Melancholia: definitions, risk factors, personality, neuroendocrine markers and differential antidepressant response

Objective: To evaluate the CORE measure of melancholia, against the DSM-IV construct of melancholia. To evaluate the validity of both the CORE and DSM-IV constructs of melancholia against psychosocial risk factors, anxiety and personality disorder comorbidity, neuroendocrine markers and differential antidepressant response to fluoxetine and nortriptyline. Method: One hundred and ninety-five outpatients with major depression were evaluated for melancholia with both the DSM-IV criteria and the CORE evaluation. Both constructs were evaluated for validity against psychosocial risk factors, comorbidity, biological markers and differential antidepressant response. Results: The CORE measure has satisfactory interrater reliability when used dimensionally, but has unacceptably low agreement for making a categorical diagnosis of melancholia. There is remarkably poor agreement (kappa = 0.11) between the CORE and DSM-IV criteria for melancholia. Neither the DSM-IV nor CORE criteria for melancholia identified subgroups of patients with better childhood environments or less anxiety or personality disorder comorbidity. The CORE criteria for melancholia, but not DSM-IV, identified patients with neuroendocrine disturbance. CORE scores also were associated with differential responses to fluoxetine and nortriptyline, but not in anticipated directions. Thus, high CORE scores were associated with a higher recovery rate with fluoxetine than nortriptyline. Conclusion: While the episode specifier of melancholia should be retained in diagnostic systems, the DSM-IV criteria were not validated against any of the variables examined in this study. The CORE construct of melancholia, was validated against neuroendocrine measures, and was associated with a differential antidepressant response. However, the limits imposed by interrater reliability, suggest the CORE measure should be used dimensionally and not to make a categorical diagnosis of melancholia.