Affective Distress and the Selective Permeability of Environments: Ecological and Enactive Perspectives on Neural, Neuroendocrine, Neuroimmune and Gut–Brain Mechanisms

Environmental factors can exacerbate or alleviate affective distress, but not independently of neurobiological mechanisms. This narrative review examines the hypothalamic–pituitary–adrenal axis; threat circuitry (the amygdala, bed nucleus of the stria terminalis, hippocampus and prefrontal cortex); monoaminergic, neurotrophic and glutamatergic signaling; neuroinflammation; the kynurenine pathway; reward circuitry; and the microbiota–gut–brain axis. Each of these responds to features of the environment, or niche. The review proposes a coupling criterion: responses that track current conditions and remain responsive to their own consequences are likely to be adaptive, whereas those that persist after conditions change, or amplify through internal feedback loops, are likely to be pathological. Because a response can track real adversity and still cause harm, this criterion is offered as one dimension of clinical judgment alongside severity, duration and impairment. Two ideas help apply this standard. The first, from ecological psychology and enactive cognitive science, is that bodily processes and capacities shape the action possibilities, or affordances, that a person perceives. The second, selective permeability, describes how the same setting can be supportive for some people and hostile for others. The review compares the proposed account with predictive processing, allostatic load theory and the biopsychosocial model. It sets out candidate indicators and testable predictions and considers possible implications for assessment and care—all offered as hypotheses requiring empirical validation. The account brings the organism–environment relation into judgments of pathology, without implying that all distress is environmentally driven.