Le stress psychologique induit une dérégulation de l’axe hypothalamo-hypophyso-surrénalien (HHS) qui entraîne une perturbation de la physiologie cérébrale. Ces éléments biologiques ont conduit à promouvoir l’hypothèse selon laquelle le stress pourrait influencer l’émergence de pathologies psychiatriques et en particulier l’émergence de la schizophrénie (transition psychotique). Cette revue de la littérature vise à réaliser un état des lieux de la question du stress dans la psychose et des méthodes d’investigation notamment le dosage du cortisol. Le rôle de la dérégulation de l’axe HHS dans le déclenchement de la schizophrénie est discuté. Cette dérégulation pourrait être une cause spécifique de l’entrée dans la maladie ou refléter uniquement la détresse psychologique liée à l’émergence des symptômes. La revue s’est attachée à mettre en relief les études sur l’implication du stress à différentes phases de la maladie psychotique. La littérature met en évidence une dérégulation de l’axe HHS dans la schizophrénie suivant le modèle vulnérabilité–stress. Cette dérégulation, présente dès la phase prodromique (sujets à ultra-haut risque) et dès le premier épisode psychotique, pourrait favoriser le déclenchement de la pathologie. En effet, la dérégulation de l’axe HHS et donc de la réponse au stress semble associée à l’émergence de symptômes psychotiques. Toutefois, les mécanismes précis de l’implication du stress dans le déclenchement de la maladie sont encore mal connus et nécessitent de plus amples investigations, d’autant que de nombreux facteurs confondants modulent le taux de cortisol et la réponse au stress, y compris la consommation de cannabis ou la prise de traitements. En outre, la réactivité au stress semble être modulée par des facteurs génétiques. La découverte de facteurs biologiques associés à la transition psychotique pourrait apporter une aide diagnostique et pronostique ainsi que des cibles thérapeutiques.

Psychiatric disorders are consistent with the gene x environment model, and non-specific environmental factors such as childhood trauma, urbanity, and migration have been implicated. All of these factors have in common to dysregulate the biological pathways involved in response to stress. Stress is a well-known precipitating factor implicated in psychiatric disorders such as depression, bipolar disorder, anxiety, and possibly schizophrenia. More precisely, psychosocial stress induces dysregulation of the hypothalamic-pituitary-adrenal axis (HPA) and could modify neurotransmission, which raises the question of the involvement of stress-related biological changes in psychotic disorders. Indeed, the literature reveals dysregulation of the HPA axis in schizophrenia. This dysregulation seems to be present in the prodromal phases (UHR subjects for ultra-high risk) and early schizophrenia (FEP for first episode psychosis). Thus, and following the stress–vulnerability model, stress could act directly on psychotic onset and precipitate the transition of vulnerable subjects to a full-blown psychosis.

The present paper reviews the literature on stress and onset of schizophrenia, with consideration for the causal role vs. associated role of HPA axis dysregulation in schizophrenia and the factors that influence it, in particular during prodromal and earlier phases. We also discuss different methods developed to measure stress in humans.

We performed a bibliographic search using the keywords ‘cortisol’, ‘glucocorticoid’, ‘HPA’ with ‘UHR’, ‘CHR’, ‘at-risk mental state’, ‘first episode psychosis’, ‘schizotypal’, ‘prodromal schizophrenia’ in Medline, Web of Knowledge (WOS), and EBSCO completed by a screening of the references of the selected articles.

Stress has been studied for many years in schizophrenia, either by subjective methods (questionnaires), or objective methods (standardized experimental protocols) with biological sampling and/or brain imaging methods. These methods have suggested a link between dysregulation of the HPA axis and psychotic symptoms both through abnormal basal levels of cortisol and flattened reactivity to social stress. Imaging results suggest indirect modifications, including abnormal pituitary or hippocampal volume. Several factors dysregulating the HPA axis have also been highlighted, such as consumption of drugs (i.e. cannabis), childhood trauma or genetic factors (such as COMT, or MTHFR variants). Psychological stress induces subcortical dopaminergic activation attributable to hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This dysregulation is present in the prodromal phase (UHR) in patients who have experienced a first psychotic episode (FEP) and in siblings of schizophrenic patients. Stress dysregulation is a plausible hypothesis to understand the psychosis onset.

The effect of stress on brain pathways could participate to the mechanisms underlying the onset of psychotic symptoms, both as a precipitating factor and as a marker of a predisposing vulnerability. This dysregulation fits into the gene x environment model: in subjects with genetic predispositions, stressful environmental factors can modify biological pathways implicated in psychiatric disorders, promoting the emergence of symptoms. However, many confounding factors obscure the literature, and further studies are needed in schizophrenic patients, UHR and FEP patients to clarify the precise role of stress in psychotic transition. Identification of stress biomarkers could help diagnosis and prognosis, and pave the way for specific care strategies based on stress-targeted therapies.