There is a steadily growing literature on the role of the immune system in psychiatric disorders. So far, these advances have largely taken the form of correlations between specific aspects of inflammation (e.g. blood plasma levels of inflammatory markers, genetic mutations in immune pathways, viral or bacterial infection) with the development of neuropsychiatric conditions such as autism, bipolar disorder, schizophrenia and depression. A fundamental question remains open: why are psychiatric disorders and immune responses intertwined? To address this would require a (...) step back from a historical mind–body dualism that has created such a dichotomy. We propose three contributions of active inference when addressing this question: translation, unification, and simulation. To illustrate these contributions, we consider the following questions. Is there an immunological analogue of sensory attenuation? Is there a common generative model that the brain and immune system jointly optimise? Can the immune response and psychiatric illness both be explained in terms of self-organising systems responding to threatening stimuli in their external environment, whether those stimuli happen to be pathogens, predators, or people? Does false inference at an immunological level alter the message passing at a psychological level (or vice versa) through a principled exchange between the two systems? (shrink)

BackgroundAntipsychotic-induced weight gain is a contributing factor in the reduced life expectancy reported amongst people with psychotic disorders. CYP2D6 is a liver enzyme involved in the metabolism of many commonly used antipsychotic medications. We investigated if CYP2D6 genetic variation influenced weight or BMI among people taking antipsychotic treatment.MethodsWe conducted a systematic review and a random effects meta-analysis of publications in Pubmed, Embase, PsychInfo, and CENTRAAL that had BMI and/or weight measurements of patients on long-term antipsychotics by their CYP2D6-defined metabolic groups.ResultsTwelve (...) studies were included in the systematic review. All cohort studies suggested that the presence of reduced-function or non-functional alleles for CYP2D6 was associated with greater antipsychotic-induced weight gain, whereas most cross-sectional studies did not find any significant associations. Seventeen studies were included in the meta-analysis with clinical data of 2,041 patients, including 93 poor metabolizers, 633 intermediate metabolizers, 1,272 normal metabolizers, and 30 UMs. Overall, we did not find associations in any of the comparisons made. The estimated pooled standardized differences for the following comparisons were PM versus NM; weight = –0.07, BMI = 0.40. IM versus NM; weight = 0.09 and BMI = 0.09. UM versus EM; weight = 0.01 and BMI = –0.08.ConclusionOur systematic review of cohort studies suggested that CYP2D6 poor metabolizers have higher BMI than normal metabolizers, but the data of cross-sectional studies and the meta-analysis did not show this association. Although our review and meta-analysis constitutes one of the largest studies with comprehensively genotyped samples, the literature is still limited by small numbers of participants with genetic variants resulting in poor or UMs status. We need further studies with larger numbers of extreme metabolizers to establish its clinical utility in antipsychotic treatment. CYP2D6 is a key gene for personalized prescribing in mental health. (shrink)

Animal personality refers to the consistency of variation in behavior among individuals which may be the driving force behind variations in complex behaviors as well. Individual personality could predict how well an organism would perform in behavior and cognition related tasks, as well as survive and thrive in its environment. Therefore, we would expect inter-individual variations in many behaviors, which would persist even if habituation to the experimental setup occurs, which generally results in convergence of behavior. Our study used wild-caught (...) zebrafish from three natural habitats with differing ecological regimes, to understand how consistency and repeatability in specific traits such as boldness, exploration, and spatial ability varies across and within populations even when habituation causes change in behavior. We found that the extent of individual variation differs between populations, with dynamic habitats showing similar repeatability. This indicates that habitat conditions are important drivers of individual variation in addition to other factors, such as sex or size of individuals within populations. Although we found that sex and size played an important role within some populations for some behaviors, in others, the variation was likely caused by other factors, for which we have not accounted. This study underlines the importance of studying inter-individual differences as the phenomenon that underpins multiple behavioral traits and explains the possible role of environmental and inherent factors that drive these differences. (shrink)

People who habituate to stress show a repetition-induced response attenuation—neuroendocrine, cardiovascular, neuroenergetic, and emotional—when exposed to a threatening environment. But the exact dynamics underlying stress habituation remain obscure. The free energy principle offers a unifying account of self-organising systems such as the human brain. In this paper, we elaborate on how stress habituation can be explained and modelled using the free energy principle. We introduce habituation priors that encode the agent’s tendency for stress habituation and incorporate them in the agent’s (...) decision-making process. Using differently shaped goal priors—that encode the agent’s goal preferences—we illustrate, in two examples, the optimising behaviour of agents. We show that habituation minimises free energy by reducing the precision of goal preferences. Reducing the precision of goal priors means that the agent accepts adverse states. Acceptance or tolerance of adverse outcomes may explain why habituation causes people to exhibit an attenuation of the stress response. Given that stress habituation occurs in brain regions where goal priors are encoded, i.e., in the ventromedial prefrontal cortex and that these priors are encoded as sufficient statistics of probability distributions, our approach seems plausible from an anatomical-functional and neuro-statistical point of view. The ensuing formal and generalisable account—based on the free energy principle—further motivate our novel treatment of stress habituation. Our analysis suggests that stress habituation has far-reaching consequences, protecting against the harmful effects of toxic stress, but on the other hand making the acceptability of precarious living conditions and the development of the obese type 2 diabetes mellitus phenotype more likely. (shrink)