Depression is now the leading health condition in Western societies, and also the leading cause of disability. Its causes remain opaque, and although we have had a strong gravitation to both molecular reductionism and serial primary factor concepts in biological psychiatry, many nominated ‘primary factors’ are in fact deeply interactive with each other rather than any version of isolated ‘prime movers’.
Additionally, depression may have a privileged and special relationship with several classes of common organismic stressors, particularly social loss/defeat, physical pain, and inflammation, especially from innate immunity. Biological drivers within the depressive process however have been indexed to virtually every neural signaling and regulatory system influencing the brain: three classic amine systems, the cholinergic system, multiple social neuropeptide systems, small molecule GABA and glutamate systems, the immune system, the HPA stress axis and perhaps beyond that, several endocrine systems. These various factors create complex interactive loops in their relationships with each other, and where trailing and leading edges are often elusive, suggesting a highly distributed causality into a final shared trajectory. Depression also has sibling relationships (indexed by heavy mechanistic overlap) with other conserved behavioral shutdown mechanisms, particularly sickness behavior, but also hibernation, suggesting mammalian conservation.
The crisis of depression has been amplified by the protraction of the Covid 19 pandemic, which has underscored (among other things) the intimate relationship between sickness behavior and risk for depression, and how social isolation and the pre-existing epidemic of loneliness in Western societies have been further exacerbated in Covid 19. Emerging pro-inflammatory perspectives on depression that emphasize its intrinsic kinship with sickness behavior have been complemented by an increasing focus on moderating pro-inflammatory lifestyles, as both preventing and potentially treating or at least mitigating depression, most especially exercise but also improved sleep and reduction of pro-inflammatory diet patterns.
The goal would be to assemble pieces of disparate literatures, often not assembled in the same place, that might together constitute much of the full fabric of a ‘big picture’ of depression, including summaries of recent paradigm shifting treatment options (psychedelic therapies, ketamine and also EBS results).
One can see from this list of topics in the background statement that we are deliberately trying to cast a wide net. Part of the problem with depression has been a monocular focus and a serial gravitation to single factor theories, and an unproductive search for a prime mover when the evidence argues increasingly that depression emerges from recursive interactions between many neurobiological systems. On the treatment side, there is also much evidence for multiple and disparate antidepressant interventions and putative mechanisms. This multifactorial nature of both the syndrome and its treatments have contrasted with the general assumption that reductive molecular approaches, often linked to a putative primary factor theory, will eventually yield better rational therapeutics, but this hope for the most part has not been realized.
Contributions might summarize research related to all of the relevant neurobiological systems, most particularly the immune system, and the stress axis, two systems traditionally modelled in isolation but where changes in these systems are conjoined in prototypical depressogenic social stressors of loss and defeat. Summaries of changes in relevant aminergic, peptidergic and small molecule GABA and glutamate systems in depression, would also be valuable. Given that depression is associated with large-scale corticolimbic network changes, summaries of work neural network perspectives would be valuable.
Summaries of outcome research in traditional pharmacology, in various modes and types of psychotherapy, and other nontraditional models of intervention (such as yoga, meditation, exercise, nutritional interventions, improved sleep hygiene etc. etc.) would also be a contribution. Additionally, summaries of relevant animal models, along with summaries of work on emerging biomarkers, two areas with many challenges, but therefore also much opportunity for scientific progress, would also be welcomed. Summaries of newer non-traditional pharma approaches with ketamine and psychedelics would be valuable. Summaries of EBS results would also be welcomed. Because of the large number of relevant topical areas, we are seeking overviews and literature summaries rather than primary empirical studies. Summaries of many relevant empirical studies that have already been vetted through standard peer review of course would be clearly part of the topical reviews.
Depression is now the leading health condition in Western societies, and also the leading cause of disability. Its causes remain opaque, and although we have had a strong gravitation to both molecular reductionism and serial primary factor concepts in biological psychiatry, many nominated ‘primary factors’ are in fact deeply interactive with each other rather than any version of isolated ‘prime movers’.
Additionally, depression may have a privileged and special relationship with several classes of common organismic stressors, particularly social loss/defeat, physical pain, and inflammation, especially from innate immunity. Biological drivers within the depressive process however have been indexed to virtually every neural signaling and regulatory system influencing the brain: three classic amine systems, the cholinergic system, multiple social neuropeptide systems, small molecule GABA and glutamate systems, the immune system, the HPA stress axis and perhaps beyond that, several endocrine systems. These various factors create complex interactive loops in their relationships with each other, and where trailing and leading edges are often elusive, suggesting a highly distributed causality into a final shared trajectory. Depression also has sibling relationships (indexed by heavy mechanistic overlap) with other conserved behavioral shutdown mechanisms, particularly sickness behavior, but also hibernation, suggesting mammalian conservation.
The crisis of depression has been amplified by the protraction of the Covid 19 pandemic, which has underscored (among other things) the intimate relationship between sickness behavior and risk for depression, and how social isolation and the pre-existing epidemic of loneliness in Western societies have been further exacerbated in Covid 19. Emerging pro-inflammatory perspectives on depression that emphasize its intrinsic kinship with sickness behavior have been complemented by an increasing focus on moderating pro-inflammatory lifestyles, as both preventing and potentially treating or at least mitigating depression, most especially exercise but also improved sleep and reduction of pro-inflammatory diet patterns.
The goal would be to assemble pieces of disparate literatures, often not assembled in the same place, that might together constitute much of the full fabric of a ‘big picture’ of depression, including summaries of recent paradigm shifting treatment options (psychedelic therapies, ketamine and also EBS results).
One can see from this list of topics in the background statement that we are deliberately trying to cast a wide net. Part of the problem with depression has been a monocular focus and a serial gravitation to single factor theories, and an unproductive search for a prime mover when the evidence argues increasingly that depression emerges from recursive interactions between many neurobiological systems. On the treatment side, there is also much evidence for multiple and disparate antidepressant interventions and putative mechanisms. This multifactorial nature of both the syndrome and its treatments have contrasted with the general assumption that reductive molecular approaches, often linked to a putative primary factor theory, will eventually yield better rational therapeutics, but this hope for the most part has not been realized.
Contributions might summarize research related to all of the relevant neurobiological systems, most particularly the immune system, and the stress axis, two systems traditionally modelled in isolation but where changes in these systems are conjoined in prototypical depressogenic social stressors of loss and defeat. Summaries of changes in relevant aminergic, peptidergic and small molecule GABA and glutamate systems in depression, would also be valuable. Given that depression is associated with large-scale corticolimbic network changes, summaries of work neural network perspectives would be valuable.
Summaries of outcome research in traditional pharmacology, in various modes and types of psychotherapy, and other nontraditional models of intervention (such as yoga, meditation, exercise, nutritional interventions, improved sleep hygiene etc. etc.) would also be a contribution. Additionally, summaries of relevant animal models, along with summaries of work on emerging biomarkers, two areas with many challenges, but therefore also much opportunity for scientific progress, would also be welcomed. Summaries of newer non-traditional pharma approaches with ketamine and psychedelics would be valuable. Summaries of EBS results would also be welcomed. Because of the large number of relevant topical areas, we are seeking overviews and literature summaries rather than primary empirical studies. Summaries of many relevant empirical studies that have already been vetted through standard peer review of course would be clearly part of the topical reviews.