RESUMEN
Bipolar disorder (BD) and alcohol dependence (AD) frequently co-occur, and co-occurring BD and AD are associated with devastating public health costs. Minimal neurobiological research exists to guide the development of effective treatments for this treatment-resistant population. We believe the present study represents the first investigation of prefrontal gamma-aminobutyric acid (GABA) and glutamate levels in co-occurring BD and current AD. The participants were 78 individuals who met DSM-IV criteria for BD I/II and current AD (n=20), BD I/II alone (n=19), current AD alone (n=20) or no diagnosis (n=19). The participants completed a baseline diagnostic visit, then returned approximately 4 days later for a two-dimensional J-resolved proton magnetic resonance spectroscopy (1H-MRS) acquisition in dorsal anterior cingulate cortex (dACC). All participants were required to demonstrate ⩾1 week of abstinence from alcohol/drugs via serial biomarker testing before 1H-MRS. A 2 × 2 factorial analysis of variance of cerebrospinal fluid (CSF)-corrected GABA/water concentrations demonstrated a significant BD × AD interaction (F=2.91, P<0.05), signifying uniquely low levels of GABA in BD+AD; this effect doubled when the sample was restricted to individuals who consumed alcohol within 2 weeks of 1H-MRS. There were no overall effects of BD/AD on CSF-corrected glutamate/water levels. However, the BD × AD interaction, signifying uniquely low levels of glutamate in BD+AD, approached statistical significance (F=3.83, P=0.06) in individuals who consumed alcohol within 2 weeks of 1H-MRS. The dACC GABA levels were significantly, negatively associated with Barratt Impulsiveness Scale (r=-0.28, P=0.02) and Obsessive Compulsive Drinking Scale (r=-0.35, P<0.01) scores. If replicated, these results may suggest that future treatment studies should preferentially evaluate therapeutics in BD+AD known to increase prefrontal GABA and glutamate levels.
Asunto(s)
Alcoholismo/metabolismo , Trastorno Bipolar/metabolismo , Ácido Glutámico/metabolismo , Giro del Cíngulo/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Adulto , Alcoholismo/complicaciones , Alcoholismo/psicología , Trastorno Bipolar/complicaciones , Trastorno Bipolar/psicología , Ansia , Femenino , Humanos , Conducta Impulsiva , Masculino , Persona de Mediana Edad , Corteza Prefrontal/metabolismo , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
BACKGROUND: Deficits in executive function have been associated with risk for relapse. Data from previous studies suggest that relapse may be triggered by stress and drug-paired cues and that there are significant sex differences in the magnitude of these responses. The aim of this study was to examine the impact of the pharmacological stressor and alpha-2 adrenergic receptor antagonist yohimbine and cocaine cues on executive function in cocaine-dependent men and women. METHODS: In a double-blind placebo controlled cross-over study, cocaine-dependent men (n=12), cocaine-dependent women (n=27), control men (n=31) and control women (n=25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Participants performed the Connors' Continuous Performance Test II prior to medication/placebo administration and immediately after each cue exposure session RESULTS: Healthy controls had a significant increase in commission errors under the yohimbine condition [RR (95% CI)=1.1 (1.0-1.3), χ(2)1=2.0, p=0.050]. Cocaine-dependent individuals exhibited a significant decrease in omission errors under the yohimbine condition [RR (95% CI)=0.6 (0.4-0.8), χ(2)1=8.6, p=0.003]. Cocaine-dependent women had more omission errors as compared to cocaine-dependent men regardless of treatment [RR (95% CI)=7.2 (3.6-14.7), χ(2)1=30.1, p<0.001]. Cocaine-dependent women exhibited a slower hit reaction time as compared to cocaine-dependent men [Female 354 ± 13 vs. Male 415 ± 14; t89=2.6, p=0.012]. CONCLUSIONS: These data add to a growing literature demonstrating significant sex differences in behaviors associated with relapse in cocaine-dependent individuals.
Asunto(s)
Atención/efectos de los fármacos , Trastornos Relacionados con Cocaína/tratamiento farmacológico , Trastornos Relacionados con Cocaína/psicología , Cocaína/farmacología , Conducta Impulsiva/efectos de los fármacos , Yohimbina/uso terapéutico , Adulto , Estudios Cruzados , Señales (Psicología) , Método Doble Ciego , Femenino , Humanos , Masculino , Caracteres SexualesRESUMEN
BACKGROUND: Evidence supporting the continuous latent structure of mood phenomena has not been incorporated into psychiatric diagnostic systems, in part because the evidence has been incomplete. For example, no studies have investigated the boundary between 'sick' and 'well' periods in individuals with bipolar disorder, despite agreement that characterization of mood disorders as having a discrete episodic course is inaccurate. The present study examined the validity of mood episode symptom thresholds in out-patients with bipolar disorder using multiple methodologies: taxometrics and information-theoretic latent distribution modeling (ITLDM), to evaluate the continuity/discontinuity of mood symptoms; and structural equation mixture modeling (SEMM), to evaluate the continuity/discontinuity of associations between mood symptoms and general functioning. METHOD: A total of 3721 out-patients with bipolar disorder from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were available for analysis. Data were collected at participants' baseline STEP-BD visit. Taxometric [maximum covariance/means above minus below a cut (MAXCOV/MAMBAC) with simulated comparison data], ITLDM and SEMM methods were applied twice, once to the Montgomery-Åsberg Depression Rating Scale and again to the Young Mania Rating Scale. RESULTS: Taxometric results unequivocally supported a continuous interpretation of the data. ITLDM results favored many valued 'discrete metrical' models, suggesting that mood symptoms have continuous, but potentially non-normally distributed, latent structures in out-patients with bipolar disorder. Finally, SEMM results demonstrated that latent associations between mood symptoms and general functioning were linear. CONCLUSIONS: Results from the present study argue against the validity of DSM mood episode thresholds and argue for a graded continuum of care of bipolar symptom management.
Asunto(s)
Trastorno Bipolar/clasificación , Trastorno Bipolar/psicología , Trastorno Depresivo/clasificación , Trastorno Depresivo/psicología , Adolescente , Adulto , Trastorno Bipolar/terapia , Trastorno Depresivo/terapia , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Humanos , Escalas de Valoración Psiquiátrica , Psicometría , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Observed co-morbidity among the mood and anxiety disorders has led to the development of increasingly sophisticated dimensional models to represent the common and unique features of these disorders. Patients often present to primary care settings with a complex mixture of anxiety, depression and somatic symptoms. However, relatively little is known about how somatic symptoms fit into existing dimensional models. METHOD: We examined the structure of 91 anxiety, depression and somatic symptoms in a sample of 5433 primary care patients drawn from 14 countries. One-, two- and three-factor lower-order models were considered; higher-order and hierarchical variants were studied for the best-fitting lower-order model. RESULTS: A hierarchical, bifactor model with all symptoms loading simultaneously on a general factor, along with one of three specific anxiety, depression and somatic factors, was the best-fitting model. The general factor accounted for the bulk of symptom variance and was associated with psychosocial dysfunction. Specific depression and somatic symptom factors accounted for meaningful incremental variance in diagnosis and dysfunction, whereas anxiety variance was associated primarily with the general factor. CONCLUSIONS: The results (a) are consistent with previous studies showing the presence and importance of a broad internalizing or distress factor linking diverse emotional disorders, and (b) extend the bounds of internalizing to include somatic complaints with non-physical etiologies.
Asunto(s)
Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Atención Primaria de Salud/estadística & datos numéricos , Trastornos Somatomorfos/epidemiología , Afecto , Trastornos de Ansiedad/clasificación , Trastornos de Ansiedad/psicología , Comorbilidad , Trastorno Depresivo/clasificación , Trastorno Depresivo/psicología , Europa (Continente)/epidemiología , Análisis Factorial , Asia Oriental/epidemiología , Humanos , India/epidemiología , Control Interno-Externo , Entrevista Psicológica , Modelos Teóricos , Análisis de Regresión , Índice de Severidad de la Enfermedad , Trastornos Somatomorfos/clasificación , Trastornos Somatomorfos/psicología , América del Sur/epidemiología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Although psychiatric diagnostic systems have conceptualized mania as a discrete phenomenon, appropriate latent structure investigations testing this conceptualization are lacking. In contrast to these diagnostic systems, several influential theories of mania have suggested a continuous conceptualization. The present study examined whether mania has a continuous or discrete latent structure using a comprehensive approach including taxometric, information-theoretic latent distribution modeling (ITLDM) and predictive validity methodologies in the Epidemiologic Catchment Area (ECA) study. METHOD: Eight dichotomous manic symptom items were submitted to a variety of latent structural analyses, including factor analyses, taxometric procedures and ITLDM, in 10105 ECA community participants. In addition, a variety of continuous and discrete models of mania were compared in terms of their relative abilities to predict outcomes (i.e. health service utilization, internalizing and externalizing disorders, and suicidal behavior). RESULTS: Taxometric and ITLDM analyses consistently supported a continuous conceptualization of mania. In ITLDM analyses, a continuous model of mania demonstrated 6.52:1 odds over the best-fitting latent class model (LCM) of mania. Factor analyses suggested that the continuous structure of mania was best represented by a single latent factor. Predictive validity analyses demonstrated a consistent superior ability of continuous models of mania relative to discrete models. CONCLUSIONS: The present study provided three independent lines of support for a continuous conceptualization of mania. The implications of a continuous model of mania are discussed.
Asunto(s)
Trastorno Bipolar/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trastorno Bipolar/clasificación , Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Adulto JovenRESUMEN
BACKGROUND: Taxometric research on depression has yielded mixed results, with some studies supporting dimensional solutions and others supporting taxonic solutions. Although supplementary tests of construct validity might clarify these mixed findings, to date such analyses have not been reported. The present study represents a follow-up to our previous taxometric study of depression designed to evaluate the relative predictive validities of dimensional and categorical models of depression. METHOD: Two sets of dimensional and categorical models of depression were constructed from the depression items of the Composite International Diagnostic Interview: (1) empirically derived models obtained using latent structure analyses and (2) rationally selected models, including an additive depressive symptoms scale (dimensional) and DSM major depressive episodes (categorical). Both sets of dimensional and categorical models were compared in terms of their abilities to predict various clinically relevant outcomes (psychiatric diagnoses and impairment). RESULTS: Factor analyses suggested a two-factor model ('cognitive-affective' and 'somatic' symptoms) and latent class analyses suggested a three-class model ('severe depression', 'moderate depression' and 'cognitive-affective distress'). In predictive analyses that simultaneously included dimensional and categorical models as predictors, the dimensional models remained significant unique predictors of outcomes while the categorical models did not. CONCLUSIONS: Both dimensional models provided superior predictive validity relative to their categorical counterparts. These results provide construct validity evidence for the dimensional findings from our previous taxometric study and thus inspire confidence in dimensional conceptualizations of depression. It remains for future research to evaluate the construct validity of the taxonic solutions reported in the literature.