Factors associated with poor functional outcome in bipolar disorder: sociodemographic, clinical, and neurocognitive variables.

OBJECTIVE: The current investigation aimed at studying the sociodemographic, clinical, and neuropsychological variables related to functional outcome in a sample of euthymic patients with bipolar disorder(BD) presenting moderate-severe levels of functional impairment. METHODS: Two-hundred and thirty-nine participants with BD disorders and with Functioning Assessment Short Test(FAST) scores equal or above 18 were administered a clinical and diagnostic interview, and the administration of mood measure scales and a comprehensive neuropsychological battery. Analyses involved preliminary Pearson bivariate correlations to identify sociodemographic and clinical variables associated with the FAST total score. Regarding neuropsychological variables, a principal component analysis (PCA) was performed to group the variables in orthogonal factors. Finally, a hierarchical multiple regression was run. RESULTS: The best fitting model for the variables associated with functioning was a linear combination of gender, age, estimated IQ, Hamilton Depression Rating Scale (HAM-D), number of previous manic episodes, Factor 1 and Factor 2 extracted from the PCA. The model, including all these previous variables, explained up to 29.4% of the observed variance. CONCLUSIONS: Male gender, older age, lower premorbid IQ, subdepressive symptoms, higher number of manic episodes, and lower performance in verbal memory, working memory, verbal fluency, and processing speed were associated with lower functioning in patients with BD.

Clinical implications of predominant polarity and the polarity index in bipolar disorder: a naturalistic study.

OBJECTIVE: Predominant polarity (PP) is an important variable in maintenance treatment of bipolar disorder (BD). This study aimed at determining the role of polarity index (PI), a metric indicating antimanic versus antidepressive prophylactic potential of drugs, in clinical decision-making. METHOD: Two hundred and fifty-seven of 604 (43%) of patients with BD-I or II fulfilled criteria for manic (MPP) or depressive PP (DPP). The PI, representing the ratio of number needed to treat (NNT) for depression prevention to NNT for mania prevention, was calculated for patients' current treatment. MPP and DPP groups were compared regarding sociodemographic, clinical and therapeutic characteristics. RESULTS: One hundred and forty-three patients (55.6%) fulfilled criteria for DPP and 114 (44.4%) for MPP. Total PI, Antipsychotics' PI, and mood stabilizers PI were higher, indicating a stronger antimanic action, in MPP. MPP presented higher prevalence of BD-I, male gender, younger age, age at onset and at first hospitalization, more hospitalizations, primary substance misuse, and psychotic symptoms. DP correlated with BD-II, depressive onset, primary life events, melancholia, and suicide attempts. CONCLUSION: The results confirm the usefulness of the PI. In this large sample, clinical differences among these groups justify differential treatment approach. The PI appears to be a useful operationalization of what clinicians do for maintenance therapy in BD.

The impact of repeated manic episodes and executive dysfunction on work adjustment in bipolar disorder.

The aim of this study was to study the clinical and neurocognitive variables that best explain poor work adjustment in a sample of bipolar I euthymic patients. Eighty-five euthymic patients at the Hospital Clinic of Barcelona were assessed for this study by means of a comprehensive neuropsychological battery and a work-focused interview to determine work adjustment. Clinical and sociodemographic variables were also collected. Direct logistic regression was performed to assess the impact of demographic, clinical and neuropsychological variables on the likelihood of presenting poor work adjustment. The model that best fitted contained five variables (Hamilton Depression Rating scores, number of manic episodes, number of perseverative errors in the Wisconsin Card Sorting Test (WCST), number of depressive episodes and Trail Making Test-part B). However, only two out of these variables made a unique statistically significant contribution to the model, which were number of manic episodes (OR 1.401; CI 1.05-1.86; p = 0.021) and number of perseverative errors in the WCST (OR 1.062; CI 1.00-1.12; p = 0.044). The model explained up to 36 % of the variance in work adjustment. This study highlights the role of manic relapses and neurocognitive impairment, specifically the role of executive function, in work adjustment.

Factors associated with the discrepancy between objective and subjective cognitive impairment in bipolar disorder.

OBJECTIVE: The aim of this study is to evaluate the discrepancy between objective cognitive measures and cognitive subjective complaints in a sample of euthymic patients with bipolar disorder (BD). METHODS: One hundred and sixteen participants (83 euthymic patients with BD and 33 healthy controls) were enrolled for this study. Patients were assessed with a comprehensive neuropsychological battery and they also reported their subjective cognitive complaints with the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA). The discrepancy between objective and subjective data was calculated using a novel methodology proposed in a previous study (Miskowiak, 2016). Statistical analyses included Pearson correlations and multiple linear regression. RESULTS: Higher number of previous depressive episodes was identified as one variable associated with the global sensitivity composite score (Beta = 0.25; t = 2.1; p = 0.04) and with the verbal learning and memory sensitivity score (Beta = 0.26; t = 2.16; p = 0.03). That is, patients with more previous depressive episodes tend to over-report cognitive complaints. In contrast, higher number of previous hospitalizations was associated with stoicism in the global total score (Beta = -0.27; t = -2.24: p = 0.029) and in the domain of attention/processing speed (Beta = -0.34; t = -2.52; p = 0.016), indicating patients with more hospitalizations tend to report less cognitive complaints. DISCUSSION: Our study identified some factors that might help to explain the discrepancy between objective and subjective cognitive measures in BD, including number of previous depressive episodes and number of previous hospitalizations. This highlights the need of the combined use of both types of cognitive measures to make an accurate assessment of cognitive dysfunctions and their effective treatment.

An event-based adaptation of the relay feedback experiment for frequency response identification of stable processes.

An event-based modification of the classical relay feedback experiment without the inclusion of additional elements (integrator, time delay, …) for identification of the spectrum of stable processes between zero and the phase cross-over frequency is presented. By inserting an event-based sampler in the control loop, the natural behaviour of a classical relay is simulated and the system is forced to work in two modes. The event-based sampler activates the first mode by sending control actions to the process every time the error signal crosses zero; this mode is to discover the approximated value of the cross-over frequency [Formula: see text] . During the second mode, the event-based sampler sends samples to the process simulating that the error signal crosses zero at [Formula: see text] where N is the number of points to identify in the range [Formula: see text] . One advantage of this procedure is that the logic used in an already existing relay feedback experiment to fit a transfer function model or tune a controller could be maintained just replacing the relay block by the event-based sampler block presented in the paper. Simulations and experiments with different processes and in presence of noise demonstrate the effectivity of the procedure.

Are bipolar II patients cognitively impaired? A systematic review.

BACKGROUND: There is evidence that bipolar disorder (BD) is associated with significant neurocognitive deficits and this occurs in individuals with BD type I (BD I) and with BD type II (BD II). Only a few studies have focused on cognitive impairment in BD II. The aim of this study was to describe the pattern of cognitive impairment in patients with BD II, in order to identify specific cognitive deficits that distinguish BD II from BD I patients as well as from healthy subjects. METHOD: We performed a systematic review of the literature of neuropsychological studies of BD II published between 1980 and July 2009. Fourteen articles fulfilled the inclusion criteria and were included in this review. RESULTS: Main cognitive deficits found in BD II include working memory and some measures of executive functions (inhibitory control) and approximately half of the studies also detected verbal memory impairment. CONCLUSIONS: There are subtle differences between the two subtypes regarding cognition. This may suggest neurobiological differences between the two subgroups which will be helpful in order to determine cognitive endophenotypes in BD subtypes.

[Bipolar disorder, cognitive functioning and hypothalamic-pituitary-thyroid axis]. / Trastorno bipolar, funciones cognitivas y eje hipotalámico-pituitario-tiroideo.

In psychoneuroendocrinology there's a scarcity of knowledge of hypothalamic-pituitary-thyroid axis (HPT) in relation to bipolar disorder (BD) and neuropsychological functions. The aim of this study is to review the current state of the following issues: (1) neuropsychological dysfunctions in BD, as well as their hypothetic aetiology; (2) response of HPT in each phase of BD, and, finally, (3) connection between alterations in HPT and neuropsychological deficits.

Group psychoeducation for stabilised bipolar disorders: 5-year outcome of a randomised clinical trial.

BACKGROUND: The long-term efficacy of psychological interventions for bipolar disorders has not been tested. AIMS: This study assessed the efficacy of group psychoeducation to prevent recurrences and to reduce time spent ill for people with bipolar disorders. METHOD: A randomised controlled trial with masked outcome assessment comparing group psychoeducation and non-structured group intervention during 5-year follow-up. One hundred and twenty people with bipolar disorders were included in the study and 99 completed 5-year follow-up. Time to any recurrence, number of recurrences, total number of days spent ill, frequency and length of hospitalisations were the main outcome measures. RESULTS: At the 5-year follow-up, time to any recurrence was longer for the psychoeducation group (log rank=9.953, P<0.002). The psychoeducation group had fewer recurrences (3.86 v. 8.37, F=23.6, P<0.0001) of any type and they spent less time acutely ill (154 v. 586 days, F=31.66, P=0.0001). The median number of days of hospitalisation per hospitalised participant was also lower for the psychoeducation group (45 v. 30, F=4.26, P=0.047). CONCLUSIONS: Six-month group psychoeducation has long-lasting prophylactic effects in individuals with bipolar disorders. Group psychoeducation is the first psychological intervention showing such a long-term maintained efficacy in people with bipolar disorders.

Functioning and disability in bipolar disorder: an extensive review.

BACKGROUND: Bipolar disorder has generally been regarded as having a better functional outcome than schizophrenia. However, studies have suggested low functioning in bipolar patients even when they are in clinical remission. Our aim was to determine the degree of functioning and disability in bipolar patients. Secondly, we reviewed factors potentially associated with the low functioning of bipolar patients. METHOD: The authors conducted an extensive Medline and Pubmed search of the published literature from 1980 up to December 2007, using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Articles that reported clinically significant findings on functioning and disability, and research reports were reviewed in detail. RESULTS: From these articles, we determined that bipolar disorder is associated with significant impairment in work, family and social life, beyond the acute phases of the illness. The aspects that appear to increase the risk of low functioning and disability in bipolar patients are mainly subsyndromal symptoms and neurocognitive impairment, among others. CONCLUSIONS: Suitable pharmacological and psychological interventions may improve the level of functioning and reduce the disability in bipolar patients. Potential targets to be considered for intervention should be residual symptoms, comorbid conditions and neurocognitive deficits. Further research is required to better identify the factors that best predict functioning in bipolar patients.

Treatment-resistant bipolar depression: towards a new definition.

OBJECTIVE: To summarize the conceptual and operational definitions of treatment-resistant bipolar depression and to review the evidence-based therapeutic options. METHOD: Structured searches of PubMed, Index Medicus, Excerpta Medica and Psyclit conducted in December 2008. RESULTS: Criteria for treatment resistance in bipolar depression are commonly based on concepts stemming from treatment resistance as defined for unipolar depression, an approach that proved to be inadequate. In fact, the addition of an ad hoc criterion based on lithium and other mood stabilizer unresponsiveness after reaching adequate plasma levels appears to be a patch that attempts to take into account the uniqueness of bipolar depression but fails to become operational. Recent data from randomized clinical trials of new anticonvulsants and second-generation antipsychotics should lead to the development of a modern definition of treatment-resistant bipolar depression, and specific therapeutic algorithms. CONCLUSION: We suggest a redefinition of resistant bipolar I and II depression. We propose different degrees of severity within bipolar depression in a stepwise manner.

Psychoeducation for bipolar II disorder: an exploratory, 5-year outcome subanalysis.

BACKGROUND: Bipolar II represents a significant subgroup of bipolar patients. However, there is limited evidence regarding the efficacy of pharmacological and/or psychosocial therapies. METHOD: Post-hoc analyses were undertaken using data on 20 (out of 120) patients who fulfilled DSM-IV criteria for BP II who had participated in a single-blind randomized controlled treatment trial (RCT) exploring the acute and long-term efficacy of group psychoeducation plus standard pharmacological treatment as compared with unstructured support groups plus standard pharmacological treatment. Eight BP II subjects had been randomized to a psychoeducation group and 12 to an unstructured support group. RESULTS: Psychoeducated, as compared to control group bipolar II patients, had significantly better 5-year outcomes, with lower mean number of BP episodes (p<.02), hypomanic episodes (p<.03) and depressive episodes (p<.03), fewer days spent in mood episodes (p=.004) and higher mean levels of functioning (p<.05). CONCLUSIONS: Although these findings should be treated with caution, it appears that psychoeducation plus medication can benefit bipolar II subjects. Dedicated treatment trials will need to clarify whether these therapies require modifications in duration and/or content to meet the needs of bipolar II patients.

Adaptation and validation of the Spanish version of the Mood Disorder Questionnaire for the detection of bipolar disorder.

OBJECTIVE: The Mood Disorder Questionnaire (MDQ) is an instrument for the detection of patients with bipolar disorder (BD). The original English version is validated in both the psychiatric and the general population, but a validated Spanish version is not yet available. Psychometric properties of the Spanish adaptation of the MDQ in psychiatry are described. METHODS: The MDQ is a self-administered questionnaire comprising a list of 13 hypomanic symptoms and two questions about concurrence of symptoms and functional impairment caused by the symptoms. We selected patients from 15 psychiatric outpatient departments, diagnosed with BD type I and II (BDI and BDII) and major depression (MD) according to DSM-IV-TR criteria (concurrent validity instrument). A control group of healthy subjects (HS) was selected. The patient-selection criteria included stability of the disorder and pharmacological treatment. The MDQ was administered to 236 subjects, distributed among the four groups, on two occasions, four weeks apart. We analysed the internal consistency, test-retest reliability, and discriminative capacity of the MDQ for the detection of patients with BD. RESULTS: Concurrent validity based on diagnosis according to DSM-IV-TR was 0.83. The internal consistency, evaluated by Cronbach's alpha, was 0.90. The mean (SD) number of affirmative responses by group was: 9.8 (2.4) for BDI, 8.5 (2.8) for BDII, 2.7 (2.2) for MD, and 1.02 (1.9) for HS. Statistically significant differences between all the groups were found (Kruskal-Wallis test, p < 0.001). Concurrent validity using the diagnostic variable was 0.83. Test-retest reliability was 0.92. We analysed the scale's discriminative capacity, revealing a sensitivity value of 0.60 [95% confidence interval (CI) = 0.51-0.69] and a specificity value of 0.98 (95% CI = 0.94-0.99) in the detection of BD. The positive and negative probability ratios were 35.5 and 2.4, respectively. If we consider only seven positive responses as the discriminative criterion, sensitivity increases to 0.81 (95% CI = 0.73-0.88), the specificity value is 0.95 (95% CI = 0.89-0.98) and the positive and negative probability quotients are 16 and 5.3. CONCLUSIONS: The psychometric characteristics of the Spanish version are similar to those of the original version. In the Spanish adaptation of the MDQ, seven positive responses to hypomanic symptoms show a good discriminative capacity for BD in patients attending psychiatric outpatient facilities; therefore, this cut-off score is proposed for the detection of BD in psychiatric outpatients.

Weight gain in bipolar disorder: pharmacological treatment as a contributing factor.

OBJECTIVE: The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder. METHOD: Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder. RESULTS: Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight. CONCLUSION: Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues.

Subsyndromal depressive symptoms in patients with bipolar and unipolar disorder during clinical remission.

BACKGROUND: Subsyndromal depressive symptoms seem to be quite prevalent in mood disorders although very few studies have assessed them in patients considered to be in remission by clinical and psychometric criteria. This study sought to evaluate the presence of subsyndromal depressive symptoms in bipolar and unipolar patients in clinical remission. METHODS: One-hundred seventy-six patients with DSM-IV bipolar (62 bipolar I, 58 bipolar II) or unipolar mayor depression (n=58) in clinical remission and 60 healthy subjects were assessed using several psychometric instruments including the 17 items Hamilton Depression Rating Scale (HDRS). To be considered in clinical remission patients assessed with the Clinical Impression for Bipolar Disorder-Modified (CGI-BP-M) had to be stable for 6 months and scoring 6 or less in the Young Mania Rating Scale (YMRS) and 8 or less in the HDRS. RESULTS: Both Unipolar Disorder (UD) and Bipolar Disorder (BD) patients in clinical remission presented statistically significant higher HRSD scores, than healthy subjects. The HRSD scores were statistically higher in UD patients under remission than in BD patients. The subsyndromal symptoms more strongly associated with a clinical diagnosis of either UD or BD were Depressed Mood, Somatic Anxiety, Impact on Work and Activities, Psychic Anxiety, Gastrointestinal and Somatic Symptoms, Retardation during the Interview and Genital Symptoms. CONCLUSION: Subsyndromal depressive symptoms are present in affective disorder patients, both UD and BD, who apparently are in clinical remission. Remitted unipolar patients may have more residual symptoms than bipolar patients, particularly in items related to anxiety and somatic complaints.

Predominant polarity in bipolar disorder: diagnostic implications.

BACKGROUND: It has been reported that patients with bipolar disorder (BD) remain about 10 years symptomatic before the correct diagnosis is made. This fact is particularly important for patients with predominantly depressed polarity who tend to be diagnosed as suffering from unipolar major depressive disorder and treated with antidepressants. The present study was carried out to assess clinical differences between predominantly manic and depressed BD patients with a special focus on the time that patients remained undiagnosed. METHODS: Clinical and socio-demographic characteristics were obtained from a sample of 149 euthymic bipolar outpatients. Patients were divided into depressive or manic predominance of polarity. Clinical features, number of years undiagnosed (NYU) and occupational functioning were assessed in the two groups. RESULTS: Forty-five patients were classified as a "Depressive Polarity" whilst forty-seven were considered as "Manic Polarity". Depressive Polarity was associated with a longer delay to be diagnosed (F=14.43, df=89, p=0.001). The predominantly depressive patients tended to present a depressive onset of illness, earlier age of onset, longer duration of illness and higher number of suicide attempts than manic polarity patients. CONCLUSION: There was a marked clinical difference between predominantly manic and depressive bipolar patients. Predominantly depressive polarity is associated with a longer delay in receiving a correct diagnosis and effective treatment which has an important impact on the management of the illness.

Ethical questions in human clinical psychopharmacology: should the focus be on placebo administration?

Of all ethical issues in clinical trial designs, only placebo use is dealt with acrimony and unwarranted, rhetoric emphasis. Many misconceptions are biased and may hamper research in the mechanisms of healing and recovery if placebo is banned from clinical trials, as some influential ethicists propose. Current treatments in psychiatry are by no means optimal and may vary in their effect across studies, rendering difficult to find the best available therapeutic method with which to compare new drugs. Because drugs possess specific mechanisms, it is not possible to compare drugs with different mechanisms as to their relevance in the pathophysiology of a given disorder. Placebo acts through non-specific mechanisms and is the ideal control for any disorder whose pathophysiology is relatively unknown and its treatment is still suboptimal. Sticking to short-term patient benefit in a trial reflects an individualistically oriented thinking in contemporary ethics and is likely to limit further research and efforts to better understand the mechanisms of disease and drug action, but also those related to general body reactance and self-healing, which are enhanced by placebo administration. Because in history ethics are swinging between two opposed views, it is possible that in the near future, the balance will move towards communitarianism, which is more likely to better serve long-term patient needs. Ethicists should also consider some other aspects of human experimentation, such as the consistency of research lines and the trend to substitute older drugs with their metabolites or enantiomers.

Depression subtypes in bipolar I and II disorders.

BACKGROUND: Depression is the predominant mood alteration in bipolar I and II disorders. In this study, the nature of major depressive episodes of bipolar I versus bipolar II patients is specifically assessed, as regards lifetime history of rapid cycling, melancholia, atypical and psychotic symptoms. METHODS: The patient sample consisted of 184 bipolar I and 80 bipolar II patients, according to the research diagnostic criteria, who entered the bipolar disorders program in our hospital. Subsets of patients are compared according to DSM-IV criteria for rapid cycling, melancholic, atypical and psychotic features. RESULTS: Bipolar I patients had significantly more psychotic symptoms in their lifetime histories (p < 0.001), whereas bipolar II patients had significantly more atypical symptoms in their lifetime histories (p < 0.003). Although melancholia was more prevalent in the bipolar I and rapid cycling was more prevalent in the bipolar II subgroup, these differences did not reach statistical significance. CONCLUSIONS: The results of the study suggest that marked differences exist in the nature of major depressive episodes between bipolar I and II patients, as they in the long term emerge from the two conditions. To what extent both conditions are related cannot be ascertained in the present study. Clinical differences may have relevant therapeutic implications and separate trials for bipolar I and bipolar II depression are warranted.

Psychometric properties of the well-being index (WHO-5) spanish version in a sample of euthymic patients with bipolar disorder.

BACKGROUND: The concept of well-being which focuses on positive emotions has received increased research attention. However, a consensus definition of this term is lacking. The Well-Being Index scale (WHO-5) is a generic, self-report scale that contains five Likert-type items to evaluate psychological well-being. This construct may provide a relevant outcome in bipolar disorder (BD) research and care beyond the rating of mood symptoms. Thus, in the current study, the psychometric properties of the WHO-5 Spanish version were assessed in a sample of euthymic patients with BD. METHODS: Patients with BD- I and BD-II and healthy controls completed the Well-Being Index (WHO-5) together with an assessment of depressive (Hamilton Depression Rating Scale-17; HAM-D) and manic symptoms (Young Mania Rating Scale; YMRS); and a measure of psychosocial functioning (Functioning Assessment Short Test; FAST). Internal consistency reliability was measured through Cronbach's alpha. Test-retest reliability was calculated comparing the WHO-5 total score at baseline and after 10 days of the first administration. To assess the structure of the scale, a principal component analysis (PCA) was carried out. Correlations between the WHO-5, HAM-D, YMRS and FAST were calculated. Finally, a t-test for independent samples was applied to compare the WHO-5 total score in the patient and control groups. RESULTS: A total of 104 patients with BD and 40 healthy controls were included in this study. A Chronbach's alpha of 0.83 indicated acceptable internal consistency. A paired sample t-test revealed no significant differences between WHO-5 total score at baseline and at follow-up (tn = - 0.72; df = 15; p = 0.48). The PCA provided a single factor solution that accounted for 59.74% of the variation in WHO-5. Test-retest reliability was high (r = 0.83; p < 0.001). Moderate negative correlations were observed between the WHO-5 total score, the FAST (r = - 0.46.; p < 0.001) and the HAM-D (r = - 0.68; p < 0.001), but not with the YMRS (r = - 0.07; p = 0.42). Finally, significant differences were found when comparing the WHO-5 total score between patient and healthy controls (t = 5.1; df = 147; p < 0.001). LIMITATIONS: some limitations include the lack of a comparator scale to test for validity construct and the small sample size in the test-retest reliability CONCLUSIONS: The WHO-5 shows an acceptable reliability index and measures a unitary construct in a Spanish population of euthymic patients with BD.

Cross validation with the mood disorder questionnaire (MDQ) of an instrument for the detection of hypomania in Spanish: the 32 item hypomania symptom check list (HCL-32).

BACKGROUND: The detection and diagnosis of present or past hypomanic episodes is of key importance for the differential diagnosis between depressive disorders and type II bipolar disorder. However, there are few instruments available to satisfactorily screen for the latter condition. The Hypomania Symptom Checklist-32 (HCL-32) is a self-applied questionnaire with 32 hypomania items and 8 severity and functional impact items which is being developed in several European countries for this purpose. Our aim was to develop and validate the psychometric properties of the HCL-32 scale in Spain in patients with bipolar disorder and to compare its properties with other instruments available for the detection of bipolar II disorder. METHODS: Patients were selected from 15 psychiatric outpatient departments, diagnosed with type I or type II bipolar disorder (BDI and BDII) and unipolar major depression (MD) according to DSM-IV-TR criteria. A control group of healthy subjects (HS) was likewise assessed. The patient selection criteria included a well-established diagnosis and a stable disorder and pharmacological treatment. The HCL-32 was administered to 237 subjects distributed among the above groups, on two occasions four weeks apart. We analysed the internal consistency, test-retest reliability and discriminative capacity of the HCL-32. RESULTS: The internal consistency of the Spanish version of the HCL-32, evaluated by Cronbach's alpha, was 0.94. Mean of affirmative questions by group were 21.2 (SD 5.8) for BDI, 19.3 (SD 6.2) for BDII, 8.6 (SD 6.6) for MD and 6.6 (SD 6.1) for HS, with statistically significant differences between them (Kruskal-Wallis test, p<0.001). Concurrent validity using the diagnosis variable was 0.72. Test-retest reliability was 0.90. We analysed the best cut-off point by means of a ROC curve analysis; for 14 affirmative responses, a sensitivity of 0.85 95%CI (0.78, 0.91) and specificity of 0.79, 95%CI (0.72, 0.87) were obtained. The positive and negative probability ratios were 4.1 and 5.3 (1/0.19 respectively). HCL-32 shows a dual factor structure of items, one as an energy-activity factor and another one as a factor involving items related to disinhibition and problems with self-control and attention. LIMITATIONS: The sample size of bipolar patients (particularly type BDII) should be increased in further studies. CONCLUSIONS: The Spanish version of the HCL-32 has good psychometric properties and sufficient sensitivity and specificity, detecting 8 out of every 10 patients with BD. The HCL-32 is a useful screening tool of patients with bipolar disorder in clinical settings. In its present form it adequately discriminates between bipolar and unipolar or healthy subjects, but not between BD I and BII.

Treatment of neurocognitive symptoms in unipolar depression: A systematic review and future perspectives.

BACKGROUND: Cognitive symptoms in Major Depressive Disorder (MDD) are persistent and commonly entail neurocognitive impairment and a decline in quality of life. This systematic review gathers the current scientific evidence on therapeutic strategies for neuropsychological impairment in MDD. METHOD: A systematic search on PubMed, PsycINFO and Clinicaltrials.gov was carried out on December 2016 according to PRISMA using Boolean terms to identify interventions for the treatment of cognitive dysfunction in MDD. Only English-written articles providing original data and focusing in adults with MDD were included with no time restrictions. RESULTS: A total of 95 studies reporting data on 40 pharmacological and non-pharmacological interventions were included. Interventions were grouped into the following categories: 1) Pharmacological Therapies (antidepressants, stimulants, compounds acting on NMDA receptors, compounds acting on the cholinergic system, compounds showing anti-inflammatory or antioxidant properties, other mechanisms of action), 2) Physical Therapies and 3) Psychological Therapies, 4) Exercise. There are some promising compounds showing a positive impact on cognitive symptoms including vortioxetine, lisdexamfetamine or erythropoietin. LIMITATIONS: The studies included showed significant methodological differences in heterogeneous samples. The lack of a standardized neuropsychological battery makes comparisons between studies difficult. CONCLUSION: Current evidence is not sufficient to widely recommend the use of procognitive treatments in MDD although promising results are coming to light.