What clinical features precede the onset of bipolar disorder?

Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12–30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD (‘AR’), b) participants from families without mental illness (‘controls’), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.     

CBCL-pediatric bipolar disorder phenotype: severe ADHD or bipolar disorder?

Summary Background. In children with pediatric bipolar disorder (PBD), a consistent pattern of elevations in hyperactivity, depression/anxiety, and aggression has been identified on the child behavior checklist (CBCL-PBD profile). The aim of the present study was to estimate the prevalence of the CBCL-PBD profile in a child psychiatric sample, and to determine ICD-10 diagnoses in CBCL-PBD patients. Methods. We studied a sample of 939 consecutively referred children and adolescents, aged 4–18 years. ICD-10 discharge diagnoses were established in consensus conferences. The CBCL 4–18 was completed by parents as part of the diagnostic routine. Results. A total of 62 subjects (6.6%; 95% CI=5.2–8.4) met criteria for the CBCL-PBD phenotype. More than 75% of CBCL-PBD subjects were clinically diagnosed with disruptive behavior disorders (ADHD, ODD, and CD). Two patients (0.2% of the total sample) received a formal diagnosis of bipolar disorder, but did not show the CBCL-PBD phenotype. Conclusions. A considerable number of children in Germany are referred to psychiatric care with a mixed phenotype of aggression, anxiety, depression and attention problems. Our study demonstrated a comparable prevalence and similar clinical characteristics as reported from other countries using different diagnostic approaches. However, the CBCL-PBD phenotype does not correspond with clinical consensus diagnoses of bipolar disorder, but with severe disruptive behavior disorders. Correspondence: Martin Holtmann, Department of Child and Adolescent Psychiatry and Psychotherapy, J.W. Goethe-University, Deutschordenstrasse 50, 60528 Frankfurt/Main, Germany     

Theory of mind impairment: a distinct trait‐marker for schizophrenia spectrum disorders and bipolar disorder?

Objective: The aim of this study was to critically review the literature in order to determine if Theory of Mind (ToM) impairment can be considered a trait‐marker for schizophrenia spectrum disorders and bipolar disorder (BD). Method: After a thorough literature search, we reviewed the empirical studies investigating ToM impairments in remitted schizophrenia patients, first episode patients, subjects at high‐risk (HR) for psychosis and first‐degree relatives of schizophrenia patients. Studies investigating ToM impairment in other schizophrenia spectrum conditions, affective psychosis and BD were also reviewed. Results: ToM abnormalities exist at onset and continue throughout the course of schizophrenia, persist into remission, and while less severe, are apparent in HR populations. Mentalizing impairments are also observed in other forms of psychotic illness and BD. Conclusion: Mentalizing impairment in schizophrenia spectrum disorders and BD might reflect underlying general cognitive deficits and residual symptom expression, rather than representing a specific trait‐marker.     

Obsessive compulsive symptoms in bipolar disorder patients: a comorbid disorder or a subtype of bipolar disorder?

概述

在过去十年中，人们越来越关注同时符合两种或两种以上精神障碍诊断标准的患者。上述共病情况之一就是双相障碍合并强迫症，这在以双相障碍为主要诊断的患者中比较常见。但是，关于这种共病的诊断和治疗的研究很少，在中国尤为如此。现有的研究主要集中在小样本的横断面研究，因此它们在对理解这种共病情况的病因和病程作用有限。对有限的文献进行回顾发现这是双相障碍中一种相对严重的、难治性的亚型，只有少数情况可以被认为是一种共病障碍。要阐明这种共病的病因、预后以及合适的治疗方法，则需要大样本的前瞻性研究。

中文全文

本文全文中文版从2015年10月26日起在http://dx.doi.org/10.11919/j.issn.1002-0829.215091可供免费阅览下载 The Forum by Peng and Jiang[1] highlights the lack of literature about comorbid bipolar disorder and obsessive compulsive (OCD) disorder. To provide a preliminary summary of the available English-language literature, a search of PubMed using three relevant keywords (‘bipolar disorder’, ‘obsessive compulsive disorder’, and ‘comorbidity’) was conducted in July 2015. Only a few of the 176 papers retrieved by this search were directly related to the topic of interest: most of the relevant papers described the incidence and clinical features of comorbid bipolar disorder and OCD in relatively small samples of patients; some discussed the etiology and treatment of the comorbid condition; and a few reported on prospective, multi-center studies with relatively large samples. Bipolar-OCD comorbidity was first reported in a 1995 study from Germany[2] which found that more than half of all patients with bipolar disorder had experienced other mental disorders, including OCD, during the course of the bipolar disorder. The study reported that the prevalence of comorbid OCD was higher in patients with unipolar depression than among patients with bipolar disorder. A subsequent systematic review[3] of 64 relevant articles in 2014 reported that from 11 to 21% of persons with bipolar disorder experience comorbid OCD at some time during the course of their bipolar disorder. Most reports indicate that comorbid OCD exacerbates the symptoms of bipolar disorder and makes the diagnosis and treatment of bipolar disorder more difficult. Compared to OCD patients and bipolar disorder patients without other comorbid conditions, bipolar patients with comorbid OCD have: a) higher rates of obsessive ideas about sex and religion and lower rates of ritual checking;[4] b) higher rates of substance abuse (including use of alcohol, sedatives, caffeine, etc.);[5,6] more episodes of depression, higher rates of suicide, and more frequent admissions to hospitals;[7] and d) more chronic episodes and residual symptoms.[8,9] There were no differences between bipolar patients with and without comorbid OCD in age, gender, education, marital status, age of onset of bipolar disorder, personality, prevalence of psychotic symptoms or rapid cycling, history of suicide attempts, the type of initial bipolar episode (i.e., depressed or manic), and the type of episode that was most prevalent throughout the course of bipolar disorder.[9] The systematic review by Amerio and colleagues[3] found that compared to bipolar patients without comorbid OCD, patients with bipolar disorder with comorbid OCD were more likely to experience OCD symptoms during an affective disorder episode (75% v. 3%), had a higher mean (sd) number of depressive episodes (8.9 [4.2] v. 4.1 [2.7] episodes), and were more likely to experience an antidepressant-induced manic episode (39% v. 9%). They also found that among patients with comorbid bipolar disorder and OCD, OCD symptoms were more like to occur during depressive episodes than manic episodes (78% v. 64%). Based on their findings, these authors argue that the obsessive-compulsive symptoms observed in these patients were secondary to bipolar disorder, not a co-occurring independent disorder.[3] Following this logic, I recommend that the occurrence of obsessivecompulsive symptoms during the depressive (or manic) episodes of a bipolar disorder should not be sufficient to merit a diagnosis of comorbid bipolar disorder and OCD; this comorbid diagnosis should be restricted to situations in which a patient with bipolar disorder also meets the full OCD symptomatic and duration criteria when the patient is not experiencing a depressive or manic episode. There are only a few articles about the possible etiology of bipolar-OCD comorbidity. A long-term family study based on a multi-generational dataset[10] (cases registered from January 1969 to 2009 included 19, 814 with OCD, 58, 336 with schizophrenia, 48, 180 with bipolar disorders, and 14, 904 with schizoaffective disorder) found familial associations among individuals with bipolar disorder, OCD, and schizophrenia spectrum disorders. There are also few reports about the long-term prognosis of comorbid bipolar disorder and OCD. One study[11] that followed 20 patients with bipolar disorder without comorbid disorders and 20 patients with comorbid bipolar disorder and OCD for 4 years found no significant differences in the long-term outcomes between the two groups. The treatment of bipolar-OCD comorbidity is difficult because the use of antidepressants to treat obsessive compulsive disorder may induce manic episodes. The existing literature about the treatment is primarily composed of case reports, retrospective cross-sectional studies, and a few treatment studies with small samples. A recent systematic review that combined the results of four treatment studies[12] found that 42% of patients with comorbid bipolar disorder and OCD were simultaneously treated with multiple mood stabilizers and another 10% needed combined treatment with mood stabilizers and anti-psychotic medications. One of the four studies reported that the combined use of antidepressants and mood stabilizers was effective and another study reported that some patients benefitted from the combined use of mood stabilizers and psychological therapy.[11] Based on currently available information, I recommend that patients with comorbid bipolar disorder and OCD be initially treated with mood stabilizers; if mono-therapy with mood stabilizers is ineffective, adjunctive treatment with selective serotonin reuptake inhibitor antidepressants (which are less likely to induce mania) should be considered. In my opinion, the basic treatment for bipolar-OCD is mood stabilizers and could be combined with antidepressants if the patients do not respond to the single treatment (ineffective). Despite ongoing debates about the etiology, diagnosis, and treatment of comorbid bipolar disorder and OCD, the clinicians who regularly treat bipolar patients need more high-quality, evidence-based information to improve their identification and management of this relatively severe and refractory subgroup of bipolar patients. Well-designed prospective studies with relatively large samples that are specifically focused on this important subgroup of bipolar disorder patients are needed.     

Do personality traits predict first onset in depressive and bipolar disorder?

The aim was to investigate whether personality traits predict onset of the first depressive or manic episode (the vulnerability hypothesis) and whether personality might be altered by the mood disorder (the scar hypothesis). A systematic review of population-based and high-risk studies concerning personality traits and affective disorder in adults was conducted. Nine cross-sectional high-risk studies, seven longitudinal high-risk studies and nine longitudinal population-based studies were found. Most studies support the vulnerability hypothesis and there is evidence that neuroticism is a premorbid risk factor for developing depressive disorder. The evidence for the scar hypothesis is sparse, but the studies with the strongest design showed evidence for both hypotheses. Only few studies of bipolar disorder were found and the association between personality traits and bipolar disorder is unclear. Neuroticism seem to be a risk factor by which vulnerable individuals can be identified, thus preventing the development of depressive disorder. A connection between personality traits and development of bipolar disorder, and evidence of a personality-changing effect of affective episodes need to be further investigated.     

Chemokines in bipolar disorder: Trait or state?

Recent evidence has suggested that inflammatory and immune mechanisms may play a role in the pathophysiology of bipolar disorder (BD). Only a few studies have assessed the profile of chemokines, a family of chemotactic cytokines related to the recruitment of leukocytes, in BD. The objective of our study was to evaluate the plasma levels of chemokines in BD patients in different mood states in comparison with healthy controls. Seventy BD type I patients (35 in euthymia and 35 in mania), and 50 healthy controls matched by age, gender, and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of CCL2, CCL3, CCL11, CCL24, CXCL8, and CXCL10 were measured by enzyme-linked immunosorbent assay. BD patients presented higher plasma levels of CCL11 (1.69-fold increase; p < 0.001), CCL24 (1.40-fold increase; p = 0.02), CXCL10 (1.45-fold increase; p < 0.001) and decreased plasma levels of CXCL8 (8.68-fold decrease p < 0.001). Logistic regression stressed the main effect of increased plasma levels of CXCL10 (OR = 1.009, 95 % CI = 1.000–1.018, p = 0.042) and CCL11 (OR = 1.002, 95 % CI = 1.001–1.003, p = 0.003) and decreased plasma levels of CXCL8 (OR = 0.995, 95 % CI = 0.990–0.999, p = 0.013) to BD. This study reinforces the view that BD is associated with an immune dysfunction.     

Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes?

Consolidation of new memories depends on a crucial phase of protein synthesis. It is widely held that, once consolidated, memories are stable and resilient to disruption. However, established memories become labile when recalled and require another phase of protein synthesis to be maintained. Therefore, it has been proposed that when a memory is reactivated it must undergo additional consolidation (reconsolidation) to persist. To determine whether reconsolidation recapitulates consolidation, in the past few years several groups have investigated whether the same molecules and pathways mediate the formation of a memory and its maintenance after reactivation. At first glance, the results appear conflicting: although both processes appear to engage the same molecules and mechanisms, brain areas involved in consolidation after initial training are not required for reconsolidation. In addition, the formation of a memory and its maintenance after reactivation seem to have distinctive temporal molecular requirements. This review concludes with a working model that could explain the apparent controversy of memory vulnerability after reactivation.     

Genetics of early onset bipolar affective disorder: Are we making progress?

Though considerable progress has been made in understanding the molecular genetics of bipolar affective dis order, few studies are currently focusing on the genetics of prepubertal or early adolescent onset illness. A variety of studies of the phenomenology, imaging and comorbidity of early onset bipolarity find significant differences from late onset illness. These studies raise the notion that early onset cases may represent a distinct genetic form or forms of manic-depressive illness.     

Fibromyalgia and bipolar disorder: a potential problem?

Wilke WS, Gota CE, Muzina DJ. Fibromyalgia and bipolar disorder: a potential problem?
Bipolar Disord 2010: 12: 514–520. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objective: To screen patients with fibromyalgia for bipolar disorder and to determine if there were any clinical clues, other than the Mood Disorders Questionnaire (MDQ), which might suggest a diagnosis of comorbid bipolar disorder. Methods: A total of 128 consecutive new fibromyalgia patients referred to a tertiary care center rheumatology practice were enrolled and assessed using a standard clinical protocol that included the completion of four screening questionnaires: (i) MDQ for bipolar disorder, (ii) Beck Depression Inventory (BDI) for depression, (iii) Epworth Sleepiness Scale (ESS) for daytime sleepiness, and (iv) Fibromyalgia Impact Questionnaire Disability Index (FIQ‐DI) to assess for functional capacity. Results: A quarter of the fibromyalgia subjects, 25.19%, had a positive screen for bipolar disorder (MDQ ≥ 7); 78.12% were clinically depressed (BDI ≥ 10); and 52.13% reported daytime sleepiness (ESS ≥ 10). Fibromyalgia subjects who screened positive for bipolar disorder had more severe depression than those with a negative screen [median BDI: 26.0 (19.0, 32.0) versus 15.0 (9.0, 24.0), p < 0.001]. Conclusions: We report a high prevalence of positive testing for bipolar disorder in this fibromyalgia cohort. Clinical data and questionnaire instruments other than nonspecific high depression severity failed to identify these patients. Since the norepinephrine serotonin reuptake inhibitors duloxetine and milnacipran have been recently approved by the U.S. Food and Drug Administration for the treatment of fibromyalgia, and because patients with bipolar disorder may experience destabilization of mood when treated with such agents, patients with fibromyalgia should be systematically screened for bipolar disorder prior to treatment.     

The relationship of major depressive disorder to bipolar disorder: Continuous or discontinuous?

Recent studies have questioned current diagnostic systems that split mood disorders into the independent categories of bipolar disorders and depressive disorders. The current classification of mood disorders runs against Kraepelin’s unitary view of manic-depressive insanity (illness). The main findings of recent studies supporting a continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder are presented. The features supporting a continuity between bipolar II disorder and major depressive disorder currently are 1) depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support a splitting of mood disorders); 2) family history (major depressive disorder is the most common mood disorder in relatives of bipolar probands); 3) lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; 4) major depressive disorder with bipolar features such as depressive mixed states, young onset age, atypical features, bipolar family history, irritability, racing thoughts, and psychomotor agitation; 5) a high proportion of major depressive disorders shifting to bipolar disorders during long-term follow-up; 6) a high proportion of major depressive disorders with history of manic and hypomanic symptoms; 7) factors of hypomania present in major depressive disorder episodes; 8) recurrent course of major depressive disorder; and 9) depressive symptoms much more common than manic and hypomanic symptoms in the course of bipolar disorders.     

Borderline or bipolar? Distinguishing borderline personality disorder from bipolar spectrum disorders

This article addresses the question whether borderline personality disorder (BPD) can be understood as a variant of bipolar disorder. In the past, borderline pathology has been seen as a variant of psychosis, depression, or posttraumatic stress disorder, but there are important differences between all of these conditions and BPD. The proposal that BPD falls within the bipolar spectrum depends on the assumption that affective instability develops through the same mechanism in both diagnostic categories. There are major differences in phenomenology, family history, longitudinal course, and treatment response between BPD and bipolar disorder, and the findings of comorbidity studies are equivocal. Thus, existing evidence is insufficient to support the concept that BPD falls in the bipolar spectrum.