C-reactive protein: A differential biomarker for major depressive disorder and bipolar II disorder

Objectives We aimed to examine whether the C-reactive protein (CRP) level could be used to differentiate between major depressive disorder (MDD) and bipolar II disorder (BD II). Methods Ninety-six healthy controls, 88 BD II and 72 MDD drug-naïve patients in their major depressive episodes were enrolled. The fasting plasma level of high-sensitivity CRP was assessed at baseline and after treatment. Results The BD II patients presented significantly higher 17-item Hamilton Depression Rating Scale (HDRS) scores and CRP levels at baseline when adjustment for age, gender, and body mass index (P?< 0.001 and P?< 0.001, respectively). After treatment the CRP levels remained significantly different (P?< 0.001), although the HDRS score was not significantly different between the BD II and MDD patients. A receiver-operating characteristic analysis showed that a baseline CRP level of 621.6?ng/mL could discriminate between BD II and MDD, with an area under the curve of 0.816 and a sensitivity and specificity of 0.699 and 0.882, respectively. Furthermore, the baseline CRP level greater than 621.6?ng/ml had 28.2 higher odds of a diagnosis of BD II (P?< 0.001, 95% confidence interval: 10.96–72.35). Conclusions The level of CRP plays a role of biomarker to differentiate between MDD and BD II depression in both their depressed and euthymic state.     

Cognition in older adults with bipolar disorder versus major depressive disorder

Gildengers AG, Butters MA, Chisholm D, Anderson SJ, Begley A, Holm M, Rogers JC, Reynolds CF III, Mulsant BH. Cognition in older adults with bipolar disorder versus major depressive disorder. Bipolar Disord 2012: 14: 198–205. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive dysfunction in older age during both acute mood episodes and remitted states. The purpose of this study was to investigate for the first time the similarities and differences in the cognitive function of older adults with BD and MDD that may shed light on mechanisms of cognitive decline. Methods: A total of 165 subjects with BD (n = 43) or MDD (n = 122), ages ≥ 65 years [mean (SD) 74.2 (6.2)], were assessed when euthymic, using comprehensive measures of cognitive function and cognitive–instrumental activities of daily living (C‐IADLs). Test results were standardized using a group of mentally healthy individuals (n = 92) of comparable age and education level. Results: Subjects with BD and MDD were impaired across all cognitive domains compared with controls, most prominently in Information Processing Speed/Executive Function. Despite the protective effects of having higher education and lower vascular burden, BD subjects were more impaired across all cognitive domains compared with MDD subjects. Subjects with BD and MDD did not differ significantly in C‐IADLs. Conclusion: In older age, patients with BD have worse overall cognitive function than patients with MDD. Our findings suggest that factors intrinsic to BD appear to be related to cognitive deterioration and support the understanding that BD is associated with cognitive decline.     

Quantitative separation of the depressive phase of bipolar disorder and major depressive disorder using electrovestibulography

Abstract

Objectives: No electrophysiological, neuroimaging or genetic markers have been established that strongly relate to the diagnostic separation of bipolar disorder (BD) and major depressive disorder (MDD). This paper’s objective is to describe the potential of features, extracted from the recording of electrical activity from the outer ear canal, in a process called electrovestibulography (EVestG), for identifying depressed and partly remitted/remitted MDD and BD patients from each other.

Methods: From EVestG data four sensory vestibulo-acoustic features were extracted from both background (no movement) and using a single supine-vertical translation stimulus to distinguish 27 controls, 39 MDD and 43 BD patients.

Results: Using leave-one-out-cross-validation, unbiased parametric and non-parametric classification routines resulted in 78–83% (2–3 features), 80–81% (1–2 features) and 66–68% (3 features) accuracies for separation of MDD from BD, controls from depressed (BD & MDD) and the 3-way separation of BD from MDD from control groups, respectively. The main limitations of this study were the inability to fully disentangle the impact of prescribed medication from the responses and also the limited sample size.

Conclusions: EVestG features can reliably identify depressed and partly remitted/remitted MDD and BD patients from each other.     

Higher serum VGF protein levels discriminate bipolar depression from major depressive disorder

Misdiagnosis between major depressive disorder (MDD) and bipolar depression (BD) is quite common. Our previous study found significantly lower serum VGF (non-acronymic) in MDD patients. However, it is unclear whether same changes occur in BD patients. Therefore, we aimed to investigate the relationship between serum VGF levels in BD and MDD patients. General information, scores of 17-item Hamilton Depression Rating Scale (HDRS), and fasting blood samples of all participants including 30 MDD patients, 20 BD patients, and 30 healthy controls (HC) were collected. Serum VGF levels were measured by Enzyme-linked immunosorbent assay kits. Pearson correlation analysis was used to analyze correlations between serum VGF levels and clinical information. Receiver operating characteristic (ROC) curve and likelihood ratios (LRs) were used to analyze the differential potential of serum VGF. Serum VGF levels were significantly lower in MDD patients but higher in BD patients compared with HC (both P_Tukey < 0.01). No correlation was found between serum VGF levels and any data of subjects. The optimal cutoff for serum VGF in discriminating BD patients from MDD patients was ≥1093.85 pg/ml (AUC = 0.990, sensitivity of 95%, specificity of 100% and accuracy of 95%). LRs further confirmed the differential efficiency of serum VGF in distinguishing BD and MDD patients with +LR of infinity and –LR of 0. The results suggest that serum VGF level changed significantly in MDD and BD patients and serum VGF may be an indicator for differentiating BD patients from MDD patients.     

Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder

BACKGROUND: As patients with mood disorders manifest heterogeneity in phenomenology, pathophysiology, etiology, and treatment response, a biological classification of mental disease is urgently needed to advance research. Patient and methodological variability complicates the comparison of neuroimaging study results and limits heuristic model development and a biologically-based diagnostic schema. OBJECTIVE: We have critically reviewed and compared the magnetic resonance neuroimaging literature to determine the degree and directionality of volumetric changes in brain regions putatively implicated in the pathophysiology of major depressive disorder (MDD) versus bipolar disorder (BD). METHODS: A total of 140 published magnetic resonance imaging investigations evaluating subjects with BD or MDD were selected to provide a summary and interpretation of volumetric neuroimaging results in MDD and BD. Further commentary on the pathophysiological implications, and putative cellular and pharmacological mechanisms, is also provided. RESULTS: While whole brain volumes of patients with mood disorders do not differ from those of healthy controls, regional deficits in the frontal lobe, particularly in the anterior cingulate and the orbitofrontal cortex, appear to consistently differentiate subjects with mood disorders from the general population. Preliminary findings also suggest that subcortical structures, particularly the striatum, amygdala, and hippocampus, may be differentially affected in MDD and BD. CONCLUSIONS: Structural neuroimaging studies have consistently identified regional abnormalities in subjects with mood disorders. Future studies should strive to definitively establish the influence of age and medication.     

Proteomic Analysis of Serum from Patients with Major Depressive Disorder to Compare Their Depressive and Remission Statuses

ObjectiveCurrently, there are a few biological markers to aid in the diagnosis and treatment of depression. However, it is not sufficient for diagnosis. We attempted to identify differentially expressed proteins during depressive moods as putative diagnostic biomarkers by using quantitative proteomic analysis of serum.MethodsBlood samples were collected twice from five patients with major depressive disorder (MDD) at depressive status before treatment and at remission status during treatment. Samples were individually analyzed by liquid chromatography-tandem mass spectrometry for protein profiling. Differentially expressed proteins were analyzed by label-free quantification. Enzyme-linked immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC) curves were used to validate the differentially expressed proteins. For validation, 8 patients with MDD including 3 additional patients and 8 matched normal controls were analyzed.ResultsThe quantitative proteomic studies identified 10 proteins that were consistently upregulated or downregulated in 5 MDD patients. ELISA yielded results consistent with the proteomic analysis for 3 proteins. Expression levels were significantly different between normal controls and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 and complement component 1qC, which were upregulated during the depressive status. The depressive status could be distinguished from the euthymic status from the ROC curves for these proteins, and this discrimination was enhanced when all 3 proteins were analyzed together.ConclusionThis is the first proteomic study in MDD patients to compare intra-individual differences dependent on mood. This technique could be a useful approach to identify MDD biomarkers, but requires additional proteomic studies for validation.     

HTR2A−1438A/G polymorphism influences the risk of schizophrenia but not bipolar disorder or major depressive disorder: A meta‐analysis

The incidence of psychiatric disorders has been shown to have a strong genetic component, and we conducted this study to investigate whether the ?1438A/G polymorphism of the HTR2A gene was associated with susceptibility to schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using data obtained from a total 27 studies that investigated an association between the HTR2A ?1438A/G polymorphism and SZ (15), BD (7), and MDD (4). We failed to observe an association between the HTR2A ?1438A/G polymorphism and BD and MDD, and we found contrary results with regard to SZ. Our results showed that the ?1438A/G polymorphism was a risk factor for SZ, especially in Caucasians (allele model: OR, 1.12; 95% CI, 1.05–1.20; I² = 17.3%; dominant model: OR, 1.14; 95% CI, 1.03–1.27; I² = 15.3%; recessive model: OR, 1.20; 95% CI, 1.06–1.37; I² = 0.0%; codominant model 1: OR, 1.16; 95% CI, 1.01–1.32; I² = 0.0%). We found that the association of the HTR2A ?1438A/G polymorphism with SZ depends on the ethnic origin of the study population, and this genetic variant does not modify the susceptibility to BD or MDD. © 2013 Wiley Periodicals, Inc.     

Metabolic syndrome in subjects with bipolar disorder and major depressive disorder in a current depressive episode: Population-based study: Metabolic syndrome in current depressive episode

ObjectiveTo assess the differences in the prevalence of the metabolic syndrome (MetS) and their components in young adults with bipolar disorder (BD) and major depressive disorder (MDD) in a current depressive episode.MethodsThis was a cross-sectional study with young adults aged 24–30 years old. Depressive episode (bipolar or unipolar) was assessed using the Mini International Neuropsychiatric Interview – Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III).ResultsThe sample included 972 subjects with a mean age of 25.81 (±2.17) years. Both BD and MDD patients showed higher prevalence of MetS compared to the population sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of HDL cholesterol, and a higher prevalence of abdominal obesity were observed in both BD and MDD individuals with current depressive episode compared to the general population. Moreover, there was a significant difference on BMI values in the case of BD and MDD subjects (p = 0.016).ConclusionMetabolic components were significantly associated with the presence of depressive symptoms, independently of the diagnosis.     

A psychometric evaluation of the clinician‐rated Quick Inventory of Depressive Symptomatology (QIDS‐C16) in patients with bipolar disorder

The clinician‐rated, 16‐item Quick Inventory of Depressive Symptomatology (QIDS‐C₁₆) has been extensively evaluated in patients with major depressive disorder (MDD). This report assesses the psychometric properties of the QIDS‐C₁₆ in outpatients with bipolar disorder (BD, N = 405) and MDD (N = 547) and in bipolar patients in the depressed phase only (BD‐D) (N = 99) enrolled in the Texas Medication Algorithm Project (TMAP) using classical test theory (CTT) and the Samejima graded item response theory (IRT) model. Values of coefficient alpha were very similar in BD, MDD, and BD‐D groups at baseline (α = 0.80–0.81) and at exit (α = 0.82–0.85). The QIDS‐C₁₆ was unidimensional for all three groups. MDD and BD‐D patients (n = 99) had comparable symptom levels. The BD‐D patients (n = 99) had the most, and bipolar patients in the manic phase had the least depressive symptoms at baseline. IRT analyses indicated that the QIDS‐C₁₆ was most sensitive to the measurement of depression for both MDD patients and for BD‐D patients in the average range. The QIDS‐C₁₆ is suitable for use with patients with BD and can be used as an outcome measure in trials enrolling both BD and MDD patients. Copyright © 2009 John Wiley & Sons, Ltd.     

Resting state functional network switching rate is differently altered in bipolar disorder and major depressive disorder

The clinical misdiagnosis ratio of bipolar disorder (BD) patients to major depressive disorder (MDD) patients is high. Recent findings hypothesize that the ability to flexibly recruit functional neural networks is differently altered in BD and MDD patients. This study aimed to explore distinct aberrance of network flexibility during dynamic networks configuration in BD and MDD patients. Resting state functional magnetic resonance imaging of 40 BD patients, 61 MDD patients, and 61 matched healthy controls were recruited. Dynamic functional connectivity matrices for each subject were constructed with a sliding window method. Then, network switching rate of each node was calculated and compared among the three groups. BD and MDD patients shared decreased network switching rate of regions including left precuneus, bilateral parahippocampal gyrus, and bilateral dorsal medial prefrontal cortex. Apart from these regions, MDD patients presented specially decreased network switching rate in the bilateral anterior insula, left amygdala, and left striatum. Taken together, BD and MDD patients shared decreased network switching rate of key hubs in default mode network and MDD patients presented specially decreased switching rate in salience network and striatum. We found shared and distinct aberrance of network flexibility which revealed altered adaptive functions during dynamic networks configuration of BD and MDD.     

重性抑郁障碍与双相障碍患者躯体疾病共病调查

目的:了解重性抑郁障碍(MDD)与双相障碍(BD)患者躯体疾病共病情况。方法:对141例MDD和52例BD患者进行一般情况、躯体疾病调查及精神疾病评估。结果:MDD和BD患者躯体疾病的共病率分别为68.1%、46.2%,共病的躯体疾病以慢性病为主,依次为高血压、慢性胃炎、腰椎间盘突出、糖尿病。与非共病患者比较,共病患者年龄及起病年龄大,精神疾病复发次数多(P0.05或P0.01)。MDD共病患者自杀意念风险明显增加(P0.01)。结论:较高龄及较高龄起病的MDD、BD患者更易共病慢性躯体疾病。     

A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects

Périco CA‐M, Duran FLS, Zanetti MV, Santos LC, Murray RM, Scazufca M, Menezes PR, Busatto GF, Schaufelberger MS. A population‐based morphometric MRI study in patients with first‐episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects.
Bipolar Disord 2011: 13: 28–40. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: Many morphometric magnetic resonance imaging (MRI) studies that have investigated the presence of gray matter (GM) volume abnormalities associated with the diagnosis of bipolar disorder (BD) have reported conflicting findings. None of these studies has compared patients with recent‐onset psychotic BD with asymptomatic controls selected from exactly the same environment using epidemiological methods, or has directly contrasted BD patients against subjects with first‐onset psychotic major depressive disorder (MDD). We examined structural brain differences between (i) BD (type I) subjects and MDD subjects with psychotic features in their first contact with the healthcare system in Brazil, and (ii) these two mood disorder groups relative to a sample of geographically matched asymptomatic controls. Methods: A total of 26 BD subjects, 20 subjects with MDD, and 94 healthy controls were examined using either of two identical MRI scanners and acquisition protocols. Diagnoses were based on DSM‐IV criteria and confirmed one year after brain scanning. Image processing was conducted using voxel‐based morphometry. Results: The BD group showed increased volume of the right dorsal anterior cingulate cortex relative to controls, while the MDD subjects exhibited bilateral foci GM deficits in the dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons). Direct comparison between BD and MDD patients showed a focus of GM reduction in the right‐sided dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons) and a trend (p < 0.10, corrected) toward left‐sided GM deficits in the dorsolateral prefrontal cortex of MDD patients. When analyses were repeated with scanner site as a confounding covariate the finding of increased right anterior cingulate volumes in BD patients relative to controls remained statistically significant (p = 0.01, corrected for multiple comparisons). Conclusions: These findings reinforce the view that there are important pathophysiological distinctions between BD and MDD, and indicate that subtle dorsal anterior cingulate abnormalities may be relevant to the pathophysiology of BD.     

Self‐esteem in remitted bipolar disorder patients: a meta‐analysis

Nilsson KK, Jørgensen CR, Craig TKJ, Straarup KN, Licht RW. Self‐esteem in remitted bipolar disorder patients: a meta‐analysis.
Bipolar Disord 2010: 12: 585–592. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Low self‐esteem has been found to be a risk factor for depression in major depressive disorder (MDD). In contrast, the role of self‐esteem in bipolar disorder (BD) is still uncertain. In order to examine the characteristics of self‐esteem in BD, we synthesized studies comparing self‐esteem in BD patients with self‐esteem in MDD patients and in normal controls. Methods: Database searches and identification of studies were conducted by two of the authors independently. Remission of BD and MDD was a major selection criterion. The results were generated through meta‐analyses. Results: Random‐effects models of 19 between‐group comparisons (N = 1,838) suggested that the self‐esteem of remitted BD patients was significantly lower than that of normal controls (Cohen’s d = ?0.83), while significantly higher than that of remitted MDD patients (Cohen’s d = 0.54). Fail‐safe numbers and tests for funnel plot asymmetry indicated that the results were robust and unlikely to reflect publication biases. Additional studies indicated that self‐esteem may take a fluctuating course during remission of BD. Conclusions: By revealing that BD patients do experience low self‐esteem, the findings implicate a need for further understanding the causes and therapeutic impact of such abnormality in BD.     

Metabolic,hormonal and stress-related molecular changes in post-mortem pituitary glands from schizophrenia subjects

Abstract

Objectives. To identify a molecular profile for schizophrenia using post-mortem pituitaries from schizophrenia and control subjects. Methods. Molecular profiling analysis of pituitaries from schizophrenia (n = 14) and control (n = 15) subjects was carried out using a combination of liquid chromatography tandem mass spectrometry (LC-MS^E), multiplex analyte profiling (MAP), two-dimensional difference gel electrophoresis (2D-DIGE) and Western blot analysis. Results. This led to identification of differentially expressed molecules in schizophrenia patients including hypothalamic–pituitary–adrenal axis-associated constituents such as cortisol, pro-adrenocorticotropic hormone, arginine vasopressin precursor, agouti-related protein, growth hormone, prolactin and secretagogin, as well as molecules associated with lipid transport and metabolism such as apolipoproteins A1, A2, C3 and H. Altered levels of secretagogin in serum from a cohort of living first onset schizophrenia patients were also detected, suggesting disease association and illustrating the potential for translating some components of this molecular profile to serum-based assays. Conclusions. Future studies on the molecules identified here may lead to new insights into schizophrenia pathophysiology and pave the way for translation of novel diagnostics for use in a clinical setting.     

Biochemical markers subtyping major depressive disorder

The pathophysiology of major depressive disorder (MDD) remains elusive, and there is no established biochemical marker used in the daily clinical setting. This situation may result in part from the heterogeneity of MDD, which might include heterogeneous subgroups with different biological mechanisms. In this review, we discuss three promising biological systems/markers to potentially subtype MDD: the dopamine system, the hypothalamic–pituitary–adrenal axis, and chronic inflammatory markers. Several lines of evidence suggest that a facet of MDD is a dopamine agonist‐responsive subtype. Focusing on the hypothalamic–pituitary–adrenal axis, depressive spectrum disorders show hypercortisolism to hypocortisolism, which could be detected by hormonal challenge tests, such as the dexamethasone/corticotrophin‐releasing hormone test. Finally, accumulating evidence suggests that at least some MDD patients show characteristics similar to those of chronic inflammatory diseases, including neuroinflammatory markers and reduced tryptophan due to the increased activation of the tryptophan–kynurenine pathway. Future studies should examine the inter‐relations between these systems/markers to subtype and integrate the pathophysiology of MDD.     

Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions

Moreno C, Hasin DS, Arango C, Oquendo MA, Vieta E, Liu S, Grant BF, Blanco C. Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Bipolar Disord 2012: 14: 271–282. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: To compare the clinical features and course of major depressive episodes (MDEs) occurring in subjects with bipolar I disorder (BD‐I), bipolar II disorder (BD‐II), and major depressive disorder (MDD). Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001–2002), a nationally representative face‐to‐face survey of more than 43000 adults in the USA, including 5695 subjects with lifetime MDD, 935 with BD‐I and lifetime MDE, and 494 with BD‐II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Results: Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequent—and number of depressive symptoms per MDE was higher—among subjects with BD‐I, followed by BD‐II, and MDD. BD‐I individuals experienced a higher number of lifetime MDEs, had a poorer quality of life, and received significantly more treatment for MDE than BD‐II and MDD subjects. Individuals with BD‐I and BD‐II experienced their first mood episode about ten years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Conclusions: Our results support the existence of a spectrum of severity of MDE, with highest severity for BD‐I, followed by BD‐II and MDD, suggesting the utility of dimensional assessments in current categorical classifications.     

Clinical correlates and significance of separation anxiety in patients with bipolar disorder

OBJECTIVES: To evaluate frequency and severity of separation anxiety (SA) symptoms, as well as frequency of DSM-IV diagnosis of childhood separation anxiety disorder (CSAD) and adult separation anxiety disorder (ASAD), in a group of patients with bipolar disorder (BD) when compared with patients with panic disorder (PD) or major depression (MDD) and to a control group of healthy individuals (HC). METHODS: Outpatients with, respectively, bipolar I disorder (BD), PD, MDD and a group of individuals with no psychiatric diagnoses (HC) were assessed for diagnosis by the SCID-I and for SA by the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), the Separation Anxiety Symptoms Inventory (SASI) and the Adult Separation Anxiety Checklist (ASA-CL). RESULTS: Thirty-one patients with BD without comorbid PD (BD-PD), 22 with BD with comorbid PD (BD + PD), 24 with PD, 20 with MDD and 15 HC were included in the analyses. As to childhood SA, the BD-PD group had higher scores than PD group and HC. The BD + PD group had higher scores than the PD group, MDD group and HC. As to adulthood SA, the BD-PD group had higher scores than HC on both SCI-SAS and Adult Separation Anxiety Questionnaire (ASA-27). The BD + PD had higher scores on both scales than BD-PD, PD group, MDD group and HC. The PD group and MDD group had higher scores than HC on the ASA-27. Adult SA symptoms were significantly associated with an earlier age at onset of BD. CONCLUSIONS: This is the first study, to our knowledge, exploring the frequency and severity of SA symptoms during childhood and adulthood in a sample of bipolar patients in comparison to subjects with other anxiety and mood disorders. Our data appear to be preliminary grounds for investigating further the possibility that SA may deserve greater recognition in adults with BD.     

Obsessive-compulsive disorder with and without bipolar disorder

Aim: Bipolar disorder (BD) is often comorbid with obsessive–compulsive disorder (OCD). In this study, we compared clinical profile and course of subjects with a primary diagnosis of OCD with and without BD. Methods: We compared 34 subjects with primary diagnosis of OCD with BD and 57 subjects with a diagnosis of OCD without BD. Structured interview schedules, clinical rating scales, and information from clinical charts were utilized to assess patients. Results: OCD with BD was characterized by: (i) an episodic course; (ii) a higher number of depressive episodes, greater suicidality and a higher rate of hospitalization; (iii) fewer pathological doubts and more miscellaneous compulsions; and (iv) poorer insight into obsessive–compulsive symptoms. Conclusions: Episodic course appears to be typical of OCD with BD. Bipolarity has a pathoplastic effect on OCD and it is possible that some forms of OCD and BD are pathophysiologically related. Bipolar OCD is associated with a higher rate of depressive episodes, higher suicidality and more frequent hospitalizations, suggesting greater morbidity. Long‐term prospective follow‐up studies and studies addressing pathophysiology and genetic basis are needed to understand the complexity of such comorbidity.