Differentiate between unipolar and bipolar depression through studies investigating objective sleep markers using polysomnography and actigraphy.

Studies comparing unipolar and bipolar depression using objective markers often lack power and present heterogeneous results. However, in a recent actigraphy study (Leseur et al., 2024), which included 66 patients with unipolar depression and 24 with bipolar depression, notable and encouraging variations in sleep markers were found between the two disorders. Specifically, a decrease in sleep duration and efficiency was observed in people diagnosed with depression compared to those diagnosed with bipolar depression.

Currently, there is a major challenge in distinguishing between unipolar and bipolar major depressive episodes. A significant body of research has been dedicated to identifying biomarkers that can aid in this differentiation due to its crucial implications, particularly for therapeutic and prognostic purposes. Among the biomarkers of interest, markers related to sleep and circadian rhythms show promise and could potentially aid in making this distinction. A few studies have evaluated these markers objectively, but they often lack power, or the results stay highly heterogeneous. We conducted a systematic review and meta-analysis of published studies comparing sleep disorders between unipolar or bipolar depression using PubMed, Cochrane Library, and Web of Science databases. Actigraphy, polysomnography, and nocturnal Electroencephalography (EEG) were considered. The qualitative analysis retained 11 original studies, including 666 participants (355 patients diagnosed with bipolar depression and 311 with unipolar depression) and 8 studies were included for the meta-analysis. Depression in unipolar disorder was associated with a shorter total sleep time (SMD -0.3539, [CI: -0.5486 to -0.1592]; p < 0.001; MD: -27.9592; I2 = 0 %) and a poorer sleep efficiency (SMD -0.3105, [95 % CI: -0.5207 to -0.1003]; p = 0.004; MD: -0.3105; I2 = 0 %) than patients diagnosed with bipolar depression. There were no significant differences between the two groups in sleep onset latency, REM latency and REM % during the night. In summary, when examining objective sleep markers through polysomnography or actigraphy to distinguish between the two disorders, it appears that unipolar depressive disorder is associated with a reduced total sleep time and a poorer sleep efficiency than bipolar depressive disorder. These findings have substantial implications for identifying individuals with either unipolar or bipolar disorder using objective sleep markers, as well as for crafting tailored and effective therapeutic approaches.

Mood, activity, and instability in symptomatology hold significant roles in bipolar disorder (BD) and unipolar disorder (UD). The objectives were to examine disparities in these symptoms among patients with BD and UD.

Data from two studies including patients with BD and UD, respectively, were combined for exploratory analyses. Patients provided daily smartphone-based evaluations of mood and activity/energy for a 6-month period. A total of 47 patients with BD and 59 patients with UD were included in the analyses. The dataset contains more than 13,000 patient-reported evaluations of mood and activity. Daily mood and activity instability measures were calculated using the root squared successive difference method.

In linear mixed effect regression models adjusted for age, sex, and work status, there were statistically significant lower levels of activity in patients with BD as compared with patients with UD overall, during euthymic states and during depressive states (B: -0.61, 95% CI: -0.98; -0.24, p = 0.001). There were no statistically significant differences in mood instability and activity instability between patients with BD and patients with UD overall, during euthymic states and during depressive states, when accounting for multiple testing (p > 0.012).

Analyses were exploratory and post hoc. Findings should be interpreted with caution. The sample size was modest.

Patients with BD presented with lower level of activity as compared with patients with UD. There were no differences in mood and activity instability between these groups. Future studies including larger sample sizes should investigate differences between BD and UD.

ClinicalTrials.gov identifier: NCT03033420.

Background: The initial stages of bipolar disorder (BD) and schizophrenia (SCZ) often exhibit depressive symptoms and syndromes, leading to potential misdiagnosis and treatment for unipolar depression (UD). However, no consensus exists on individualized and time-varying intervenable conversion predictors for both BD and SCZ. Methods: This study examined the rate of true conversion from UD to BD and SCZ, considering factors such as sex, family history of mental illness, psychotic features, recurrent depression, and treatment patterns. The objective was to develop predictive models for short-, medium-, and long-term risk stratification for BD/SCZ conversion. Data were extracted from electronic medical records (EMRs) between January 2009 and December 2020 in a large academic medical center-based health system in China. Participants included 12,182 depressive inpatients without previous or comorbid diagnoses of BD and SCZ. The outcome measure was a subsequent admission record with a diagnostic code reflective of BD or SCZ. Four machine-learning algorithms using sociodemographic, clinical, laboratory, vital signs, symptoms, and treatment features were applied to predict this outcome. Explainable methodologies, specifically SHapley Additive exPlanations (SHAP) and Break Down, were employed to analyze the contribution of each individual feature. Results: Among 12,182 individuals, 344 (2.82%) and 64 (0.53%) received a subsequent diagnosis of BD and SCZ, respectively. Higher risk factors for BD progression included being female, having severe depression, being prescribed mood stabilizers, β receptor blockers (e.g., metoprolol tartrate and propranolol hydrochloride), and antipsychotics (e.g., sulpiride and quetiapine). Higher risk factors for SCZ progression included being male, exhibiting psychotic symptoms, being prescribed antipsychotics (e.g., risperidone and sulpiride), antiside effects drugs (e.g., trihexyphenidyl and hemp seed pill), and undergoing psychotherapy. Individuals with a family history of mental illness were particularly susceptible to conversion to BD and SCZ. Conclusions: The model's performance on the test dataset declined over time, with area under the curve (AUC) values for predicting BD conversion decreasing from 0.771 in 1 year to 0.749 in 2 years and 0.733 in 7 years, and for SCZ conversion, from 0.866 in 1 year to 0.829 in 3 years and 0.752 in 7 years. A key finding is that individuals with refractory (particularly psychotic) UD had an elevated risk of transitioning to BD and SCZ, with social-demographic factors, lifestyle behaviors, vital signs, and blood markers becoming significant risk factors over follow-up. Upon further validation, these models could provide clinicians with dynamic information regarding a patient's risk of disease conversion.

While patients with major depressive disorder (MDD) and bipolar disorder (BD) exhibited default mode network (DMN) dysfunction revealed by aberrant resting-state functional connectivity (rsFC) patterns, previous findings have been inconsistent. Little is known about the similarities and differences in DMN rsFC between MDD and BD.

A voxel-wise meta-analysis of seed-based DMN rsFC studies on MDD or BD was performed using the Seed-based d Mapping software with permutation of subject images (SDM-PSI). Aberrant DMN rsFC in both disorders was investigated separately, followed by conjunction and between-disorder comparison analyses. Functional decoding was performed to implicate the psychophysiological underpinnings of derived brain abnormalities.

Thirty-four studies comparing 1316 MDD patients with 1327 HC, and 22 studies comparing 1059 BD patients with 1396 HC were included. Compared to HC, MDD patients exhibited DMN hyperconnectivity with frontolimbic systems, and hypoconnectivity with temporal lobe and posterior cingulate cortex. BD patients displayed increased DMN connectivity with bilateral precuneus, and reduced connectivity with prefrontal cortex and middle temporal gyrus. No common patterns of DMN rsFC abnormalities were observed between MDD and BD. Compared to BD, MDD patients showed DMN hyperconnectivity with triangular part of the left inferior frontal gyrus and left fusiform gyrus. Functional decoding found that patterns of DMN rsFC alteration between MDD and BD were primarily related to action and perception domains.

Distinct DMN dysfunction patterns in MDD and BD enhance current understanding of the neural substrates of mood disorders and may provide a potential biomarker for differentiation.

The first year of life is the period of greatest brain plasticity. Postpartum depression can adversely affect the first interactions with the child and, consequently, their emotional, social, and cognitive development.

First, to describe the developmental profile of six-month-old infants of mothers suffering from severe postpartum depression, and, second, to compare the development of infants whose mothers suffer from depression with or without bipolar disorder.

This is a retrospective descriptive study on 6-month-old babies hospitalized with their mothers at the Marseille Mother-Baby Unit (MBU) for maternal postpartum depression with or without bipolar disorder. Mothers were clinically diagnosed by a psychiatrist specialized in postpartum depression using the DSM-5; infant development was assessed at 6 months by an independent health professional using the revised Brunet-Lézine Scale, which allowed the calculation of global and partial developmental quotients (DQ).

We followed 40 mother-infant dyads. None of the 40 infants had a global developmental delay. However, maternal depression was significantly associated with poorer sociability (mean sociability DQ score of 94 ± 9.6, p < 0.001) and lower postural development (mean postural DQ score of 96.2 ± 8.9 *, p < 0.001) in the infants at 6 months of age. Postural development was significantly lower in children of bipolar mothers than in children of non-bipolar mothers (p = 0.03).

Postpartum depression was associated with a weakness in sociability and posture at the age of 6 months, without relevant developmental delay. Screening infants at an early age with specific tools allows for earlier intervention, which would positively influence their developmental trajectory.

Currently, there is a major challenge in distinguishing between unipolar and bipolar major depressive episode. A significant body of research has been dedicated to identifying biomarkers that can aid in this differentiation due to its crucial implications, particularly for therapeutic and prognostic purposes. Among the biomarkers of interest, markers related to sleep and circadian rhythms show promise and could potentially aid in making this distinction. Nevertheless, no study has simultaneously examined sleep-wake disorders, circadian rhythms, and seasonal patterns using both subjective and objective measures. This study aims to characterize and compare the sleep-wake and rhythm disorders including patients with unipolar major depressive episode (n = 72) and with bipolar major depressive episode (n = 43) using both subjective markers (using self-report questionnaires and sleep complaints) and objective markers (using actigraphy). Patients with unipolar major depressive episode seem to experience significantly poorer quality of sleep, more symptoms of insomnia and lower sleep efficiency compared to patients with bipolar major depressive episode. On the other hand, patients with bipolar major depressive episode exhibit significantly more symptoms of motor retardation and hypersomnia compared to patients with unipolar disorder. These results hold significant implications for identifying individuals with unipolar major depressive episode or bipolar major depressive episode using sleep and circadian markers, and for developing recommended and personalized therapeutic strategies.

Anhedonia is a core symptom in patients with unipolar and bipolar depression. However, sex-specific markers reflecting biological heterogeneity are lacking. Emerging evidence suggests that sex differences in immune-inflammatory markers and lipoprotein profiles are associated with anhedonia.

The demographic and clinical data, immune-inflammatory markers (CD3, CD4, and CD8), and lipoprotein profiles [TC, TG, LDL-C, HDL-C, lipoprotein(a) Lp (a)] of 227 patients with unipolar and bipolar depression were collected. The Hamilton Depression Rating Scale (HAMD) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess depression and anhedonia symptoms. Data were analyzed using ANOVA, logistic regression, and receiver operating characteristic curves.

Male patients in the anhedonia group had higher levels of CD3, CD4, and CD8, and lower levels of Lp (a) than the non-anhedonia group, while no significant difference was identified in female patients with and without anhedonia. Logistic regression analysis showed that CD3, CD4, CD8, and Lp (a) levels were associated with anhedonia in male patients. Furthermore, the combination of CD3, CD4, CD8, and Lp (a) had the strongest predictive value for distinguishing anhedonia in male patients than individual parameters.

We identified sex-specific associations between immune-inflammatory markers, lipoprotein profiles, and anhedonia in patients with unipolar and bipolar depression. The combination of CD3, CD4, CD8, and Lp (a) might be a possible biomarker for identifying anhedonia in male patients with unipolar and bipolar depression.

Non-suicidal self-injury (NSSI) has a higher prevalence in adolescents with depressive disorders than in community adolescents. This study examined the differences in NSSI behaviors between adolescents with unipolar depression (UD) and those with bipolar depression (BD).

Adolescents with UD or BD were recruited from 20 general or psychiatric hospitals across China. The methods, frequency, and function of NSSI were assessed by Functional Assessment of Self-Mutilation. The Beck Suicide Ideation Scale was used to evaluate adolescents' suicidal ideation, and the 10-item Kessler Psychological Distress Scale to estimate the anxiety and depression symptoms.

The UD group had higher levels of depression (19.16 vs.17.37, F=15.23, P<0.001) and anxiety symptoms (17.73 vs.16.70, F=5.00, P=0.026) than the BD group. Adolescents with BD had a longer course of NSSI than those with UD (2.00 vs.1.00 year, Z=-3.39, P=0.001). There were no statistical differences in the frequency and the number of methods of NSSI between the UD and BD groups. Depression (r=0.408, P<0.01) and anxiety (r=0.391, P<0.01) were significantly and positively related to NSSI frequency.

Adolescents with BD had a longer course of NSSI than those with UD. More importantly, NSSI frequency were positively and strongly correlated with depression and anxiety symptoms, indicating the importance of adequate treatment of depression and anxiety in preventing and intervening adolescents' NSSI behaviors.

Major depressive disorder (MDD) with atypical features, namely depression with atypical features (AFD), is one of the most common clinical specifiers of MDD, closely associated with bipolar disorder (BD). However, there is still a lack of clinical guidelines for the diagnosis, treatment, and prognosis of AFD. Our study mainly focuses on three issues about how to identify AFD, what is the appropriate individualized treatment for AFD, and what are the predictive biomarkers of conversion to BD.

The Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD) is a multicenter, prospective, open-label study consisting of a 12-week randomized controlled trial (RCT) and a continued follow-up until 4 years or reaching the study endpoint. It is enrolling 480 patients with AFD (120 per treatment arm), 100 patients with BD, and 100 healthy controls (HC). Multivariate dimension information is collected including clinical features, cognitive function, kynurenine pathway metabolomics, and multimodal magnetic resonance imaging (MRI) data. Firstly, multivariate informatics analyses are performed to recognize patients with AFD from participants including the first-episode and recurrent atypical depression, patients with BD, and patients with HC. Secondly, patients with atypical depression are randomly allocated to one of the four treatment groups including "single application of selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI)", "SSRI/SNRI combined with mood stabilizer," "SSRI/SNRI combined with quetiapine (≥ 150 mg/day)," or "treatment as usual (TAU)" and then followed up 12 weeks to find out the optimized treatment strategies. Thirdly, patients with atypical depression are followed up until 4 years or switching to BD, to explore the risk factors of conversion from atypical depression to BD and eventually build the risk warning model of conversion to BD.

The first enrolment was in August 2019. The iDoT-AFD study explores the clinical and biological markers for the diagnosis, treatment, and prognosis of AFD and further provides evidence for clinical guidelines of AFD.

ClinicalTrials.gov NCT04209166. Registered on December 19, 2019.

There is little research reporting the outcome of internet delivered cognitive behaviour therapy, (iCBT), which helps patients identify and modify unhelpful cognitions and behaviours, for the depressed phase of bipolar disorder as part of routine care. Demographic information, baseline scores and treatment outcomes were examined for patients of MindSpot Clinic, a national iCBT service who reported taking Lithium and their clinic records confirmed the diagnosis of bipolar disorder. Outcomes were completion rates, patient satisfaction and changes in measures of psychological distress, depression and anxiety measured by the Kessler-10 item (K-10), Patient Health Questionnaire 9 Item (PHQ-9), and Generalized Anxiety Disorder Scale 7 Item (GAD-7), compared to clinic benchmarks. Out of 21,745 people who completed a MindSpot assessment and enrolled in a MindSpot treatment course in a 7 year period, 83 reported taking Lithium and had a confirmed a diagnosis of bipolar disorder. Outcomes of reductions in symptoms were large on all measures (effect sizes > 1.0 on all measures, percentage change between 32.4% and 40%), and lesson completion and satisfaction with the course were also high. MindSpot treatments appear to be effective in treating anxiety and depression in people diagnosed with bipolar, and suggest that iCBT has the potential to overcome the under-use of evidence based psychological treatments of people with bipolar depression.

Distinguishing postpartum women with bipolar from unipolar depression remains challenging, particularly in obstetrical and primary care settings. The post-birth period carries the highest lifetime risk for the onset or recurrence of Bipolar Disorder (BD). Characterization of differences between unipolar and bipolar depression symptom presentation and severity is critical to differentiate the two disorders.

We performed a secondary analysis of a study of 10,000 women screened by phone with the Edinburgh Postnatal Depression Scale at 4-6 weeks post-birth. Screen-positive mothers completed the Structured Clinical Interview for DSM-4 and those diagnosed with BD and unipolar Major Depressive Disorder (UD) were included. Depressive symptoms were assessed with the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-ADS).

The sample consisted of 728 women with UD and 272 women with BD. Women with BD had significantly elevated levels of depression severity due to the higher scores on 8 of the 29 SIGH-ADS symptoms. Compared to UD, women with BD had significantly higher rates of comorbid anxiety disorders and were twice as likely to report sexual and/or physical abuse.

Only women who screened positive for depression were included in this analysis. Postpartum women with unstable living situations, who were hospitalized or did not respond to contact attempts did not contribute data.

Severity of specific symptom constellations may be a useful guide for interviewing postpartum depressed women along with the presence of anxiety disorder comorbidity and physical and/or sexual abuse.

When depressive symptoms in bipolar and unipolar patients were compared, a number of studies reported that atypical vegetative features such as hypersomnia and hyperphagia were more common in bipolar patients. Moreover, neuropeptides such as orexin-A (ORX-A), ghrelin (GRL), and neuropeptide Y (NPY) are involved in the regulation of these vegetative functions.

A total of 45 unipolar and 24 bipolar depressive patients, and 36 euthymic healthy controls were included in the study. The groups were compared in terms of peripheral blood samples of ORX-A, GRL, and NPY levels, as well as HAM-D, Epworth Sleepiness Scale, Three-Factor Eating Questionnaire-Revised, and Suicide Probability Scale scores.

Both unipolar and bipolar patients had lower ORX-A, GRL, and NPY levels compared to the controls, whereas NPY levels of bipolar patients were lower than unipolar patients. There was a negative correlation between NPY levels and emotional eating in the bipolar group.

While lower ORX-A, GRL, and NPY levels are associated with depressive episodes regardless of the diagnosis; NPY levels also differ in bipolar and unipolar depression patients.

The Bipolar Depression Rating Scale (BDRS) is a structured rating scale designed to assess depressive and mixed symptoms in bipolar disorder (BD). Previous studies evaluating the scale have been performed on small samples or on patients in a depressive phase, but not on patients in a mixed or manic phase. This study evaluated the Persian version of the BDRS regarding its factor structure, reliability, and validity in a large sample of Iranian women with BD in a depressive or mixed/manic phase.

Three-hundred and one female BD inpatients completed the BDRS, the Beck Depression Inventory-II (BDI-II), the Hamilton Depression Rating Scale (HDRS), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Young Mania Rating Scale (YMRS).

The BDRS demonstrated a three-factor structure with good reliability. The BDRS and its psychological and somatic symptom clusters had stronger correlations with other measures of depressive symptoms than a measure of mania. The BDRS mixed symptom cluster also had a stronger correlation with a measure of mania than other measures of depression, supporting the scales' convergent and discriminant validity.

The BDRS demonstrated psychometric validity in assessing depressive and mixed symptoms in Iranian women with BD in a depressive or mixed/manic phase.KEY POINTSThe Bipolar Depression Rating Scale (BDRS) was validated in Iranian women with BD.The BDRS showed a three-factor structure, similar to the original validation.The BDRS had good reliability based on Omega and test-retest coefficients.The findings provided evidence for the convergent and discriminant validity of the BDRS.

Anhedonia is a hallmark feature of depression and is highly prevalent among individuals with mood disorders. The history and neurobiology of anhedonia has been most extensively studied in the context of unipolar Major Depressive Disorder (MDD), with converging lines of evidence indicating that marked anhedonia heralds a more chronic and treatment-refractory illness course. Furthermore, findings from neuroimaging studies suggest that anhedonia in MDD is associated with aberrant reward-related activation in key brain reward regions, particularly blunted reward anticipation-related activation in the ventral striatum. However, the ongoing clinical challenge of treating anhedonia in the context of Bipolar Disorder (BD) also highlights important gaps in our understanding of anhedonia's prevalence, severity, and pathophysiology along the entire mood disorder spectrum. In addition, although current theoretical models posit a key role for reward hyposensitivity in BD depression, unlike studies in MDD, studies in BD do not clearly show evidence for reduced reward-related activation in striatal or other brain regions. Although further research is needed, the evidence to date hints at a divergent pathophysiology for anhedonia in unipolar and bipolar mood disorders, which, if better understood, could lead to significant improvements in the diagnosis and treatment of MDD and BD.

Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking.

Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders.

Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at-risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed.

The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.

Lithium remains the gold standard maintenance treatment for Bipolar Disorder (BD). However, weight gain is a side effect of increasing relevance due to its metabolic implications. We conducted a systematic review and meta-analysis aimed at summarizing evidence on the use of lithium and weight change in BD. We followed the PRISMA methodology, searching Pubmed, Scopus and Web of Science. From 1003 screened references, 20 studies were included in the systematic review and 9 included in the meta-analysis. In line with the studies included in the systematic review, the meta-analysis revealed that weight gain with lithium was not significant, noting a weight increase of 0.462 Kg (p = 0158). A shorter duration of treatment was significantly associated with more weight gain. Compared to placebo, there were no significant differences in weight gain. Weight gain was significantly lower with lithium than with active comparators. This work reveals a low impact of lithium on weight change, especially compared to some of the most widely used active comparators. Our results could impact clinical decisions.

Although differences in symptom profiles and outcome between depressive patients with an underlying major depressive disorder (MDD) and bipolar depression (BD) have been reported, studies with sequential short-interval assessments in a real-life inpatient setting are scarce.

To examine potential differences in symptom profile and course of depressive symptomatology in depressive inpatients with underlying MDD and BD.

A cohort of 276 consecutive inpatients with MDD (n = 224) or BD (n = 52) was followed during their hospitalization using routine outcome monitoring (ROM), which included a structured diagnostic interview at baseline (Mini-International Neuropsychiatric Interview Plus [MINI-Plus]) and repeated 17-item Hamilton Depression Rating Scale every 2 weeks. MDD and BD were compared regarding their symptom profiles and time to response and remission. Furthermore, the concordance between the MINI-Plus and clinical diagnosis was analyzed.

Patients were on average 52 and 47 years old in the MDD and BD group, respectively, and 66 versus 64% were female. Compared to patients with BD, patients with MDD scored higher on weight loss (p = 0.02), whereas the BD group showed a higher long-term likelihood of response (hazard ratio = 1.93, 95% confidence interval 1.16-3.20, p for interaction with time = 0.04). Although the same association was seen for remission, the interaction with time was not significant (p = 0.48). Efficiency between the MINI-Plus and clinical diagnosis of BD was high (0.90), suggesting that the MINI-Plus is an adequate ROM diagnostic tool.

In routine clinical inpatient care, minor differences in the symptom profile and the course of depressive symptomatology may be helpful in distinguishing MDD and BD, particularly when using sequential ROM assessments.

Neuroinflammation plays a role in the pathophysiology of Bipolar Disorder Depression (BDD) and altered levels of inflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1, aka CCL2) have been reported. This study reports specifically on MCP-1 levels, as a potential marker of BDD and/or treatment response in patients receiving combination treatment with the cyclooxygenase-2 inhibitor, celecoxib (CBX).

In this randomized, 10-week, double-blind, two-arm, placebo-controlled study, 47 patients with treatment resistant BDD received either escitalopram (ESC) + CBX, or ESC + placebo (PBO). Plasma MCP-1 levels were measured at 3 time points in the BDD subjects, and in a healthy control (HC) group. Depression severity was quantified using the Hamilton Depression Scale (HAMD-17).

The CBX group had significantly lower HAMD-17 scores vs. PBO at week 4 (P = 0.026) and week 8 (P = 0.002). MCP-1 levels were not significantly different in BDD vs. HC subjects at baseline (P = 0.588), nor in CBX vs. PBO groups at week 8 (P = 0.929). Week 8 HAMD-17 scores and MCP-1 levels were significantly negatively correlated in treatment non-responders to CBX or PBO (P = 0.050). Non-responders had significantly lower MCP-1 levels vs. responders at weeks 4 (P = 0.049) and 8 (P = 0.014). MCP-1 was positively correlated with pro-inflammatory analytes in the PBO group and with anti-inflammatory analytes in the CBX group.

Combination treatment reduced treatment resistance and augmented antidepressant response. Baseline plasma MCP-1 levels were not altered in BDD patients. Since non-responders had lower levels of MCP-1, elevated MCP-1 may indicate a better response to CBX + SSRI treatment.

Several studies have challenged the traditional unipolar-bipolar dichotomy in favor of a more dimensional approach.

To evaluate the differences in mood spectrum between patients with bipolar disorder (BD) and major depressive disorder (MDD) during a major depressive episode (MDE).

Study participants were 145 patients with BD and 155 patients with MDD recruited at three University Medical Centers in Italy. All study subjects met Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for MDE and completed the Mood Spectrum-Self-Report-Last Month questionnaire.

Patients with BD endorsed more items in the mood manic/hypomanic and energy depressive subdomains of the MOODS-SR questionnaire. Significant differences were also found for specific depressive and manic items, which were more frequently endorsed by patients with BD. A large number of patients with BD, but also a considerable number of patients with MDD, endorsed manic items during a depressive episode.

There are differences between BD and MDD in terms of the number and type of mood spectrum items that are endorsed during a MDE, which may help to identify patients with BD when a retrospective assessment of a history of mania or hypomania is not possible or not reliable. A high number of patients with BD and a considerable number of patients with MDD endorsed several items in the manic section of the mood, energy, and cognition domains, this confirming the centrality of mixed features in patients with mood disorders and the need for a unitary, dimensional, descriptive and dynamic approach to MDD and BD, such as the recently proposed ACE (Activity, Cognition, Energy) model.

Affective disorders, such as major depressive (MDD), bipolar I (BD I) and II (BD II) disorders, are overlapped at a continuum, but their exact loci are not clear. The self-reports from patients with affective disorders might help to clarify this issue.

We invited 738 healthy volunteers, 207 individuals with BD I, 265 BD II, and 192 MDD to answer a 79 item-MATRIX about on-going affective states.

In study 1, all 1402 participants were divided random-evenly and gender-balanced into two subsamples; one subsample was used for exploratory factor analysis, and another for confirmatory factor analysis. A structure-validated inventory with six domains of Overactivation, Psychomotor Acceleration, Distraction/ Impulsivity, Hopelessness, Retardation, and Suicide Tendency, was developed. In study 2, among the four groups, MDD scored the highest on Retardation, Hopelessness and Suicide Tendency, whereas BD I on Distraction/ Impulsivity and Overactivation.

Our patients confirmed the affective continuum from Suicide Tendency to Overactivation, and described the different loci of MDD, BD I and BD II on this continuum.

Predicting patients who convert to bipolar disorder is important for deciding appropriate treatment for young adults with major depressive disorder (MDD). We focused on the predictive factors of bipolar conversion in a large population of young adults.

A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment service of South was used to investigate adjusted hazard ratio (HR) of each potential predictor of the bipolar converter group compared to the non-converter group using Cox regression analysis including age of onset, medication use, clinical features, comorbid disorders, admission, self-harm, and negative life events in childhood.

Among 291,721 subjects who were initially diagnosed with MDD in young adults, 12,376 subjects experienced diagnostic conversion to bipolar disorder. The cumulative incidence was 6.46% during the average 3.26 years of follow-up. Among the predictive factors during diagnosis of MDD, antipsychotic use (HR 3.12, 95%CI, 2.99-3.26, p < 0.0001) and mood stabilizers (HR 2.45, 95%CI, 2.35-2.55, p < 0.0001) showed the strongest association with diagnostic conversion to bipolar disorder. In addition, female sex, younger age of onset, mood stabilizer use, recurrent depression, psychotic symptoms, and admission to a psychiatric ward during diagnosis of MDD were also associated with diagnostic conversion to bipolar disorder.

In young adults with MDD, antipsychotic and mood stabilizer use during diagnosis of MDD were the strongest predictive factors with diagnostic conversion to bipolar disorder during follow-up. If young adults with MDD need antipsychotics or mood stabilizer, patients should be carefully evaluated for possibility of bipolar disorder.

current classifications of mood disorders focus on polarity rather than recurrence, separating bipolar disorder from major depressive disorder (MDD). The aim of the present study is to explore the possible relationships between number and frequency of depressive episodes and clinical variables associated to bipolarity, in a large sample of MDD patients.

the clinical characteristics of 7055 patients with MDD were analyzed and compared according to the number and frequency of depressive episodes. Two stepwise backward logistic regression model were used to identify the predictive value of clinical features based on the presence of high number (≥3 episodes) and high frequency (≥3 episodes/year) of depressive episodes.

high-recurrence and high-frequency MDD patients showed greater family history for bipolar disorder, higher prevalence of psychotic features, more suicide attempts, higher rates of treatment resistance and mood switches with antidepressants (ADs) and higher rates of bipolarity diagnosis according to Angst criteria, compared to low-recurrence and low-frequency patients. Logistic regressions showed that a brief current depressive episode, a previous history of treatment resistance and AD-induced mood switches, a diagnosis of bipolarity and comorbid borderline personality disorder were the variables associated with both high-recurrence and high-frequency depression.

the study participating centers were not randomly selected and several variables were retrospectively assessed.

even in the absence of hypomanic/manic episodes, high-recurrence and high-frequency MDD seem to be in continuity with the bipolar spectrum disorders in terms of clinical features and, perhaps, treatment response.

Hypersomnia is a common problem amongst individuals with Bipolar Disorder (BD). The objective of this meta-analysis is to estimate the frequency of hypersomnia in individuals with BD, and identify associated factors METHODS: Our search focused on articles documenting the frequency of hypersomnia among individuals with BD indexed in PubMed database and in the Cochrane Library, following the recommendations from the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) Group. A meta-analysis of proportion was conducted; funnel plot and Egger's test were used for the assessment of publication bias. Subgroups analyses were performed in order to evaluate possible confounders and associated factors.

We identified 10 studies, which included 1824 patients with BD. The overall estimate of the proportion of BD cases that reported hypersomnia was 29.9% [95% confidence interval (CI): 25.8 - 34.1%, I² = 59.2%; p < .05]. The funnel plot and the Egger's test suggest a low risk of publication bias (p = .527). The polarity of mood state, Bipolar Disorder type, use of medication, age, diagnostic criteria and hypersomnia criteria were not significantly related to hypersomnia.

There is a possibility that smaller cross-sectional studies were not included. The high heterogeneity between studies is frequent in meta-analysis of both interventional and observational studies. Hypersomnia was not the primary outcome in some of the included studies.

To our knowledge, this is the first systematic review and meta-analysis of hypersomnia prevalence in patients with BD. Further studies focused on clinical correlates and implications for health outcomes in BD are warranted.

Major affective conditions including both unipolar (UD) and bipolar disorders (BD) are associated with significant disability throughout the life course. We aimed to investigate the most relevant socio-demographic/clinical differences between UD and BD subjects. Our sample included 180 inpatients, of which 82 (45.5%) participants were diagnosed with UD and 98 (54.5%) with BD. Relative to UD patients, BD individuals were more likely to report prior psychoactive medications, lifetime psychotic symptoms, nicotine abuse, a reduced ability to provide to their needs, gambling behavior, and fewer nonsuicidal self-harm episodes. Moreover, BD patients were more likely to report severe side effects related to medications, a younger age at illness onset and first hospitalization, higher illness episodes, and longer illness duration in years than UD subjects. In a multivariate logistic analysis accounting for age, gender, and socio-demographic characteristics, a significant positive contribution to bipolarity was found only for higher lifetime psychotic symptoms (β = 1.178; p ≤ .05) and number of illness episodes (β = .155; p ≤ .05). The present findings suggest that specific clinical factors may be used in order to better distinguish between UD and BD subgroups. Further studies are required to replicate these findings in larger samples.

Background: Aim of the study was the validation of the Bipolar Disorder Rating Scale (BDRS) in an Italian population. Secondary aim was the evaluation of differences between unipolar and bipolar depression and between bipolar I and II depressed patients. Method: 125 Bipolar Disorder and 60 Major Depressive Disorder patients were administered an Italian translation of the BDRS (I-BDRS), Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Temperament and Character Inventory-Revised (TCI-R). Results: I-BDRS showed considerable validity and reliability. Factor analysis found 3 subscales, two linked to depressive symptoms and one to mixed symptoms. Measures concerning depression (MADRS and HAM-D) were positively related to the I-BDRS's subscales, but mostly to the two subscales measuring depression. In mixed symptoms, the mean of the bipolar group was significantly higher than the unipolar group suggesting that the BDRS was able to distinguish between unipolar and bipolar depressed patients. Conclusion: I-BDRS is a valid scale for the measurement of depression in BD patients, with a notable internal consistency (Cronbach's α 0.82), a significant consistency between items/total (Cronbach's α from 0.80 to 0.82) and positive correlation with other scales (MADRS r = 0.67, p < 0.001; HDRS r = 0.81, p < 0.001; YMRS r = 0.46 p < 0.0001). The mixed state sub-scale shows usefulness in differentiating bipolar from unipolar patients. I-BDRS could be a sensitive tool, both in pure depression and in mixed states, and could be used in the everyday screening and treatment of Bipolar Disorder.

The impact of psychosis on the treatment of bipolar depression is remarkably understudied. The primary aim of this study was to compare treatment outcomes of bipolar depressed individuals with and without psychosis. The secondary aim was to compare the effect of lithium and quetiapine, each with adjunctive personalized treatments (APTs), in the psychotic subgroup.

We assessed participants with DSM-IV bipolar depression included in a comparative effectiveness study of lithium and quetiapine with APTs (the Bipolar CHOICE study). Severity was assessed by the Bipolar Inventory of Symptoms Scale (BISS) and by the Clinical Global Impression Scale-Severity-Bipolar Version (CGI-S-BP). Mixed models were used to assess the course of symptom change, and Cox regression survival analysis was used to assess the time to remission.

Psychotic features were present in 10.6% (n = 32) of the depressed participants (n = 303). Those with psychotic features had higher scores on the BISS before (75.2 ± 17.6 vs. 54.9 ± 16.3; P < .001) and after (37.2 ± 19.7 vs. 26.3 ± 18.0; P = .003) 6-month treatment. The CGI-S-BP yielded similar results. Participants with and without psychosis had similar course of symptom improvement and similar time to remission. There was no significant difference in the treatment outcomes of lithium (n = 11) and quetiapine (n = 21) among the psychotic subgroup.

Bipolar depressive episodes with psychotic features are more severe, and compared to nonpsychotic depressions, present a similar course of improvement. Given the small number of participants presenting psychosis, the lack of statistically significant difference between lithium- and quetiapine-based treatment of psychotic bipolar depressive episodes needs replication in a larger sample.

Few actigraphy studies in mood disorders have simultaneously included unipolar (UP) and bipolar (BD) depression or BD mixed states as a separate subgroup from mania. This study compared objectively measured activity in UP, BD depression, mania and mixed states and examined if patterns differed according to time of day and/or diagnostic group.

Eighty -eight acutely admitted inpatients with mood disorders (52 UP; 18 mania; 12 BD depression; 6 mixed states) underwent 24 hours of actigraphy monitoring. Non-parametric analyses were used to compare median activity level over 24 h (counts per minute), two time series (64-min periods of continuous motor activity) in the morning and evening, and variability in activity across and within groups.

There was no between-group difference in 24-h median level of activity, but significant differences emerged between BD depression compared to mania in the active morning period, and between UP and mania and mixed states in the active evening period. Within-group analyses revealed that UP cases showed several significant changes between morning and evening activity, with fewer changes in the BD groups.

Mean activity over 24 hours has limited utility in differentiating UP and BD. In contrast, analysis of non-linear variability measures of activity at different times of day could help objectively distinguish between mood disorder subgroups.

ClinicalTrials.gov Identifier: NCT01415323 , first registration July 6, 2011.

This study explores the feasibility and psychometric properties of the Korean version of the Bipolar Depression Rating Scale (BDRS) in adolescents with Early-onset bipolar disorders.

Fifty-three participants (aged 13-18) with early-onset bipolar disorders (40 depressed and 18 euthymic, 5 patients were assessed at depressed state and reassessed after remission) were recruited. All participants were assessed using the BDRS, the Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asperg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Modified Overt Aggression scale (MOAS).

BDRS exhibited good internal validity and significant correlations with the HAM-D and the MADRS. In item to scale correlations, all items on the BDRS were significantly correlated with the BDRS total scores except for 'increased motor drive' and 'increased speech', 'depressed mood' and 'worthlessness' showed the highest mean scores and endorsement rates. BDRS score of the depressed group was significantly higher compared with the euthymic group. Three factors (i.e., psychosomatic, mood, and mixed) were identified in the principal component analysis and hierarchical cluster analysis of the BDRS.

In this study, we report that the Korean version of BDRS is a feasible and reliable tool for the assessment of depression in adolescents with Early-onset bipolar disorders.

Expanding our understanding of the factors that influence depression is crucial for prognosis and treatment. In light of increasing evidence of an association between disrupted circadian rhythms and affective symptoms, a meta-analysis was used to examine the relationship between an eveningness chronotype and depression.

Electronic searches of the PsycINFO, Medline, Scopus, and Google Scholar databases were conducted in February 2016. Relevant reviews, related journals, and reference lists were manually searched. Statistical data were reported or transformed to a Fisher's z correlational coefficient for effect size analysis.

Data from 36 studies (n =15734) met the inclusion criteria and were analysed under a random effects model. Nearly all included studies utilised the Composite Scale of Morningness (CSM) or the Morningness-Eveningness Questionnaire (MEQ) as a measure of chronotype. Overall effect size from 58 effect sizes was small (z=-.20; 95% CI: -.18 to -.23). Effect sizes based on the CSM were significantly larger than those based on the MEQ. There was no evidence of publication bias.

The number of studies comparing different mood disorders or the potential moderating effects of gender and age were too few to draw conclusions regarding their respective effect sizes. Future research should utilise longitudinal designs to draw causal inferences on the directionality of this relationship.

Findings from this meta-analysis indicate an eveningness orientation is somewhat associated with more severe mood symptoms. Chronobiological approaches may contribute to the prevention and treatment of depressive disorders.

Psychotic bipolar depressive episodes remain remarkably understudied despite being common and having a significant impact on bipolar disorder. The aim of this study is to identify the characteristics of depressed bipolar patients with current psychosis compared to those without psychosis.

We used baseline data of a comparative effectiveness study of lithium and quetiapine for bipolar disorder (the Bipolar CHOICE study) to compare demographic, clinical, and functioning variables between those with and without psychotic symptoms. Of the 482 participants, 303 (62.9%) were eligible for the present study by meeting DSM-IV criteria for an acute bipolar depressive episode. Univariate analyses were conducted first, and then included in a model controlling for symptom severity.

The sample was composed mostly of women (60.7%) and the mean age was 39.5±12.1 years. Psychosis was present in 10.6% (n=32) of the depressed patients. Psychotic patients had less education, lower income, and were more frequently single and unemployed. Psychosis was also associated with a more severe depressive episode, higher suicidality, more comorbid conditions and worse functioning. Most group differences disappeared when controlling for depression severity.

Only outpatients were included and the presence of psychosis in previous episodes was not assessed.

Psychosis during bipolar depressive episodes is present even in an outpatient sample. Psychotic, depressed patients have worse illness outcomes, but future research is necessary to confirm if these outcomes are only associated with the severity of the disorder or if some of them are independent of it.

Here, we present the first description of the Andalusian Bipolar Family (ABiF) Study. This longitudinal investigation of families from Andalusia, Spain commenced in 1997 with the aim of elucidating the molecular genetic causes of bipolar affective disorder. The cohort has since contributed to a number of key genetic findings, as reported in international journals. However, insight into the genetic underpinnings of the disorder in these families remains limited.

In the initial 1997-2003 study phase, 100 multiplex bipolar disorder and other mood disorder families were recruited. The ongoing second phase of the project commenced in 2013, and involves follow-up of a subgroup of the originally recruited families. The aim of the follow-up investigation is to generate: i) longitudinal clinical data; ii) results from detailed neuropsychological assessments; and iii) a more extensive collection of biomaterials for future molecular biological studies.

The ABiF Study will thus generate a valuable resource for future investigations into the aetiology of bipolar affective disorder; in particular the causes of high disease loading within multiply affected families.

We discuss the value of this approach in terms of new technologies for the identification of high-penetrance genetic factors. These new technologies include exome and whole genome sequencing, and the use of induced pluripotent stem cells or model organisms to determine functional consequences.

Research on deep brain stimulation (DBS) for treatment-resistant psychiatric disorders has established preliminary efficacy signals for treatment-resistant depression. There are only few studies on DBS that included patients suffering from bipolar disorder. This article gives an overview of these studies concerning DBS targets, antidepressant efficacy, and the occurrence of manic/hypomanic symptoms under stimulation. First, promising results show that all patients experienced significant improvement in depressive symptomatology. In a single case, hypomanic symptoms occurred, but they could be resolved by adjusting stimulation parameters. Furthermore, this article highlights important clinical differences between unipolar and bipolar depression that have to be considered throughout the course of treatment.

Excessive daytime sleepiness is defined as the inability to maintain wakefulness during waking hours, resulting in unintended lapses into sleep. It is important to distinguish sleepiness from fatigue. The evaluation of a sleep patient begins with a careful clinical assessment that includes a detailed sleep history, medical and psychiatric history, a review of medications, as well as a social and family history. Physical examination should include a general medical examination with careful attention to the upper airway and the neurologic examination. Appropriate objective testing with a polysomnogram and a multiple sleep latency test if needed will help confirm the diagnosis and direct the appropriate treatment plan.

Multiple models of aberrant emotional processing in depression have been advanced. However, it is unclear which of these models best applies to emotional disturbances in subclinical depressive symptoms. The current study employed a battery of psychophysiological measures and emotional ratings in a picture-viewing paradigm to examine whether the underarousal, low positive emotion, heightened negative emotion, or emotion context insensitivity model of emotional dysfunction in subclinical depressive symptoms received greatest support. Postauricular reflex and skin conductance response potentiation for pleasant minus neutral pictures (measuring low positive emotion), overall skin conductance magnitude and late positive potential (LPP) amplitude (measuring underarousal), and pleasant minus aversive valence ratings (measuring emotion context insensitivity) and aversive minus neutral arousal ratings (measuring heightened negative emotionality) were all negatively related to depressive symptomatology. Of these, postauricular reflex potentiation and overall LPP amplitude were incrementally associated with depressive symptoms over the other measures. Postauricular reflex potentiation, overall skin conductance magnitude, and aversive minus neutral arousal ratings were incrementally associated with depressive symptomatology after controlling for other symptoms of internalizing disorders. Though no model was unequivocally superior, the low positive emotion and underarousal models received the most support from physiological measures and symptom reports, with self-report data matching patterns consistent with the emotion context insensitivity model.

Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.