Adult ADHD Self-Report Scale (ASRS), were more likely to have had less successful school performance, unemployment, lower socioeconomic status, less marriage and more divorce, as well as more substance abuse, suicide attempts, and [hypo]mania, but were less likely to have an anxiety disorder or a family history of mood disorder. Multivariable logistic regression modeling found six factors differing between BD subjects with versus without ADHD: less education after high school, higher ASRS score for inattention, ever separated or divorced, irritable temperament, male sex, and lower scores on the Hamilton Depression Rating Scale (HDRS) at intake. CommentsCo-occurrence of ADHD with BD was identified at a moderate rate, and was associated with several unfavorable outcomes as well as a tendency toward [hypo]mania.

Hand functions in patients with schizophrenia: A clinical comparison with bipolar disorder and healthy subjects

ObjectiveFailure to achieve expected level of motor functioning may be a significant contributor to social withdrawal and further attenuation of life quality in patients with schizophrenia. Hand functioning is one of the most crucial entities in that manner. This study aimed to reveal this question by means of comparing patients with schizophrenia and bipolar disorder who are receiving similar antipsychotic psychopharmacological agents along with healthy control subjects. Methods99 patients with schizophrenia were compared to 40 patients with bipolar disorder matched according to the received pharmacotherapy comprising similar antipsychotics and 81 medication-free socio-demographically matched healthy control subjects. The materials were Hand Functional Index (HFI), Duruoz Hand Index (DHI), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS) along with clinical characteristics. ResultsDifference in total scores of DHI and HFI between schizophrenia, bipolar disorder and control groups were extremely significant (p < 0.001). Further post-hoc subgroup analysis revealed that patients with schizophrenia demonstrated higher scores of HFI indicating worse performance when compared to both bipolar disorder and control group. Significantly higher scores of DHI in patients with schizophrenia than healthy controls were noted. ConclusionIndependent from the impact of the medication use, impairment in hand functions was found to be more frequently seen in schizophrenia when compared to patients with bipolar disorder and healthy subjects. It is evident that hand function impairment is seen independent from psychopharmacological side effect, and is recommended to be assessed as a possible preventable and retractable manifestation of schizophrenia.