Affective Episodes Research Articles

Mixed features: evolution of the concept, past and current definitions, and future prospects.

Mixed states address the relationships between episodes and the course of an illness, presenting significant clinical challenges. Recurrent affective disorders were described thousands of years ago as dimensional disturbances of the basic elements of behavior, combining the characteristics of what we would now consider manic and depressive episodes. It was recognized from the beginning that combinations of depressive and manic features are associated with a severe illness course, including increased suicide risk. Early descriptions of affective disorders formulated them as systemic illnesses, a concept supported by more recent data. Descriptions of affective disorders and their course, including mixed states, became more systematic during the 19th century. Structured criteria achieved importance with evidence that, in addition to early onset, frequent recurrence, and comorbid problems, mixed states had worse treatment outcomes than other episodes. In contrast to 2000 years of literature on recurrent affective episodes and mixed states, the unipolar-bipolar disorder distinction was formalized in the mid-20th century. Mixed-state criteria, initially developed for bipolar disorder, ranged from fully combined depression and mania to the DSM-5 criteria, no longer limited to bipolar disorder, of a primary depressive or manic episode with at least three symptoms of the other episode type. The challenges involved in understanding and identifying mixed states center largely on what drives them, including (1) their formulation as either categorical or dimensional constructs, (2) the specificity of their relationships to depressive or manic episodes, and (3) specificity for bipolar versus major depressive disorder. Their existence challenges the distinction between bipolar and major depressive disorders. The challenges involved in identifying the underlying physiological mechanisms go to the heart of these questions.

Functional Outcome in the Middle Course of Bipolar Disorder: A Longitudinal Study.

The aim of this study was to assess the long-term functional outcome of patients with bipolar disorder (BD). At baseline and after a follow-up period of at least 48 months, three measures of functioning were administered: psychosocial functioning (GAF), employment status (full-time, part-time, and unemployment/disability), and a self-reported measure of functional recovery. At baseline, patients with more than five previous affective episodes exhibited poorer outcomes on all measures of functioning than patients with less than five previous episodes. However, along a mean follow-up period of 77 months, measures of functioning tended to remain stable or improved slightly. These results highlight the limitation of studies comparing measures of functioning between patients with many and few episodes to evaluate functional outcome. Likewise, these preliminary results do not support the hypothesis that functional outcome deteriorates over the course of BD.

Early clinical predictors and correlates of long-term morbidity in bipolar disorder

ObjectivesIdentifying factors predictive of long-term morbidity should improve clinical planning limiting disability and mortality associated with bipolar disorder (BD). MethodsWe analyzed factors associated with total, depressive and mania-related long-term morbidity and their ratio D/M, as %-time ill between a first-lifetime major affective episode and last follow-up of 207 BD subjects. Bivariate comparisons were followed by multivariable linear regression modeling. ResultsTotal % of months ill during follow-up was greater in 96 BD-II (40.2%) than 111 BD-I subjects (28.4%; P=0.001). Time in depression averaged 26.1% in BD-II and 14.3% in BD-I, whereas mania-related morbidity was similar in both, averaging 13.9%. Their ratio D/M was 3.7-fold greater in BD-II than BD-I (5.74 vs. 1.96; P<0.0001). Predictive factors independently associated with total %-time ill were: [a] BD-II diagnosis, [b] longer prodrome from antecedents to first affective episode, and [c] any psychiatric comorbidity. Associated with %-time depressed were: [a] BD-II diagnosis, [b] any antecedent psychiatric syndrome, [c] psychiatric comorbidity, and [d] agitated/psychotic depressive first affective episode. Associated with %-time in mania-like illness were: [a] fewer years ill and [b] (hypo)manic first affective episode. The long-term D/M morbidity ratio was associated with: [a] anxious temperament, [b] depressive first episode, and [c] BD-II diagnosis. ConclusionsLong-term depressive greatly exceeded mania-like morbidity in BD patients. BD-II subjects spent 42% more time ill overall, with a 3.7-times greater D/M morbidity ratio, than BD-I. More time depressed was predicted by agitated/psychotic initial depressive episodes, psychiatric comorbidity, and BD-II diagnosis. Longer prodrome and any antecedent psychiatric syndrome were respectively associated with total and depressive morbidity.

Diagnostic and therapeutic hardships with mixed affective state presenting as catatonia in a patient with intellectual disability

Mixed affective episodes can be misdiagnosed, especially in patients with intellectual disability (ID). We describe the case of an 18-year-old girl with mild ID, who presented with features of catatonia during the first mixed episode. These symptoms responded well to electroconvulsive therapy, following which clear affective symptoms emerged. Her affective episode did not respond adequately to olanzapine but improved significantly after the addition of sodium valproate. The difficulties of diagnosing affective episodes in persons with intellectual disabilities are discussed. This case suggests that mixed affective episodes should be considered in the differential diagnosis when poorly elaborated affective and psychotic symptoms are present in a patient with ID.

A factor analytical study report on mania from Nepal.

Background and Objectives:Phenomenological studies on mood disorder are rare in Nepal which prompted us to undertake the current factor analytical study of mania.Materials and Methods:It was a cross-sectional descriptive study for which we did purposive sampling technique according to certain inclusion and exclusion criteria. The study sample consists of fifty patients, who fulfilled the International Classification of Diseases, Tenth Edition (ICD-10) diagnostic criteria for Manic Episode and/or Bipolar Affective Disorder-current episode mania. Tools used were ICD-10 Diagnostic Criteria for Research, Young's Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). Principal component factor analysis was applied to the 35 symptoms taken from YMRS and BPRS.Results:Factor analysis revealed the presence of four main factors, which explained 51.082% of the total variance. These are “pure mania” which isolated 11 manic symptoms, “dysphoric mania” which isolated five depressive symptoms, “hostile mania” which isolated six symptoms, and the fourth factor, we called it “delirious mania,” isolated four symptoms.Conclusion:The identified factors and subtypes are a useful conceptualization of atypical features among patients with acute mania. Further validation studies are required to determine whether the identified subtypes are of clinical and theoretical importance.

Lost emotion: Disrupted brain-based tracking of dynamic affective episodes in anxiety and depression

In our day-to-day lives we are confronted with dynamic sensory inputs that elicit a continuously evolving emotional response. Insight into the brain basis of the dynamic nature of emotional reactivity may be critical for understanding chronic symptoms of anxiety and depression. Here, individuals with generalized anxiety disorder, major depressive disorder, and healthy controls watched a video with dynamic affective content while fMRI activity was recorded. Across all participants there was a large-scale tracking of affective content in emotion processing regions and the default mode network. Anxious and depressed individuals displayed less brain-based coupling within these regions and the extent of this uncoupling correlated with variability in emotional numbing. Thus, abnormal neural tracking of affective information during dynamic emotional episodes appears to represent a disconnection between affective cues in the environment and an individual’s response to these cues—providing a putative neural basis for context insensitive affective reactivity and emotional numbing.

An exploration of metacognitive beliefs and thought control strategies in bipolar disorder

BackgroundMetacognitive factors influence depression, but are largely unexplored in bipolar disorders. We examined i) differences in metacognitive beliefs and thought control strategies between individuals with bipolar disorder and controls, and ii) to what extent clinical characteristics were related to levels of metacognitive beliefs and thought control strategies in bipolar disorder. MethodEighty patients with bipolar disorder were assessed for age at onset of affective disorder, number of affective episodes, symptoms of mania and depression, metacognitive beliefs (MCQ-30) and thought control strategies (TCQ). Control subjects (N=166) completed MCQ-30 and TCQ. Factors impacting on metacognitive beliefs and thought control strategies were explored with multiple linear regressions. ResultsPatients with bipolar disorder reported higher levels of unhelpful metacognitive beliefs and thought control strategies than controls. Metacognitive beliefs were mainly influenced by depressive symptoms, and age at onset of affective illness. Thought control strategies were mainly influenced by metacognitive beliefs and age at onset of affective illness. ConclusionOur findings suggest that metacognitive beliefs and control strategies are relevant in bipolar disorder. Depression and age at onset of affective disorder could contribute to metacognitive beliefs in bipolar disorder, and influence the use of thought control strategies. This indicates potential relationships that warrant further investigation for clinical relevance.

A longitudinal mirror-image assessment of morbidity in bipolar disorder

BackgroundEvidence about the clinical course of bipolar disorder is inconsistent and limited. The aim of this study was to assess changes in morbidity in patients with bipolar disorder along a mean follow-up period of 80months. MethodsBased on a mirror-image design, the follow-up period of each patient was divided into two halves. Then, three measures of morbidity — number of affective episodes, time spent ill, and cycle length — were recorded and compared between each half of the follow-up period. ResultsOn average, there was a trend to a smaller amount of time spent with subclinical symptomatology during the second half of the follow-up period. In contrast, there were no differences in terms of number of episodes, time spent with clinical symptoms, or cycle length between the first and second half of the follow-up period. A subgroup analysis identified 21.9% of patients with consistent data of a worsening during follow-up. ConclusionsThe results suggest that, on average, there is stability or slight improvement of clinical morbidity over the course of BD. Then, worsening of the clinical course may be a feature of a subgroup of patients rather than an inherent characteristic of the disorder. These subgroups or patient profiles could represent an opportunity for further studies to assess clinical, pathophysiologic, and therapeutic features associated with them.

Evidence for clinical progression of unipolar and bipolar disorders.

It is a widely held belief that affective disorders are progressive of nature; however, some recent reviews have questioned this belief. The objective of the present systematic literature review was to present evidence for associations between number of affective episodes and (i) the risk of recurrence of episodes, (ii) probability of recovery from episodes, (iii) severity of episodes, (iv) the threshold for developing episodes, and (v) progression of cognitive deficits in unipolar and bipolar disorders. A systematic review comprising an extensive literature search conducted in Medline, Embase, and PsychInfo up to September 2016 and including cross-references from identified papers and reviews. Most of the five areas are superficially investigated and hampered by methodological challenges. Nevertheless, studies with the longest follow-up periods, using survival analysis methods, taking account of the individual heterogeneity all support a clinical progressive course of illness. Overall, increasing number of affective episodes seems to be associated with (i) increasing risk of recurrence, (ii) increasing duration of episodes, (iii) increasing symptomatic severity of episodes, (iv) decreasing threshold for developing episodes, and (v) increasing risk of developing dementia. Although the course of illness is heterogeneous, there is evidence for clinical progression of unipolar and bipolar disorders.

Affective Disorders, Psychosis and Dementia in a Community Sample of Older Men with and without Parkinson’s Disease

BackgroundDementia and affective and psychotic symptoms are commonly associated with Parkinson’s disease, but information about their prevalence and incidence in community representative samples remains sparse.MethodsWe recruited a community-representative sample 38173 older men aged 65–85 years in 1996 and used data linkage to ascertain the presence of PD, affective disorders, psychotic disorders and dementia. Diagnoses followed the International Classification of Disease coding system. Age was recorded in years. Follow up data were available until December 2011.ResultsThe mean age of participants was 72.5 years and 333 men (0.9%) had PD at study entry. Affective and psychotic disorders and dementia were more frequent in men with than without PD (respective odds ratios: 6.3 [95%CI = 4.7, 8.4]; 14.2 [95%CI = 8.4, 24.0] and 18.2 [95%CI = 13.4, 24.6]). Incidence rate ratios of affective and psychotic disorders were higher among men with than without PD, although ratios decreased with increasing age. The age-adjusted hazard ratio (HR) of an affective episode associated with PD was 5.0 (95%CI = 4.2, 5.9). PD was associated with an age-adjusted HR of 8.6 (95%CI = 6.1, 12.0) for psychotic disorders and 6.1 (95%CI = 5.5, 6.8) for dementia. PD and dementia increased the HR of depressive and psychotic disorders.ConclusionsPD increases the risk of affective and psychotic disorders, as well as dementia, among community dwelling older men. The risk of a recorded diagnosis of affective and psychotic disorders decreases with increasing age.

Topiramate for acute affective episodes in bipolar disorder in adults.

Topiramate for acute affective episodes in bipolar disorder in adults.

GADL1 variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder.

BackgroundGenetic variants and medication adherence have been identified to be the main factors contributing to lithium treatment response in bipolar disorders.AimsTo simultaneously examine effects of variant glutamate decarboxylase-like protein 1 (GADL1) and medication adherence on response to lithium maintenance treatment in Han Chinese patients with bipolar I (BPI) disorder.MethodFrequencies of manic and depressive episodes between carriers and non-carriers of the effective GADL1 rs17026688 T allele during the cumulative periods of off-lithium, poor adherence to lithium treatment and good adherence to lithium treatment were compared in Han Chinese patients with BPI disorder (n=215).ResultsGADL1 rs17026688 T carriers had significantly lower frequencies of recurrent affective episodes than non-T carriers during the cumulative period of good adherence, but not during those of poor adherence.ConclusionsGADL1 rs17026688 and medication adherence jointly predict response to lithium maintenance treatment in Han Chinese BPI patients.Declaration of interestNone.Copyright and usage© The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Sleep Complaints as Risk Factor for Suicidal Behavior in Severely Depressed Children and Adolescents.

SummaryObjectivesTo investigate the association between sleep complaints and suicidal behaviors among severely depressed children and adolescents.MethodsThe sample was 214 youths (56.1% males, mean age 12.5 years) with diagnosis of DSM‐IV major depressive disorder consecutively recruited from a university‐based outpatient clinic specialized in mood disorders. The structured interview for children and adolescents was applied to participants. The Children's Depression Rating Scale—revised version—scored the severity of depression, and the Children's Global Assessment Scale assessed the global functioning. Subgroups of patients were compared for psychopathological association by means of logistic regression, in accordance with presence and absence of sleep complaints and suicidality.ResultsThe frequency of sleep complaints and suicidal behaviors was, respectively, 66.4% and 52.3%, and both symptoms were observed in 37.9% of patients. Initial insomnia was the most frequent manifestation (58%), followed by night awakening (36%), daytime sleepiness (31%), and early awakening (29.9%). Significant association between sleep disturbance and suicidal behavior was found (odds ratio range of 2.3–10.8).ConclusionSleep disturbances are potential warning manifestations of suicidal behaviors in depressed youth. Possibly, the severity of the active affective episode likely underlies in both sleep complaints and suicidal behaviors among depressed underage patients.

Bipolar affective disorder, pregnancy and childbirth: clinical characteristics and heredity

ABSTRACTBipolar affective disorder has higher frequency among women of reproductive age and can relapse both during pregnancy and immediately after childbirth. The presence of family history is one of the leading risk factors for bipolar affective disorder. A cross-sectional study was performed as part of a large naturalistic study. It included 81 women with pronounced symptoms of bipolar disorder who required hospitalization. The clinical method included comprehensive assessment of patients in the cohort, assessment of the severity of symptoms and the family history. The results showed that more than 50% of the women were at an average age of 25 years and experienced bipolar affective disorder mostly in the first and third trimester, whereas, in the puerperal period, the risk was highest in the first two weeks after childbirth. There was previous history of bipolar affective disorder in about 50% of the women. In 55.6% of the women, there was family history of bipolar affective disorder. The presence of previous history of bipolar affective disorder, first-degree family history and pregnancy at later age were shown to be risk factors for a new relapse during pregnancy and after childbirth. Clinical expression of manic–psychotic symptoms was more typical of the period of lactation than manic symptoms, which were associated rather with younger age and the period of pregnancy. In the studied cohort of patients, the risk of repeatability of affective episodes was significantly higher with each subsequent pregnancy.

Effect of Lithium on Neurocognitive Functioning.

Lithium is the first choice drug for the long-term prophylaxis of depressive and manic episodes in bipolar disorder (BD). Both experimental and clinical studies show either neuroprotective or neurotoxic effects of lithium on brain function, reflecting the propensity of lithium to affect different brain structures. In most experimental studies, lithium, in therapeutic doses, exerts a favourable influence on various cognitive functions. Patients with BD present cognitive problems of mild intensity across mood states, worsening during manic or depressive episodes and, sometimes, also persisting during euthymia. Meta-analyses, comparing bipolar patients treated with lithium with those without the drug show a moderate negative effect of this drug on cognition and, among clinicians, negative impact on cognitive functioning is considered one of the side effect of the drug. In some studies, the effect of lithium on cognitive function in BD was shown to be associated with a prophylactic efficacy of the drug against an occurrence of affective episodes. Excellent lithium responders, having no affective recurrences during lithium therapy, perform on cognitive functions tests similar to those of age-matched, healthy control subjects. Some studies also found a reduction by lithium the risk of dementia in BD subjects. Possible mechanisms alleviating negative impact of lithium on cognition in BD can be connected with the prevention of affective recurrences, improvement of neural plasticity, antiviral action against herpes infection and using the drug in appropriate doses.

Epigenetic basis of sensitization to stress, affective episodes, and stimulants: implications for illness progression and prevention.

The process of sensitization (increased responsivity) to the recurrence of stressors, affective episodes, and bouts of substance abuse that can drive illness progression in the recurrent affective disorders requires a memory of and increased reactivity to the prior exposures. A wealth of studies now supports the postulate that epigenetic mechanisms underlie both normal and pathological memory processes. We selectively reviewed the literature pertinent to the role of epigenetics in behavioral sensitization phenomena and discuss its clinical implications. Epigenetics means above genetics and refers to environmental effects on the chemistry of DNA, histones (around which DNA is wound), and microRNA that change how easily genes are turned on and off. The evidence supports that sensitization to repeated stressor, affective episodes, and substance is likely based on epigenetic mechanisms and that these environmentally based processes can then become targets for prevention, early intervention, and ongoing treatment. Sensitization processes are remediable or preventable risk factors for a poor illness outcome and deserve increased clinical, public health, and research attention in the hopes of making the recurrent unipolar and bipolar affective disorders less impairing, disabling, and lethal by suicide and increased medical mortality. The findings that epigenetic chemical marks, which change in the most fundamental way how genes are regulated, mediate the long-term increased responsivity to recurrent stressors, mood episodes, and bouts of substance abuse should help change how the affective disorders are conceptualized and move treatment toward earlier, more comprehensive, and sustained pharmacoprophylaxis.

Mood and motor activity in euthymic bipolar disorder with sleep disturbance

BackgroundThe aims of this observational study of patients with euthymic bipolar disorder and sleep disturbance were to 1) compare characteristics related to mood and sleep between two groups with stable and unstable rest-activity cycles and 2) detect between-group differences in motor activity patterns. Methods43 patients wore an actigraph for 6–8 days while reporting daily mood and sleep. Patients were defined as having an unstable rest-activity cycle if their diurnal active period duration presented variation above 2h from the mean during one week: 22 patients had stable and 21 unstable rest-activity cycles. Mood variability was defined as at least moderate symptoms and a change across two levels on a 7-point mood scale during one week. ResultsPatients with unstable rest-activity cycles were younger (37 vs. 48 years, p=0.01) and displayed more mood variability (p=0.02). Ten of 11 patients diagnosed with delayed sleep phase disorder were in the unstable group (p<0.01), and the unstable group had later and more variable get-up-times and bedtimes. In actigraphy recordings, the mean activity counts per minute did not differ between groups, but the minute-to-minute variability was elevated (p=0.04) and increased relative to the overall variability (p=0.03). LimitationsA relatively small study sample and a 1-week study period prevent exploration of long-term clinical implications of results. ConclusionsA subgroup of euthymic patients with bipolar disorder displayed unstable rest-activity cycles combined with mood variability and motor activity patterns that resemble findings in affective episodes.

The feasibility and acceptability of a preventive intervention programme for children with depressed parents: study protocol for a randomised controlled trial

BackgroundOne of the most important risk factors for childhood depression is being the child of a depressed parent. These at-risk children have two to four times the probability of having an affective episode compared with their peers. Preventive interventions such as Beardslee’s Preventive Intervention Program (PIP) that are targeted at children of depressed parents have proven effective in many countries. The PIP is a family-based approach that works by promoting resilience in children and increasing positive interactions within the family. In this pilot randomised controlled trial (RCT), we will determine the acceptability and feasibility of an adapted version of this intervention in Chile.Methods/designWe are conducting a pilot RCT with a manualized intervention. The intervention will be delivered in seven weekly sessions at the family home. It is targeted mostly at parents but will also measure outcomes among the children. Control subjects will follow their treatment as usual. Feasibility and acceptability will be assessed by recruitment, adherence, dropout and level of missing data, as well as the burden of scales and measurement tools. Families will be followed for 11 months.DiscussionGiven the negative lifelong consequences of depression and the burden they represent, preventive programmes are not only feasible but necessary. Despite the successful implementation of this intervention in different countries, an adaptation to the Chilean reality will be prerequisite. The results of this pilot study will inform a definitive trial that will make the case for its national implementation.Trial registrationClinicaltrials.gov trial identifier: NCT02593266. Registration date: 30 Octo 2015.

Magnesium, C-reactive protein, and cortisol in drug-naïve patients with short illness-duration, first episode major depressive disorder: possible immunomodulatory role for magnesium.

Plasma magnesium concentration alterations, hypercortisolaemia, and systemic inflammation are observed in major depressive disorder (MDD). This exploratory study examined whether, and to what extent, plasma magnesium is related to C-reactive protein (CRP) levels and cortisolaemia in MDD. The concentrations of plasma magnesium, salivary CRP, and baseline plasma cortisol were studied in 20, treatment-naïve MDD patients with short-illness-duration, first affective episodes and 20 matched controls. Depressed patients showed a basal score higher than 20 on the Hamilton Rating Scale for Depression (HAMD-17). Significantly higher magnesium (p=0.016) and baseline cortisol (p=0.01) concentrations were observed in MDD as compared to controls. No significant difference in CRP concentrations between the MDD and control groups was observed. A significant negative correlation was seen between magnesium and CRP in MDD (p<0.01), whereas no correlation was found in controls. A significant positive correlation was found between cortisol and CRP, both in MDD subjects (p=0.008) and controls (p=0.004). No significant correlations were observed between magnesium and cortisol levels. The study supports data for hypercortisolaemia in MDD, but provides no evidence of primary hypomagnesaemia or elevated CRP levels in drug-naïve MDD patients with short-illness-duration. The study supports the hypothesis linking hypercortisolaemia to systemic inflammation, with hypermagnesaemia exerting an immunomodulatory action at early stages of the disease.

Unipolar mania: Prevalence, socio-demographic and clinical correlates

The concept of unipolar mania (UM) arose from the observation that some patients with bipolar disorder (BD) presented manic episodes in the absence of depressive episodes. The frequency of UM ranges from 4 to 52% in bipolar populations. The aim of our study was therefore to add to existing research by establishing the prevalence of UM in a sample of patients with BD and by studying their socio-demographic and clinical characteristics. Of the 100 patients, 67 had been diagnosed with MD phases and 33 with UM. The mean age of the MD group was 43.21 years whereas it was 39.36 years in the UM group. Males represented 41.8% of the MD group and 72.7% of the UM group. The two groups were similar with regards to marital status, level of education and work activity. Age of illness onset was lower in the UM group (mean=24.45) compared to the MD group (mean=26). UM group patients had more relatives with affective illness (42.4% versus 32.8%). The type of first affective episode was manic in 46.3%, mixed in 11.9%, depressive in 31.3% and not specified in 10.4% of the MD group whereas it was manic in 93.9% and not specified in 6.1% in the UM group. The two groups were similar with regards to the presence or the absence of psychotic features. The results of our study show that patients with UM were distinct from patients with a bipolar course of the illness in a range of clinical aspects.