Correlates of neurological soft signs in bipolar disorder.

Recent research has focused on neurological soft signs (NSS) in bipolar disorder (BD), but there is still scarce evidence on their correlates with other relevant variables. The aim of this study was to explore the association between NSS and clinical demographic, neurocognitive, and functional variables. Eighty-eight euthymic BD patients were included in whom NSS were assessed using the Neurological Evaluation Scale. All subjects performed an extensive neurocognitive battery selected to assess premorbid IQ, attention, language, verbal memory, and executive functions. Psychosocial outcomes were assessed by means of the Functioning Assessment Short Test. Among the demographical variables, NSS tended to be negatively associated with years of education and increased with age. Likewise, NSS were higher in BD type I than in BD type II, but independent of age at illness onset and number of previous affective episodes. There was a negative correlation between NSS and premorbid IQ, as well as with performance in attention, language, and executive functions. Results tended to be unchanged when controlled for potential confounders. Although NSS were associated with poor psychosocial functioning in the bivariate analysis, when added to a multiple regression model including neurocognition, these neurological features did not significantly contribute to the variance of the functional outcome. Our findings contribute to a better characterization of NSS in BD; their potential clinical and theoretical implications are discussed in the manuscript.

Clinical Characteristics of Melancholic and Nonmelancholic Depressions.

ABSTRACT: This study aimed to compare clinical-demographic features of melancholic and nonmelancholic depressions. We included 141 depressed inpatients classified as melancholic and nonmelancholic by the Sydney Melancholia Prototype Index (SMPI) and Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. Results were controlled for confounders, including severity measures. Melancholic patients by both diagnostic systems were more severely depressed and presented more psychotic symptoms, neurological soft signs, and psychomotor disturbances. Melancholic patients classified by the SMPI were also older at illness onset and had fewer suicide attempts. After controlling for confounders, although all differences remained significant for SMPI diagnosis, the DSM-5 diagnosis of melancholia was only associated with further impaired motor sequencing. The results obtained with the SMPI support the hypothesis that melancholia has clinical features qualitatively different from those of nonmelancholic depressions. Contrarily, the DSM-5 specifier seems to reflect the severity of depressive episodes rather than core clinical features of melancholia.

Neurocognitive function of patients with melancholic and non-melancholic major depressive episodes: An exploratory study.

OBJECTIVE: The aim of this exploratory study was to compare the neurocognitive performance of patients undergoing melancholic and non-melancholic major depressive episodes. Considering potential limitations of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) specifier, we employed an additional tool that has proven useful in identifying melancholia (the Sydney Melancholia Prototype Index). METHODS: One hundred forty-one depressed inpatients were classified as melancholic or non-melancholic according to the Sydney Melancholia Prototype Index and the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria and compared on a neurocognitive battery selected to assess attention and processing speed, verbal memory, working memory and executive functions. Results were controlled for several potential confounders. RESULTS: Patients diagnosed as melancholic by the two diagnostic systems displayed lower scores in executive measures, semantic verbal fluency and phonological verbal fluency. On attention and processing speed, patients with melancholia underperformed those with non-melancholic depression only when diagnosed by the Sydney Melancholia Prototype Index. After controlling for confounders, associations between melancholic status and executive dysfunction remained significant for the Sydney Melancholia Prototype Index but not for the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) diagnosis. CONCLUSION: In this study, melancholia diagnosed by the Sydney Melancholia Prototype Index (but not by the Diagnostic and Statistical Manual of Mental Disorders [5th ed.] criteria) was characterized by a greater compromise of tests assessing executive functions than non-melancholic depressions, even after controlling for depressive severity. These preliminary results might contribute to generating hypotheses about differences in the cognitive profile and pathophysiological substrate between melancholic and non-melancholic depressions. Likewise, the pattern of findings supports the hypothesis that the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) melancholia specifier might identify more severe forms of depressive episodes rather than a qualitatively different subtype.

Clinical Course in Patients With Melancholic and Nonmelancholic Bipolar Depression.

ABSTRACT: The aim of the current study was to compare the longitudinal clinical course of patients with a history of melancholic and nonmelancholic bipolar depression. Seventy-seven euthymic outpatients with bipolar disorder were categorized as melancholic or nonmelancholic through the clinician-rated Sydney Melancholia Prototype Index. Clinical course was assessed for a period longer than 48 months by time spent ill, density of affective episodes, severity and duration of depressive episodes, and time to depressive recurrence. The mean follow-up time was 69.05 months. Patients with melancholic depressions had more severe and longer depressive episodes during follow-up, whereas patients with nonmelancholic depressions had a shorter time to depressive recurrence and more subsyndromal depressive symptoms and affective instability. These findings highlight the heterogeneity inherent to the current construct of bipolar depression and position melancholia as an interesting target for comparison with nonmelancholic depressions in other external validators in the field of bipolar disorder.

Episodic density, subsyndromic symptoms, and mood instability in late-life bipolar disorders: A 5-year follow-up study.

OBJECTIVES: Characterization of clinical course in old age bipolar disorder (OABD) is scarce and based solely on episode density (ED). The aim of this study was to explore mood instability (MI) and subsyndromal symptomatology (SS) in a prospective cohort of OABD. Further, we contrasted these measures with a cohort of young age bipolar disorder (YABD). METHODS: Life charts from weekly mood ratings were used to compute the number of weeks spent with subsyndromal symptoms (SD), the ED, and the MI during follow-up for a cohort of OABD (N = 38) that excluded late onset BD. Linear and logistic regression models were fitted to compare the clinical course of OABD with a cohort of YABD (N = 52) and to explore the relationship between these measures and functional outcomes. RESULTS: Median follow-up was 5 years (IQR: 3.6-7.9). OABD (61.6 years, SD: 8.3) spent 15%, 6%, and 3% of their follow-up with depressive, manic, and mixed symptoms, respectively, and suffered 4.2 mood changes per year (SD: 2.6). No significant differences between OABD and YABD regarding ED or MI emerged in multivariate analysis, while a higher subsyndromal manic symptom burden was observed in OABD (ß coefficient: 3.79, 95%CI: 0.4-7.2). Both SS and MI were associated with functional outcomes in OABD. CONCLUSIONS: The course of illness throughout OABD was similar to the one observed in YABD except for a higher subsyndromal manic burden. This study extended the association of MI and SD with global functioning to the late-life BD.

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

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

Accuracy of the number of previous episodes reported by patients with bipolar disorder.

BACKGROUND: The number of previous episodes in patients with BD is a variable widely used for both clinical and research purposes. The aim of this study was to compare the number of episodes retrospectively reported by euthymic BD subjects with that registered by their psychiatrists during a follow-up period. METHODS: Fifty euthymic patients with BD and more than 2years of follow-up were retrospectively asked in a standardized fashion about the number of hypomanic/manic and depressive episodes suffered during that period. Patient-reported outcomes were compared with the number of episodes registered by psychiatrists in a life chart during the same period. RESULTS: The mean follow-up of patients was 66.70months. There was a mean difference of 2.74 episodes between reports of patients' and psychiatrists' reports during the complete follow-up period; Intraclass correlation coefficient was 0.40 (CI95%=0.15-0.61). This difference increased with the duration of the follow-up period (R=0.33, p=0.023) and with the number of episodes occurred during that (R=0.32, p=0.023). The difference between patient-reported and clinician-rated in the number of depressive during the follow-up period was more pronounced in BDII than in BDI (Z=-2.47, p=0.014), and it correlated with the number of previous depressive episodes at baseline (R=0.28, p=0.047) and subclinical depressive symptoms (R=0.41, p=0.003). CONCLUSIONS: The number of previous episodes referred by patients with BD is not an accurate measure of the true number of episodes suffered. The theoretical and practical implications of these findings are discussed.

Long-term worsening of bipolar disorder related with frequency of antidepressant exposure.

BACKGROUND: The aim of this study of 53 persons with bipolar disorder (BD) was to evaluate the relationship between history of exposure to antidepressants (AD) and mood stabilizers (MS) and the percentage of time spent ill. METHODS: BD outpatients with more than 12 months of prospective follow-up were included. Outcome was documented using a life charting technique. Current and previous exposure to AD and MS were assessed using a scale that provides a quantitative measure of exposure to psychotropic medications. Regression models were used to correct for possible confounders. RESULTS: Previous treatment with AD was an independent predictor of polarity changes (P < .001) and mixed symptoms (P = .01). In contrast, "years of exposure to MS" was an independent predictor of time spent asymptomatic (P = .019). The ratio between exposure to AD vs MS was associated with less weeks asymptomatic (P = .03), more mixed symptomatology (P = .019), and more polarity changes (P = .001). CONCLUSIONS: Antidepressant exposure was a major predictor of mood instability in the long-term outcome of BD. The ratio used of previous exposure to AD vs MS was associated with poor outcomes, suggesting that the harmful effect of AD may be additive and related to how much they are used.

Theory of mind and facial emotion recognition in euthymic bipolar I and bipolar II disorders.

The main aim of this study was to compare patients with euthymic bipolar I (BDI) and bipolar II (BDII) disorders and healthy controls in measures of social cognition. Additional aims were to explore the association between social cognition performance with neurocognitive impairments and psychosocial functioning. Eighty one euthymic patients with BDI or BDII and 34 healthy controls were included. All subjects completed tests to assess verbal memory, attention, and executive functions. Additionally theory of mind (ToM) and facial emotion recognition measures were included. Psychosocial functioning was assessed with the GAF. Both groups of patients had lower performance than healthy controls in ToM, and a lower recognition of fear facial expression. When neurocognitive impairments and exposure to medications were controlled, performance in ToM and recognition of fear facial expression did not allow predicting if a subject was patient or healthy control. Social cognition measures not enhance variance beyond explained by neurocognitive impairments and they were not independent predictors of psychosocial functioning. Impairments in facial emotion recognition and ToM are mediated, at least partly, by attention-executive functions deficits and exposure to psychotropic medications. Likewise, social cognition measures did not contribute to variance beyond neurocognitive impairments.

Neurocognitive impairments and their relationship with psychosocial functioning in euthymic bipolar II disorder.

The aim of this study was to compare neurocognitive functioning between euthymic patients with bipolar I disorder (BDI), bipolar II disorder (BDII), and healthy controls. An additional aim was to estimate the relationship between neurocognitive impairments and psychosocial functioning. Eighty-seven patients with BDI (n = 48) or BDII (n = 39) and 39 healthy controls were included. All subjects completed an extensive neurocognitive battery. Psychosocial functioning was assessed using the General Assessment of Functioning. Patients with BDII performed more poorly than did the controls in measures of psychomotor speed, verbal memory, and executive functioning. Patient groups did not show differences in any of the cognitive measures assessed. The performance in trail-making test B was the only independent predictor of psychosocial functioning in both patient groups. Patients with BDII have cognitive impairments, and this has a negative influence on their functional outcome. Our results bring additional support to the notion that BDII disorder is not a merely mild type of BDI.

[Clinical concepts associated with lithium underutilization in the treatment of bipolar disorder]. / Conceptos clínicos asociados a la subestimación del litio en el tratamiento del Trastorno Bipolar.

OBJECTIVES: Bipolar Disorders are among the ten leading causes of morbity and lithium is considered first-line treatment and the most cost-effective. Nevertheless, its use takes a back seat to other treatment options less effective, safe and more expensive; and the reasons for this remains unclear. The present study investigates clinical concepts related to its underutilization. METHOD: An anonymous questionnaire concerning different aspects of lithium clinical use (compared efficacy, adverse effects, practical aspects regarding its use, use in special populations) was administered during the XXV Congress of the Argentinean Psychiatrist Association. RESULTS: 164 questionnaires were analyzed. Less than one-third of the sample referred lithium as their most frequent treatment option, although almost 60% qualified it as effective. Almost two-thirds considered its utilization as more complex and ill-ascribed adverse effects to it. One third referred not to use it in youth and senior populations. CONCLUSIONS: Contrary to current recommendations, lithium is under utilized. This is the first report on the possible causes leading to such phenomena, which can be related to ill concepts regarding its safety, clinical use and adverse effects; although not to its effectiveness.

Social cognition in first episode bipolar disorder patients.

The aim of this study was to describe theory of mind (ToM) and emotional processing (EP) functioning in recently diagnosed bipolar disorder (BD). We evaluated 26 first episode BD (mean age 22.9 ±â€¯7.4) and 26 controls matched on age, gender, education, and premorbid intelligence. A significant poorer performance on the capacity of patients to infer other's intentions (cognitive ToM) that was partially independent from neurocognitive deficits (p < 0.01) as well as a lower recognition of fear was observed among patients. No significant association between any of these deficits and psychosocial functioning emerged in multivariate regression analyses.

Cognitive and motor features in elderly people with bipolar disorder.

BACKGROUND: Although elderly people will represent one third of the bipolar population in a few years, data about cognitive and motor features in these patients are very scarce. The aim of this study was to compare the cognitive and motor functioning between elderly euthymic patients with bipolar disorder (BD) and healthy controls, as well as to determine the degree of correlation with psychosocial functioning. METHODS: Euthymic older adults with BD (n=20) and healthy controls (n=20) were evaluated with traditional clinical instruments and measures of exposure to psychotropic drugs and extrapyramidal symptoms. All subjects completed an extensive neuropsychological battery. RESULTS: Patients with BD had more extrapyramidal symptoms and worse performance than healthy controls in psychomotor speed, verbal memory, and executive functions even after controlling sub-clinical symptomatology. These findings were not associated with age at onset or length of illness or with current pharmacological exposure. Psychosocial functioning correlated negatively with performance in psychomotor speed and executive function, and with extrapyramidal symptoms. LIMITATIONS: The small sample size and cross-sectional design. CONCLUSIONS: Older adult patients with BD in a euthymic state could have a similar cognitive and motor profile to that described in younger euthymic bipolar patients. Cognitive-motor disturbances may help to explain impairments in daily functioning among elderly patients with bipolar disorder during remission.

Heterogeneity in cognitive functioning among patients with bipolar disorder.

BACKGROUND: Nowadays it is not clear if in bipolar disorders (BD) cognitive impairments are heterogeneous and if so which are the variables that determine it. METHODS: Fifty patients with BD and thirty healthy controls were clinically evaluated including measures of obstetric complications history. All subjects completed an extensive neuropsychological battery selected to asses premorbid IQ and different cognitive domains. RESULTS: Compared with standardized norms, 38% of patients had none cognitive domain affected, while 40% had 1 to 2, and 22% had 3 to 5. Patients with cognitive functioning within normal limits had higher psychosocial functioning and premorbid IQ, and lower history of obstetric complications. LIMITATIONS: The small sample size could limit the generalizability of the results; since these data should be taken as preliminaries. CONCLUSIONS: The extension and severity of cognitive impairments may be heterogeneous in patients with BD, and it might contribute to explain the variability in functional outcome. Bipolar patients with low premorbid IQ and history of obstetric complications may represent a subgroup with lower cognitive performance and psychosocial functioning.

[Valproate-induced hyperammonemic encephalopathy. Review of cases in the psychiatric setting]. / Encefalopatía hiperamonémica asociada al uso de ácido valproico. Revisión de casos en psiquiatría.

Valproate-induced hyperammonemic encephalopathy is a rare but severe and potentially fatal adverse event. Frequently, the use of valproic acid produces an elevation of ammonia levels. In some people, this is associated with the development of encephalopathy without evidence of liver failure, usually reversible with discontinuation or dose reduction. Although there is important evidence about this adverse event in patients with neurologic disorders, the data in the psychiatric setting is scarce. We review the available studies and case reports about valproate-induced hyperammonemic encephalopathy in people treated with valproic acid for psychiatric disorders. We describe the clinical and therapeutic characteristics, and the physiology of this adverse event.

Neurocognitive heterogeneity in older adults with bipolar disorders.

The aim of this study was to estimate the prevalence of clinically significant cognitive deficits in a sample of euthymic older age bipolar disorder (OABD) patients, and its relationship with functional outcome. Sixty-six outpatients and 30 controls completed a neuropsychological battery and a measure of psychosocial functioning. There were 33.3% (CI95% 22-44%) of patients without clinically significant cognitive deficits, 36.4% (CI95% 24-48%) with selective deficits, and 30.3% (CI95% 19-41%) with global deficits. Patients without cognitive deficits were indistinguishable of healthy controls in terms of psychosocial functioning, while patients with cognitive impairments had lower functional outcome. Neurocognitive and psychosocial functioning might be heterogeneous among patients with OABD.

Longitudinal relationship between clinical course and neurocognitive impairments in bipolar disorder.

BACKGROUND: The aim of this study was to estimate the relationship between clinical course and trajectory of neurocognitive functioning during a follow-up period in a sample of euthymic bipolar patients. METHODS: Fifty-one patients with BD performed two-neurocognitive assessment separated by a period of at least 48 months. The clinical course during the follow-up period was documented by: three measures 1) number of affective episodes, 2) time spent ill, and 3) mood instability. RESULTS: Patients were followed-up for a mean period of 73.21 months. Neurocognitive performance tended to be stable throughout the follow-up. Performance in verbal memory and executive functions at the end of study were related with the number of hypo/manic episodes and time spent with hypo/manic symptoms during the follow-up. None of the clinical measures considered were related to changes in neurocognitive performance over the follow-up period. LIMITATIONS: The relatively small sample size limits the value of subgroup analysis. The study design does not rule out some risk of selection bias. CONCLUSIONS: Although there may be a positive relationship between number of episodes and neurocognitive deficits in patients with bipolar disorder, successive episodes do not seem to modify the trajectory of neurocognitive functioning over time. Theoretical implications of these findings are discussed.

Neurocognitive functioning in first-episode Bipolar Disorder: Relationship with functional status.

BACKGROUND: The aim of this study was to assess if an association between neurocognitive deficits and psychosocial functioning exists in first-episode BD patients. METHODS: Twenty-five euthymic first-episode BD patients and thirty-seven healthy controls were recruited. History of suicide attempts, psychiatric comorbidities, pharmacological exposure, and previous depressive episodes were investigated. Performances on neurocognitive domains (verbal memory, attention, processing speed, and executive functions) as well as a measure of psychosocial functioning were used as outcomes. RESULTS: First-episode BD patients showed medium-to-large size deficits on measures of attention, processing speed, and executive functions. A significant association between verbal memory and psychosocial functioning at the moment of BD diagnosis was detected (beta coefficient -3.9, IC 95% -6.7 to -1.2, p < 0.01). CONCLUSIONS: A relationship between cognitive performance at the moment of BD diagnosis and psychosocial functioning was detected. Possible therapeutic implications of this finding are discussed.