RESUMEN
BACKGROUND: Cognitive dysfunction in major depressive disorder (MDD) is identified as a primary therapeutic target; no current treatment is approved for the treatment of cognitive dysfunction in MDD. We examined whether intranasal insulin offered a beneficial effect across measures of cognitive function in adults with MDD. METHODS: Thirty-five adults (18-65 years of age: 47.09±9.89) meeting criteria for a major depressive episode as per the Diagnostic and Statistical Manual (DSM)-IV-Treatment Revised were included in this randomized, double blind, placebo-controlled, crossover design study. Subjects were not stratified based on baseline cognitive deficit. Subjects were randomized to 4 weeks of either intranasal insulin 40 International Units (IU) taken four times a day (i.e., morning, afternoon, evening, and before bed) (QID) (n=19) or placebo (n=16). RESULTS: No between group differences were observed in change from baseline on total Montgomery Åsberg Depression Rating Scale (MADRS) score (25.98±2.81), in either of the Positive or Negative subscales of the Positive and Negative Affect Schedule (PANAS), or on a global index of neurocognition. The possibility of practice and/or carry over effect could not be excluded. Methodological refinement (e.g., stratification of subjects based on baseline cognitive deficit) may have augmented assay sensitivity. CONCLUSION: Intranasal insulin did not demonstrate statistically significant improvements on overall mood, aspects of emotional processing, neurocognitive function, or self-reported quality of life patient reported outcomes.
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Afecto/efectos de los fármacos , Cognición/efectos de los fármacos , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Insulina/administración & dosificación , Insulina/uso terapéutico , Administración Intranasal , Adolescente , Adulto , Anciano , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Estudios Cruzados , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Resistente al Tratamiento/complicaciones , Trastorno Depresivo Resistente al Tratamiento/psicología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Calidad de Vida , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia. METHOD: A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations. RESULTS: A total of 369 adults with DSM-IV-TR-defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery-Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007). CONCLUSIONS: These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.
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Anhedonia , Disfunción Cognitiva/psicología , Trastorno Depresivo Mayor/psicología , Adulto , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autoinforme , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Major depressive disorder (MDD) is a leading cause of disability. Impairment in work function considerably adds to symptom burden and increases the economic impact of this disorder. Our study aimed to investigate the factors associated with work status in MDD within primary and tertiary care. METHOD: We used data from 2 large databases for our analysis--Study 1: the InSight database, a chart review of MDD patients treated by primary care physicians across Canada (n=986); and Study 2: the International Mood Disorders Collaborative Project, a cross-sectional study of mood disorder patients (Canadian data only: n=274). RESULTS: Both studies demonstrated high rates of unemployment and disability (30.3% to 42.1%). Quebec showed the highest rate of unemployment (21%) and British Columbia had the greatest percentage of patients on disability (15%). Employed and unemployed groups were similar based on clinical characteristics; however, unemployed people may have higher age, prevalence of medical comorbidity, and greater likelihood of receiving a benzodiazepine. Increased disability rates were associated with history of childhood abuse, duration of current major depressive episode, comorbidity, benzodiazepine use, as well as greater depression and anxiety severity. The unemployed-disability groups had greater somatic symptoms and anhedonia. In keeping with this, anhedonia was the strongest predictor of disability. Absenteeism was also high across both studies. CONCLUSIONS: Unemployment and disability rates in MDD are high. The presence of anhedonia and medical comorbidity significantly influenced work status, emphasizing the need for treatment strategies to alleviate the additional symptom burden in this subpopulation.
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Costo de Enfermedad , Trastorno Depresivo Mayor , Evaluación de la Discapacidad , Desempleo , Adulto , Anciano , Anhedonia , Colombia Británica/epidemiología , Comorbilidad , Estudios Transversales , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/economía , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Prevalencia , Atención Primaria de Salud/estadística & datos numéricos , Quebec/epidemiología , Factores de Riesgo , Factores Socioeconómicos , Atención Terciaria de Salud/estadística & datos numéricos , Desempleo/psicología , Desempleo/estadística & datos numéricosRESUMEN
BACKGROUND: A substantial proportion of individuals with mood disorders present with sub-syndromal hypo/manic features. The objective of this analysis was to evaluate the prevalence and illness characteristics of the Diagnostic and Statistical Manual Version-5 (DSM-5) - defined mixed features specifier (MFS) in adults with major depressive disorder (MDD) and bipolar disorder (BD). METHOD: Data from participants who met criteria for a current mood episode as part of MDD (n=506) or BD (BD-I: n=216, BD-II: n=130) were included in this post-hoc analysis. All participants were enrolled in the International Mood Disorders Collaborative Project (IMDCP): a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto and the Cleveland Clinic, Cleveland, Ohio. Mixed features specifier was operationalized as a score ≥ 1 on 3 or more select items on the Young Mania Rating Scale (YMRS) or ≥ 1 on 3 select items of the Montgomery Åsberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAMD-17) during an index major depressive episode (MDE) or hypo/manic episode, respectively. RESULTS: A total of 26.0% (n=149), 34.0% (n=65), and 33.8% (n=49) of individuals met criteria for MFS during an index MDE as part of MDD, BD-I and BD-II, respectively. Mixed features specifier during a hypo/manic episode was identified in 20.4% (n=52) and 5.1% (n=8) in BD-I and BD-II participants, respectively. Individuals with MDE-MFS as part of BD or MDD exhibited a more severe depressive phenotype (p=0.0002 and p<0.0002, respectively) and reported a higher rate of alcohol/substance use disorder in the context of BD but not MDD (p=0.002). Individuals with MFS were more likely to have co-existing heart disease suggestive of a distinct pattern of comorbidity and neurobiology. LIMITATIONS: Data were post-hoc and obtained from individuals utilizing a university-based mood disorder centre which may affect generalizability. CONCLUSIONS: Diagnostic and Statistical Manual Version-5-defined MFS is common during an MDE as part of MDD and BD. The presence of MFS identifies a subgroup of individuals with greater illness complexity and possibly a higher rate of cardiovascular comorbidity. The results herein underscore the common occurrence of MFS in adults with either BD or MDD. Moreover, the results of our analysis indicate that adults with mood disorders and MFS have distinct clinical characteristics and comorbidity patterns.
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Trastorno Bipolar/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Trastornos del Humor/diagnóstico , Adulto , Afecto , Trastorno Bipolar/epidemiología , Comorbilidad , Trastorno Depresivo Mayor/epidemiología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Trastornos del Humor/epidemiología , Prevalencia , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
OBJECTIVES: We primarily sought to determine the effect of adjunctive lisdexamfetamine dimesylate (LDX) on anthropometric and metabolic parameters. Our secondary aim was to evaluate the effect of LDX on attention deficit hyperactivity disorder (ADHD) symptom severity in adults with bipolar I/II disorder. METHODS: Forty-five stable adults (i.e., non-rapid cycling, absence of clinically significant hypo/manic symptoms) with bipolar I/II disorder and comorbid ADHD were enrolled in a phase IV, 4-week, flexible dose, open-label study of adjunctive LDX. All subjects were initiated at 30 mg/day of adjunctive LDX for the first week with flexible dosing (i.e., 30-70 mg/day) between weeks 2 and 4. RESULTS: Of the 45 subjects enrolled, 40 received adjunctive LDX (mean dose = 60 ± 10 mg/day). A statistically significant decrease from baseline to endpoint was evident in weight (p < 0.001), body mass index (p < 0.001), fasting total cholesterol (p = 0.011), low density lipoprotein cholesterol (p = 0.044), high density lipoprotein cholesterol (p = 0.015) but not triglycerides, or blood glucose. Significant reductions were also observed in leptin (p = 0.047), but not in ghrelin, adiponectin, or resistin levels. Diastolic blood pressure and pulse increased significantly over time but on average remained within the normal range (p < 0.001). There was a significant reduction from baseline to endpoint in the total score of the ADHD Self-Report Scale. Significant improvement from baseline to endpoint was also observed in the Montgomery-Åsberg Depression Rating Scale total score as well as the Clinical Global Impression Severity and Improvement score. CONCLUSIONS: Short-term adjunctive LDX treatment was well tolerated by this sample of adults with stable bipolar I/II disorder. Lisdexamfetamine dimesylate offered beneficial effects on body weight, body mass index and several metabolic parameters. In addition to demonstrating short-term (i.e., 4 weeks) safety and tolerability, beneficial effects of LDX were also observed in mitigating depressive and ADHD symptom severity.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/metabolismo , Peso Corporal/efectos de los fármacos , Dextroanfetamina/uso terapéutico , Adulto , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno Bipolar/psicología , Peso Corporal/fisiología , Dextroanfetamina/farmacología , Femenino , Humanos , Dimesilato de Lisdexanfetamina , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Functional impairment associated with mood disorders may be related to a characteristic "profile" of normative personality dimensions. METHODS: Individuals (age ≥ 18 years) with MDD (n = 400) or BD (n = 317), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), were enrolled in the IMDCP. Personality was evaluated with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI), and functionality with the Sheehan Disability Scale and Endicott Work Productivity Scale. Path analysis using linear multiple regressions was performed to identify direct and indirect effects of personality on functional impairment. RESULTS: Lower conscientiousness exerted a significant direct effect on global (p = 0.017) and family life dysfunction in individuals with MDD (p = 0.002), as well as lower work productivity in both MDD (p = 0.020) and BD (p = 0.018). Lower extraversion exerted a significant direct effect on social impairment in individuals with BD (p = 0.017). Higher neuroticism and agreeableness as well as lower extraversion exerted indirect effects on global and social dysfunction in individuals with MDD via their effects on depression severity. In BD, higher neuroticism and openness indirectly affected global dysfunction. Family dysfunction was indirectly affected by higher neuroticism and openness as well as lower extraversion in MDD and BD. CONCLUSION: The results suggest that discrete personality dimensions may exert direct and indirect effects on functional outcomes in individuals with mood disorders. Personalizing disease management approaches in mood disorders with emphasis on vocational rehabilitation may benefit from measurement and intervention targeting personality.
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Trastorno Bipolar/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Personalidad , Adulto , Eficiencia , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Inventario de PersonalidadRESUMEN
BACKGROUND: Few reports have aimed to describe the mediational effect of cognitive deficits on functional outcomes in major depressive disorder (MDD), and relatively few interventions are demonstrated to mitigate cognitive deficits in MDD. METHODS: Studies enrolling subjects between the ages of 18-65 were selected for review. Bibliographies from identified articles were reviewed to identify additional original reports aligned with our objectives. RESULTS: Cognitive deficits in MDD are consistent, replicable, nonspecific, and clinically significant. The aggregated estimated effect size of cognitive deficits in MDD is small to medium. Pronounced deficits in executive function (≥1 SD below the normative mean) are evident in â¼20-30% of individuals with MDD). Other replicated abnormalities are in the domains of working memory, attention, and psychomotor processing speed. Mediational studies indicate that cognitive deficits may account for the largest percentage of variance with respect to the link between psychosocial dysfunction (notably workforce performance) and MDD. No conventional antidepressant has been sufficiently studied and/or demonstrated robust procognitive effects in MDD. CONCLUSIONS: Cognitive deficits in MDD are a principal mediator of psychosocial impairment, notably workforce performance. The hazards posed by cognitive deficits in MDD underscore the need to identify a consensus-based neurocognitive battery for research and clinical purposes. Interventions (pharmacological, behavioral, neuromodulatory) that engage multiple physiological systems implicated in cognitive deficits hold promise to reduce, reverse, and prevent cognitive deficits.
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Trastornos del Conocimiento/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Adolescente , Adulto , Anciano , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/etiología , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVES: This study aimed to determine the distributions of the age at onset (AAO) in patients with major depressive disorder (MDD) using admixture analysis and to determine the clinical differences between subgroups with different AAO. METHODS: Participants were administered the Mini-International Neuropsychiatric Interview to obtain clinical data. Admixture analysis was performed using the STATA module DENORMIX to identify subgroups characterized by differences in AAO. RESULTS: The best fit model was the three-component model with the following means, standard deviations and proportions: 14.60 (3.75) years (49.1%), 29.15 (6.75) years (34.1%) and 46.96 (6.06) years (16.8%) (χ(2)=3.64, 2 df, P=.162). The three subgroups were divided by AAO of 22 and 40. After controlling for duration of illness, there were no significant differences between the three AAO subgroups in terms of gender and psychiatric family history. However, the early-onset subgroup was significantly more likely to report being single compared to the intermediate- and late-onset groups. The proportion of individuals meeting criteria for lifetime comorbid panic disorders and obsessive-compulsive disorder did not differ significantly between the AAO groups. However, the early-onset group reported a higher incidence of attention-deficit/hyperactivity disorder (5.1% vs. 1.7% and 1.2%, P=.086), although this was not statistically significant. CONCLUSIONS: Our study identified three characteristically different AAO subgroups in individuals suffering from MDD. The subgroups may reflect different underlying neurobiological mechanisms involved.