Number Of Past Episodes Research Articles

P339. Imaging Biomarkers of Major Depression Progression Using Subcallosal Cingulate Cortex Functional Connectivity

The course of MDD can be highly variable among individuals. Patients can have treatable discrete episodes, a more chronic form of the illness, or a transition over time from treatable to treatment-resistant. As such treatment decisions for a given episode are informed not only by past treatment exposure and outcomes but also by information about chronicity and the number of past episodes. We examined the impact of past treatment, chronicity, and the number of past episodes on brain connectivity in patients presenting with a new depressive episode.

Concepts of Neuroinflammation and Their Relationship With Impaired Mitochondrial Functions in Bipolar Disorder.

Bipolar disorder (BD) is a chronic psychiatric disease, characterized by frequent behavioral episodes of depression and mania, and neurologically by dysregulated neurotransmission, neuroplasticity, growth factor signaling, and metabolism, as well as oxidative stress, and neuronal apoptosis, contributing to chronic neuroinflammation. These abnormalities result from complex interactions between multiple susceptibility genes and environmental factors such as stress. The neurocellular abnormalities of BD can result in gross morphological changes, such as reduced prefrontal and hippocampal volume, and circuit reorganization resulting in cognitive and emotional deficits. The term “neuroprogression” is used to denote the progressive changes from early to late stages, as BD severity and loss of treatment response correlate with the number of past episodes. In addition to circuit and cellular abnormalities, BD is associated with dysfunctional mitochondria, leading to severe metabolic disruption in high energy-demanding neurons and glia. Indeed, mitochondrial dysfunction involving electron transport chain (ETC) disruption is considered the primary cause of chronic oxidative stress in BD. The ensuing damage to membrane lipids, proteins, and DNA further perpetuates oxidative stress and neuroinflammation, creating a perpetuating pathogenic cycle. A deeper understanding of BD pathophysiology and identification of associated biomarkers of neuroinflammation are needed to facilitate early diagnosis and treatment of this debilitating disorder.

Predictors of Symptomatic Kidney Stone Recurrence After the First and Subsequent Episodes

ObjectiveTo predict symptomatic recurrence among community stone formers with one or more previous stone episodes. Patients and MethodsA random sample of incident symptomatic kidney stone formers in Olmsted County, Minnesota, was followed for all symptomatic stone episodes resulting in clinical care from January 1, 1984, through January 31, 2017. Clinical and radiographic characteristics at each stone episode predictive of subsequent episodes were identified. ResultsThere were 3364 incident kidney stone formers with 4951 episodes. The stone recurrence rates per 100 person-years were 3.4 (95% CI, 3.2-3.7) after the first episode, 7.1 (95% CI, 6.4-7.9) after the second episode, 12.1 (95% CI, 10.3-13.9) after the third episode, and 17.6 (95% CI, 15.1-20.0) after the fourth or higher episode (P<.001 for trend). A parsimonious model identified the following independent risk factors for recurrence: younger age; male sex; higher body mass index; family history of stones; pregnancy; incident asymptomatic stone on imaging before the first episode; suspected stone episode before the first episode; history of a brushite, struvite, or uric acid stone; no history of calcium oxalate monohydrate stone; kidney pelvic or lower pole stone on imaging; no ureterovesical junction stone on imaging; number of kidney stones on imaging; and diameter of the largest kidney stone on imaging. The model had a C-index corrected for optimism of 0.681 and was used to develop a prediction tool. The risk of recurrence in 5 years ranged from 0.9% to 94%, depending on risk factors, number of past episodes, and years since the last episode. ConclusionThe revised Recurrence Of Kidney Stone tool predicts the risk of symptomatic recurrence by using readily available clinical characteristics of stone formers.

Sociodemographic and Clinical Predictors of Response in Manic Episodes: A Naturalistic, Prospective, Cohort Study.

Background:Response to treatment of a manic episode is dependent on several sociodemographic and clinical factors as reported by researchers from other countries. The prescription of mood stabilizers and/or antipsychotics for manic episode depends on these factors. There is a lack of availability of data from India on this topic. Hence, this study was planned to identify the predictors of pharmacological response.Materials and Methods:Forty-two patients with a diagnosis of bipolar affective disorder current episode manic were enrolled and assessed for sociodemographic variables and clinical variables such as age of onset, family history, comorbidities, index episode, and number of past episodes. They were divided into four groups depending on the treatment they were receiving, namely, lithium with an antipsychotic (n = 25), lithium with divalproex and an antipsychotic (n = 8), divalproex with an antipsychotic (n = 5), and the miscellaneous group (n = 4). The primary outcome measure was improvement in the Young Mania Rating Scale score and secondary outcome measure was duration of ward stay.Results:There was a significant improvement in all the treatment modalities and it was comparable. There was no significant impact of any sociodemographic or clinical variable on treatment outcome except that females had significantly better response than males. There was nearly significant shorter duration of hospitalization in the lithium and antipsychotics groups compared to divalproex group.Conclusion:All treatment modalities are equally efficacious in the management of manic episode in short term. However, lithium and antipsychotics tend to produce early response than divalproex. Other sociodemographic and clinical predictors were not significantly associated with response.

Kindling of life stress in bipolar disorder: comparison of sensitization and autonomy models.

Research on life stress in bipolar disorder largely fails to account for the possibility of a dynamic relationship between psychosocial stress and episode initiation. The kindling hypothesis (Post, 1992) states that over the course of recurrent affective disorders, there is a weakening temporal relationship between major life stress and episode initiation that could reflect either a progressive sensitization or progressive autonomy to life stress. The present study involved a comprehensive and precise examination of the kindling hypothesis in 102 participants with bipolar II disorder that allowed for a direct comparison of sensitization and autonomy models. Polarity-specific tests were conducted across the continuum of event severity with respect to impact and frequency of life events. Hypotheses were polarity- and event-valence specific and were based on the stress sensitization model. Results were only partially consistent with the sensitization model: Individuals with more prior mood episodes had an increased frequency of minor negative events before depression and of minor positive events before hypomania. However, the number of past episodes did not moderate relationships between life events and time until prospective onset of mood episodes. These results are more consistent with a sensitization than an autonomy model, but several predictions of the sensitization model were not supported. Methodological strengths, limitations, and implications are discussed regarding putative changes in stress reactivity that may occur with repeated exposure to mood episodes in bipolar II disorder.

RECURRENCE OF MAJOR DEPRESSIVE EPISODES IS STRONGLY DEPENDENT ON THE NUMBER OF PREVIOUS EPISODES

A history of past major depressive episodes (MDEs) is known to be a risk factor for future MDEs. Additional information about the relationship between past and future episodes would be useful in clinical practice, it is therefore important to fully understand the epidemiology of major depression. We asked whether the number of previous MDEs is related to the probability of recurrence in the general population. Data were used from the Canadian National Population Health Survey (NPHS) that was repeated every 2 years from 1994/1995 to 2009/2010 (i.e., nine cycles). Prior year depression was assessed with the Composite International Diagnostic Interview Short Form (CIDI-SF). We estimated the total number of MDEs in individuals over the first eight cycles and examined recurrence in the ninth cycle. These analyses employed a generalized linear model (identity link) where recurrence in cycle 9 was the outcome and the predictor variables were age, gender, and the number of MDEs in the first eight cycles. The risk for recurrence of depression in cycle 9 was found to progressively increase with the number of prior episodes, reaching a value of greater than 46% when the number of prior episodes was five to eight. Independent of this association, the risk of recurrence was greater in younger people and women, but the strength of association of these variables was much weaker for past episodes. MDE recurrence strongly depended on the number of preceding episodes. Those at highest risk of recurrence can be easily identified by their number of past episodes.

Major depression epidemiology from a diathesis-stress conceptualization

BackgroundMajor depression is a widely used diagnostic category but there is increasing dissatisfaction with its performance. The diathesis-stress model is an alternative approach that does not require the (sometimes arbitrary) imposition of categories onto the spectrum of depressive morbidity. However, application of this model has not been well explored and its consistency with available epidemiologic data is uncertain.MethodsSimulation provides an opportunity to explore these issues. In this study, a simulation model based on an intuitive representation of diathesis-stress interaction was developed. Both diathesis and stress were represented using continuous distributions, without categorization. A diagnostic threshold was then applied to the simulation output to create nominal categories and to explore their consistency with available information.ResultsAn apparently complex epidemiologic pattern emerged from the diathesis-stress interaction when thresholds were applied: incidence was time dependent, recurrence depended on the number of past episodes, baseline symptoms were associated with an increased risk of subsequent episodes and the remission rate declined with increasing episode duration.ConclusionsA diathesis-stress conceptualization coupled with application of a threshold-based diagnostic definition may explain several of the apparent complexities of major depression epidemiology. Some of these complexities may be artifacts of the nominal diagnostic approach. These observations should encourage an empirical exploration of whether diathesis-stress interactions provide a more parsimonious framework for understanding depression than current approaches.

1311 – Response trajectories during antidepressant treatment of major mood disorder

A recent study by Levine and Leucht described several kinetics of treatment response among schizophrenic patients with antipsychotics. We aimed so to test this methodology in a population of depressed patients. 2938 outpatients with major depressive disorder were included in a multicentre, non interventional study, assessing at inclusion, week 2 and week 6, mood (QIDS-C, CGI, PGI and VAS) and functionality (SDS). To identify homogeneous groups of patients on the evolution of QIDS criteria over time (D0, W2 and W6), the latent class linear mixed model was used. Then, the groups were described at each time by several clinical characteristics and scores using ANOVA or the chi-square test. All metrics at day 0 and week 2 were tested for their capacity to predict a kinetic of response, all patients being treated by Agomelatine. 1200 patients were drug naïve for the current episode; 3 types of response kinetics were found: early, intermediate et late responders. The principal factor in relationship with a later response was the number of past episodes. Among the 1700 patients with a previous antidepressant treatment, 6 types of kinetics were distinguished: early response kinetics, intermediate and late response, non response and a singular one with early response at W2 and relapse at W6. The principal factor in relationship with a bad response kinetic was the age at first episode of mood disorder. Previous reports stressing the interest of an assessment at week 2 were reinforced by the present results.

Recurrence Rates in Ontario Physicians Monitored for Major Depression and Bipolar Disorder

Physicians with recurrent conditions that may affect job performance are sometimes referred for monitoring to help ensure compliance with treatment, ongoing remission of illness, and patient safety. Little is known about recurrence rates among doctors monitored for mood disorders. Our primary objective was to describe recurrence rates among Ontario physicians monitored for recurrent unipolar depression and bipolar disorder (BD). Our secondary objective was to explore predictors of recurrence. We used a retrospective cohort design to describe the time to recurrence, defined as either stopping work owing to symptoms or any re-emergence of symptoms meeting a pre-established clinical threshold. Our exploratory analysis of recurrence predictors included age, sex, psychiatric diagnosis, psychiatric comorbidity, medical comorbidity, number of past episodes, past hospitalizations, and family history of psychiatric disorder. During a median observation of 24 months, 36% (18 of 50) of physicians stopped work owing to recurrence of symptoms, with the median time to stopping work being 11 months. As well, 52% (26 of 50) had a re-emergence of clinical symptoms, with the median time to any level of symptom re-emergence being 13 months. Physicians with psychiatric comorbidity stopped work sooner (hazard ratio [HR] 3.53; 95% CI 1.24 to 10.03, P = 0.01) and had more rapid symptom re-emergence (HR 2.96; 95% CI 1.34 to 6.52, P = 0.004) than those without comorbidity. The most common psychiatric comorbidity was a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, anxiety disorder. Recurrence rates are high among Ontario physicians referred for formal monitoring of recurrent unipolar depression and BD, and are markedly hastened by the presence of psychiatric comorbidity.

Quality of life of bipolar patients

Several studies have examined QoL in patients with major depressive disorder (MDD), and few studies have evaluated the impact of bipolar disorder on health-related quality of life. Namjoshi and colleagues assessed all relevant English-language articles published prior to 1999, identifying 10 studies for inclusion: quite heterogeneous; a variety of generic and depression-specific instruments to assess different aspects of HRQOL; rarely included descriptions of the psychometric properties of the instruments; small samples. Second review (Dean et. al. 2004) examined studies that had assessed HRQOL, workimpairment or healthcare costs and utilization in BDP published prior to November 2002; Using a broad definition of HRQOL (e.g studies that had assessed social or physical functioning in isolation) identified 65 HRQOL articles. The described deficits in HRQOL in patients with BD were similar to those observed in patients with unipolar depression and equal or lower than levels of HRQOL observed in patients with other chronic medical conditions. Another comprehensive literature search in several databases up to November 2004 (e.g. MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Database) was performed by Michalak Erin E, et al., 2005. Several studies addressed the question how significant the QoL in patients with BD is related with the different stages of the disorder. They conclude that: BD type II reported significantly poorer HRQOL than BD type I in the areas of social functioning and mental health ; women numerically lower scores in all of the questionnaire's domains except for mental health; the number of past episodes of depression was a stronger determinant of HRQOL than number of previous manic episodes; mania/hypomania patients significantly lower SF-12 mental health scores than euthymic patients? depressed or mixed patients significantly poorer HRQOL; depressed or experiencing a recent episode of depression; SF-36 scores remarkably low in the role-physical, vitality, social functioning, role-emotional and mental health sub-scales.

The stress sensitization hypothesis: Understanding the course of bipolar disorder

Background The influence of psychosocial stress on the course of bipolar disorder has been increasingly recognized. The authors tested hypotheses about both stress and early adversity “sensitization” on the course of bipolar disorder over a one-year period. Methods The participants were 58 adults (29 male and 29 female) with a diagnosis of bipolar I disorder. They were evaluated every three months for one year. Stressful life events and the presence of early adversity were assessed by structured interview. Results There was no significant interaction between stress and episode number in the prediction of bipolar recurrence. The interaction of early adversity severity and stressful life events significantly predicted recurrence in a manner consistent with the sensitization hypothesis. Participants with early adversity reported lower levels of stress prior to recurrence than those without early adversity. Individuals with early adversity also had a significantly younger age of bipolar onset. Limitations The sample size was small and the number of past episodes was determined retrospectively, mainly through self-report. Conclusions Severe early adversity may result in a greater effect of stress on bipolar recurrence and earlier onset of bipolar disorder, suggesting the need for further studies of stress mechanisms in bipolar disorder and of treatments designed to intervene early among those at risk.

Life events exposure before a treated major depressive episode depends on the number of past episodes

A cross-sectional survey investigated the relationship between the number of previous depressive episodes and life events, testing the kindling hypothesis, in a sample of 13,377 treated patients with unipolar depression. A linear decline of average life events exposure is observed for more frequent past episodes, even when age, gender and severity are taken into account.

Does the Clinical Course of Depression Determine Improvement in Symptoms and Quality of Life?

Clinical course factors characterizing individuals' history with depression may be helpful in predicting treatment-related change in quality of life (QOL). Such factors have been studied in relation to symptomatic change with mixed results. This 9-week single-blind treatment trial using reboxetine (1 week placebo lead-in) evaluated the impact of age of onset, history of antidepressant treatment, duration of index episode, number of past episodes, and the presence of precipitating stress on depressed individuals' treatment response. We found that QOL did not normalize along with clinical remission in all areas. Using multivariate analysis, we found that age of onset, history with antidepressants, and the presence of identifiable precipitating stress were all significant predictors of QOL change (controlling for symptomatic change); some factors also predicted symptomatic improvement. Our results support the trend of distinguishing between treatment-related change in QOL and symptomatic change and suggest clinical course factors as promising predictors of QOL.

Tardive dyskinesia in bipolar patients

Although it is recognized that tardive dyskinesia (TD) occurs also in bipolar patients who receive long-term neuroleptic treatment, there has been limited research on the clinical and biological correlates of TD in this population. We examined the prevalence of TD and its relations to select clinical and biological measures in 50 bipolar patients admitted to a research unit at a state psychiatric center. Diagnosis of TD was based on the criteria proposed by Schooler and Kane (1982). Twenty-two (44%) of the 50 bipolar patients fulfilled criteria for TD, a prevalence rate that is slightly higher than the 35% noted in bipolar patients in an outpatient clinic (Mukherjee et al, 1986), but not significantly different from the 43% rate in 90 research schizophrenic patients. Limb dyskinesia scores were significantly higher in schizophrenic patients (.83 + .95) than in the bipolar patients (.38 + .78) [p < .02], while orofacial ratings did not differ between the groups. The presence of TD was associated with a greater number of past episodes of depression but not mania. None of the five unipolar manic patients was noted to have TD. TD was not related to measures of ventricular enlargement or cortical atrophy on CT scan. Our findings indicate that TD in bipolar patients may be related to a past history of depressive episodes, but not to morphological brain abnormalities such as ventricular enlargement and cortical atrophy. The different topographic distributions of abnormal involuntary movements in bipolar and schizophrenic patients suggest that pathological processes contributing to the development of TD may vary across the diagnostic groups.