Physical co-morbidity among treatment resistant vs. treatment responsive patients with major depressive disorder

Co-morbid physical illness has been suggested to play an important role among the factors contributing to treatment resistance in patients with major depressive disorder. In the current study we compared the rate of physical co-morbidity, defined by ICD-10, among a large multicenter sample of 702 patients with major depressive disorder. A total of 356 of the participants were defined as treatment resistant depression (TRD) patients-having failed two or more adequate antidepressant trials. No significant difference was found between TRD and non-TRD participants in the prevalence of any ICD-10 category. This finding suggests that although physical conditions such as diabetes, thyroid dysfunction, hypertension, ischemic heart disease, and peptic diseases are often accompanied by co-morbid MDD, they do not necessarily have an impact on the course of MDD or the likelihood to respond to treatment. Marginally higher rates of co-morbid breast cancer, migraine and glaucoma were found among TRD participants. Possible explanations for these findings and their possible relation to TRD are discussed

Aggression is related to frontal serotonin-1A receptor distribution as revealed by PET in healthy subjects

Objectives: Various studies indicate that serotonin regulates impulsivity and the inhibitory control of aggression. Aggression is also known to be modified by sex hormones, which exert influence on serotonergic neurotransmission. The present study aimed to elucidate potential interactions between human aggression, the inhibitory serotonergic 5-HT1A receptor, and sex hormones. Experimental Design: Thirty-three healthy volunteers (16 women, aged 26.24 ± 5.5 yr) completed a validated questionnaire incorporating five dimensions of aggression. Subsequently, all subjects underwent positron emission tomography with the radioligand [carbonyl-11C]WAY-100635 to quantify 5-HT1A binding potentials (BPNDs) in the prefrontal cortex, limbic areas, and midbrain. Also, plasma levels of testosterone, 17ß-estradiol and sex hormone-binding globulin (SHBG) were measured. Relations between aggression scores, regional 5-HT1A BPNDs, and hormone levels were analyzed using correlations, multivariate analyses of variance, and linear regressions. Principal Observations: Statistical analyses revealed higher 5-HT1A receptor BPNDs in subjects exhibiting higher aggression scores in prefrontal (all P < 0.041) and anterior cingulate cortices (P = 0.016). More aggressive subjects were also characterized by lower SHBG levels (P = 0.015). Moreover, higher SHBG levels were associated with lower 5-HT1A BPNDs in frontal (P = 0.048) and cingulate cortices (all P < 0.013) and in the amygdala (P = 0.03). Conclusions: The present study provides first-time evidence for a specific interrelation between the 5-HT1A receptor distribution, sex hormones, and aggression in humans. Our findings point to a reduced down-stream control due to higher amounts or activities of frontal 5-HT1A receptors in more aggressive subjects, which is presumably modulated by sex hormones