Age of onset and studies of late‐life depression

Investigations of the heterogeneity of major depression must include studies of geriatric patients. This will facilitate identification of correlates of age of onset in an age‐matched sample. The inclusion of young adult depressives could confound the affect of age and wash out a phenomenon occurring only in late life unless systematically carried out as part of the study design. Thus, a comparison of early‐onset first‐episode depressives with late‐onset first‐episode and early‐onset multiple‐episode patients who have aged provides a mathematical approach for separating the influences of multiple episodes, age at index episode and age of onset. Studies of geriatric depressives have not demonstrated a greater role for either medical or social factors in late‐onset illness. The possibility that some cases of late‐onset depression directly result from biogenic amine depletion caused by age and that these individuals are examples of acceleration of a normal distributed rate of brain ageing remains. If this hypothesis is valid, these cases might be related to senile onset Alzheimer's disease. A longitudinal study could determine if this ‘brain failure’ hypothesis is associated with depression‐related dementia, systemic signs of accelerated ageing, a decreased interval before death, and neurotransmitter depletion at autopsy. Future investigations that carefully examine questions of age of onset, age, and clinical and biological correlates are required to address these important questions.