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Depressive disorders that onset in the juvenile years have been linked to far reaching adverse consequences, making it imperative to elucidate key mechanisms and contributory factors. Excessive use of regulatory responses that exacerbate sadness (maladaptive mood repair) or insufficient use of regulatory responses that reduce it (adaptive mood repair) may reflect behavioral mechanisms of depression risk. Cardiac vagal control, indexed by patterns of respiratory sinus arrhythmia (RSA), has received attention as a putative physiological risk factor for depression. Although mood repair and RSA are related, the nature of this relationship is not well characterized in the context of depression risk. Therefore, we tested alternative models of the relationships between RSA patterns (at rest and in response to a sad film), trait mood repair, and the effectiveness of a mood repair response in the laboratory (state mood repair) among adolescents with depression histories (n=210) and emotionally healthy peers (n=161). In our data, a mediation model best explained the association between the key constructs: Adolescents with normative RSA patterns exhibited lower levels of depression and trait maladaptive mood repair, and benefited more from instructed (state) mood repair in the laboratory. By contrast, adolescents with atypical RSA patterns exhibited higher levels of depression and dispositional maladaptive mood repair, which, in turn, mediated the relations of RSA patterns and depression symptoms. Atypical RSA patterns also predicted reduced benefits from laboratory mood repair.

Objective Depression in adults is associated with risk factors for cardiovascular disease (CVD). It is unclear, however, when the association between clinical depression and cardiac risk factors develops, or how early in life this association can be detected. Methods In an ongoing study of pediatric depression, we compared CVD risk factors, including smoking, obesity, physical activity level, sedentary behavior, and parental history of CVD, across three samples of adolescents: probands with established histories of childhood-onset major depressive disorder (MDD; N=210), never-depressed siblings of probands (N=195), and controls with no history of any major psychiatric disorder (N=161). Results When assessed during adolescence, 85% of the probands were not in a major depressive episode. Nevertheless, at that assessment, probands had a higher prevalence of regular smoking ([odds ratio [OR] 12.54, 95% confidence interval [CI] = 4.36–36.12) and were less physically active than controls (OR .59, CI = .43–.81) and siblings (OR .70, CI = .52–.94), and had a higher rate of obesity than did controls (OR 3.67, CI = 1.42–9.52). Parents of probands reported high rates of CVD (significantly higher than did parents of controls), including myocardial infarction and CVD-related hospitalization (ORs 1.62–4.36; CIs = 1.03–15.40). Differences in CVD risk factors between probands and controls were independent of parental CVD. Conclusions Major depression in childhood is associated with an unfavorable CVD risk profile in adolescence, and risks for pediatric depression and CVD may coincide in families. Effective prevention and treatment of childhood depression may be a means to reduce the incidence of adult CVD.

Migraine can be triggered by systemic administration of the nitric oxide (NO) donor nitroglycerin (NTG) and by abrupt falls in plasma oestradiol. Calmodulin-dependent protein kinase II (CamKII) present in superficial dorsal horns is thought to play a role in sensitization of central nociceptors, a phenomen present in migraineurs. We therefore examined in rats the expression of CamKII in the caudal trigeminal nucleus (TNC) after subcutaneous NTG (10 mg/kg) and its modulation by oestrogen. In male rats and in ovariectomized females, after 4 h NTG increased significantly CamKII expression in the superficial layers of TNC, but not in the upper thoracic spinal cord. NTG had no effect on CamKII expression in oestradiol-treated ovariectomized animals. Thus NTG, i.e. NO, selectively enhances CamKII in the rat TNC and oestradiol blocks this effect. These data may help to understand the mechanisms by which NO triggers migraine attacks and oestrogens influence migraine severity.

Migraine is a common neurological condition, causing high disability, but the pathomechanism of the disease is not yet fully understood. Activation of the trigeminovascular system could play a crucial role in the manifestation of the symptoms, but initial step of this activation remains unknown. Functional imaging studies have revealed that certain brainstem areas, referred to as migraine generators, are activated during a migraine attack, including the dorsal raphe, the periaqueductal gray, the locus coeruleus, and the nucleus raphe magnus. However, the studies performed to date have not demonstrated whether this activation is a trigger or a consequence of the migraine attack. With the aim of evaluating the functional relationship between activation of the trigeminal system and migraine generators, we examined the changes in c-Fos immunoreactivity in the above-mentioned nuclei after stimulation of the trigeminal ganglion, an animal model for trigeminovascular activation. The stimulation led to significant increases in the number of c-Fos immunoreactive cells in the nucleus raphe magnus and in the caudal part of the spinal trigeminal nucleus, 2 and 4 h after the stimulation. Activation of the trigeminal system failed to exhibit uniform activation of the brain stem nuclei related to migraine. Our results suggest that the activation of the trigeminal system in the rat by electrical stimulation of the trigeminal ganglion leads to the activation of the descending pain modulatory system, but not to the activation of "migraine generator" nuclei. Therefore, the activity pattern seen in functional studies may reflect a unique feature, exclusively present in migraine.

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These findings suggest that metabolites deriving from COX-2 (but not COX-1) may be the most important factors in the NTG-induced nNOS expression. These data could help to better understand the pathogenesis of headaches and the action of antimigraine drugs.