Major Mood Episodes Research Articles

Sleep disturbances in the context of neurohormonal dysregulation in patients with bipolar disorder

BackgroundSleep dysfunction is a core symptom in bipolar disorder (BD), especially during major mood episodes. This study investigated the possible link between subjective and objective sleep disturbances in inter-episode BD, changes in melatonin and cortisol levels, and circadian melatonin alignment. The study included 21 euthymic BD patients and 24 healthy controls. Participants had to wear an actigraphy device, keep a weekly sleep diary and take salivary samples: five samples on the last evening to determine the dim light melatonin onset (DLMO) and one the following morning to measure rising cortisol. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and Regensburg Insomnia Scale (RIS), and circadian alignment by the phase angle difference (PAD).ResultsIn comparison to healthy controls, BD patients had: (1) higher PSQI (5.52 ± 3.14 vs. 3.63 ± 2.18; p = 0.022) (significant after controlling for age and gender), and higher RIS scores (8.91 ± 5.43 vs. 5.83 ± 3.76; p = 0.031); (2) subjective a longer mean TST (p = 0.024) and TIB (p = 0.002) (both significant after controlling for age and gender), longer WASO (p = 0.019), and worse SE (p = 0.036) (significant after controlling for gender); (3) actigraphically validated earlier sleep onset (p = 0.002), less variation in sleep onset time (p = 0.005) and no longer TST (p = 0.176); (4) no differing melatonin levels (4.06 ± 2.77 vs. 3.35 ± 2.23 p = 0.352), an 1.65 h earlier DLMO (20.17 ± 1.63 vs. 21.82 ± 1.50; p = 0. 001) (significant after controlling for gender), and a phase advance of melatonin (6.35 ± 1.40 vs. 7.48 ± 1.53; p = 0.017) (significant after controlling for gender); and (5) no differing cortisol awakening response (16.97 ± 10.22 vs 17.06 ± 5.37 p = 0.969).ConclusionsPatients with BD, even in euthymic phase, have a significantly worse perception of their sleep. Advanced sleep phases in BD might be worth further investigation and could help to explain the therapeutic effects of mood stabilizers such as lithium and valproate.

CON

There is a considerable overlap of psychotic and mood symptoms in patients with severe mental disorders, and a large proportion of patients meeting diagnostic criteria experience significant mood symptoms. The diagnosis of schizophrenia – schizoaffective type /schizoaffective disorder has been a part of the Diagnostic and statistical manual since the DSM-I. Even if the need for a diagnosis capturing this particular clinical picture obviously is needed, the agreement about when to use the diagnosis of schizoaffective disorder as well as the diagnostic reliability is low. There is an agreement that the diagnosis covers episodes with an overlap between a psychotic episode meeting the A criteria for schizophrenia and a major mood episode where the psychotic symptoms continue after the end of the mood symptoms. Given the prevalence of depression in schizophrenia, some episodes, however, meet the criteria for schizoaffective disorders while others do not. The DSM-5 thus argues that the pattern of overlapping symptoms should be present in the majority of episodes. Keeping the cross-sectional approach favoured by previous versions of the DSM and the ICD will here continue to spread diagnostic confusion.DisclosureNo significant relationships.

This Winter, Pandemic May Intensify Seasonal Depression

This Winter, Pandemic May Intensify Seasonal Depression

The association between self-reported and clinically determined hypomanic symptoms and the onset of major mood disorders.

BackgroundHypomanic symptoms may be a useful predictor of mood disorder among young people at high risk for bipolar disorder.AimsTo determine whether hypomanic symptoms differentiate offspring of parents with bipolar disorder (high risk) and offspring of well parents (control) and predict the development of mood episodes.MethodHigh-risk and control offspring were prospectively assessed using semi-structured clinical interviews annually and completed the Hypomania Checklist-32 Revised (HCL-32). Clinically significant sub-threshold hypomanic symptoms (CSHS) were coded.ResultsHCL-32 total and active or elated scores were higher in control compared with high-risk offspring, whereas 14% of high-risk and 0% of control offspring had CSHS. High-risk offspring with CSHS had a fivefold increased risk of developing recurrent major depression (P=0.0002). The median onset of CSHS in high-risk offspring was 16.4 (6–31) years and was before the onset of major mood episodes.ConclusionsCSHS are precursors to major mood episodes in high-risk offspring and could identify individuals at ultra-high risk for developing bipolar disorder.Declaration of interestNone.Copyright and usage© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Design and Methods of the Mood Disorder Cohort Research Consortium (MDCRC) Study.

The Mood Disorder Cohort Research Consortium (MDCRC) study is designed as a naturalistic observational prospective cohort study for early-onset mood disorders (major depressive disorders, bipolar disorders type 1 and 2) in South Korea. The study subjects consist of two populations: 1) patients with mood disorders under 25 years old and 2) patients with mood disorders within 2 years of treatment under 35 years old. After successful screening, the subjects are evaluated using baseline assessments and serial follow-up assessments at 3-month intervals. Between the follow-up assessments, subjects are dictated to check their own daily mood status before bedtime using the eMood chart application or a paper mood diary. At the regular visits every 3 months, inter-visit assessments are evaluated based on daily mood charts and interviews with patients. In addition to the daily mood chart, sleep quality, inter-visit major and minor mood episodes, stressful life events, and medical usage pattern with medical expenses are also assessed. Genomic DNA from blood is obtained for genomic analyses. From the MDCRC study, the clinical course, prognosis, and related factors of early-onset mood disorders can be clarified. The MDCRC is also able to facilitate translational research for mood disorders and provide a resource for the convergence study of mood disorders.

Prevalence of current anxiety disorders in people with bipolar disorder during euthymia: a meta-analysis.

Anxiety disorders are highly prevalent in people with bipolar disorder, but it is not clear how many have anxiety disorders even at times when they are free of major mood episodes. We aimed to establish what proportion of euthymic individuals with bipolar disorder meet diagnostic criteria for anxiety disorders. We performed a random-effects meta-analysis of prevalence rates of current DSM-III- and DSM-IV-defined anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder, specific phobia, obsessive-compulsive disorder, post-traumatic stress disorder, and anxiety disorder not otherwise specified) in euthymic adults with bipolar disorder in studies published by 31 December 2015. Across 10 samples with 2120 individuals with bipolar disorder, 34.7% met diagnostic criteria for one or more anxiety disorders during euthymia [95% confidence interval (CI) 23.9-45.5%]. Direct comparison of 189 euthymic individuals with bipolar disorder and 17 109 population controls across three studies showed a 4.6-fold increase (risk ratio 4.60, 95% CI 2.37-8.92, p < 0.001) in prevalence of anxiety disorders in those with bipolar disorder. These findings suggest that anxiety disorders are common in people with bipolar disorder even when their mood is adequately controlled. Euthymic people with bipolar disorder should be routinely assessed for anxiety disorders and anxiety-focused treatment should be initiated if indicated.

Affective lability mediates the association between childhood trauma and suicide attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders.

Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD. A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro. Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset. Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.

Maladaptive interpersonal schemas as sensitive and specific markers of borderline personality disorder among psychiatric inpatients

Diagnostic criteria for borderline personality disorder (BPD) and mood and psychotic disorders characterized by major mood episodes (i.e., major depressive, bipolar and schizoaffective disorder) share marked overlap in symptom presentation, complicating differential diagnosis. The current study tests the hypothesis that maladaptive interpersonal schemas (MIS) are characteristic of BPD, but not of the major mood disorders. One hundred psychiatric inpatients were assessed by SCID I, SCID II and the Young Schema Questionnaire (YSQ-S2). Logistic regression analyses tested the association between MIS (measured by the YSQ-S2) and BPD, bipolar, major depressive and schizoaffective disorder. Receiver operator characteristic (ROC) curve analyses assessed the sensitivity and specificity of MIS as a marker of BPD. After covariation for comorbidity with each of the 3 mood disorders, BPD was robustly associated with 4 out of 5 schema domains. In contrast, only one of fifteen regression analyses demonstrated a significant association between any mood disorder and schema domain after covariation for comorbid BPD. ROC analyses of the 5 schema domains suggested Disconnection/Rejection had the greatest power for identification of BPD cases. These data support the specific role of maladaptive interpersonal schemas in BPD and potentially contribute to greater conceptual clarity about the distinction between BPD and the major mood disorders.

Les troubles maniaco-dépressifs à l’adolescence : aspects cliniques

More than 50% of bipolar disorders diagnosed among adults first appeared before the age of 18. It is well established that adolescence is the high-risk period for the onset of major mood episodes associated with bipolar disorders. Even though there are few early-onset bipolar disorders, they are very severe. The most robust risk factor predicting bipolar disorder is a positive family history. Morbidity, mortality, and suicidality are high and have a severe impact on overall functioning, professional integration, family life, and affective relationships. Improving diagnosis of early symptoms should ameliorate these patients’ prognosis.

Early-onset and very-early-onset bipolar disorder: distinct or similar clinical conditions?

This study aimed to examine differences in the clinical presentation of very-early-onset (VEO) and early-onset (EO) bipolar disorder (BD) not fully explored previously. We selected two groups of subjects with BD from the Maritime Bipolar Registry based on age at onset of first major mood episode (VEO with onset prior to age 15 years; EO ranging from 15 to 18years) and compared them with a reference group (onset after 18years of age). There were 363 subjects (240 with bipolar I disorder and 123 with bipolar II disorder; mean age 44.2±12.8 (SD)years), with 41 subjects in the VEO and 95 in the EO groups. In comparison with the EO and reference groups, more subjects in the VEO group developed major depression as an index episode (88% for the VEO group versus 61% for the EO group and 54% for the reference group), and had an unremitting clinical course (65% versus 42% and 42%, respectively), rapid cycling (54% versus 34% and 28%, respectively), and comorbid attention-deficit hyperactivity disorder (17% versus 1% and 3%, respectively); a higher proportion of the VEO group had first-degree relatives with affective disorders compared with the EO and reference groups (0.41 versus 0.32 and 0.29, respectively), and they had lower scores on the Global Assessment of Functioning scale (mean scores of 64 versus 70 and 70). Overall, the EO group was similar to the reference group on most measures, except for increased suicidal behavior VEO 53%, EO 44% and reference group 25%). The results of polychotomous logistic regression also support the view that VEO BD represents a rather specific subtype of BD. Our results suggest the recognized correlates of early-onset BD may be driven by subjects at the lowest end of the age at onset spectrum.

Control-related frontal-striatal function is associated with past suicidal ideation and behavior in patients with recent-onset psychotic major mood disorders

ObjectiveSuicide is highly-prevalent in major mood disorders, yet it remains unclear how suicidal ideation and suicidal behavior relate to brain functions, especially those that support control processes. We evaluated how prefrontal cortex (PFC) activity during goal-representation (an important component of cognitive control) relates to past suicidal ideation and behavior in patients with psychotic major mood disorders. Method30 patients with recent-onset of either DSM-IV-TR-defined bipolar disorder type I (n=21) or major depressive disorder (n=9) with psychotic features, but neither in a major mood episode nor acutely psychotic at study, were evaluated for past suicidal ideation and behavior (Columbia Suicide Severity Rating Scale) and functional MRI during cognitive control task performance. Group-level regression models of brain activation accounted for current depression, psychosis and trait impulsivity. ResultsIntensity of past suicidal ideation was associated with higher control-related activation in right-hemisphere regions including the ventrolateral PFC (VLPFC) and orbitofrontal cortex, rostral insula, and dorsal striatum. Among those with past suicidal ideation (n=16), past suicidal behavior (n=8) was associated with higher control-related activation in right-hemisphere regions including VLPFC, rostrolateral PFC, and frontal operculum/rostral insula; and relatively lower activity in midline parietal regions, including cuneus and precuneus. LimitationsThe sample size of subjects with past suicidal behavior was modest, and all subjects were taking psychotropic medication. ConclusionsThis study provides unique evidence that in early-course psychotic major mood disorders, suicidal ideation and behavior histories directly relate to PFC-based circuit function in support of cognitive control.

The relationship between chronotype and mood fluctuation in the general population

There is a lack of evidence for the relationship between chronotype and subthreshold mood fluctuation. The present study aims to investigate the relationship between chronotypes and mood fluctuation in the general population. Participants (n=302) who have had no experience of major mood episodes were included. The Korean version of the Composite Scale of Morningness (CSM) was used to classify participants according to three chronotypes. Mood fluctuation was measured using the Mood Disorder Questionnaire (MDQ) and the Bipolar Spectrum Diagnostic Scale (BSDS). Mean scores achieved by the three chronotype groups on the MDQ and the BSDS were compared. There were no significant differences in the frequency of positive responses on the MDQ for the three chronotype groups. However, there was a significant group difference in total BSDS scores. The eveningness group had significantly higher BSDS-D scores than did either the morningness or the intermediate group have. In addition, the eveningness group had significantly higher BSDS-M scores than the morningness group. After adjusting for age by the analysis of covariance (ANCOVA), there were still significant group differences in total BSDS scores. The present results suggest that eveningness may be more related to mood fluctuation than morningness. The eveningness may be an important factor related to soft bipolarity or mood fluctuation.

The Importance of Measuring Multi-level Risk and Illness Progression Markers in High-risk Youth From Well-characterized Bipolar Parents

Convergent evidence from longitudinal population and high-risk studies has supported that psychiatric disorders in adults typically onset in childhood and adolescence which not uncommonly debut as non-specific symptoms and syndromes (i.e. heterotypy) (Kim-Cohen et al., 2003, Duffy, 2015). Studying multiple indicators of illness risk and development longitudinally within high-risk subjects is increasingly recognized as important in order to differentiate vulnerability from burden of illness effects and to identify patterns of abnormalities associated with the clinical trajectory of illness development. Taken in this context, the paper in this issue of EBioMedicine by Lee and colleagues reports on findings of a cross-sectional study of neural correlates and clinical outcomes up to 2 years later in 44 offspring of bipolar parents (Lin et al., 2015). High-risk offspring were divided into subgroups comprising well (HR) or symptomatic/ultra-high-risk (UHR) compared to healthy controls (C). Structural and functional neuroimaging and neurocognitive performance (i.e. processing speed and visual spatial) and global functioning differences were found between the groups and interpreted as evidence of differential indicators of BD vulnerability and illness progression. This study demonstrates the current and important trend of incorporating a multidimensional approach to assessing interactive illness risk and progression processes in youth at confirmed high-risk (Lin et al., 2015). However, the interpretation of the specific findings should be taken as preliminary given several limitations. Firstly, the study of neural correlates was cross-sectional including only a small number of high-risk offspring of a relatively wide age range (i.e. 8–28 years) and with a limited clinical follow-up period (i.e. up to 2 years). The fact that offspring with a prior diagnosis were excluded, suggests that those included over age 20 may be resilient and different in measured outcomes from younger subjects. In fact, other high-risk studies have reported that the mean age of onset for major mood episodes is in mid-adolescence and early risk syndromes, such as full-blown anxiety or sleep disorders, manifest years earlier in mid-childhood (Duffy et al., 2010, Mesman et al., 2013). Furthermore, in this study – as in most others – the nature of the subtype of BD in the parent is neglected (Lin et al., 2015). Yet, given the substantial heterogeneity of the BD diagnosis – subsuming different subtypes associated with characteristic differences in clinical, neurobiological and neurocognitive findings – this is a major oversight that has contributed to difficulties in replication of findings between studies (Alda, 2004, Manchia et al., 2013). For example, heterogeneity of the subtype of BD segregating in the family may explain counter-intuitive and contradictory findings reported in this study (i.e. increased small-world properties in UHR). The smaller volumes in regions of interest in HR offspring in this paper seems counter to findings reported by Hajek et al. of increased right inferior frontal gyrus volumes in HR offspring and BD patients early in the illness course, while BD patients with substantial illness burden showed decreased volumes which appeared to be mitigated in those treated with lithium (Hajek et al., 2013). Finally, this study divided high-risk offspring based on symptom status following an approach used in conversion to psychosis studies (Yung et al., 2004). The problem here is that the ultra-high-risk concept has typically been used to refer to clinical at risk groups of youth. Ideally, if the question is one of mapping biomarkers to clinical illness progression, offspring should ideally be re-assessed in remission or at their best level of functioning and their clinical course carefully documented to place them on a clinical continuum of risk (clinical staging) and map changes in outcomes to clinical progression taking into account burden of illness. These points notwithstanding, this study contributes to an important international effort to characterize markers of BD risk and development at the clinical, biological and psychological levels and to explore the relationship between these processes (Lin et al., 2015). It is an exciting and timely effort, and we will undoubtedly continue to learn from one another, comparing and contrasting similarities and differences in findings taken in context of the methods applied, in order to advance understanding. A single comprehensive clinical staging model based on the evidence from longitudinal prospective offspring studies specific to BD subtypes (rather than extrapolated from findings of studies of heterogeneous populations of psychotic youth), would be exceedingly helpful to this effort (Duffy, 2014, Duffy, 2015). While there may be some similarities between different illness trajectories and associated risk indicators and processes across subtypes, it is important that we do not simply generalize from one disease model to the next or develop some one size fits all approach based on assumptive leaps rather than the evidence. This would be akin to lumping other illnesses together (i.e. Parkinson's disease and Alzheimer's dementia) based on some overlapping findings, despite important differences in etiology, clinical course and treatment response.

Early Maladaptive Schemas: A Comparison Between Bipolar Disorder and Major Depressive Disorder

It is still unclear how bipolar disorder (BD) differentiates from major depressive disorder (MDD) outside major mood episodes. To further elucidate this area, the present study compared the two mood disorders in terms of early maladaptive schemas (EMSs) during remission. The sample consisted of 49 participants with BD and 30 participants with MDD who were currently in remission. The participants completed the Young Schema Questionnaire. The BD group scored significantly higher than the MDD group on seven EMSs: abandonment, failure to achieve, insufficient self-control, subjugation, unrelenting standards, enmeshment and entitlement. By suggesting that EMSs are more severe in BD compared with MDD, the findings highlight potential vulnerabilities in BD, which merit further examination in terms of their underlying causes and potential treatment implications. Early maladaptive schemas are relevant psychological dimensions to consider in remitted phases of major mood disorders. Findings from the current study suggest that early maladaptive schemas are more prevalent in adults with bipolar disorder compared to adults with major depressive disorder when measured during remission. Interventions targeting early maladaptive schemas may be valuable in treatment of bipolar disorder.

Psychosis Within vs Outside of Major Mood Episodes

No question in psychiatric nosology has attracted such consistent controversyover thepast several generationsas the setting of the boundary between schizophrenia andmajormood disorders. Indeed, Kraepelin,1 the originator of this diagnostic distinction, was well aware of the difficulties of defining precisely this boundary. A closely related question has been whether there exists, between these 2 pivotal diagnostic entities, a third valid disorder that shares some clinical features with each: schizoaffective disorder (SAD). In this issue, Kotov and colleagues2 address these questionsusing thewell-knownSuffolkCountyMentalHealthProject cohort.A total of 526participantswere followedclosely for 4 years after admission, with their symptom course charted and 10-year outcome data obtained for 413 of these individuals. The percentages of their course that theywere psychotic, manic, and depressed were assessed, as was their nonaffectivepsychosis (NAP) ratio,definedas thepercentof their course when they were psychotic but not in a mood episode. The key parts of the article on which I will focus here are their results with the NAP ratio. This concept has a long and distinguished genealogy. The first operationalized diagnosis for SAD from the Research Diagnostic Criteria3 contained a “mainly schizophrenic” subtype, one criterion of which was thepresence of core psychotic symptoms for at least 1 week in the absence of major mood symptoms. When the authors of DSM-III-R4 struggled to provide operationalized criteria for SAD, which had been lacking in DSM-III,5 that would define a boundary with psychotic mood disorders, they adopted this as criterion B, increasing theminimal length to 2 weeks. This wasmaintained in theSADcriteria forDSM-IV6 andDSM-5.7We thereforehave a tradition dating back more than 35 years that the presence of psychotic symptoms for sustained periods outside of mood episodes is important in setting a boundary between psychotic mood disorders and more schizophrenia-like syndromes. Turning to theirmodel,Kotovandcolleagues sought touse the course of illness during the first 4 years to predict 10-year outcome.Adapting themodelof regressiondiscontinuity from Kendell andBrockington8 to theNAP ratio, they sought todiscriminatebetween3hypotheses that they termed linear,kraepelinian, and DSM-IV. That is, would they see (1) a smooth monotonic relationship between an increasing NAP ratio and poor outcome, (2) 2 flat regions of the regression line separatedby a sharp “step function” representingpsychoticmood disorders and schizophrenia, or (3) 3 flat regions separated by 2 step functions representingpsychoticmooddisorders, SAD, and schizophrenia? Before we turn to the empirical evaluation of these hypotheses by Kotov and colleagues, we should look at the distribution of their data for theNAP ratio (Supplement [eFigure 2, bottom right graph]). It is very U-shaped, which is a potential problem: 51% of their sample was psychotic only while in moodepisodes and21%hadonlynonaffectivepsychosis. This leaves just28%of theparticipants toprovide informationabout nonlinearity or discontinuities other than at the boundaries. Even this large study may be underpowered to evaluate the subtle but important distinctions between their hypotheses that they are seeking to evaluate. Using a statistical method of locally weighted scatterplot smoothing andpredicting 10-yearGlobalAssessmentof FunctionalPerformance levels, their key result is seen in thebottom rightgraphofFigure1.Whenexaminedclosely, thiscurveshows a gradually decliningGlobal Assessment of Functional Performance score at the 10-year follow-upas theNAP ratio assessed over the first 4years of illness rises fromzero to approximately 40%.The line thenflattens,meaningthatNAPratiosofapproximately40%havenopredictiverelationshipwithoutcome.These findings, which fit significantly better than a standard linear model, effectively ruleoutmodel 1, (whichbycontrast is clearly seen for the “%timepsychotic” factor [top left graphofFigure 1]). There is no single smooth continuum between NAP ratios andoutcome.The figure alsopresents 95%CIs asdotted lines. Noticehowwide theyare forNAPratiosof 10%to30%, indicating the sparsity of data in this critical region. Discriminating hypotheses 2 and 3 for the NAP ratio from these data is a subtler problem for which Kotov and colleagues use spline regression models (Table 3). With 4 fit indexes and4outcomemeasures,wehave 16 results for each of 8 models. For all 16, the 2 best-fitting models reflect hypotheses 2 and 3 (“2 flat kraepelinian” and “3 flat [DSM-IV]”), with 13 of them, often by verymodest amounts, favoringmodel 2, and 3 of them favoring model 3. Althoughmodels 2 and 3 are clearly better than the alternatives, andalthoughmodel 2 performs somewhatbetter thanmodel 3, the results donot, tomy eye, permit as confident a distinction between them as argued by the authors. My concerns are increased when examining the results from their best-fitting splinemodels (Figure 2). The figures show the predicted single-step function but at a very lowNAP ratio of 1.5%. This does not agreewellwith the results from the locallyweighted scatterplot smoothingmodels that show a curve declining rather steeply from NAP ratios of zero to 20%. Related article page 1276 Opinion

Impulsivity in patients with panic disorder-agoraphobia: The role of cyclothymia

The relationship between Panic Disorder (PD) and impulsivity is not well explored. The present investigation aims to compare impulsivity, measured by different rating tools, in PD patients vs. healthy controls and to explore the influence of co-morbid Cyclothymic Disorder (CD) on the relationship between PD and impulsivity. Sixty-four subjects with PD and 44 matched controls underwent a diagnostic and symptomatological evaluations by the Mini Neuropsychiatric Interview (M.I.N.I) Plus 5.0; the Bech-Rafaelsen Depression and Mania Scale (BRDMS), the State-Trait Anxiety Inventory (STAI), the Hypomania Check List (HCL-32) and the Clinical Global Impression (CGI); the Questionnaire for the Affective and Anxious Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Modified (TEMPS-M), the Separation Anxiety Sensitivity Index (SASI), the Interpersonal Sensitivity Symptoms Inventory (ISSI). Finally, psychometric and neurocognitive evaluations of impulsivity was carried out using the Barratt Impulsiveness Scale (BIS-11) and the Immediate and Delayed Memory Task (IMT/DMT). Subjects with PD were more impulsive than the controls in all the explored measures, reporting higher scores in symptomatological and temperamental scales. The comparison between PD patients with (Cyclo+) and without (Cyclo−) comorbid CD and controls showed that Cyclo+ are the most impulsive subjects in all the investigated measures and are characterized by the greatest symptomatological impairment, the highest scores in temperamental scales, and the highest levels of interpersonal sensitivity and separation anxiety. In our patients with PD, without lifetime comorbidity with major mood episodes, trait and state impulsivity may be related to the presence of comorbid cyclothymic mood instability.

Significant sleep disturbances in euthymic bipolar patients

ObjectiveA growing amount of data suggests that sleep dysfunction is frequently observed in bipolar disorder (BD) patients even when they do not fulfill the criteria for major mood episodes. Thus, we performed a case–control study assessing sleep status in a group of euthymic BD patients and a group of health controls. MethodsA total of 209 subjects (104 health controls and 105 BD patients) were enrolled in the study. The Pittsburgh Sleep Quality Index (PSQI) was used for sleep assessment. Inclusion criteria for the BD group were a diagnosis of BD, following DSM-IV-TR criteria, according to the MINI-plus structured clinical interview. Euthymia was established as a score lower than 7 both in the Hamilton Depression Rating Scale (HDRS) and in the Young Mania Rating Scale (YMRS). Health controls were also interviewed using the MINI-plus and included in this study if they were free of any current or past DSM-IV-TR axis I psychiatric disorder as well the actual use of psychopharmacological medications. ResultsWhile 21.2 % of the control group displayed poor sleep quality according to the global PSQI-BR score, 82.9 % of the euthymic BD patients had poor sleep quality (p=0.000). PSQI sleep duration subcomponent showed comparable results in the two groups (p=0.535), even though BD patients had significant disruptions in sleep latency (p=0.000) and sleep efficiency (p=0.000) subcomponents. ConclusionWe were able to show that BD patients, even in euthymic phase, exhibit a significantly worse sleep quality as compared with health controls as assessed by PSQI total score and five of its seven subcomponents.

Affective temperament, history of suicide attempt and family history of suicide in general practice patients

BackgroundUntreated major affective disorders are strongly associated with suicidal behaviour; however, clinical, psychological and psycho-social risk factors also play a contributory role. Personal history and family history of suicide are also important predictors of suicidal behaviours, and are also a powerful marker of current major depressive episode in general practice patients. Affective temperaments, which can be considered the subaffective manifestations of major mood disorders also show a specific pattern of association with suicidal behaviour. In the present study our aim was to investigate the association between affective temperaments, personal history of suicide attempts and family history of completed suicide in primary practice patients. MethodsFive hundred and nine patients from 6 primary care practices completed the TEMPS-A, and were assessed concerning self-reported history of personal or family suicide. ResultsWe found that among those answering questions concerning suicide, 9.1% reported a family history of suicide in first and second degree relatives and 4.8% had at least one prior suicide attempt. Among those giving a positive answer to both questions, those who had a positive family history had significantly more frequent suicide attempts (15.4% vs. 4.0%). Patients with prior suicide attempts had a significantly higher score on the cyclothymic and depressive, and those with positive family history of suicide had on cyclothymic and anxious subscales. LimitationsIn the present study, personal and family history of suicide was assessed retrospectively and in a self-report way. The cross-sectional nature of this study and the facts that no current psychiatric morbidity has been investigated and only the documented history of depressive and anxiety disorders have been detected limit the generalisability of this study. DiscussionWe found a significant relationship between depressive and cyclothymic affective temperament and personal history of suicide attempts, and between cyclothymic and anxious temperament and family history of completed suicide in first and second degree relatives. This is in line with previous findings showing a strong relationship between these affective temperaments and major mood episodes and that these temperaments are overrepresented among suicide attempters. Our findings also suggest that the presence of cyclothymic (and to lesser extent depressive) affective temperament in a patient with family history of completed suicide indicates a very high risk of suicidal behaviour.

Déficits cognitifs des troubles bipolaires : repérage et prise en charge

Persistent cognitive deficits in euthymic bipolar patients are now well documented. Indeed, several studies and meta-analyzes clearly establish the existence of cognitive deficits in specific domains: attention (in particular sustained attention), Memory (in particular verbal memory) and executive functions. The impact of cognitive deficits on patient's functioning is also well documented and their role appear to be more important than expected by comparison with the impairment related to thymic residual symptoms. The development of specific cognitive remediation strategies is therefore a major hope for improving the quality of remission and functional outcome. The aetiology of these deficits remains poorly understood. However, the implication of factors related to the biological/genetic vulnerability to bipolar disorder is likely well as a "neurotoxic" effects of major mood episodes, in particular acute manic episodes that seems to play a important role in the worsening of these deficits over time. This further stresses the importance maintenance strategies for long-term functional outcome.

Duration of untreated bipolar disorder: missed opportunities on the long road to optimal treatment

Duration of untreated illness represents a potentially modifiable component of any diagnosis-treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically defined or not been applied to large clinically representative samples. In a well-characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood stabilizer). Associations between DUB and clinical onset and the temporal sequence of key clinical milestones were examined. The mean DUB was 9.6 years (SD 9.7; median 6). The median DUB for those with a hypomanic onset (14.5 years) exceeded that for depressive (13 years) and manic onset (8 years). Early onset BD cases have the longest DUB (P < 0.0001). An extended DUB was associated with more mood episodes (P < 0.0001), more suicidal behaviour (P = 0.0003) and a trend towards greater lifetime mood instability (e.g. rapid cycling, possible antidepressant-induced mania). Duration of untreated bipolar disorder (DUB) will only be significantly reduced by more aggressive case finding strategies. Reliable diagnosis (especially for BD-II) and/or instigation of recommended treatments is currently delayed by insufficient awareness of the early, polymorphous presentations of BD, lack of systematic screening and/or failure to follow established guidelines.