RESUMEN
BACKGROUND: It is well known that the hypothalamic-pituitary-adrenal (HPA) axis is compromised in major depression and bipolar disorder. There is increasing evidence that subtle HPA abnormalities, such as elevated cortisol levels, precede the development of an affective disorder. Interpersonal stress is also associated with the development of affective disorders. The present study sought to determine whether interpersonal chronic and episodic stress moderated the relationship between cortisol levels in the natural environment and risk status, defined as having a parent with bipolar disorder. METHOD: Sixty-two offspring of parents with bipolar disorder (OBD) and 60 offspring with no family history of affective disorders (OFH-), aged 19.48 years (s.d.=3.38, range 14-28), completed interviews assessing mental disorders and chronic and episodic stress, and provided saliva samples over 3 days. RESULTS: Regression analyses revealed that the OBD who experienced high interpersonal chronic stress displayed a larger cortisol rise following awakening than the OBD reporting low interpersonal chronic stress. The same relationship was also found for levels of non-interpersonal chronic stress. The OBD who reported experiencing severe interpersonal episodic stress exhibited higher levels of daytime cortisol than the OBD reporting interpersonal episodic stress of mild severity. Importantly, none of the above relationships were detected in the OFH-. Each of the interactions between family history of affective disorders and stress remained after controlling for age, gender and offspring lifetime affective disorders and current non-affective disorders. CONCLUSIONS: A biological sensitivity to stress may underlie the susceptibility to affective disorders among the OBD.
Asunto(s)
Trastorno Bipolar , Hijo de Padres Discapacitados/psicología , Hidrocortisona/metabolismo , Trastornos del Humor/fisiopatología , Estrés Psicológico/metabolismo , Adolescente , Adulto , Enfermedad Crónica , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Estudios Longitudinales , Masculino , Trastornos del Humor/etiología , Análisis Multivariante , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiopatología , Quebec , Riesgo , Saliva/metabolismo , Estrés Psicológico/psicología , Adulto JovenRESUMEN
The hypothalamic-pituitary-adrenal (HPA) axis is compromised at several levels in major depressive and bipolar disorder (BD). However, it is not known whether HPA abnormalities predate the onset of these disorders. We conducted a pilot study comparing salivary cortisol levels of 10 adolescent offspring of parents with BD and 10 offspring of parents with no mental disorder (NMD). For two days, samples were collected at awakening and during the day in the adolescents' natural environment. The offspring of parents with BD had higher mean cortisol levels in the mornings and afternoons than the offspring of parents with NMD. When controlling for age, group differences in cortisol persisted in the afternoon, but not morning samples. None of the adolescents met diagnostic criteria for anxiety, affective, attention-deficit, or conduct disorders. Although preliminary, the results suggest that there is an early abnormality in the HPA system of the offspring of parents with BD.
Asunto(s)
Trastorno Bipolar/genética , Trastorno Bipolar/metabolismo , Hidrocortisona/análisis , Saliva/química , Adolescente , Factores de Edad , Análisis de Varianza , Trastorno Bipolar/diagnóstico , Hijo de Padres Discapacitados , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Análisis por Apareamiento , Pruebas Neuropsicológicas , Proyectos Piloto , Medición de RiesgoRESUMEN
BACKGROUND: Acute tryptophan depletion (ATD), a means of reducing brain serotonin synthesis, lowers mood in normal males with a multi-generational family history of major affective disorder (MAD) and in normal women devoid of any family history of psychiatric illness. As both a family history of MAD and female sex are factors predisposing to depression, the hypothesis that a mood lowering response to ATD may reflect a susceptibility to depression was further investigated in young women with an extensive, multi-generational family history of MAD. In addition, the temporal stability of mood change following repeated trials of ATD was also assessed in this study. METHODS: To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested on two separate occasions. The control treatment, administered on a third occasion, was a nutritionally balanced amino acid mixture containing tryptophan. RESULTS: A marked lowering of plasma tryptophan (85-90 %) was achieved by both depletions. In comparison to the balanced condition, family history positive (FH +) women showed no lowering of mood to either the first or second ATD (N = 13) and N = 12, respectively). Mood change between the two ATD trials (N = 13) exhibited poor temporal stability. CONCLUSIONS: These results may indicate that serotonin responsiveness is not an important characteristic of vulnerability to depression in these women. Alternately, these negative results may be due to the exclusion of a large number of FH + women who had already experienced an episode of depression, resulting in the selection of a biased FH + sample who are resistant to the mood lowering effects of ATD.
Asunto(s)
Encéfalo/metabolismo , Trastorno Depresivo , Triptófano/deficiencia , Triptófano/uso terapéutico , Adolescente , Adulto , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/genética , Trastorno Depresivo/psicología , Femenino , Humanos , Linaje , Serotonina/biosíntesis , Factores Sexuales , Triptófano/sangreRESUMEN
Acute tryptophan depletion (ATD) induces transient clinical relapse in medicated patients with major affective disorder. Our objective was to determine whether this effect persists once patients are euthymic and off antidepressants. Thus, we examined the effects of ATD in fully remitted, medication-free, former patients with major depression (n = 14). ATD had no significant effect on mood. These results suggest that the previous report that ATD substantially lowers mood in pharmacologically treated patients reflects a reversal of mechanisms involved in the therapeutic effects of antidepressants. Alternatively, ATD might induce clinical relapse only in subgroups that have yet to be identified.
Asunto(s)
Afecto/fisiología , Trastornos del Humor/metabolismo , Trastornos del Humor/psicología , Triptófano/fisiología , Adulto , Dieta , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración PsiquiátricaRESUMEN
We investigated (1) the mood response of normal women, without a family history of major affective disorder, to acute tryptophan depletion, and (2) the temporal stability of the mood change, within subjects, when rechallenged at least 1 month later. To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested. The control treatment was a nutritionally balanced amino acid mixture containing tryptophan. A marked lowering of plasma tryptophan (80% to 90%) was achieved by both depletions. Compared to the balanced condition, the women exhibited a significant lowering of mood after the first tryptophan depletion on the elation-depression (p < .05), energetic-tired (p < .005), confident-unsure (p < .01), and clearheaded-confused (p < .01) scales of the bipolar profile of mood states. Whereas a lowering of mood was not found in a comparable sample of males studied earlier, these results were similar to those obtained in healthy males at genetic risk for major affective disorder (MAD). Inasmuch as a family history of MAD and female sex are predisposing factors to depression, these results suggest that a mood-lowering response to acute tryptophan depletion may occur preferentially in subjects with a susceptibility to lowered mood. However, the mood response to tryptophan depletion exhibited poor temporal stability in individual subjects.
Asunto(s)
Afecto , Triptófano/deficiencia , Adolescente , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Ciclo Menstrual , Factores Sexuales , Factores de Tiempo , Triptófano/sangreRESUMEN
METHODS: A double-blind placebo-controlled cross-over study in which plasma tryptophan was manipulated by administration of a tryptophan-deficient amino acid mixture. In the placebo condition, all subjects received a nutritionally balanced amino acid mixture that contained tryptophan. To further standardize baseline amino acids, each subject was provided with a low-protein diet the day before amino acid challenges. Subjects were euthymic, healthy men aged 18 to 30 years with either a multigenerational family history of affective illness or no family history of psychiatric illness in the present or in the two previous generations. Each subject was screened with a structured clinical interview to rule out a personal history of psychiatric illness. RESULTS: Plasma tryptophan was reduced by 89% 5 hours after the administration of the tryptophan-deficient amino acid mixture. Six of 20 subjects with a family history of affective illness and none of 19 subjects without a family history of psychiatric illness showed a lowering of mood of 10 or more points on the Profile of Mood States depression scale (P = .012, Fisher's Exact Test) 5 hours after tryptophan depletion. No significant mood changes were observed following the control treatment (balanced amino acid mixture) in either group. CONCLUSIONS: Our data support the hypothesis that subjects with no prior depressive episodes but with a multigenerational family history of major affective disorder show a greater reduction in mood after tryptophan depletion. They are also consistent with theories that implicate deficient serotonergic function as one possible etiological factor in major depressive disorders.