Paul Benjamin Badcock

Depression is one of the most disabling of all disorders across the community, yet many aspects of the disorder remain contentious. Psychosocial and biological perspectives are often placed in opposition to one another, which in part reflects a failure of our explanatory frameworks. The active inference account of brain function breaks down this dualism, demonstrating that bodily processes are deeply integrated with the social world. It shows us that there is no contradiction in understanding depression as a product of the social environment at the same time as having a brain basis and manifesting in biological symptoms. From an active inference perspective, depression can be thought of as a synaptopathy: a disorder that arises from alterations to the excitatory-inhibitory balance enacted at the synapse, reflecting the interoceptive precision-weightings that have changed in the context of psychosocial instability. Therapies that alleviate depressive symptoms act at different levels of the active inference framework to re-weight precision estimates and the confidence we have in our predictions: this is true for psychotherapies, lifestyle interventions and antidepressant medications. Their effectiveness is often only partial, and while different treatment modalities can complement one another, there is a need for continued development of new and better treatment options.

Systemic autoinflammatory disorders (SAID), immune dysregulation disorders with onset frequently occurring in youth, are defined by unprovoked inflammation. Research suggest inflammation is associated with the pathogenesis of mental ill-health. Separately, research has identified that mental ill-health is prevalent in people with immune dysregulation disorders compared to healthy controls or those with other chronic diseases, and the psychosocial impacts of these diseases on quality of life can be debilitating. This review aimed to broadly identify the extent and nature of research involving young people with SAIDs and mental ill-health. A scoping review was conducted across 6 databases of peer-reviewed articles referring to SAIDs and mental ill-health in young people. Of 727 studies, 41 met the inclusion criteria. Thirty-seven were observational studies, including 18 case studies or series. Four studies were treatment trials. Fourteen observational studies investigated the prevalence of mental ill-health in a SAID population with large sample sizes. Most studies were conducted in Türkiye, involving Behçet’s syndrome or familial Mediterranean fever and anxiety, depression, and psychosis were strongly represented. Findings suggest an association between mental ill-health and SAID activity in young people. Anxiety and depression were associated with some specific SAIDs duration, symptom severity, SAID flare recency and frequency, and SAID treatment effects. Co-occurrence and resolution of SAID flares and mental ill-health with treatment were frequent themes in case studies of some SAIDs. Further research is required on the prevalence and risk of developing mental ill-health among young people with SAIDs, along with associations between mental ill-health, other SAIDs and disease activity, other participant variables, and appropriate management of mental ill-health in this population.

The free energy principle is a formal theory of adaptive self-organising systems that emerged from statistical thermodynamics, machine learning and theoretical neuroscience and has since been translated into biologically plausible ‘process theories’ of cognition and behaviour, which fall under the banner of ‘active inference’. Despite the promise this theory holds for theorising, research and practical applications in psychology and psychiatry, its impact on these disciplines has only now begun to bear fruit. The aim of this treatment is to consider the extent to which active inference has informed theoretical progress in psychology, before exploring its contributions to our understanding and treatment of psychopathology. Despite facing persistent translational obstacles, progress suggests that active inference has the potential to become a new paradigm that promises to unite psychology’s subdisciplines, while readily incorporating the traditionally competing paradigms of evolutionary and developmental psychology. To date, however, progress towards this end has been slow. Meanwhile, the main outstanding question is whether this theory will make a positive difference through applications in clinical psychology, and its sister discipline of psychiatry.

The free energy principle (FEP) is a formulation of the adaptive, belief-driven behaviour of self-organizing systems that gained prominence in the early 2000s as a unified model of the brain

We provide a proof of principle for an evolutionary systems theory (EST) of depression. This theory suggests that normative depressive symptoms counter socioenvironmental volatility by increasing interpersonal support via social signalling and that this response depends upon the encoding of uncertainty about social contingencies, which can be targeted by neuromodulatory antidepressants. We simulated agents that committed to a series of decisions in a social two-arm bandit task before and after social adversity, which precipitated depressive symptoms. Responses to social adversity were modelled under various combinations of social support and pharmacotherapy. The normative depressive phenotype responded positively to social support and simulated treatments with antidepressants. Attracting social support and administering antidepressants also alleviated anhedonia and social withdrawal, speaking to improvements in interpersonal relationships. These results support the EST of depression by demonstrating that following adversity, normative depressed mood preserved social inclusion with appropriate interpersonal support or pharmacotherapy.