Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine.

OBJECTIVE: In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance. DESIGN: This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals. RESULTS: After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression. CONCLUSION: Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging.

Neuronal Circuits for Social Decision-Making and Their Clinical Implications.

Social living facilitates individual access to rewards, cognitive resources, and objects that would not be otherwise accessible. There are, however, some drawbacks to social living, particularly when competing for scarce resources. Furthermore, variability in our ability to make social decisions can be associated with neuropsychiatric disorders. The neuronal mechanisms underlying social decision-making are beginning to be understood. The momentum to study this phenomenon has been partially carried over by the study of economic decision-making. Yet, because of the similarities between these different types of decision-making, it is unclear what is a social decision. Here, we propose a definition of social decision-making as choices taken in a context where one or more conspecifics are involved in the decision or the consequences of it. Social decisions can be conceptualized as complex economic decisions since they are based on the subjective preferences between different goods. During social decisions, individuals choose based on their internal value estimate of the different alternatives. These are complex decisions given that conspecifics beliefs or actions could modify the subject's internal valuations at every choice. Here, we first review recent developments in our collective understanding of the neuronal mechanisms and circuits of social decision-making in primates. We then review literature characterizing populations with neuropsychiatric disorders showing deficits in social decision-making and the underlying neuronal circuitries associated with these deficits.

Social agent identity cells in the prefrontal cortex of interacting groups of primates.

The ability to interact effectively within social groups is essential to primate and human behavior. Yet understanding the neural processes that underlie the interactive behavior of groups or by which neurons solve the basic problem of coding for multiple agents has remained a challenge. By tracking the interindividual dynamics of groups of three interacting rhesus macaques, we discover detailed representations of the groups' behavior by neurons in the dorsomedial prefrontal cortex, reflecting not only the other agents' identities but also their specific interactions, social context, actions, and outcomes. We show how these cells collectively represent the interaction between specific group members and their reciprocation, retaliation, and past behaviors. We also show how they influence the animals' own upcoming decisions and their ability to form beneficial agent-specific interactions. Together, these findings reveal prefrontal neurons that code for the agency identity of others and a cellular mechanism that could support the interactive behavior of social groups.