Improved functioning following computerized working memory training (COGMED®) in euthymic patients with bipolar disorder and cognitive complaints: An exploratory study.

BACKGROUND: Patients with bipolar disorder (BD) frequently have cognitive deficits even when euthymic. These deficits are considered one of the main drivers of functional disability in BD. This study investigated whether computerized working memory training using the COGMED® program in patients with BD can improve global functioning, therapeutic compliance, and subjective quality of life. METHODS: For this naturalistic prospective study, 40 patients with BD and cognitive complaints were recruited. Sociodemographic, clinical, neurocognitive and functional data were collected before starting the remediation intervention (baseline). At home, patients used the web-based working memory training program COGMED® that included a battery of interactive games (daily sessions, five days per week for five weeks), supported by weekly phone-based feedback. The clinical, neurocognitive and functional assessment was repeated four weeks after the intervention end and compared with the baseline data. RESULTS: Thirty-two patients completed the study. Compared with baseline, general functioning was improved after the working memory training program, as indicated by a mean reduction of 6.78 (SD 4.65) points in the Functioning Assessment Short Test (p<0.001). This result remained significant after controlling for depressive symptomatology improvement. Similarly, the scores of neuropsychological tests for cognitive complaints, as well as verbal and visuospatial working memory components were significantly different before and after the intervention (p<0.05). Conversely, the subjective quality of life and therapeutic compliance did not change. LIMITATIONS: The naturalistic open-label, non-controlled design of this study precludes the conclusion regarding causality. CONCLUSIONS: In patients with BD, global functioning is improved by computerized working memory remediation.

Use of a serious game to strengthen medication adherence in euthymic patients with bipolar disorder following a psychoeducational programme: A randomized controlled trial.

BACKGROUND: Although psychoeducation programmes are the gold-standard intervention in bipolar disorder (BD), more innovative tools are needed to broaden and consolidate their effects, especially on treatment adherence. Serious games could be an option. METHODS: We carried out a two-arm open randomized controlled trial to compare the add-on use of the serious game BIPOLIFE® for one month (n = 20) vs. treatment as usual (TAU; n = 21) following the completion of a psychoeducation programme in euthymic adults with BD. The primary outcome was the percentage of adherent patients (i.e., patients with a Medication Adherence Rating Scale, MARS, total score >7) at 4 months after the end of the psychoeducation programme. We also measured the changes in therapeutic adherence and beliefs on pharmacological treatments (Drug Attitude Inventory, DAI) between study inclusion and the 1-month (end of BIPOLIFE® use) and 4-month visits, healthcare use during the study period, and BIPOLIFE® acceptability. RESULTS: The percentage of adherent patients was lower in the BIPOLIFE® group than in the TAU group at inclusion (p = 0.02). Conversely, the absolute variation of the MARS and DAI scores was higher in the BIPOLIFE® than in the TAU group at the 1-month visit (p = 0.03 and p = 0.002, respectively) but not at the 4-month visit (p = 0.22 and p = 0.07, respectively). LIMITATIONS: Small sample size, and low frequency of connexion to BIPOLIFE® declared by the patients. CONCLUSION: BIPOLIFE® may help patients with BD to increase their confidence in medications, if used regularly.

Hypnotic susceptibility and affective states in bipolar I and II disorders.

BACKGROUND: Highly hypnotizable individuals have impaired executive function, elevated motor impulsivity and increased emotional sensitivity, which are sometimes found in bipolar disorder patients. It is then reasonable to assume that certain aspects of hypnotic susceptibility differ with the types of bipolar disorder. METHODS: The Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) test, the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32) and the Plutchick-van Praag Depression Inventory (PVP) were applied to 62 patients with bipolar I disorder, 33 bipolar II disorder, and 120 healthy volunteers. RESULTS: The passing rate of the SHSS:C 'Moving hands apart' item was higher in bipolar I patients than in controls, whereas for 'Mosquito hallucination' the rate was lower. Bipolar I and II patients scored significantly higher on MDQ, HCL-32 and PVP scales than controls. The passing rates of 'Mosquito hallucination' in controls, 'Arm rigidity' in bipolar I, and 'Age regression' in bipolar II predicted the respective MDQ scores. CONCLUSION: In contrast to cognitive suggestions, bipolar I patients followed motor suggestions more often under hypnosis. Furthermore, both bipolar disorder patients and healthy volunteers demonstrated associations between mania levels and certain hypnotic susceptibility features. Our study aids in better understanding the altered conscious states in bipolar disorders, and encourages the use of related psychotherapy for these patients.

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.

A Randomized Controlled Trial of Individual Family Psychoeducational Psychotherapy and Omega-3 Fatty Acids in Youth with Subsyndromal Bipolar Disorder.

OBJECTIVE: This pilot study evaluates efficacy of omega-3 fatty acid supplementation (Ω3), individual family psychoeducational psychotherapy (IF-PEP), and their combination in youth with subsyndromal bipolar disorders (bipolar disorder not otherwise specified [BP-NOS], cyclothymic disorder [CYC]). METHODS: This study was a 12 week, randomized trial of Ω3 versus placebo and IF-PEP versus active monitoring (AM) using a 2 × 2 design (Ω3 + PEP: n = 5; Ω3 + AM: n = 5; placebo + PEP: n = 7; placebo + AM: n = 6). Twenty-three youth ages 7-14 with BP-NOS or CYC were recruited via community advertisements and clinician referrals. Participants could be taking stable medication for attention-deficit/hyperactivity disorder and sleep aids, but no other psychotropics. Independent evaluators assessed participants at screen, baseline, and 2, 4, 6, 9, and 12 weeks. Primary outcome measures were the Kiddie Schedule for Affective Disorders (K-SADS) Depression (KDRS) and Mania (KMRS) Rating Scales, Children's Depression Rating Scale-Revised (CDRS-R), and Young Mania Rating Scale (YMRS). Ω3/placebo conditions were double-blind; independent evaluators were blind to psychotherapy condition. RESULTS: Most participants (83%) completed the 12 week trial. Side effects were uncommon and mild. Intent-to-treat analyses indicated significant improvement in depressive symptoms (KDRS) for combined treatment relative to placebo and AM (p = 0.01, d = 1.70). Across groups, manic symptoms improved over time without significant treatment effects. Effect of IF-PEP on child depression compared with AM was medium (d = 0.63, CDRS-R) to large (d = 1.24, KDRS). Effect of Ω3 on depression was medium (d = 0.48, KDRS). CONCLUSION: IF-PEP and Ω3 are well tolerated and associated with improved mood symptoms among youth with BP-NOS and CYC. Clinicaltrials.gov Identifier: NCT01507753.

Mixed states in DSM-5: implications for clinical care, education, and research.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) nomenclature for the co-occurrence of manic and depressive symptoms (mixed states) has been revised in the new DSM-5 version to accommodate a mixed categorical-dimensional concept. The new classification will capture subthreshold non-overlapping symptoms of the opposite pole using a "with mixed features" specifier to be applied to manic episodes in bipolar disorder I (BD I), hypomanic, and major depressive episodes experienced in BD I, BD II, bipolar disorder not otherwise specified, and major depressive disorder. The revision will have a substantial impact in several fields: epidemiology, diagnosis, treatment, research, education, and regulations. The new concept is data-driven and overcomes the problems derived from the extremely narrow definition in the DSM-IV-TR. However, it is unclear how clinicians will deal with the possibility of diagnosing major depression with mixed features and how this may impact the bipolar-unipolar dichotomy and diagnostic reliability. Clinical trials may also need to address treatment effects according to the presence or absence of mixed features. The medications that are effective in treating mixed episodes per the DSM-IV-TR definition may also be effective in treating mixed features per the DSM-5, but new studies are needed to demonstrate it.

The significance of at-risk or prodromal symptoms for bipolar I disorder in children and adolescents.

While in the early identification and intervention of psychosis-specific instruments and risk criteria have been generated and validated, research into indicated preventive strategies for bipolar I disorder (BD I) has only recently gained momentum. As the first signs of BD I often start before adulthood, such efforts are especially important in the vulnerable pediatric population. Data are summarized regarding the presence and nature of potentially prodromal, that is, subsyndromal, symptoms prior to BD I, defined by first-episode mania, focusing on pediatric patients. Research indicates the possibility of early identification of youth at clinical high risk for BD. Support for this proposition comes from retrospective studies of BD I patients, as well as prospective studies of community samples, offspring of BD I subjects, youth with depressive disorders, and patients at high risk for psychosis or with bipolar spectrum disorders without lifetime history of mania. These data provide essential insight into potential signs and symptoms that may enable presyndromal identification of BD I in youth. However, except for offspring studies, broader prospective approaches that focus on youth at clinical high risk for BD I and on developing specific interviews and (or) rating scales and risk criteria are mostly missing, or in their early stage. More work is needed to determine valid and sufficiently specific clinical high-risk criteria, to distinguish risk factors, endophenotypes, and comorbidities from prodromal symptomatology, and to develop phase-specific interventions that titrate the risk of intervention to the risk of transition to mania and to functional impairment or distress. Moreover, studies are needed that determine potential differences in prodromal symptoms and trajectories between children, adolescents, and adults, and the best phase-specific interventions.

Cognitive behavioural therapy for cyclothymia: cognitive regulatory control as a mediator of mood change.

BACKGROUND: Regulatory control of cognition is implicated in the amplification of mood variability in cyclothymia. AIMS: This study examined whether cognitive behavioural therapy (CBT) directed at enhanced awareness and mood change could change global functioning, mood variability and regulatory control. METHOD: Using a prospective single case experimental design, mood and cognitive control ratings were recorded every 4 hours for 51 weeks by a patient diagnosed with cyclothymia, including a 5-week baseline, a 35-week (19 session) CBT intervention period and an 11-week follow-up period. RESULTS: Findings indicated that the patient experienced reduced mood variability and greater regulatory control, became happier and less anxious but felt less energetic. Following CBT, high energy became negatively associated with positive mood, and this change was mediated by an increase in control over thoughts. CONCLUSIONS: The results suggest that CBT directed at cognitive control and mindfulness skills may help in the treatment of cyclothymia.

[Temperamental endophenotypes]. / Les endophénotypes tempéramentaux.

Temperament has been defined as the heritable biologically determined core of personality that remains stable throughout the life span and establishes the baseline level of reactivity, mood, and energy of a person. If the link between temperament and mental disorder goes back to the Greco-Roman medicine, Kraepelin was among the first authors to pay attention to the temperamental bases of bipolar disorder. He proposed four temperamental types that he described in the premorbid histories of the majority of manic-depressive patients, and found overrepresented in the biologic relatives of these patients. Building on this ancestry, Akiskal formulated the modern concept of affective temperament, and described five temperaments: depressive, hyperthymic, cyclothymic, irritable, and anxious. According to Akiskal's model, bipolar disorder lies along a continuum from temperament to full-blown episodes of affective illness. A series of recent studies have shown the role played by temperaments in the outbreak of bipolar episodes, their clinical presentation, as well as the illness course and comorbidities. Furthermore modern familial and genetic studies have confirmed the first observations of Kraepelin. It has been recently proposed that affective temperaments may carry distinct evolutionary advantages on the individual or a group level, so that affective disorders would be genetic reservoirs for adaptative temperaments and the price to be paid for the chance of exceptionality. Apart from these theoretical perspectives, paying attention to temperamental components may have important implications for the treatment of bipolar disorder. Finally recent studies confirmed as well, that the concept of affective temperament fulfilled the criteria required to be considered as an endophenotype.

[Mixed states]. / États mixtes.

The issue of mixed states has an important place in the debate on psychiatric nosography since the end of 19th century. The current definition of mixed states according to the DSM- IV, as a thymic episode of bipolar disorder type I, is probably somewhat too restrictive in clinical practice. Due to the clinical heterogeneity of bipolar disorder, the mixed states will define within a dimensional approach, likely in the next DSM- V. As the evolution, the prognosis or the therapeutic strategies differ from what is applied in other thymic episodes, this transition from "mixed state" to manic or depressive episodes "with mixed features" may be relevant in practice.

The sequential combination of cognitive behavioral treatment and well-being therapy in cyclothymic disorder.

BACKGROUND: There is a lack of controlled studies of psychological treatment of cyclothymic disorder. The aim of this investigation was to examine the benefits of the sequential combination of cognitive behavioral therapy (CBT) and well-being therapy (WBT) compared to clinical management (CM) in DSM-IV cyclothymic disorder. METHODS: Sixty-two patients with DSM-IV cyclothymic disorder were randomly assigned to CBT/WBT (n = 31) or CM (n = 31). Both CBT/WBT and CM consisted of ten 45-min sessions every other week. An independent blind evaluator assessed the patients before treatment, after therapy, and at 1- and 2-year follow-ups. The outcomes included total score of the change version of the Clinical Interview for Depression, and the Mania Scale. All analyses were performed on an intent-to-treat basis. RESULTS: Significant differences were found in all outcome measures, with greater improvements after treatment in the CBT/WBT group compared to the CM group. Therapeutic gains were maintained at 1- and 2-year follow-ups. CONCLUSIONS: A sequential combination of CBT and WBT, which addresses both polarities of mood swings and comorbid anxiety, was found to yield significant and persistent benefits in cyclothymic disorder.

The induction of noninterpreted benevolent transference as a vehicle for change.

It has become widely accepted that nontransference interpretation can have power (Blum, 1983). My intent in this paper is to describe an active, intentionally evoked, but uninterpreted, positive transference that is designed to effect change in the patient in an otherwise psychoanalytically oriented therapy. The changes may range from symptom relief to more significant change, as reflected in modifications in the patient's self-perception, perception of others (self-object constellations), and experience in the world. Apart from interpretation of conflict revealed in the patient's experience of the world, the uninterpreted positive transference offers a new object relationship devoid of significant conflict that may closely approximate an ideal of the good parent (the internalization of a good object). In this respect, it contributes strongly to a change in the representational world. The positive transference is not only the substrate of the ongoing process of therapy, but also a useful product of the process. To implement this change the therapist develops a therapeutic stance through specific actions and an attitude that offers the patient a new and benevolent object.

[Evaluation of affective temperaments in the postpartum depressive symptomatology]. / Evaluation des tempéraments affectifs dans la symptomatologie dépressive du post-partum.

INTRODUCTION: Postpartum depression (PPD) is a frequent psychiatric condition, but little is known about its potential bipolar nature and the implication of affective temperaments. The goal of this study is to estimate the prevalence of PPD and assess the affective temperamental profile of those affected. METHOD: The study was conducted in the department of gynecology and obstetrics of the CHU of Sfax, Tunisia. The selected population included all 213 consecutive admissions (mean age=29 years). Postpartum depressive symptomatology (SPPD) was assessed during the first week after delivery by using the Postnatal Edinburgh Scale Depression (EPDS) in its Arab version. The Arabic version of the Temperaments Auto-questionnaire of Memphis, Pisa, Paris, and San Diego (TEMPS-A) was simultaneously filled out by subjects. The subjects were divided into two subgroups, depressed (D+) versus not depressed (D-), for comparative analyses. For affective temperaments, dimensional (mean scores) and categorical (quartiles) approaches were used. RESULTS: Forty-one women (19,2%) had a score higher than 9 on the EPDS (group D+). Lower educational level, lower social and family support, dysfunctional marital relationship, problems with accepting the pregnancy and prior psychiatric disorders were significantly more present in the D+ group. The majority of the affective temperaments, excepting hyperthymic, were correlated between them. The EPDS scores were correlated with all temperamental scores, except for hyperthymic. Higher scores on the depressive, irritable, anxious and cyclothymic temperaments were observed in the group D+. Women belonging to the 3rd and 4th quartiles of the depressive, cyclothymic and irritable temperaments and those belonging to the 4th quartile of the anxious temperament were significantly more depressed. Cyclothymic and depressive temperaments seemed to influence the pregnancy acceptance. Other interactions were observed between SPPD, temperamental profiles and quality of marital relation, and family support. The opposite seems true for the hyperthymic temperament, which could be protective against SPPD through better psychosocial conditions. Multivariate regression analysis showed that cyclothymic and anxious temperaments are significant risk factors independently from psychosocial factors, such as problems with accepting the pregnancy, which seemed to be the most important risk factor. CONCLUSION: PPD represents a frequent disorder, which needs to be correctly screened and recognized especially with its temperamental attributes, a mixture of anxious, irritable, depressive and cyclothymic traits. This complex unstable temperament should be considered as a predisposing factor, which interacts also with other common risk factors.

Mindfulness-based cognitive therapy for bipolar disorder: a feasibility trial.

BACKGROUND: The present open study investigates the feasibility of Mindfulness-based cognitive therapy (MBCT) in groups solely composed of bipolar patients of various subtypes. MBCT has been mostly evaluated with remitted unipolar depressed patients and little is known about this treatment in bipolar disorder. METHODS: Bipolar outpatients (type I, II and NOS) were included and evaluated for depressive and hypomanic symptoms, as well as mindfulness skills before and after MBCT. Patients' expectations before the program, perceived benefit after completion and frequency of mindfulness practice were also recorded. RESULTS: Of 23 included patients, 15 attended at least four MBCT sessions. Most participants reported having durably, moderately to very much benefited from the program, although mindfulness practice decreased over time. Whereas no significant increase of mindfulness skills was detected during the trial, change of mindfulness skills was significantly associated with change of depressive symptoms between pre- and post-MBCT assessments. CONCLUSIONS: MBCT is feasible and well perceived among bipolar patients. Larger and randomized controlled studies are required to further evaluate its efficacy, in particular regarding depressive and (hypo)manic relapse prevention. The mediating role of mindfulness on clinical outcome needs further examination and efforts should be provided to enhance the persistence of meditation practice with time.

Rapid cycling bipolar disorders in primary and tertiary care treated patients.

OBJECTIVE: Rapid cycling (RC) affects 13-30% of bipolar patients. Most of the data regarding RC have been obtained in tertiary care research centers. Generalizability of these findings to primary care populations is thus questionable. We examined clinical and demographic factors associated with RC in both primary and tertiary care treated populations. METHOD: Clinical data were obtained by interview from 240 bipolar I disorder (BDI) or bipolar II disorder (BDII) community-treated patients and by chart reviews from 119 bipolar patients treated at an outpatient clinic of a teaching hospital. RESULTS: Lifetime history of rapid cycling was present in 33.3% and 26.9% of patients from the primary and tertiary care samples, respectively. Among community-treated patients, lifetime history of RC was significantly associated with history of suicidal behavior and higher body mass index. There was a trend for association between RC and BDII, psychiatric comorbidity, diabetes mellitus, as well as lower age of onset of mania/hypomania. In the tertiary care treated sample there was a trend for association between lifetime history of RC and suicidal behavior. Tertiary versus primary care treated subjects with lifetime history of RC demonstrated markedly lower response to mood stabilizers. CONCLUSIONS: Lifetime history of RC is highly prevalent in both primary and tertiary settings. Even primary care treated subjects with lifetime history of RC seem to suffer from a more complicated and less treatment-responsive variant of bipolar disorder. Our findings further suggest relatively good generalizability of data from tertiary to primary care settings.