Thomas Vaessen

The dopaminergic response to acute stress in health and psychopathology: A systematic review

Previous work in animals has shown that dopamine (DA) in cortex and striatum plays an essential role in stress processing. For the first time, we systematically reviewed the in vivo evidence for DAergic stress processing in health and psychopathology in humans. All studies included (n studies=25, n observations=324) utilized DA D2/3 positron emission tomography and measured DAergic activity during an acute stress challenge. The evidence in healthy volunteers (HV) suggests that physiological, but not psychological, stress consistently increases striatal DA release. Instead, increased medial prefrontal cortex (mPFC) DAergic activity in HV was observed during psychological stress. Across brain regions, stress-related DAergic activity was correlated with the physiological and psychological intensity of the stressor. The magnitude of stress-induced DA release was dependent on rearing conditions, personality traits and genetic variations in several SNPs. In psychopathology, preliminary evidence was found for stress-related dorsal striatal DAergic hyperactivity in psychosis spectrum and a blunted response in chronic cannabis use and pain-related disorders, but results were inconsistent. Physiological stress-induced DAergic activity in striatum in HV may reflect somatosensory properties of the stressor and readiness for active fight-or-flight behavior. DAergic activity in HV in the ventral striatum and mPFC may be more related to expectations about the stressor and threat evaluation, respectively. Future studies with increased sample size in HV and psychopathology assessing the functional relevance of stress-induced DAergic activity, the association between cortical and subcortical DAergic activity and the direct comparison of different stressors are necessary to conclusively elucidate the role of the DA system in the stress response.

Early-Life Stress Affects Stress-Related Prefrontal Dopamine Activity in Healthy Adults, but Not in Individuals with Psychotic Disorder

Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual’s fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0–11 years) and late (12–18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23) = -3.35, p = .004) and late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11) = 3.06, p = .016) as well as late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11) = -2, p = .07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11) = .01, p = .99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis.

Acceptance and Commitment Therapy in Daily Life Training: A Feasibility Study of an mHealth Intervention

Background With the development of mHealth, it is possible to treat patients in their natural environment. Mobile technology helps to bridge the gap between the therapist’s office and the “real world.” The ACT in Daily Life training (ACT-DL) was designed as an add-on intervention to help patients practice with acceptance and commitment therapy in their daily lives. The ACT-DL consists of two main components: daily monitoring using experience sampling and ACT training in daily life. Objectives To assess the acceptability and feasibility of the ACT-DL in a general outpatient population. A secondary objective was to conduct a preliminary examination of the effectiveness of the ACT-DL. Methods An observational comparative study was conducted. The experimental group consisted of 49 patients who volunteered for ACT-DL, and the control group consisted of 112 patients who did not volunteer. As part of an inpatient treatment program, both groups received a 6-week ACT training. Participants went home to continue their treatment on an outpatient basis, during which time the experimental group received the 4-week add-on ACT-DL. Acceptability and feasibility of the ACT-DL was assessed weekly by telephone survey. Effectiveness of the ACT-DL was evaluated with several self-report questionnaires ( Flexibility Index Test (FIT-60): psychological flexibility, Brief Symptom Inventory: symptoms, Utrechtse Coping List: coping, and Quality of life visual analog scale (QoL-VAS): quality of life). Results More than three-quarters of the participants (76%) completed the full 4-week training. User evaluations showed that ACT-DL stimulated the use of ACT in daily life: participants practiced over an hour a week (mean 78.8 minutes, standard deviation 54.4), doing 10.4 exercises (standard deviation 6.0) on average. Both ACT exercises and metaphors were experienced as useful components of the training (rated 5 out of 7). Repeated measures ANCOVA did not show significant effects of the ACT-DL on psychological flexibility (P=.88), symptoms (P=.39), avoidant coping (P=.28), or quality of life (P=.15). Conclusions This is the first study that uses experience sampling to foster awareness in daily life in combination with acceptance and commitment therapy to foster skill building. Adherence to the ACT-DL was high for an intensive mHealth intervention. ACT-DL appears to be an acceptable and feasible mHealth intervention, suitable for a broad range of mental health problems. However, short-term effectiveness could not be demonstrated. Additional clinical trials are needed to examine both short-term and long-term effects.

Experience sampling methodology in mental health research: new insights and technical developments

In the mental health field, there is a growing awareness that the study of psychiatric symptoms in the context of everyday life, using experience sampling methodology (ESM), may provide a powerful and necessary addition to more conventional research approaches. ESM, a structured self‐report diary technique, allows the investigation of experiences within, and in interaction with, the real‐world context. This paper provides an overview of how zooming in on the micro‐level of experience and behaviour using ESM adds new insights and additional perspectives to standard approaches. More specifically, it discusses how ESM: a) contributes to a deeper understanding of psychopathological phenomena, b) allows to capture variability over time, c) aids in identifying internal and situational determinants of variability in symptomatology, and d) enables a thorough investigation of the interaction between the person and his/her environment and of real‐life social interactions. Next to improving assessment of psychopathology and its underlying mechanisms, ESM contributes to advancing and changing clinical practice by allowing a more fine‐grained evaluation of treatment effects as well as by providing the opportunity for extending treatment beyond the clinical setting into real life with the development of ecological momentary interventions. Furthermore, this paper provides an overview of the technical details of setting up an ESM study in terms of design, questionnaire development and statistical approaches. Overall, although a number of considerations and challenges remain, ESM offers one of the best opportunities for personalized medicine in psychiatry, from both a research and a clinical perspective.

Is sensitivity to daily stress predictive of onset or persistence of psychopathology

PURPOSE The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology. METHODS We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15-34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model. RESULTS Linear analyses showed that emotional stress reactivity was not associated with onset (β=.02; P=.56) or persistence (β=-.01; P=.78) of symptoms. There was a significant effect of baseline symptom score (β=.53; P<.001) and average negative affect (NA: β=.19; P<.001) on follow-up symptoms. Using the categorical approach, we found that affective sensitivity to mild (β=.25; P<.001), but not moderate (β=-.03; P=.65) or severe (β=-.06; P=.42), stressors was associated with symptom persistence one year later. DISCUSSION We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology.

Overall cortisol, diurnal slope, and stress reactivity in psychosis: An experience sampling approach

OBJECTIVE Results from experimental studies suggest that psychosis and psychosis liability are associated with increased cortisol levels and blunted cortisol reactivity, and that use of antipsychotics may reduce these aberrations. Here, we report on overall cortisol, diurnal slope, and cortisol stress reactivity in everyday life in psychosis and psychosis liability using the experience sampling method (ESM). METHODS Our sample consisted of individuals diagnosed with psychotic disorder currently on (MPD; n = 53) or off antipsychotic medication (NMPD; n = 20), first-degree relatives of psychotic patients (REL; n = 47), and healthy volunteers (HV; n = 67). Saliva samples were collected throughout the day on six consecutive days and analyzed for cortisol levels. Simultaneously, stressfulness of the current activity was assessed with ESM questionnaires. RESULTS We found no group differences in overall cortisol level between groups, but REL had a steeper diurnal slope than HV; in MPD a trend was found in the same direction. Regarding reactivity to stressful activities, results indicated attenuation of the cortisol response in both patient groups compared to HV. CONCLUSION These results do not confirm reports of increased cortisol levels in psychosis, but provide evidence of stress-related cortisol alterations in everyday life.