Chronic social stressors and striatal dopamine functioning in humans: A systematic review of SPECT and PET studies.

The dopamine hypothesis of schizophrenia posits that elevated striatal dopamine functioning underlies the development of psychotic symptoms. Chronic exposure to social stressors increases psychosis risk, possibly by upregulating striatal dopamine functioning. Here we systematically review single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies that examined the relationship between chronic social stress exposure and in vivo striatal dopamine functioning in humans. We searched the scientific databases PubMed and PsycINFO from inception to August 2023. The quality of the included studies was evaluated with the ten-item Observational Study Quality Evaluation (PROSPERO: CRD42022308883). Twenty-eight studies were included, which measured different aspects of striatal dopamine functioning including dopamine synthesis capacity (DSC), vesicular monoamine transporter type 2 binding, dopamine release following a pharmacological or behavioral challenge, D2/3 receptor binding, and dopamine transporter binding. We observed preliminary evidence of an association between childhood trauma and increased striatal DSC and dopamine release. However, exposure to low socioeconomic status, stressful life events, or other social stressors was not consistently associated with altered striatal dopamine functioning. The quality of available studies was generally low. In conclusion, there is insufficient evidence that chronic social stressors upregulate striatal dopamine functioning in humans. We propose avenues for future research, in particular to improve the measurement of chronic social stressors and the methodological quality of study designs.

Protocol for the development and testing of the schiZotypy Autism Questionnaire (ZAQ) in adults: a new screening tool to discriminate autism spectrum disorder from schizotypal disorder.

BACKGROUND: Autism spectrum disorder (ASD) and schizotypal disorder (SD) both have a heterogenous presentation, with significant overlaps in symptoms and behaviour. Due to elevated recognition and knowledge of ASD worldwide, there is a growing rate of referrals from primary health professionals to specialised units. At all levels of assessment, the differential diagnostic considerations between ASD and SD exert major challenges for clinicians. Although several validated screening questionnaires exist for ASD and SD, none have differential diagnostic properties. Accordingly, in this study, we aim to develop a new screening questionnaire, the schiZotypy Autism Questionnaire (ZAQ), which provides a combined screening for both conditions, while also indicating the relative likelihood of each. METHODS: We aim to test 200 autistic patients and 100 schizotypy patients recruited from specialised psychiatric clinics and 200 controls from the general population (Phase 1). The results from ZAQ will be compared to the clinical diagnoses from interdisciplinary teams at specialised psychiatric clinics. After this initial testing phase, the ZAQ will be validated in an independent sample (Phase 2). CONCLUSIONS: The aim of the study is to investigate the discriminative properties (ASD vs. SD), diagnostic accuracy, and validity of the schiZotypy Autism Questionnaire (ZAQ). FUNDING: Funding was provided by Psychiatric Centre Glostrup, Copenhagen Denmark, Sofiefonden (Grant number: FID4107425), Trygfonden (Grant number:153588), Takeda Pharma. TRIAL REGISTRATION: Clinical Trials, NCT05213286, Registered 28 January 2022, clinicaltrials.gov/ct2/show/NCT05213286?cond = RAADS&draw = 2&rank = 1.

Childhood Trauma As a Mediator of the Association Between Autistic Traits and Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children Cohort.

BACKGROUND: Little is known on whether associations between childhood autistic traits and psychotic experiences persist into adulthood and whether genetic confounding and childhood trauma influence them. Here we investigate the associations between childhood autistic traits and psychotic experiences until young adulthood and assess the influence of schizophrenia polygenic risk and childhood traumatic experiences, using the Avon Longitudinal Study of Parents and Children (ALSPAC) population-based birth cohort. STUDY DESIGN: We used a measure of broad autistic traits (autism factor mean score), and four dichotomised measures of autistic traits capturing social communication difficulties (age 7), repetitive behaviours (age 5), sociability (age 3), and pragmatic language (age 9). Psychotic experiences were assessed at ages 18 and 24 using the semi-structured Psychosis-Like Symptoms interview (PLIKSi). Traumatic experiences between ages 5 and 11 were assessed with questionnaires and interviews administered to children and parents at multiple ages. STUDY RESULTS: Broad autistic traits, as well as social communication difficulties, were associated with psychotic experiences that were distressing and/or frequent until age 24 (autism factor mean score, n = 3707: OR 1.19, 95%CI 1.01-1.39; social communication difficulties, n = 3384: OR 1.54, 95%CI 0.97-2.45). Childhood trauma mediated a substantial proportion of the identified associations (~28% and 36% respectively, maximum n = 3577). Schizophrenia polygenic risk did not appear to confound the associations. Multiple imputation analyses (maximum n = 13 105) yielded comparable results. CONCLUSIONS: Childhood trauma may be an important, potentially modifiable pathway between autistic features and later onset of psychotic psychopathology.

No indications for altered EEG oscillatory activity in patients with chronic post-burn itch compared to healthy controls.

A large proportion of patients with burn injuries develop chronic itch, which impacts quality of life. The underlying pathophysiological mechanisms are poorly understood. This cross-sectional pilot study investigates whether altered cortical oscillatory processes are involved in chronic post-burn itch. Continuous electroencephalography (EEG) data were recorded during rest and stimulation of non-injured skin, inducing itch (histamine and electrical) and cold-pressor task pain for 15 adults with chronic post-burn itch and 15 matched healthy controls. Quantitative metrics comprised oscillatory power and peak frequencies in theta, alpha, and beta bands. No statistical differences between patients and healthy controls were found in oscillatory activity during rest or stimulation, with Bayesian analysis suggesting equivocal evidence. However, post-traumatic stress symptoms and duration of chronic itch may be associated with changes in oscillatory activity. A lack of differences in cortical oscillatory processing and itch levels at non-injured sites, suggests that itch symptoms have a localised character in this sample of patients with post-burn itch. For future studies, a biopsychological approach with integration of peripheral and central nervous system techniques, linear and non-linear EEG analysis, injured and non-injured stimulation sites, and incorporation of individual characteristics is recommended. Insight into pathophysiological mechanisms underlying chronic post-burn itch could improve diagnostics and treatments.

Cerebral [18F]-FDOPA Uptake in Autism Spectrum Disorder and Its Association with Autistic Traits.

Dopaminergic signaling is believed to be related to autistic traits. We conducted an exploratory 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine positron emission tomography/computed tomography ([18F]-FDOPA PET/CT) study, to examine cerebral [18F]-FDOPA influx constant (kicer min-1), reflecting predominantly striatal dopamine synthesis capacity and a mixed monoaminergic innervation in extrastriatal neurons, in 44 adults diagnosed with autism spectrum disorder (ASD) and 22 controls, aged 18 to 30 years. Autistic traits were assessed with the Autism Spectrum Quotient (AQ). Region-of-interest and voxel-based analyses showed no statistically significant differences in kicer between autistic adults and controls. In autistic adults, striatal kicer was significantly, negatively associated with AQ attention to detail subscale scores, although Bayesian analyses did not support this finding. In conclusion, among autistic adults, specific autistic traits can be associated with reduced striatal dopamine synthesis capacity. However, replication of this finding is necessary.

Striatal dopamine synthesis capacity in autism spectrum disorder and its relation with social defeat: an [18F]-FDOPA PET/CT study.

Alterations in dopamine signalling have been implied in autism spectrum disorder (ASD), and these could be associated with the risk of developing a psychotic disorder in ASD adults. Negative social experiences and feelings of social defeat might result in an increase in dopamine functioning. However, few studies examined dopamine functioning in vivo in ASD. Here we examine whether striatal dopamine synthesis capacity is increased in ASD and associated with social defeat. Forty-four unmedicated, non-psychotic adults diagnosed with ASD and 22 matched controls, aged 18-30 years, completed a dynamic 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine positron emission tomography/computed tomography ([18F]-FDOPA PET/CT) scan to measure presynaptic dopamine synthesis capacity in the striatum. We considered unwanted loneliness, ascertained using the UCLA Loneliness Scale, as primary measure of social defeat. We found no statistically significant difference in striatal dopamine synthesis capacity between ASD and controls (F1,60 = 0.026, p = 0.87). In ASD, striatal dopamine synthesis capacity was not significantly associated with loneliness (ß = 0.01, p = 0.96). Secondary analyses showed comparable results when examining the associative, limbic, and sensorimotor sub-regions of the striatum (all p-values > 0.05). Results were similar before and after adjusting for age, sex, smoking-status, and PET/CT-scanner-type. In conclusion, in unmedicated, non-psychotic adults with ASD, striatal dopamine synthesis capacity is not increased and not associated with social defeat.

Acute effects of caffeine on threat-selective attention: moderation by anxiety and EEG theta/beta ratio.

BACKGROUND: Spontaneous EEG theta/beta ratio (TBR) probably marks prefrontal cortical (PFC) executive control, and its regulation of attentional threat-bias. Caffeine at moderate doses may strengthen executive control through increased PFC catecholamine action, dependent on basal PFC function. GOAL: To test if caffeine affects threat-bias, moderated by baseline frontal TBR and trait-anxiety. METHODS: A pictorial emotional Stroop task was used to assess threat-bias in forty female participants in a cross-over, double-blind study after placebo and 200 mg caffeine. RESULTS: At baseline and after placebo, comparable relations were observed for negative pictures: high TBR was related to low threat-bias in low trait-anxious people. Caffeine had opposite effects on threat-bias in low trait-anxious people with low and high TBR. CONCLUSIONS: This further supports TBR as a marker of executive control and highlights the importance of taking baseline executive function into consideration when studying effects of caffeine on executive functions.

A Context-Sensing Mobile Phone App (Q Sense) for Smoking Cessation: A Mixed-Methods Study.

BACKGROUND: A major cause of lapse and relapse to smoking during a quit attempt is craving triggered by cues from a smoker's immediate environment. To help smokers address these cue-induced cravings when attempting to quit, we have developed a context-aware smoking cessation app, Q Sense, which uses a smoking episode-reporting system combined with location sensing and geofencing to tailor support content and trigger support delivery in real time. OBJECTIVE: We sought to (1) assess smokers' compliance with reporting their smoking in real time and identify reasons for noncompliance, (2) assess the app's accuracy in identifying user-specific high-risk locations for smoking, (3) explore the feasibility and user perspective of geofence-triggered support, and (4) identify any technological issues or privacy concerns. METHODS: An explanatory sequential mixed-methods design was used, where data collected by the app informed semistructured interviews. Participants were smokers who owned an Android mobile phone and were willing to set a quit date within one month (N=15). App data included smoking reports with context information and geolocation, end-of-day (EoD) surveys of smoking beliefs and behavior, support message ratings, and app interaction data. Interviews were undertaken and analyzed thematically (N=13). Quantitative and qualitative data were analyzed separately and findings presented sequentially. RESULTS: Out of 15 participants, 3 (20%) discontinued use of the app prematurely. Pre-quit date, the mean number of smoking reports received was 37.8 (SD 21.2) per participant, or 2.0 (SD 2.2) per day per participant. EoD surveys indicated that participants underreported smoking on at least 56.2% of days. Geolocation was collected in 97.0% of smoking reports with a mean accuracy of 31.6 (SD 16.8) meters. A total of 5 out of 9 (56%) eligible participants received geofence-triggered support. Interaction data indicated that 50.0% (137/274) of geofence-triggered message notifications were tapped within 30 minutes of being generated, resulting in delivery of a support message, and 78.2% (158/202) of delivered messages were rated by participants. Qualitative findings identified multiple reasons for noncompliance in reporting smoking, most notably due to environmental constraints and forgetting. Participants verified the app's identification of their smoking locations, were largely positive about the value of geofence-triggered support, and had no privacy concerns about the data collected by the app. CONCLUSIONS: User-initiated self-report is feasible for training a cessation app about an individual's smoking behavior, although underreporting is likely. Geofencing was a reliable and accurate method of identifying smoking locations, and geofence-triggered support was regarded positively by participants.