Testosterone, cortisol, and serotonin as key regulators of social aggression: A review and theoretical perspective

In human and non-human animals the steroid hormones cortisol and testosterone are involved in social aggression and recent studies suggest that these steroids might jointly regulate this behavior. It has been hypothesized that the imbalance between cortisol and testosterone levels is predictive for aggressive psychopathology, with high testosterone to cortisol ratio predisposing to a socially aggressive behavioral style. In this review, we focus on the effects of cortisol and testosterone on human social aggression, as well as on how they might modulate the aggression circuitry of the human brain. Recently, serotonin is hypothesized to differentiate between impulsive and instrumental aggression, and we will briefly review evidence on this hypothesis. The aim of this article is to provide a theoretical framework for the role of steroids and serotonin in impulsive social aggression in humans

Myocardial Infarction-induced N-terminal Fragment of Cardiac Myosin-binding Protein C ( cMyBP-C) Impairs Myofilament Function in Human Myocardium

Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, is proteolyzed post-MI in humans, which results in an N-terminal fragment, C0-C1f. The presence of C0-C1f in cultured cardiomyocytes results in decreased Ca(2+) transients and cell shortening, abnormalities sufficient for the induction of heart failure in a mouse model. However, the underlying mechanisms remain unclear. Here, we investigate the association between C0-C1f and altered contractility in human cardiac myofilaments in vitro. To accomplish this, we generated recombinant human C0-C1f (hC0C1f) and incorporated it into permeabilized human left ventricular myocardium. Mechanical properties were studied at short (2 μm) and long (2.3 μm) sarcomere length (SL). Our data demonstrate that the presence of hC0C1f in the sarcomere had the greatest effect at short, but not long, SL, decreasing maximal force and myofilament Ca(2+) sensitivity. Moreover, hC0C1f led to increased cooperative activation, cross-bridge cycling kinetics, and tension cost, with greater effects at short SL. We further established that the effects of hC0C1f occur through direct interaction with actin and α-tropomyosin. Our data demonstrate that the presence of hC0C1f in the sarcomere is sufficient to induce depressed myofilament function and Ca(2+) sensitivity in otherwise healthy human donor myocardium. Decreased cardiac function post-MI may result, in part, from the ability of hC0C1f to bind actin and α-tropomyosin, suggesting that cleaved C0-C1f could act as a poison polypeptide and disrupt the interaction of native cardiac myosin-binding protein C with the thin filament

Increased neural response to peer rejection associated with adolescent depression and pubertal development.

Sensitivity to social evaluation has been proposed as a potential marker or risk factor for depression, and has also been theorized to increase with pubertal maturation. This study utilized an ecologically valid paradigm to test the hypothesis that adolescents with major depressive disorder (MDD) would show altered reactivity to peer rejection and acceptance relative to healthy controls in a network of ventral brain regions implicated in affective processing of social information. A total of 48 adolescents (ages 11-17), including 21 with a current diagnosis of MDD and 27 age- and gender-matched controls, received rigged acceptance and rejection feedback from fictitious peers during a simulated online peer interaction during functional neuroimaging. MDD youth showed increased activation to rejection relative to controls in the bilateral amygdala, subgenual anterior cingulate, left anterior insula and left nucleus accumbens. MDD and healthy youth did not differ in response to acceptance. Youth more advanced in pubertal maturation also showed increased reactivity to rejection in the bilateral amygdala/parahippocampal gyrus and the caudate/subgenual anterior cingulate, and these effects remained significant when controlling for chronological age. Findings suggest that increased reactivity to peer rejection is a normative developmental process associated with pubertal development, but is particularly enhanced among youth with depression