On the prevalence of bipolar disorder in epilepsy

Although mood disorders represent a frequent psychiatric comorbidity in epilepsy, data on bipolar disorder (BD) are still limited, and the role of possible specific confounding variables (seizures and antiepileptic drug therapy) has never been considered. Data for 143 adult outpatients with epilepsy assessed with the Mini International Neuropsychiatric Interview Plus Version 5.0.0 using the Epilepsy Addendum for Psychiatric Assessment, the Mood Disorder Questionnaire, and the Interictal Dysphoric Disorder Inventory revealed that 11.8% had the Diagnostic and Statistical Manual of Mental Disorders-based diagnosis of BD, only 1.4% of whom could be considered as having “pure” BD, because in all other cases BD symptoms were related to phenotype copies of BD such as interictal dysphoric disorder of epilepsy, postictal manic or hypomanic states, and preictal dysphoria.     

The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data

The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13 835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case–Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.     

Development of the QoL.BD: a disorder-specific scale to assess quality of life in bipolar disorder

Michalak EE, Murray G, CREST.BD. Development of the QoL.BD: a disorder‐specific scale to assess quality of life in bipolar disorder.
Bipolar Disord 2010: 12: 727–740. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Background: There is wide recognition that symptom ratings alone are inadequate to measure outcomes in bipolar disorder (BD), and quality of life (QoL) has been proposed as an important separable construct. Although a literature on QoL in BD exists, there is no disorder‐specific measure of QoL in BD. In 2004, we embarked upon a four‐year mixed‐method program of research to develop such a measure that could function as an outcome tool in clinical trials of pharmacological or psychosocial treatment interventions, longitudinal monitoring, or routine clinical care. Methods: The project was informed by standard protocols for the development of disorder‐specific QoL measures. Two phases of scale development were pursued across four empirical studies. Item generation involved a qualitative investigation of individuals with BD, family members, and field experts (Study 1), as well as a literature review. Item reduction analyses were conducted using an intensive small‐N design with affected individuals (Study 2), a large field sample (Study 3), and a final small‐N item reduction study, again involving individuals with the disorder and field experts (Study 4). Results: Initial field testing of the Quality of Life in Bipolar Disorder (QoL.BD) scale supports use of the instrument as a feasible, reliable and valid disorder‐specific QoL measure for BD. Internal reliability of the QoL.BD is impressive, test‐retest reliability is appropriate, and the direction and magnitude of correlations with external measures are as expected. As a new instrument, the QoL.BD must be compared against existing options for measuring QoL in this population. Significantly, data suggest that the greater specificity of the QoL.BD relative to the Quality of Life Enjoyment and Satisfaction Questionnaire renders the new instrument more sensitive to clinical change in BD. Conclusions: Quality of life scales can provide important information additional to that provided by traditional assessments of outcome in BD. Our intensive, mixed‐method development of the QoL.BD has produced a useful additional measure of well‐being for this complex and often disabling condition.     

非典型症状与双相障碍

概述：双相障碍（Bipolar Disorder,BD）临床症状多样,容易被误诊为抑郁症（Major depressive disorder, MDD）。非典型症状（Atypical Features,ATFs）是一个有用的指标,可以从抑郁状态中识别出双相障碍,有助于双相障碍与抑郁症的鉴别诊断。本文就非典型症状与双相障碍的相关性问题进行讨论。     

What we learn about bipolar disorder from large‐scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group

MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness.     

Early age at onset of bipolar disorder is associated with more severe clinical features but delayed treatment seeking

OBJECTIVE: Our aim was to obtain a comprehensive view of differences between bipolar disorder (BD) patients with onset at early versus adult age in a representative study cohort. METHODS: In the Jorvi Bipolar Study (JoBS), 1,630 psychiatric in- and outpatients were systematically screened for BD using the Mood Disorder Questionnaire (MDQ). A total of 191 bipolar I and II patients with a current DSM-IV episode were interviewed to obtain information about age at onset of mood symptoms, clinical course, treatment, comorbidity, and functional status. The patients were classified as either early onset (<18 years) or adult onset. RESULTS: One-third of subjects with BD (58/191, 30%) had early onset. This was associated with female gender, more lifetime psychotic symptoms, greater overall comorbidity, and a greater length of time from first episode to treatment. CONCLUSIONS: Although BD patients with early age at onset have more severe clinical features and illness course, the delays from first episode to treatment and to correct diagnosis are longer than for those with adult onset disorder. To reduce morbidity rates related to the most severe forms of BD, the recognition and diagnosis of BD during adolescence needs to be improved.     

A 10-year evaluation on adolescents with anxiety disorders: are they at risk of bipolarity?

Objective: Anxiety disorders are the most frequent disorders comorbid with bipolar disorder (BD) often preceding the BD onset. The presence of comorbid anxiety in patients diagnosed with BD is associated with worsening of their BD symptoms, increased risky behaviour, decreased response to pharmacological treatment and deterioration in their quality of life and global functioning. The aim of this study was to investigate if anxiety disorders in adolescence could be considered as predictors of BD.

Methods: Adolescents with a primary anxiety disorder were recruited consecutively from the Mood and Anxiety Disorders Unit, Department of Neuroscience, University of Turin. Subjects were evaluated for Axis I psychiatric disorders, family history and global functioning, and followed up on average 10 years later.

Results: A total of 29 patients (59.2%) were male and the mean age at the onset of anxiety disorder was 16.3 (±0.8). Ten years following recruitment, 11 (22.4%) patients fulfilled the criteria for BD. Of them, 10 (90.9%) had a family history of BD and four (36.4%) presented a comorbid substance use disorder.

Conclusions: Our study shows that both family history of BD and substance use disorder, in adolescent patients with a primary anxiety disorder, should be considered as potential predictors of BD onset.     

Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy?

Physicians have become aware of the high prevalence of psychiatric disorders (PDs) in children and adolescents with epilepsy; however, there are many controversies as to which factors may have an important role in the different types of PD. This study was designed to assess the main PD; verify the age of onset compared with the age of diagnosis of the PD; and determine which factors may be correlated with the type of PD described. For this purpose, a multidisciplinary team evaluated children and adolescents (4–18 years) with epilepsy and analyzed patient-related factors such as age (grouped according to Piaget’s cognitive scale: <6 years, 7–13 years, >13 years), sex, family history of PDs, and cognitive status. With respect to epilepsy features, we considered age of onset, duration, seizure control at the time of psychiatric evaluation, refractoriness, antiepileptic drugs (mono- vs polytherapy), seizure type (generalized vs focal), and epilepsy type (idiopathic vs symptomatic/probably symptomatic). Depression occurred in 36.4% and attention-deficit hyperactivity disorder (ADHD) in 29.1%, these being the most frequent PDs in this series. Focal epilepsy was significantly more frequent in children and adolescents with PDs. As to the type of PD, age was an important factor, with a predominance of ADHD in children and depression in adolescents (P < 0.0001). Family history was contributory for depression, but not for others PDs (P < 0.0001). Depression remained underdiagnosed and untreated for a longer period. Impact of early diagnosis and treatment remains unknown.     

The Quality of Life in Bipolar Disorder (QoL.BD) Scale: Validation of a French Cross-Cultural Adaptation

Objective:The goal of this study was to validate the French version of the Quality of Life in Bipolar Disorder (QoL.BD) scale, a condition-specific measure for bipolar disorder (BD).Method:The QoL.BD scale was translated into French in accordance with the recommendations for transcultural adaptation. It was administered to 125 participants with BD living in Quebec, Canada. Construct validity was evaluated through correlations with other measures of self-reported quality of life (QoL), functioning, and symptoms. Factorial structure was examined through an exploratory factor analysis.Results:Internal reliability and test–retest reliability standards were met. Correlations in expected directions with other QoL, functioning, and depressive symptom scales supported convergent validity. The item loadings structure of the French QoL.BD largely replicated the original English version, with some modifications.Conclusion:The French version of the QoL.BD (full and brief) is comparable in its psychometric properties to the English version. It is a valid and sound measure for the evaluation of the QoL of French-speaking patients with BD.     

The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI

Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to bipolar disorder (BD) where disease risk is determined by the summation of many alleles of small individual magnitude. Modelling polygenic risk scores may be a powerful way of identifying disrupted brain regions whose genetic architecture is related to that of BD. We determined the extent to which common genetic variation underlying risk to BD affected neural activation during an executive processing/language task in individuals at familial risk of BD and healthy controls. Polygenic risk scores were calculated for each individual based on GWAS data from the Psychiatric GWAS Consortium Bipolar Disorder Working Group (PGC-BD) of over 16 000 subjects. The familial group had a significantly higher polygene score than the control group (P=0.04). There were no significant group by polygene interaction effects in terms of association with brain activation. However, we did find that an increasing polygenic risk allele load for BD was associated with increased activation in limbic regions previously implicated in BD, including the anterior cingulate cortex and amygdala, across both groups. The findings suggest that this novel polygenic approach to examine brain-imaging data may be a useful means of identifying genetically mediated traits mechanistically linked to the aetiology of BD.     

Intervenir précocement dans les stades débutants du trouble bipolaire : pourquoi,quand et comment

ObjectivesBipolar disorder (BD) is a chronic and severe psychiatric disease. There are often significant delays prior to diagnosis, and only 30 to 40 % of patients will experience complete remission. Since BD occurs most often at a young age, the disorder can seriously obstruct future socio-professional development and integration. Vulnerability-stress model of BD is considered to be the result of an interaction between vulnerability genes and environmental risk factors, which leads to the onset of the disorder most often in late adolescence or early adulthood. The clinical “staging” model of BD situates the subject in a clinical continuum of varying degrees of severity (at-risk status, first episode, full-blown BD). Given the demonstrated effectiveness of early intervention in the early stages of psychotic disorder, we posit that early intervention for early stages of BD (i.e. at-risk status and first episode mania or hypomania) would reduce the duration of untreated illness and optimize the chances of therapeutic response and recovery.MethodsWe conducted a narrative review of the literature to gather updated data on: (1) features of early stages: risk factors, at-risk symptoms, clinical specificities of the first manic episode; (2) early screening: targeted populations and psychometric tools; (3) early treatment: settings and therapeutic approaches for the early stages of BD.Results(1) Features of early stages: among genetic risk factors, we highlighted the diagnosis of BD in relatives and affective temperament including as cyclothymic, depressive, anxious and dysphoric. Regarding prenatal environmental risk, we identified peripartum factors such as maternal stress, smoking and viral infections, prematurity and cesarean delivery. Later in the neurodevelopmental course, stressful events and child psychiatric disorders are recognized as increasing the risk of developing BD in adolescence. At-risk symptoms could be classified as “distal” with early but aspecific expressions including anxiety, depression, sleep disturbance, decreased cognitive performance, and more specific “proximal” symptoms which correspond to subsyndromic hypomanic symptoms that increase in intensity as the first episode of BD approaches. Specific clinical expressions have been described to assess the risk of BD in individuals with depression. Irritability, mixed and psychotic features are often observed in the first manic episode. (2) Early screening: some individuals with higher risk need special attention for screening, such as children of people with BD. Indeed, it is shown that children with at least one parent with BD have around 50 % risk of developing BD during adolescence or early adulthood. Groups of individuals presenting other risk factors, experiencing an early stage of psychosis or depressive disorders should also be considered as targeted populations for BD screening. Three questionnaires have been validated to screen for the presence of at-risk symptoms of BD: the Hypomanic Personality Scale, the Child Behavior Checklist-Paediatric Bipolar Disorder, and the General Behavior Inventory. In parallel, ultra-high risk criteria for bipolar affective disorder (“bipolar at-risk”) distinguishing three categories of at-risk states for BD have been developed. (3) Early treatment: clinical overlap between first psychotic and manic episode and the various trajectories of the at-risk status have led early intervention services (EIS) for psychosis to reach out for people with an early stage of BD. EIS offers complete biopsychosocial evaluations involving a psychiatric examination, semi-structured interviews, neuropsychological assessments and complementary biological and neuroimaging investigations. Key components of EIS are a youth-friendly approach, specialized and intensive care and client-centered case management model. Pharmaceutical treatments for at-risk individuals are essentially symptomatic, while guidelines recommend the use of a non-antipsychotic mood stabilizer as first-line monotherapy for the first manic or hypomanic episode. Non-pharmacological approaches including psychoeducation, psychotherapy and rehabilitation have proven efficacy and should be considered for both at-risk and first episode of BD.ConclusionsEIS for psychosis might consider developing and implementing screening and treatment approaches for individuals experiencing an early stage of BD. Several opportunities for progress on early intervention in the early stages of BD can be drawn. Training first-line practitioners to identify at-risk subjects would be relevant to optimize screening of this population. Biomarkers including functional and structural imaging measures of specific cortical regions and inflammation proteins including IL-6 rates constitute promising leads for predicting the risk of transition to full-blown BD. From a therapeutic perspective, the use of neuroprotective agents such as folic acid has shown particularly encouraging results in delaying the emergence of BD. Large-scale studies and long-term follow-up are still needed to achieve consensus in the use of screening and treatment tools. The development of specific recommendations for the early stages of BD is warranted.     

Bipolar disorder comorbidity in patients with a primary diagnosis of OCD

Objective: Bipolar disorder (BD) is considered to be a common comorbid condition in subjects with obsessive-compulsive disorder (OCD), but there is limited literature on the prevalence of BD and its clinical correlates in those with a primary diagnosis of OCD.

Methods: We studied the prevalence of BD in a sample of consecutively registered outpatients attending a specialty OCD clinic in India over a period of 13 months. One hundred and seventy-one patients with a primary diagnosis of OCD were assessed systematically using structured and semi-structured instruments.

Results: The prevalence of lifetime BD in OCD was 4%. The OCD?+?BD group had an episodic course of OCD and higher rate of lifetime suicide attempts.

Conclusions: BD may not be as highly prevalent in OCD as reported in literature. Those with OCD seem to have only a marginally higher risk for developing BD than the general population. A diagnosis of BD seems to have a pathoplastic effect on the course of OCD. Patients with OCD-BD comorbidity have to be specifically assessed for suicide risk.     

Changing name of epilepsy in Korea; cerebroelectric disorder (noi‐jeon‐jeung,뇌전증,腦電症)

Public misconception of epilepsy may lead to significant stigma to the disease itself, thereby causing impaired quality of life in people with epilepsy. Traditionally, epilepsy has been considered to be the consequence of evanescent spiritual forces, and even demonic possession (in many countries). The names of epilepsy in some East Asian countries originated from China, and include madness in their meaning. We recently changed the Korean name of epilepsy, gan‐jil (??, 癎疾: a crazy, convulsive disease having meaning similar to 癲癎), to a neutral and scientifically explainable name: noi‐jeon‐jeung (???; 腦電症; cerebroelectric disorder). We expect that changing the stigmatized name of epilepsy to a neutral and scientific term with the meaning of cerebroelectric disorder will reduce the social stigma by understanding of epilepsy as one of the neurologic disorders.     

Differential prevalence and demographic and clinical correlates of second-generation antipsychotic use in bipolar I versus bipolar II disorder

AimsTo assess second-generation antipsychotic (SGA) use, demographics, and clinical correlates in patients with bipolar I disorder (BDI) versus bipolar II disorder (BDII).MethodsStanford Bipolar Disorder (BD) Clinic outpatients enrolled during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Current SGA use, demographics, and clinical correlates were assessed for BDI versus BDII.ResultsAmong 503 BD outpatients, in BDI versus BDII, SGA use was more than twice as common (44.0% versus 21.2%), and doses were approximately twice as high. BDI patients taking (N = 107) versus not taking (N = 136) SGAs less often had current full time employment and college degree; and more often had lifetime psychiatric hospitalization, current depression, and current complex pharmacotherapy, and had a higher mean current Clinical Global Impression for Bipolar Version Overall Severity score, and these persisted significantly after covarying for employment and education. Prior psychiatric hospitalization was the most robust correlate of SGA use in BDI patients. In contrast, these demographic and clinical correlates of SGA use were not statistically significant among patients with BDII, although BDII (but not BDI) patients taking (N = 55) versus not taking (N = 205) SGAs were more likely to have current mood stabilizer use (67.3% versus 51.7%).LimitationsAmerican tertiary bipolar disorder clinic referral sample, cross-sectional design.ConclusionsCurrent SGA use was robustly associated with prior psychiatric hospitalization in BDI and to a more limited extent with current mood stabilizer use in BDII. SGA use associations with other unfavorable illness characteristics in BDI were less robust.     

Comparison of two types of dissociation in epileptic and nonepileptic seizures

Dissociation is regarded as a possible psychological mechanism in nonepileptic seizures (NES), although existing evidence for this is equivocal. It has been suggested that the contradictory findings in this area reflect the use of measures that conflate qualitatively distinct types of dissociation, and provide inadequate coverage of the aspects of dissociation most closely related to NES. The study described here addressed this shortcoming by measuring the occurrence of two different types of dissociation, “detachment” (measured using the Cambridge Depersonalisation Scale) and “compartmentalization” (measured using the Somatoform Dissociation Questionnaire), in patients with NES (n = 32) and epilepsy controls (n = 37). As predicted, patients with NES scored significantly higher on the measure of compartmentalization only; contrary to prediction, however, this difference was no longer significant when anxiety and depression were controlled for. The conceptual and methodological implications of the study are discussed.     

Increased right amygdala volume in lithium‐treated patients with bipolar I disorder

Usher J, Menzel P, Schneider‐Axmann T, Kemmer C, Reith W, Falkai P, Gruber O, Scherk H. Increased right amygdala volume in lithium‐treated patients with bipolar I disorder. Objective: The amygdala plays a major role in processing emotional stimuli. Fourteen studies using structural magnetic resonance imaging (MRI) have examined the amygdala volume in paediatric and adult patients with bipolar disorder (BD) compared with healthy controls (HC) and reported inconsistent findings. Lithium has been found to increase grey matter volume, and first evidence points towards an effect on regional brain volume such as the amygdala. Method: We examined the amygdala volume of euthymic patients with BD treated with lithium (n = 15), without lithium (n = 24) and HC (n = 41) using structural MRI. Results: Patients treated with lithium exhibited in comparison to HC a larger right absolute (+17.9%, P = 0.015) and relative (+18%, P = 0.017) amygdala volume. There was no significant difference in amygdala volume between patients without lithium treatment and HC. Conclusion: Lithium appears to have a sustained effect on a central core region of emotional processing and should therefore be considered in studies examining BD.     

Childhood Obsessive–Compulsive Disorder in the NIMH MECA Study: Parent Versus Child Identification of Cases

Because as many as 50% of obsessive–compulsive disorder (OCD) cases have had onset by age 15, interest in its detection in childhood is strong. Clinical experience indicates that children often try to keep their OCD secret and that parental report may give marked underestimates. The authors examined the prevalence of childhood OCD in the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study, a four-site community survey which allowed comparison of both parent and child report of the child's OCD and related symptoms and disorders. OCD cases, based on structured interviews (DISC-2.3 with DSM-III-R criteria) with 1,285 caretaker-child pairs, were identified separately for parent and child (aged 9 through 17) informants from the MECA database. Cases were then examined for demographic characteristics, for obsessive–compulsive symptoms and other diagnoses reported in cases “missed” by one reporter, and for comorbid disorders. Of a total of 35 (2.7%) identified cases, four (0.3%) were identified by the parent and 32 (2.5%) were identified by the child, with only one overlapping case. In general, when OCD cases were “missed” by one reporter, that reporter did not substitute another disorder. These findings support clinical data that children with OCD often hide their illness and underscore the importance of child interviews for its detection.     

Differences between prepubertal- versus adolescent- onset bipolar disorder in a Spanish clinical sample

Objective To examine patients attended and diagnosed with bipolar disorder (BD) at a child and adolescent psychiatry service; to record age of diagnosis and age of onset, and to study clinical differences between prepubertal and adolescent onset groups. Methods All patients currently attended for BD type I, type II or non specified BD were reviewed and divided into two age groups: prepubertal onset (beginning before age 13) and adolescent onset (beginning at or above age 13). Results The sample were 43 patients with BD. Fourteen (32.6%) with prepubertal onset and 29 (67.4%) with adolescent onset. Time between onset of symptoms and diagnosis was longer in the prepubertal onset group (1.2 years versus 0.8 years respectively, P = .05). Patients with prepubertal onset BD more frequently presented previous symptoms such as irritability and conduct problems and had a higher rate of comorbidity (more frequently attention-deficit/hyperactivity disorder–ADHD). The adolescent onset group more often presented psychotic symptoms. Conclusion The clinical characteristics of patients with bipolar disorder differ according to whether onset is prepubertal or adolescent.     

Impact of living with bipolar patients: Making sense of caregivers’ burden

The aim of the present review was to examine objective and subjective burdens in primary caregivers (usually family members) of patients with bipolar disorder (BD) and to list which symptoms of the patients are considered more burdensome by the caregivers. In order to provide a critical review about caregiver’s burden in patients with bipolar disorder, we performed a detailed PubMed, BioMedCentral, ISI Web of Science, PsycINFO, Elsevier Science Direct and Cochrane Library search to identify all papers and book chapters in English published during the period between 1963 and November 2011. The highest levels of distress were caused by the patient’s behavior and the patient’s role dysfunction (work, education and social relationships). Furthermore, the caregiving role compromises other social roles occupied by the caregiver, becoming part of the heavy social cost of bipolar affective disorder. There is a need to better understand caregivers’ views and personal perceptions of the stresses and demands arising from caring for someone with BD in order to develop practical appropriate interventions and to improve the training of caregivers.     

Serum brain-derived neurotrophic factor in bipolar and unipolar depression: A potential adjunctive tool for differential diagnosis

The differential diagnosis of Bipolar Disorder (BD) and Major Depressive Disorder (MDD) is a diagnostic challenge during depressive episodes. Noteworthy, the proper differentiation between BD depressive state and MDD has important treatment implications. BDNF levels may be valuable adjunctive tool for this differential diagnosis. Ten subjects with MDD, forty with BD type I and thirty healthy comparison subjects were recruited. All subjects had BDNF serum levels measured and, in patients, BDNF serum levels were assessed during acute depressive episode. Optimal sensitivity and specificity of serum BDNF for the differential diagnosis of unipolar and bipolar depression were determined by the receiver operating characteristic (ROC) curve analysis, using a nonparametric approach. Serum BDNF levels in depressive BD patients were lower compared to MDD patients and controls (0.15 ± 0.08, 0.35 ± 0.08, and 0.38 ± 0.12, respectively, p < 0.001). The area under the curve (AUC) of the ROC analysis in BD depression vs. MDD was 0.95 (ranged from 0.89 to 1.00). Overall, the AUC of the ROC analysis (BD depression vs. MDD and controls) was 0.94 (95% CI 0.89 to 0.99, p < 0.001). A proposed “best” cutoff of 0.26 resulted in 88% sensitivity and 90% specificity. Serum BDNF levels appear as a promising tool to discriminate bipolar from unipolar depression. Our results suggest the role of BDNF as an adjunctive tool to promote prompt and accurate diagnosis of BD. However, further investigation and replication of these results are warranted.