Performance of a measure to assess distress in bipolar disorder.

INTRODUCTION: Bipolar disorder is a condition that causes distress even for euthymic patients, having an impact on functional capabilities and quality of life. Personal and social variables are potential sources of distress. Yet, there is a lack of measures to identify specific distress in bipolar disorder. This study describes the development and evaluation of a brief measure for assessing distress in patients with bipolar disorder. We also identify associations with related constructs such as functioning, stigma, and personal beliefs regarding mental illness. MATERIAL AND METHODS: We used a sample of 101 euthymic bipolar outpatients. Psychological assessment consisted of the Young Mania Rating Scale (YMRS) and the Hamilton Depression Scale (HAM-D) to establish euthymia. Distress was assessed with Distress on Bipolar Patients-Short (DISBIP-S); associated variables were assessed with the Functioning Assessment Short Scale (FAST), the Internalized Stigma of Mental Illness (ISMI), and the Personal Beliefs about Illness Questionnaire (PBIQ). RESULTS: The DISBIP-S has strong internal consistency (Cronbach's alpha=0.90), and medium-high correlation coefficients with the time since last relapse (r=-0.401), predominant polarity (r=0.309), HDRS (r=-0.644), FAST (r=0.453), ISMI (r=0.789), and PBIQ (r=-0.796). Taken together, the scores on the ISMI, and PBIQ and the time since last relapse together explain 69.2% of the variability in distress. CONCLUSIONS: The DISBIP-S can be used as a first step to develop interventions aimed at dealing with problematic personal beliefs and interpersonal sources of distress. Reducing distress experienced by bipolar disorder patients could help improve their quality of life and daily functioning.

Relationships Among Delayed Sleep Phase Disorder, Emotional Dysregulation, and Affective Temperaments in Adults With Attention Deficit Hyperactivity Disorder and Cyclothymia.

This study aims to explore the relationships between delayed sleep phase disorder (DSPD) and emotional dysregulation in 240 patients (134 with cyclothymia, 81 with attention deficit hyperactivity disorder [ADHD] and 25 with both conditions). DSPD was assessed using the Morningness-Eveningness Questionnaire, followed by a clinical evaluation. Affective temperaments and emotional dysregulation were also investigated through the brief version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego and the Reactivity, Intensity, Polarity, Stability questionnaires, respectively. Clinical variables were compared in patients with and without DSPD, and a logistic regression model was used to identify the predictive value of the clinical characteristics on the presence of DSPD. DSPD patients (19% of the total sample) were significantly younger than patients without DSPD, showed an about 4 times higher lifetime history of comorbid ADHD and cyclothymia, and reported higher scores in the irritable and cyclothymic temperamental subscales and in the affective instability and impulsivity dimensions. In the multiple logistic regression, we found a negative predictive value of increasing age on the presence of DSPD, whereas comorbid cyclothymia and ADHD and cyclothymic temperament seem to represent risk factors for DSPD.

On the phenomenology of auditory verbal hallucinations in affective and non-affective psychosis.

Phenomenological comparisons of auditory verbal hallucinations (AVHs) in affective versus non-affective psychosis have not been adequately documented. The current study aimed to: a) comprehensively describe AVH phenomenology by diagnosis and mood state, b) investigate significant predictors of voice-related distress and functional impairment, and c) conduct qualitative thematic analysis of participants' experiences. Participants were diagnosed with: a) bipolar disorder (n = 31), b) major depressive disorder (n = 34), c) schizophrenia (n = 50), or d) schizoaffective disorder (n = 26). Current voice-hearers were also subdivided into prevailing mood states: a) euthymic (n = 23), b) depressed (n = 51), or c) mania-mixed (n = 12). An in-depth, semi-structured interview was conducted, accompanied by mixed-methods analyses. Of the 34 AVH characteristics, significant group differences across diagnoses were identified only for frequency, number of voices, form of address, perceived location, level of conviction, beliefs regarding origin, and functional interference. Random forests modelling (RFM) showed experienced distress and functional interference were best predicted by discrete AVH variables. Qualitative thematic analysis revealed first-order themes: a) content, b) form, c) function, and d) non-voice. There were more similarities than differences in the phenomenology of AVHs across diagnoses, yet significant predictors of voice-related distress and functional impairment differed across affective and non-affective psychosis. This has important nosological and therapeutic applications.

Neurocognitive heterogeneity in young offspring of patients with bipolar disorder: The effect of putative clinical stages.

BACKGROUND: Bipolar disorder (BD) is associated with significant cognitive heterogeneity. In recent years, a number of studies have investigated cognitive subgroups in BD using data-driven methods and found that BD includes several subgroups including a severely impaired and a neurocognitively intact cluster. Studies in offspring of BD (BDoff) are particularly important to establish the timing of emergence of cognitive subgroups but studies investigating cognitive heterogeneity in BDoff are lacking. Our aim was to investigate cognitive heterogeneity in BDoff and the relationship between cognitive heterogeneity and putative clinical stages of BD. METHODS: Seventy-one euthymic BDoff and 50 healthy controls were assessed using clinical measures and a battery of neuropsychological tests. Neurocognitive subgroups were investigated using latent class analysis. RESULTS: Three neurocognitive subgroups, including a severe impairment group, a good performance cluster, and a subgroup characterized by intermediate/selective impairment was found. Both severe and intermediate level impairment subgroups underperformed healthy controls in processing speed, verbal fluency, visual memory and working memory. Deficits in verbal memory and executive functions were only evident in severe impairment subgroup. The putative stage of the illness had no significant effect on cognitive clustering of BDoff. Trait impulsivity scores were significantly increased in severe and intermediate impairment clusters but not in the cognitively good functioning subgroup of BDoff. LIMITATIONS: The cross-sectional nature of the study was the main consideration. CONCLUSION: These results suggest that cognitive heterogeneity is premorbid characteristic of BD and cognitive subgroups of BDoff emerge prior to the onset of illness and prodromal symptoms.

Quality of life in euthymic bipolar patients: A systematic review and meta-analysis.

BACKGROUND: Patients with bipolar disorder, even euthymic, could suffer an impairment in their quality of life compared to healthy controls. Since no previous systematic review and meta-analysis has been conducted, the aim of the current study is to conduct a systematic review and meta-analysis of cross-sectional case-controlled studies on quality of life in adult euthymic Bipolar Disorder patients. METHODS: A systematic review and meta-analysis that followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) was conducted. Major electronic databases were searched on August 2018 to assess the variables associated with quality of life in euthymic bipolar disorder patients. After selecting case-control studies, data collection, quality assessment and subsequently statistical analysis were done. RESULTS: 66 studies were finally selected for systematic review and meta-analysis. Four different quality of life instruments were used among the different studies. Effect size analysis showed that there were significant differences in quality of life outcomes between euthymic bipolar disorder patients and healthy controls (d=-0.922; SE=0.316; 95%CI=-1.541--0.303; p=.004), with lower quality of life in the euthymic patients. Furthermore, time since euthymia explained 15.62% of variability, and age of control group explained 29.6% of variability. No other moderators were statiscally significant. LIMITATIONS: The instruments used were heterogeneous. Moreover, the role of other clinical moderators could not be included due to the lack of this information in most of the articles. CONCLUSIONS: Quality of life is lower in euthymic bipolar patients than in healthy controls. However, longer time in euthymia is associated with better outcomes.

Physical activity as prognostic factor for bipolar disorder: An 18-month prospective study.

INTRODUCTION: Exercise is an adjuvant therapy indicated for various psychiatric disorders. However, prospective studies in patients with bipolar disorder (BD) are scarce and with uncertain conclusions. This study aims to evaluate physical activity as a prognostic factor for BD, analyzing relationship with levels of anxiety, functionality, sleep, mood episodes and hospitalizations. METHODS: Three psychiatrists interviewed 80 BD outpatients in euthymia, referred from four different institutions in Brazil. In this moment, they evaluated the intensity of physical activities using the International Physical Activity Questionnaire (IPAQ) - short form. They reevaluated patients and reviewed medical records monthly for 18 months to identify mood episodes and psychiatric hospitalizations. RESULTS: Thirty-eight patients (47.5%) were physically inactive (or sedentary) and 42 (52.5%) active. Physically active patients had lower Body Mass Index (p = 0.006), waist circumference (p = 0.002), lower levels of anxiety (p = 0.032) and less insomnia (p = 0.001). Sedentary individuals revealed poorer global functioning (p < 0.001) and in all domains: autonomy (p < 0.001), occupational functioning (p = 0.008), cognitive functioning (p = 0.013), capacity of managing the finances (p = 0.012), interpersonal relationships (p = 0.011) and leisure time (p = 0.001). Less activity was associated with more mood episodes (p = 0.042) and psychiatric hospitalizations (p = 0.043) over 18 months. CONCLUSION: This study suggested physical activity as a good prognostic factor for BD during euthymia. This reinforces the need to encourage this practice in clinical settings. Future prospective surveys with longer duration using objective instruments are proposed.

Impulsivity and its association with childhood trauma experiences across bipolar disorder, attention deficit hyperactivity disorder and borderline personality disorder.

BACKGROUND: Impulsivity is a core feature of the attention-deficit/hyperactivity disorder (ADHD) and is one of the DSM-V diagnostic criteria for borderline personality disorder (BPD). Impulsivity is also present in bipolar disorder (BD). Impulsivity has been linked to adverse behavior (suicidality,…) and to traumatic childhood experiences. Our study explored impulsivity in BPD, BD, ADHD and healthy controls (CTRL) and investigated the impact of early trauma on impulsivity. METHODS: 744 patients with BD (n = 276), BPD (n = 168), ADHD (n = 173) or a combination (BPD_BD, n = 29; BPD_ADHD, n = 94, BD_BPD_ADHD n = 13) and 47 controls were included. All subjects were completed the Baratt Impulsivity Scale (BIS-10) and the Childhood Trauma Questionnaire (CTQ). RESULTS: BD reported the same levels of impulsiveness as CTRL. When BPD and BD are co-morbid, impulsivity increased to reach the level of BPD. Impulsiveness was significantly associated to traumatic childhood event for BD and CTRL, not for BPD and AHDH. LIMITATIONS: Impulsivity was assessed on the basis of a self-report questionnaire and not by the mean of an objective measure such as a neuropsychological test. Moreover, we don't know what treatment our pathological subjects were receiving. But, ADHD and BPD, despite the probable treatment, were more impulsive than healthy CTRLs who did not take medications. CONCLUSIONS: Impulsivity is probably not a feature of BD but is associated with the presence of traumatic childhood experiences, especially for euthymic patients, unlike BPD and ADHD. So, it seems essential to assess the presence of early trauma to reduce the impulsivity and improve the evolution of BD.

Looking for bipolarity in antidepressant discontinuation manic states: Update and diagnostic considerations of the phenomenon.

BACKGROUND: Antidepressant withdrawal manic states are intriguing and under-recognized phenomena. The associated patho-physiological pathways are ill defined and the inclusion of the phenomena in the bipolar spectrum disorders is questionable. This study aims to update a review on antidepressant discontinuation manic states published in 2008 and to look for hints alluding to bipolar disorder in the affected published cases and in the literature. It also reviews the different hypotheses proposed to explain discontinuation mania. METHODS: We searched Pubmed using the key words: 'antidepressant withdrawal' or 'antidepressant discontinuation' plus 'mania' or 'hypomania' from January 2008 until January 2018. RESULTS: Five new eligible reports were identified since the last review in 2008, involving the antidepressants Amitriptyline, Fluoxetine, Escitalopram and Mirtazapine. Hypotheses involve the implication of Catecholamines, Acetylcholine and Serotonin in the pathophysiology of this paradoxical phenomenon. Careful analysis of the total 29 cases revealed psychiatric histories in favor of a bipolar spectrum disorder in 12 individuals while five were already known to have bipolar disorder. LIMITATIONS: This review is based on case reports with associated recall bias, and lack of in-depth description at times. CONCLUSIONS: Antidepressant discontinuation manic or hypomanic states do not occur randomly. An individual susceptibility to bipolar disorder must be considered.

Depressive, anxiety and hypomanic symptoms in schizophrenia may be driven by tryptophan catabolite (TRYCAT) patterning of IgA and IgM responses directed to TRYCATs.

The aim of this study was to delineate the associations between the tryptophan catabolite (TRYCAT) pathway and affective symptoms in schizophrenia. Towards this end we measured immunoglobulin (Ig)A and IgM responses to relatively noxious TRYCATs, namely quinolinic (QA), xanthurenic (XA), picolinic (PA) acid and 3-OH-kynurenine (3HK), and generally protective TRYCATs, namely anthranilic (AA) and kynurenic (KA) acid in 80 patients with schizophrenia and 40 healthy controls. The Hamilton Rating Scale for Depression (HDRS) and anxiety (HAMA), Young Mania Rating Scale (YMRS) as well as the Positive and Negative Symptoms Scale of Schizophrenia (PANSS) were measured. Depression, anxiety and hypomanic as well as negative and positive symptoms were associated with increased IgA responses to PA. Increased IgA responses to XA were associated with anxiety, hypomanic and negative symptoms. Moreover, depressive, anxiety, hypomanic and negative symptoms were characterized by increased IgA responses to the noxious (XA+3HK+QA+PA)/protective (AA+KA) TRYCAT ratio. All symptom dimensions were associated with increased IgM responses to QA, while depressive, anxiety, positive and negative symptoms were accompanied by lowered IgM responses to 3HK. Hypomanic symptoms were additionally accompanied by lowered IgM responses to AA, and negative symptoms by increased IgM responses to KA. In conclusion, both shared and distinct alterations in the activity of the TRYCAT pathway, as well as its regulatory factors and consequences, may underpin affective and classical psychotic symptoms of schizophrenia. Increased mucosa-generated production of noxious TRYCATs, especially PA, and specific changes in IgM-mediated regulatory activities may be associated with the different symptom dimensions of schizophrenia.

Diagnosis and Treatment of Cyclothymia: The "Primacy" of Temperament.

BACKGROUND: Contrary to DSM-5 definition based on recurrence of low grade hypomanic and depressive symptoms, cyclothymia is better defined in a neurodevelopmental perspective as an exaggeration of cyclothymic temperament. Emotional dysregulation with extreme mood instability and reactivity is the core features of the complex symptomatology. METHOD: In the present article, we critically reviewed the literature on the diagnosis and treatment of cyclothymia, focusing on the temperamental and neurodevelopmental perspectives. RESULTS: Current epidemiological and clinical research showed the high prevalence and the validity of cyclothymia as a distinct form of bipolarity, frequently associated with multiple comorbidities with anxiety, impulse control, substance use, and so called "personality" disorders. Many patients receive correct diagnosis and treatments after many years of illness, when the superposition of complications reduces the possibility of complete remission. A therapeutic model combining the focus on symptomatic presentations with a temperamental perspective seems to represent an effective approach for cyclothymic patients with complex clinical presentations. CONCLUSION: Cyclothymic mood instability is an understudied issue despite the evidence of its clinical relevance. Unresolved issues concern its diagnostic delimitation and the possible relationships with emotional dysregulation observed in other neurodevelopmental disorders. We need to confirm the specificity of the disorder and to improve its recognition in early phase of the life, especially in youth. Early recognition means avoiding unnecessary complications and establishing specific treatments and clinical management since the beginning.

High cognitive reserve in bipolar disorders as a moderator of neurocognitive impairment.

BACKGROUND: Cognitive reserve (CR) reflects the capacity of the brain to endure neuropathology, minimize clinical manifestations and successfully complete cognitive tasks. The present study aims to determine whether high CR may constitute a moderator of cognitive functioning in bipolar disorder (BD). METHODS: 102 patients with BD and 32 healthy controls were enrolled. All patients met DSM-IV criteria for I or II BD and were euthymic (YMRS≤6 and HDRS≤8) during a 6-month period. All participants were tested with a comprehensive neuropsychological battery, and a Cerebral Reserve Score (CRS) was estimated. Subjects with a CRS below the group median were classified as having low CR, whereas participants with a CRS above the median value were considered to have high CR. RESULTS: Participants with BD with high CR displayed a better performance in measures of attention (digits forward: F=4.554, p=0.039); phonemic and semantic verbal fluency (FAS: F=9.328, p=0.004; and Animal Naming: F=8.532, p=0.006); and verbal memory (short cued recall of California Verbal Learning Test: F=4.236, p=0.046), after multivariable adjustment for potential confounders, including number of admissions and prior psychotic symptoms. LIMITATIONS: The cross-sectional design of the study does not allow the establishment of causal inferences. Additionally, the small size of the sample may have limited some results. CONCLUSIONS: High cognitive reserve may therefore be a valuable construct to explore for predicting neurocognitive performance in patients with BD regarding premorbid status.

Affective temperaments and emotional traits are associated with a positive screening for premenstrual dysphoric disorder.

OBJECTIVES: Preliminary evidence indicates that premenstrual dysphoric disorder (PMDD) may be frequently co-morbid with bipolar spectrum disorders. In addition, the manifestations of PMDD seem similar to a subthreshold depressive mixed state. Nevertheless, the associations between PMDD and affective temperaments and emotional traits have not been previously investigated. METHODS: A consecutive sample of 514 drug-free Brazilian women (mean age: 22.8; SD=5.4years) took part in this cross-sectional study. Screening for PMDD was obtained with the validated Brazilian Portuguese version of the Premenstrual Symptoms Screening Tool (PSST). Affective temperaments and emotional dimensions were evaluated with the Affective and Emotional Composite Temperament Scale (AFECTS). In addition, socio-demographic and data on menstrual cycle were collected. RESULTS: According to the PSST, 83 (16.1%) women screened positive for PMDD, while 216 (42.0%) women had no/mild premenstrual symptoms. The cyclothymic temperament was independently associated with PMDD (OR=4.57; 95% CI: 2.11-9.90), while the euthymic temperament had an independent association with a lower likelihood of a positive screening for PMDD (OR=0.28; 95% CI: 0.12-0.64). In addition, anger and sensitivity emerged as emotional dimensions significantly associated with PMDD. CONCLUSIONS: A positive screening for PMDD was associated with a predominant cyclothymic temperament, while an euthymic temperament was associated with a lower likelihood for a positive screening for PMDD. These data deserve replication in prospective studies.

Linear and non-linear analyses of Conner's Continuous Performance Test-II discriminate adult patients with attention deficit hyperactivity disorder from patients with mood and anxiety disorders.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a heterogeneous disorder. Therefore it is important to look for factors that can contribute to better diagnosis and classification of these patients. The aims of the study were to characterize adult psychiatric out-patients with a mixture of mood, anxiety and attentional problems using an objective neuropsychological test of attention combined with an assessment of mood instability. METHOD: Newly referred patients (n = 99; aged 18-65 years) requiring diagnostic evaluation of ADHD, mood or anxiety disorders were recruited, and were given a comprehensive diagnostic evaluation including the self-report form of the cyclothymic temperament scale and Conner's Continuous Performance Test II (CPT-II). In addition to the traditional measures from this test we have extracted raw data and analysed time series using linear and non-linear mathematical methods. RESULTS: Fifty patients fulfilled criteria for ADHD, while 49 did not, and were given other psychiatric diagnoses (clinical controls). When compared to the clinical controls the ADHD patients had more omission and commission errors, and higher reaction time variability. Analyses of response times showed higher values for skewness in the ADHD patients, and lower values for sample entropy and symbolic dynamics. Among the ADHD patients 59 % fulfilled criteria for a cyclothymic temperament, and this group had higher reaction time variability and lower scores on complexity than the group without this temperament. CONCLUSION: The CPT-II is a useful instrument in the assessment of ADHD in adult patients. Additional information from this test was obtained by analyzing response times using linear and non-linear methods, and this showed that ADHD patients with a cyclothymic temperament were different from those without this temperament.

Effect of early trauma on the sleep quality of euthymic bipolar patients.

OBJECTIVE: Poor quality of sleep is frequent in euthymic bipolar patients and conveys worse clinical outcomes. We investigated the features of euthymic bipolar patients associated with poor sleep quality, with a focus on the effect of childhood trauma. METHOD: 493 euthymic patients with DSM-IV-defined bipolar disorders were recruited in FondaMental Advanced Centers of Expertize for Bipolar Disorders (FACE-BD) between 2009 and 2014. Clinical variables were recorded. Subjective sleep quality and history of childhood trauma were respectively measured by the Pittsburgh Sleep Quality Index (PSQI) and the Childhood Trauma Questionnaire (CTQ). RESULTS: Poor sleepers were older, less professionally active, had significantly higher anxiety levels, took more anxiolytic drugs and did endorse more suicide attempts and suicidal ideas than good sleepers after adjusting for anxiety levels and age. Emotional abuse was associated with poor sleep quality after adjustment for BMI, age, professional activity, and bipolar disorders (BD) type (OR=1.83; 95% CI [1.30; 3.10]; p=0.02). However, this association was lost after adjustment for anxiety levels, anxiolytic treatment and suicide ideation/attempts. LIMITATIONS: The main limitation was the type of sleep assessment, which only measured the subjective part of sleep complaints. CONCLUSION: A history of emotional abuse might underlie sleep problems in many bipolar patients but anxiety seems to act as a confounding factor in this relationship. New studies are needed to elucidate the role of childhood maltreatment on poor sleep among bipolar patients.

Mood and motor activity in euthymic bipolar disorder with sleep disturbance.

BACKGROUND: The 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. METHODS: 43 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. RESULTS: Patients 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). LIMITATIONS: A relatively small study sample and a 1-week study period prevent exploration of long-term clinical implications of results. CONCLUSIONS: A 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.

Are manic symptoms that 'dip' into depression the essence of mixed features?

BACKGROUND: Three symptoms of (hypo)mania that clinically represent mood disorders mixed states have been omitted from the DSM-5 mixed features specifier because 'they fail to discriminate between manic and depressive syndromes'. Therefore, the present study examined the role of distractibility, irritability and psychomotor agitation (DIP) in characterising mixed depressive states. METHODS: Fifty in-patients at a specialist mood disorders unit underwent a detailed longitudinal clinical evaluation (3-6 weeks) and were assessed on a range of standardized measures to characterise their illness according to depression subtype, duration of illness and clinical features-including specifically depressive and manic symptoms and the context in which these occur. RESULTS: 49 patients met criteria for major depressive episode, and of these, 34 experienced at least one dip symptom. Patients who endorsed distractibility were more likely to be diagnosed with Bipolar Disorder than Major Depressive Disorder; patients who endorsed irritable mood were more likely to have non-melancholic depression (admixture of depressive and anxiety symptoms), and patients who reported psychomotor agitation experienced a significantly greater number of distinct periods of (hypo)manic symptoms compared with those who did not. LIMITATIONS: The present study used a modest sample size and did not control for medication or comorbid illness. Although this is inevitable when examining real-world patients in a naturalistic setting, future research needs to allow for comorbidity and its impact, specifically anxiety. CONCLUSIONS: The present findings suggest that all 3 symptoms that have been excluded from DSM-5 may be cardinal features of mixed states, as they 'dip' into depressive symptoms to create a mixed state.

Adherence to medication is associated with non-planning impulsivity in euthymic bipolar disorder patients.

BACKGROUND: Adherence to medication is a major issue in bipolar disorder. Non-planning impulsivity, defined as a lack of future orientation, has been demonstrated to be the main impulsivity domain altered during euthymia in bipolar disorder patients. It was associated with comorbidities. METHODS: To investigate relationship between adherence to medication and non-planning impulsivity, we included 260 euthymic bipolar patients. Adherence to medication was evaluated by Medication Adherence Rating Scale and non-planning impulsivity by Barrat Impulsiveness Scale. Univariate analyses and linear regression were used. We conducted also a path analysis to examine whether non-planning impulsivity had direct or indirect effect on adherence, mediated by comorbidities. RESULTS: Adherence to medication was correlated with non-planning impulsivity, even after controlling for potential confounding factors in linear regression analysis (Beta standardized coefficient = 0.156; p = 0.015). Path analysis demonstrated only a direct effect of non-planning impulsivity on adherence to medication, and none indirect effect via substance use disorders and anxiety disorders. LIMITATIONS: Our study is limited by its cross-sectional design and adherence to medication was assessed only by self-questionnaire. CONCLUSIONS: Higher non-planning impulsivity is associated with low medication adherence, without an indirect effect via comorbidities.

Bipolar disorders following initial depression: modeling predictive clinical factors.

OBJECTIVE: Most first lifetime episodes among persons eventually diagnosed with bipolar disorder are depressive, often with years of delay to a final differentiation from unipolar major depression. To support early differentiation, we tested several predictive factors for association with later diagnoses of bipolar disorder. METHOD: With data from mood-disorder patients with first-lifetime episodes of major depression, we used multivariate, logistic modeling and Bayesian methods including Receiver Operating Characteristic curves to evaluate ability of one or more selected factors to differentiate patients who later met DSM-IV-TR diagnostic criteria for bipolar disorder and not unipolar major depressive disorder. RESULTS: We analyzed data from 2146 patients (642 bipolar, 1504 unipolar) at risk for 13 years following initial depressive episodes. In multivariate modeling for 812 subjects with information on all clinical factors considered, seven significantly and independently differentiated bipolar from unipolar disorders, ranking (by significance): (a) ≥4 previous depressive episodes, (b) suicidal acts, (c) cyclothymic temperament, (d) family history of bipolar disorder, (e) substance-abuse, (f) younger-at-onset, or onset-age <25, and (g) male sex; four of these (c, d, f, g) can be identified at illness-onset. Bayesian analysis indicated optimal sensitivity and specificity at 2-4 factors/person and correct classification of 64-67% of cases, and ROC analysis of factors/person yielded a significant area-under-the-curve of 0.72 [CI: 0.68-0.75]. CONCLUSIONS: In multivariate modeling, 7 factors were significantly and independently associated with bipolar disorder diagnosed up to 13 years after initial depression.