The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a systematic review and meta-analysis of cerebrospinal fluid studies

Objectives: The kynurenine (KYN) pathway has been attracting attention as a relevant pathway in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We conducted a systematic review and meta-analysis of studies examining KYN pathway metabolites from cerebrospinal fluid (CSF) samples in SZ, BD, and MDD. Methods: The PubMed and Scopus databases were systematically searched to identify peer-reviewed case-control studies published until April 2022 that assessed KYN metabolites, namely, tryptophan (TRP), KYN, kynurenic acid (KA), quinolinic acid (QA), and 3-hydroxykynurenine (3-HK), in subjects with SZ, BD, or MDD compared with healthy controls (HC). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The random effects model method was selected for comparison of standardized mean differences (SMD) between two groups. Results: Twenty-three articles met the inclusion criteria (k = 8, k = 8, k = 11, for SZ, BD, and MDD, respectively). In SZ, KA levels were increased (SMD = 2.64, confidence interval [CI] = 1.16 to 4.13, p = 0.0005, I2 = 96%, k = 6, n=384). TRP (k = 5) and KYN (k = 4) did not differ significantly. In BD, TRP levels (k = 7) did not differ significantly. The level of KA was increased in MDD (k = 2), but the small number of studies precluded evaluation of statistical significance. Finally, in MDD, although some studies tended to show an increased level of KYN in those with remission vs. decreased levels in those with current depression, no significant difference was found in any KYN metabolite levels. Similarly, an increased level of QA was found, but the number of studies (k = 2) was small. Conclusion: KA, which has possibly neuroprotective effects, is increased in SZ. QA, which has neurotoxic effects, may be increased in MDD. There were no alterations in BD. Alterations in the KYN pathway may occur based on population characteristics and mood states. Future studies should explore the utility of these metabolites as biomarkers.

Validity and reliability of the Brazilian version of the Cognitive Reserve Assessment Scale in Health

Objective: As the older population increases, it is important to identify factors that may reduce the risks of dementia in the general population. One such factor is the concept of cognitive reserve (CR). The present study analyzed the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH) in the Brazilian population. This scale was originally developed to measure CR in individuals with severe mental illness. We also investigated the relationship between the CRASH and clinical or sociodemographic variables. Methods: This study was conducted with 398 individuals. We assessed sociodemographic variables and depression, anxiety, and stress symptoms (Depression, Anxiety and Stress Scale [DASS-21]) using a web-based survey. We constructed a confirmatory factor analysis (CFA) model in order to test the goodness of fit of the factor structure proposed in the original CRASH study. Results: The McDonald's hierarchical ω for CRASH using CFA parameters was 0.61, and the Cronbach's alpha coefficient indicated good internal consistency when considering all items (alpha = 0.7). Conclusions: Our results suggest that CRASH can be used to assess CR in the general population in Brazil.

Mapping the psychoanalytic literature on bipolar disorder: a scoping review of journal articles

Objective: To provide a review of journal articles discussing clinical cases or vignettes of psychoanalysis or psychoanalytic psychotherapy of patients affected by bipolar disorder. Methods: A thorough search of journal articles was performed in five databases to identify studies published from 1990-2021. Results: Twenty-four articles were included in this review, comprising a total of 29 case reports. The most common theoretical approach adopted by the authors was "object relations." Two main sets of clinical-theoretical considerations and recommendations emerge: the applicability of analytic treatment to patients with bipolar disorder - taking into account their analyzability and practical arrangements for conducting therapy - and theoretical speculations on the nature and development of the illness, as well as on the conceptualization of its different phases. Conclusion: Our findings reveal that there is some psychoanalytic literature providing insight into the psychological dynamics and treatment of patients with bipolar disorder. Elaboration of this literature may help improve our understanding and provide more accurate and comprehensive descriptions of the intrapsychic and interpersonal dynamics of these patients, yielding potentially valuable information for clinical and research purposes, particularly with regard to reducing interpersonal conflict, and increasing insight and engagement with lifestyle changes and other behaviors likely to promote health and stability.

Distractibility, anxiety, irritability, and agitation symptoms are associated with the severity of depressive and manic symptoms in mixed depression

Objective: To explore whether there is an association between distractibility, anxiety, irritability, and agitation (DAIA) symptoms and the severity of depressive and manic symptoms. Methods: Patients with unipolar and bipolar disorder (I and II) and mixed depression were evaluated. DAIA symptoms were assessed using previously described definitions. Results: The full analysis set comprised 100 patients. The severity of depressive symptoms in mixed depression, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample, influenced mainly by anxiety. The severity of manic symptoms in mixed depression, assessed by Young Mania Rating Scale (YMRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample and three or four DAIA symptoms in the unipolar sample. Conclusion: DAIA symptoms were associated with greater severity of manic symptoms in mixed depression. DAIA symptoms must be evaluated in all patients with mixed features and are associated with the severity of depressive and manic symptoms in mixed depression. Clinical trial registration: ClinicalTrials.gov (NCT04123301).

Psychometric properties of the modified Yale Food Addiction Scale 2 0 in a large Brazilian sample

Objective: The field of food addiction has attracted growing research attention. The modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) is a screening tool based on DSM-5 criteria for substance use disorders. However, there is no validated instrument to assess food addiction. Methods: The mYFAS 2.0 has been transculturally adapted to Brazilian Portuguese. The data for this study was obtained through an anonymous web-based research platform: participants provided sociodemographic data and answered Brazilian versions of the the mYFAS 2.0 and the Barratt Impulsivity Scale (BIS-11). Analysis included an assessment of the Brazilian mYFAS 2.0's internal consistency reliability, factor structure, and convergent validity in relation to BIS-11 scores. Results: Overall, 7,639 participants were included (71.3% females; age: 27.2±7.9 years). The Brazilian mYFAS 2.0 had adequate internal consistency reliability (Cronbach's alpha = 0.89). A single factor solution yielded the best goodness-of-fit parameters for both the continuous and categorical version of the mYFAS 2.0 in confirmatory factor analysis. In addition, mYFAS 2.0 correlated with BIS-11 total scores (Spearman's rho = 0.26, p < 0.001) and subscores. Conclusion: The Brazilian mYFAS 2.0 demonstrated adequate psychometric properties in our sample; however, future studies should further evaluate its discriminant validity.

Validity and reliability of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Brazilian bipolar patients / Validade e fidedignidade da Escala de Disfunções Cognitivas no Transtorno Bipolar (COBRA) em pacientes bipolares brasileiros

Abstract Introduction: In Brazil, there is no valid instrument to measure subjective cognitive dysfunction in bipolar disorder. The present study analyzed the psychometric properties of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Brazilian bipolar patients. We further investigated the relationship between the COBRA, objective cognitive measures, and illness course variables. Methods: The total sample (N=150) included 85 bipolar disorder patients and 65 healthy controls. The psychometric properties of the COBRA (e.g., internal consistency, concurrent validity, discriminative validity, factor analyses, ROC curve, and feasibility) were analyzed. Results: The COBRA showed a one-factor structure with very high internal consistency (Cronbach's alpha=0.890). Concurrent validity was indicated by a strong correlation with the cognitive domain of the FAST (r=0.811, p<0.001). Bipolar patients experienced greater cognitive complaints (mean=14.69; standard deviation [SD]=10.03) than healthy controls (mean=6.78; SD=5.49; p<0.001), suggesting discriminative validity of the instrument. No significant correlations were found between the COBRA and objective cognitive measures. Furthermore, higher COBRA scores were associated with residual depressive (r=0.448; p<0.001) and manic (r=0.376; p<0.001) symptoms, number of depressive episodes (r=0.306; p=0.011), number of total episodes (r=0.256; p=0.038), and suicide attempts (r=0.356; p=0.003). Conclusion: The COBRA is a valid instrument to assess cognitive complaints, and the combined use of subjective-objective cognitive measures enables the correct identification of cognitive dysfunctions in bipolar disorder.

Resumo Introdução: No Brasil, não existem instrumentos válidos para medir a disfunção cognitiva subjetiva no transtorno bipolar. O presente estudo analisou as propriedades psicométricas da Escala de Disfunções Cognitivas no Transtorno Bipolar (COBRA) em uma amostra brasileira de pacientes bipolares. Adicionalmente, investigamos a relação entre a COBRA, medidas cognitivas objetivas e curso da doença. Métodos: A amostra total (n=150) incluiu 85 pacientes com transtorno bipolar e 65 controles saudáveis. As propriedades psicométricas da COBRA (consistência interna, validade concorrente, validade discriminativa, análise fatorial, curva ROC e fidedignidade) foram analisadas. Resultados: A COBRA apresentou estrutura de um fator com alta consistência interna (alfa de Cronbach=0,890). A validade concorrente ficou demonstrada pela forte correlação com o domínio cognitivo da FAST (r=0,811, p<0,001). Pacientes bipolares tiveram mais queixas cognitivas [média=14,69; desvio padrão (DP)=10,03] que os controles (média=6,78; DP=5,49; p<0,001), sugerindo a validade discriminativa do instrumento. Não houve correlação significativa entre a COBRA e medidas cognitivas objetivas. Além disso, escores mais altos na COBRA estiveram associados com sintomas residuais depressivos (r=0,448; p<0,001) e maníacos (r=0,376; p<0,001), número de episódios depressivos (r=0,306; p=0,011), número de episódios totais (r=0.256; p=0.038) e tentativas de suicídio (r=0,356; p=0,003). Conclusão: A COBRA é um instrumento válido para avaliar queixas cognitivas, e o uso combinado das medidas cognitivas subjetivas-objetivas possibilita a correta identificação das disfunções cognitivas no transtorno bipolar.

Cognitive performance and psychosocial functioning in patients with bipolar disorder, unaffected siblings, and healthy controls

Objective: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. Methods: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. Results: Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. Conclusion: Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.

Subsyndromal Depressive Symptoms in Bipolar II Disorder: a Community Mental Health Services Cohort Study (SIN-DEPRES) / Síntomas depresivos subsintomáticos en trastorno bipolar II: un estudio de cohorte de servicios de salud comunitarios

Objectives: The aim of this study was to assess the prevalence and the impact of subclinical depressive symptoms (SDS) on the functional outcome of bipolar II (BD) outpatients in remission. Methods: Cross-sectional and prospective 16-week study of a cohort of 739 euthymic BD patients included by 94 investigators in Spain. Clinical stability was assessed at baseline and week 16 with the Clinical Global Impression scale for BD (CGI-BP-M), depressive symptoms at baseline with the Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Scale (MADRS) and the self-applied Center for Epidemiologic Studies-Depression Scale (CES-D). Functional status was evaluated with the Social and Occupational Functioning Assessment Scale (SOFAS) and Social Adaptation Self-evaluation Scale (SASS). Results: The sample of type II BD was composed by 202 patients. SDS were detected in 21.3% of patients (95% IC =15.9 to 27.6) at baseline. In apparently symptom-free patients, the incidence of SDS after 16 weeks was 29% (MADRS >7). At baseline, SDS patients compared to non-SDS presented poorer social-occupational performance (SOFAS mean difference -13.3, 95% CI from -17.1 to -9.5) and poorer social adjustment (SASS mean difference -4.3, 95% CI from -7.0 to -1.7). Depressive symptoms were inversely related to functional status and social adjustment: MADRS-SOFAS correlation coefficients r = -0.55 (p<0.0001) and MADRS-SASS correlation coefficients r = -0.43 (p<0.0001). The self-applied questionnaire identified additional cases with depressive symptoms at baseline, showing a SDS-Total prevalence of 51% identified by any method. A MADRS score 5 showed 0.75 sensitivity and 0.69 specificity in the detection of cases with possible SDS based on self-reported results as gold standard. Conclusions: Depressive symptoms in apparently remitted type II BD outpatients are common and as frequent as in other BD subtypes. These subclinical symptoms result in adverse occupational outcome and social maladjustment. MADRS and self-applied questionnaires during follow-up visits may provide important information about type II BD patients’ mood status and functionality.

Objetivos: Evaluar la prevalencia y el impacto de los síntomas depresivos subclínicos (SDS) en el resultado funcional de pacientes externos de bipolaridad II (TB) en remisión. Métodos: Estudio transversal y prospectivo, de 16 semanas de duración, de una cohorte de 739 pacientes eutímicos de TB incluidos por 94 investigadores en España. La estabilidad clínica se evaluó, en la línea base y en la semana 16, con la Escala Impresión Global Clínica para TB (CGI-BP-M); los síntomas depresivos, en la línea base, con la Escala de Calificación de la Depresión de Hamilton (HDRS), la Escala Montgomery-Asberg (MADRS) y la Escala Autoaplicada para la Depresión del Centro de Estudios Epidemiológicos (CES-D). El estado funcional se evaluó con la Escala de Evaluación del Funcionamiento Social y Ocupacional (SOFAS), y la Escala de Autoevaluación de la Adaptación Social (SASS). Resultados: La muestra de TB tipo II estuvo compuesta de 202 pacientes. Se detectaron SDS en 21,3% de los pacientes (95% IC = 15,9 a 27,6) en la línea base. En pacientes que aparentemente no presentaban síntomas, la incidencia de SDS después de 16 semanas era de un 29% (MADRS>7). En la línea base, los pacientes SDS, en comparación con los no SDS, demostraban un desempeño social-ocupacional más pobre (diferencia media SOFAS -13,3, 95% IC de -17,1 a -9,5) y un ajuste social más pobre (diferencia media SASS -4,3, 95% IC de -7,0 a -1,7). Los síntomas depresivos estaban relacionados inversamente con el estado funcional y el ajuste social: coeficientes de correlación MADRS-SOFAS r = -0,55 (p<0,0001) y coeficientes de correlación MADRS-SASS r = -0,43 (p<0,0001). El cuestionario autoaplicado identificó casos adicionales con síntomas depresivos en la línea base, y mostró una prevalencia total de SDS de 51% identificada por cualquier método. Un puntaje MADRS ≥ 5 mostró una sensibilidad de 0,75 y una especificidad de 0,69 en la detección de casos con posible SDS, basándose en los resultados autoreportados como el estándar de oro. Conclusiones: Los síntomas depresivos en pacientes externos de TB de tipo II aparentemente en remisión son comunes y son tan frecuentes como para los demás subtipos de TB. Estos síntomas subclínicos tienen resultados ocupacionales adversos así como inadaptación social. La MADRS y los cuestionarios autoaplicados durante las visitas de seguimiento pueden ofrecer información importante acerca del estado de ánimo y la funcionalidad del paciente de TB tipo II.

Bipolar disorder and age-related functional impairment / Prejuízo funcional associado à idade e transtorno bipolar

OBJECTIVE: Although bipolar disorder is a major contributor to functional impairment worldwide, an independent impact of bipolar disorder and ageing on functioning has yet to be demonstrated. The objective of the present study was to evaluate the effect of bipolar disorder on age-related functional status using matched controls as a standard. METHOD: One-hundred patients with bipolar disorder and matched controls were evaluated for disability. Age-related effects controlled for confounders were cross-sectionally evaluated. RESULTS: Patients were significantly more impaired than controls. Regression showed effects for aging in both groups. The effect, size, however, was significantly stronger in patients. CONCLUSION: Bipolar disorder was an important effect modifier of the age impact on functioning. While a longitudinal design is needed to effectively demonstrate this different impact, this study further depicts bipolar disorder as a chronic and progressively impairing illness.

OBJETIVO: O transtorno bipolar é responsável por importante parcela do prejuízo funcional ao redor do mundo. Um efeito independente do transtorno bipolar e da idade no funcionamento ainda não foi demonstrado. O presente estudo tem o objetivo de avaliar o efeito do transtorno bipolar no prejuízo funcional relacionado à idade, com controles pareados como padrão. MÉTODO: Cem pacientes com transtorno bipolar e controles pareados foram avaliados para incapacidade. Efeitos relacionados à idade, com controle para confundidores, foram investigados. RESULTADOS: Pacientes tiveram significativamente mais prejuízo que controles. A regressão mostrou efeito para a idade em ambos os grupos, e o efeito foi significativamente mais forte nos pacientes. CONCLUSÃO: O transtorno bipolar foi um importante modificador de efeito no impacto da idade no funcionamento. Enquanto um desenho de estudo longitudinal é necessário para efetivamente demonstrar este impacto diferencial, este estudo caracteriza o transtorno bipolar como uma doença crônica e incapacitante.

Cuestionario de estado disfórico (CED): evaluación de la versión piloto / Dysphoric status questionnaire: evaluation of the pilot version

In the field of the affective disorders, clinical experience and diverse factorial analysis studies raise the existence of a dysphoric syndrome as a different affective state, distinguible from depressive and maniac states. This syndrome could be more frequent in bipolar patients and be at the base of some of the denominated mixed forms. This discussion has been delineating a psychopathology for dysphoric states that is necessary to operationalize for research purposes. The present study has sought to create of a dysphoric syndrome screening tool for patients with affective disorders, and to explore its psychometric properties in an ambulatory mixed clinical sample of unipolar and bipolar patients. The instrument has encouraging psychometric properties. We found that some items separately, and the questionnaire as a whole, had good discriminating capacity to distinguish between unipolar and bipolar patients.

En el campo de los trastornos afectivos, la experiencia clínica y diversos estudios de análisis factorial plantean la existencia de un síndrome disfórico como un estado afectivo diferente y distinguible de los estados depresivos y maníacos. Este síndrome podría ser más frecuente en pacientes bipolares y estar a la base de algunas de las denominadas formas mixtas. Esta discusión, ha ido delineando una psicopatología del estado disfórico que es necesario operacionalizar para propósitos de investigación. El presente estudio ha buscado crear de un instrumento de screening para el síndrome disfórico en pacientes con trastornos afectivos, y explorar sus propiedades psicométricas en una muestra clínica mixta de pacientes psiquiátricos ambulatorios monopolares y bipolares. El instrumento posee propiedades psicométricas alentadoras. Encontramos que algunos ítems por separado, y el cuestionario en su conjunto, poseían buena capacidad discriminante para distinguir entre pacientes unipolares y bipolares.

Melhorando o desfecho do transtorno bipolar usando estratégias não farmacológicas: o papel da psicoeducação / Improving the outcome of bipolar disorder through non-pharmacological strategies: the role of psychoeducation

O presente artigo avalia a eficácia da psicoeducação e estratégias relacionadas nos transtornos bipolares. Vários ensaios clínicos aleatorizados demonstraram, recentemente, a eficácia de intervenções psicológicas - a saber: a identificação de sinais prodrômicos, terapia cognitivo-comportamental, psicoeducação e intervenções focadas na família - como um acréscimo profilático à medicação. Todos esses estudos são aqui apresentados, conjuntamente com os estudos pioneiros na área. Há vários tópicos que todo programa psicoeducacional deve incluir para assegurar sua utilidade e eles serão resumidos em doze pontos. Grosso modo, a psicoeducação deve conter informações gerais sobre a doença bipolar, elementos para a aumentar a adesão ao tratamento, ensinar o reconhecimento rápido de recaídas e questões sobre a regularidade do modo de vida. Hoje em dia, várias diretrizes para o tratamento incluem a psicoeducação como uma ferramenta profilática crucial. Os clínicos devem estar conscientes disso e começar a praticar a psicoeducação em sua prática clínica cotidiana.