A diversity of neurochemical hypotheses related to major depression (MD) suggests that further investigation is needed for uncovering the neurophysiological nature of MD. Since both temperament and mental illness have been linked to varying degrees of the same neurotransmitter imbalances in neurophysiological systems of behavioral regulation, the analysis of temperament traits as weak forms of neurochemical imbalances might give new insights into symptoms and nature of MD. This study analyzed the predictions of the opioid receptor hypothesis within the neurochemical model of functional ensemble of temperament proposing that a dysregulation of the opioid receptors acting on monoaminergic systems gives rise to the symptoms of major depression (MD). The study investigated the coupling of sex, age and temperament traits with MD across four age groups (17–24, 25–45, 46–65, 66–85) by reviewing the records of testing in 423 patients and volunteers with (210) and without (213) the MD. The records included testing with the personality assessment inventory, structure of temperament questionnaire, structured clinical interview and other diagnostic measures. In line with the hypothesis, patients with MD had significantly lower physical endurance, social-verbal endurance, mental endurance, plasticity, physical tempo, sensation seeking and self-confidence, and higher impulsivity and neuroticism than non-depressed individuals. Other sex- and age-related effects are reported. The results suggest that new versions of the DSM should consider an increase of impulsivity and a decrease in plasticity of behavior as criteria symptoms of MD.