The relevance of chronic stress for the acute stress reaction in people at elevated risk for psychosis.

BACKGROUND: Theoretical models and empirical evidence suggest that alterations of the acute stress reaction are a vulnerability indicator of psychosis. However, more studies are needed that use laboratory stressors and a multimodal assessment of the stress reaction. Furthermore, it needs to be clarified whether alterations of the acute stress reaction result from the chronic stress level. METHODS: We recruited participants at familial (n = 32) and symptomatic risk (n = 43) for psychosis and a low-risk control group (n = 35). We assessed their chronic stress levels (self-report, hair cortisol concentrations) and self-reported (subjective, affective, paranoia) as well as physiological (heart rate, skin conductance level, cortisol) reactions to the Trier Social Stress Test. RESULTS: The groups did not differ in their acute stress reaction but both at-risk groups showed higher levels of self-reported chronic stress. Chronic stress predicted changes in negative affect, paranoia and skin conductance level in the total sample. CONCLUSIONS: We could not confirm that alterations of the acute stress reaction are an early vulnerability indicator of psychosis and conclude that they might develop at a later time-point on the trajectory to psychosis. The high chronic stress level of the at-risk groups might constitute an intermediate state that increases the likelihood of altered stress reactions in later risk stages. To test this, future work needs to investigate the temporal order between chronic stress levels, acute stress reactions and symptom development across the psychosis continuum.

Hair cortisol concentrations as an indicator of potential HPA axis hyperactivation in risk for psychosis.

A chronic hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis is assumed to be an important indicator of vulnerability for psychosis. Despite the considerable research on this topic, putative social origins of HPA axis hyperactivation have received little attention in the literature so far. Also, the inconsistency of previous findings calls for new and reliable methods in the assessment of HPA axis activation. To address these issues, we used hair cortisol concentrations as an indicator of chronic HPA axis activation in participants at elevated risk for psychosis (clinical risk: n = 43, familial risk: n = 32) and low-risk controls (n = 35), and assessed its relation with a variety of social stressors. We also tested the interaction effect between social stressors and familial risk status on hair cortisol concentrations (moderation analysis). Participants at elevated risk for psychosis did not show significantly higher hair cortisol concentrations than low-risk controls. However, severe social stressors (child abuse experiences, traumatic events) predicted hair cortisol concentrations in the total sample. This relationship was not significantly moderated by familial risk status (as a marker of genetic risk). The results challenge the assumption that HPA axis hyperactivation is an early vulnerability indicator for psychosis but leave the possibility that it manifests only at more severe risk stages. Furthermore, the findings suggest that acquired experiences contribute to the emergence of HPA axis hyperactivation, which might occur via a gene-environment correlation rather than via a gene-environment interaction.

Neural mechanisms of perceptual decision-making and their link to neuropsychiatric symptoms in multiple sclerosis.

BACKGROUND: Decision-making (DM) capabilities are impaired in multiple sclerosis (MS). A variety of researchers hypothesized that this impairment is associated with reduced quality of life (QoL) and neuropsychiatric symptoms. Studies explicitly testing this hypothesis, however, are rare, provided inconclusive results, or evaluated only a limited selection of DM domains. Consequently, we conducted the first MS study on perceptual DM (e.g. deciding whether a car will fit into a parking lot based on a visual percept) to test this assumption. METHODS: Specifically, we used an fMRI task that measured brain activity in 30 MS patients and 19 healthy controls (HCs) while the participants repeatedly decided whether objects referenced indirectly via their written object names would fit into a shoebox to investigate neural mechanisms of perceptual DM. The objects varied in size and thus decision difficulty. From these data, we determined voxel-wise brain activity parameters reflecting (i) decision difficulty and (ii) decision speed and related them to behavioral DM performance, QoL, mild to moderate depressive symptoms, and fatigue. RESULTS: Patients showed reduced DM performance. Activity reflecting decision difficulty in the middle temporal gyrus was negatively related to DM performance across MS patients and HCs; activity reflecting decision speed in MS patients was associated with depressive symptoms and fatigue in areas of the dorsal visual stream. CONCLUSION: The study shows that the perceptual DM capacity is reduced in MS. Moreover, the link between neural mechanisms of perceptual DM and neuropsychiatric symptoms suggests that an impairment in this domain is clinically relevant.

Stress levels in psychosis: Do body and mind diverge?

Discrepancies between subjective and physiological stress levels may help to explain why stress leads to psychosis. We examined self-reported and physiological stress levels (heart rate, skin conductance level, cortisol level) during two conditions (noise stressor, no stressor) in patients with psychotic disorders (n = 35), patients with depression (n = 30), and healthy controls (n = 28), expecting larger discrepancies between self-reported and physiological stress levels in patients with psychosis than in controls. Difference values were calculated from standardized stress levels. Compared to healthy controls, patients with psychosis showed larger discrepancies between self-reported stress and skin conductance levels and between self-reported stress and cortisol levels. The discrepancies were similar in both patient groups and in both conditions. Paranoid symptoms, emotion awareness and antipsychotic dose were associated with the discrepancies. Future research needs to clarify whether the discrepancies causally contribute to psychotic symptoms or reflect secondary processes.

Brain activity, regional gray matter loss, and decision-making in multiple sclerosis.

BACKGROUND: Decision-making (DM) abilities deteriorate with multiple sclerosis (MS) disease progression which impairs everyday life and is thus clinically important. OBJECTIVE: To investigate the underlying neurocognitive processes and their relation to regional gray matter (GM) loss induced by MS. METHODS: We used a functional magnetic resonance imaging (fMRI) Iowa Gambling Task to measure DM-related brain activity in 36 MS patients and 21 healthy controls (HC). From this activity, we determined neural parameters of two cognitive stages, a deliberation ("choice") period preceding a choice and a post-choice ("feedback") stage reporting decision outcomes. These measures were related to DM separately in intact and damaged GM areas as determined by a voxel-based morphometry analysis. RESULTS: Severely affected patients (with high lesion burden) showed worse DM-learning than HC ( t = -1.75, p = 0.045), moderately affected (low lesion burden) did not. Activity in the choice stage in intact insular ( t = 4.60, pFamily-Wise Error [FWE] corrected = 0.034), anterior cingulate ( t = 4.50, pFWE = 0.044), and dorsolateral prefrontal areas ( t = 4.43, pFWE = 0.049) and in insular areas with GM loss ( t = 3.78, pFWE = 0.011) was positively linked to DM performance across patients with severe tissue damage and HC. Furthermore, activity in intact orbitofrontal areas was positively linked to DM-learning during the feedback stage across these participants ( t = 4.49, pFWE = 0.032). During none of the stages, moderately affected patients showed higher activity than HC, which might have indicated preserved DM due to compensatory activity. CONCLUSION: We identified dysregulated activity linked to impairment in specific cognitive stages of reward-related DM. The link of brain activity and impaired DM in areas with MS-induced GM loss suggests that this deficit might be tightly coupled to MS neuropathology.