Childhood negative experiences and subclinical psychosis in adolescence: a longitudinal general population study

Background: Accumulating evidence suggests that experiences of trauma and victimization during childhood are associated with an increased risk to develop clinical and subclinical psychosis in adulthood. A recent cross‐sectional study showed a significant association between trauma and psychotic experiences in adolescents. The current study aimed to extend these findings by investigating the longitudinal effects of negative life experiences on the risk for subclinical psychotic symptoms 2 years later in an adolescent general community sample. Methods: Data were derived from the standard health screenings of the Youth Health Care Divisions of the Public Health Services, in the South of the Netherlands. A total of 1129 adolescents filled out a self‐report questionnaire at age 13/14 years and 2 years later (15/16 years), assessing psychotic experiences, as well as experiences of being bullied, sexual trauma, and negative life events. Results: Logistic regression analyses revealed that sexual trauma increased the risk for psychotic symptoms 2 years later. Life events contributed to the risk for psychosis over time and psychosis in turn gave rise to new life events. No significant association with bullying was found after controlling for confounders. Conclusion: The results provide further evidence for an association between childhood environment and psychosis in the crucial developmental period of early adolescence. Early and later psychological stress, if severe, may impact on the risk for psychosis in adolescence through mechanisms of person–environment interaction and correlation.     

Evidence for a familial correlation between increased reactivity to stress and positive psychotic symptoms

Lataster T, Collip D, Lardinois M, van Os J, Myin‐Germeys I. Evidence for a familial correlation between increased reactivity to stress and positive psychotic symptoms. Objective: This study tested the hypothesis that stress‐reactivity may represent an intermediary phenotype underlying positive psychotic symptoms. It was examined whether: (i) stress‐reactivity clusters within families of psychotic patients and (ii) stress‐reactivity in relatives cosegregates with positive symptoms in patients. Method: The sample consisted of 40 patients and 47 siblings of these patients . The Experience Sampling Method (ESM – a structured diary technique) was used to measure stress‐reactivity. Positive symptoms in patients were measured with the Comprehensive Assessment of Symptoms and History. Results: Within‐trait, cross‐sib associations showed a significant association between stress‐reactivity in the patient and stress‐reactivity in their siblings. Significant cross‐trait, cross‐sib associations were established showing a significant association between positive psychotic symptoms in the patient and stress‐reactivity in the sibling. Conclusion: The findings show familial clustering of increased stress‐reactivity, suggesting common aetiological influences, probably both genetic and environmental, underlying stress‐reactivity in the siblings and patients. In addition, the results underscore the hypothesis that increased stress‐reactivity is an unconfounded mechanism of risk underlying the positive symptoms of psychotic disorders.     

Can obsessions drive you mad? Longitudinal evidence that obsessive‐compulsive symptoms worsen the outcome of early psychotic experiences

Van Dael F, van Os J, de Graaf R, ten Have M, Krabbendam L, Myin‐Germeys I. Can obsessions drive you mad? Longitudinal evidence that obsessive‐compulsive symptoms worsen the outcome of early psychotic experiences. Objective: Although there is substantial comorbidity between psychotic disorder and obsessive‐compulsive disorder (OCD), little is known about how these clinical phenotypes, and their subclinical extended phenotypes, covary and impact on each other over time. This study examined cross‐sectional and longitudinal associations between both (extended) phenotypes in the general population. Method: Data were obtained from the three waves of the NEMESIS‐study. A representative population sample of 7076 participants were assessed using the composite international diagnostic interview (CIDI) at baseline (T₀), 1 year later at T₁ and again 2 years later at T₂. Results: At T₀, a lifetime diagnosis of psychotic disorder was present in 1.5% of the entire sample, in 11.5% of the people with any OC symptom and in 23.0% of individuals diagnosed with OCD. OC symptoms at T₀ predicted incident psychotic symptoms at T₂. Similarly, T₀ psychotic symptoms predicted T₂ OC symptoms. The likelihood of persistence of psychotic symptoms or transition to psychotic disorder was higher if early psychosis was accompanied by co‐occurring OC symptoms, but not the other way around. Conclusion: OCD and the psychosis phenotype cluster together and predict each other at (sub)clinical level. The co‐occurrence of subclinical OC and psychosis may facilitate the formation of a more ‘toxic’ form of persistent psychosis.     

Subtle fluctuations in psychotic phenomena as functional states of abnormal dopamine reactivity in individuals at risk.

BACKGROUND: Subjects at increased risk for psychosis experience continuous variation in the intensity of subtle psychotic experiences in response to minor stressors. It was investigated whether this psychotic reactivity in individuals at risk for psychosis is the exophenotypic expression of an underlying endophenotype characterized by a hyperreactive dopamine (DA) system. METHODS: First-degree relatives (n = 47) and control subjects (n = 49) were studied with the Experience Sampling Method (ESM), a structured diary technique assessing current context and psychopathology in daily life, to assess psychotic experiences in response to stress. A metabolic perturbation paradigm (administration of 2-deoxy-D-glucose inducing a mild state of glucoprivation) causing plasma elevation of homovanillic acid (HVA) was used as a proxy of DA reactivity. RESULTS: Multilevel regression analyses revealed that the interaction between HVA reactivity and daily stress in their effect on psychotic experiences differed according to underlying vulnerability. In the first-degree relatives, underlying HVA reactivity modified the psychotic experiences to daily stress, whereas no such effect was found in control subjects. CONCLUSIONS: These results suggest that psychotic experiences in response to minor stresses in the flow of daily life may be functional states of an underlying abnormal DA reactivity in subjects at risk to develop psychosis. The results add credence to the suggestion that abnormal DA reactivity may be part of the substrate that increases risk for psychotic symptoms in individuals at risk.     

Do different psychotic experiences differentially predict need for care in the general population?

INTRODUCTION: The pathway from subclinical psychotic experiences to need for care may depend on type of psychotic experience, level of associated distress, and previous experience of psychosis. METHOD: In a general population sample with no previous Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition , psychotic disorder (n = 4722), 83 subjects displayed at least one psychotic experience. Within the group of 83, subjects with (n = 24) and without need for care (n = 59) were compared. Presence of psychotic experiences at younger ages had been assessed at earlier interviews. RESULTS: Of 7 different psychotic experiences, only hearing voices, nonverbal hallucinations, and passivity phenomena were significantly associated with need for care. These associations were largely explained by the distress associated with the psychotic experience, but whether individuals had had psychotic experiences at earlier ages did not matter. CONCLUSIONS: Different psychotic experiences differ in the associated level of need for care and the mediating role of distress. Longer prior exposure to psychosis may not influence the pathway from subclinical to clinical.     

Psychotic reactivity in borderline personality disorder

Glaser J‐P, Van Os J, Thewissen V, Myin‐Germeys I. Psychotic reactivity in borderline personality disorder. Objective: To investigate the stress relatedness and paranoia specificity of psychosis in borderline personality disorder (BPD). Method: Fifty‐six borderline patients, 38 patients with cluster C personality disorder, 81 patients with psychotic disorder and 49 healthy controls were studied with the experience sampling method (a structured diary technique) to assess: i) appraised subjective stress and ii) intensity of psychotic experiences. Results: All patient groups experienced significantly more increases in psychotic experiences in relation to daily life stress than healthy controls, borderline patients displaying the strongest reactivity. Borderline patients, moreover, reported significantly more hallucinatory reactivity than healthy controls and subjects with cluster C personality disorder. Paranoid reactivity to daily life stress did not differ between the patient groups. Conclusion: These results are the first to ecologically validate stress‐related psychosis in BPD. However, psychotic reactivity was not limited to expression of paranoia but involved a broader range of psychotic experiences including hallucinations.     

Psychosis risk screening: Validation of the youth psychosis at‐risk questionnaire – brief in a community‐derived sample of adolescents

There have been several attempts to identify individuals potentially at high risk for psychotic‐spectrum disorders using brief screening measures. However, relatively few studies have tested the psychometric properties of the psychosis screening measures in representative samples of adolescents. The main purpose of the present study was to analyse the prevalence, factorial structure, measurement invariance across gender, and reliability of the Youth Psychosis At‐Risk Questionnaire – Brief (YPARQ‐B) in a community‐derived sample of adolescents. Additionally, the relationship between YPARQ‐B, depressive symptoms, psychopathology, stress manifestations, and prosocial skills was analysed. One thousand and twenty students from high schools participated in a cross‐sectional survey. The YPARQ‐B, the Reynolds Adolescent Depression Scale, the Strengths and Difficulties Questionnaire, and the Student Stress Inventory – Stress Manifestations were used. A total of 85.1% of the total sample self‐reported at least one subclinical psychotic experience. We observed a total of 10.9% of adolescents with a cutoff score of ≥11 or 6.8% with a cutoff score of ≥13. The analysis of internal structure of the YPARQ‐B yielded an essentially unidimensional structure. The YPARQ‐B scores showed measurement invariance across gender. The internal consistency of the YPARQ‐B total score was 0.94. Furthermore, self‐reported subclinical psychotic experiences were associated with depressive symptoms, emotional and behavioural problems, poor prosocial skills, and stress manifestations. These results would appear to indicate that YPARQ‐B is a brief and easy tool to assess self‐reported subclinical psychotic experiences in adolescents from the general population. The assessment of these experiences in community settings, and its associations with psychopathology, may help us to enhance the possibility of an early identification of adolescents potentially at risk for psychosis and mental health problems.     

Childhood trauma and increased stress sensitivity in psychosis

Lardinois M, Lataster T, Mengelers R, van Os J, Myin‐Germeys I. Childhood trauma and increased stress sensitivity in psychosis. Objective: The notion that traumatic experiences in childhood may predict later psychotic outcomes would be strengthened if a plausible mechanism could be demonstrated. Because increased stress sensitivity is part of the behavioural expression of psychosis liability, the possible mediating role of childhood trauma was investigated. Method: Fifty patients with psychosis were studied with the experience sampling method to assess stress reactivity in daily life, defined as emotional and psychotic reactivity to stress. Traumatic experiences in childhood were assessed with the Childhood Trauma Questionnaire. Results: A significant interaction was found between stress and CT on both negative affect (event stress: β = 0.04, P < 0.04; activity stress: β = 0.12, P < 0.001) and psychotic intensity (event stress: β = 0.06, P < 0.001; activity stress: β = 0.11, P < 0.001), showing that a history of CT is associated with increased sensitivity to stress. Conclusion: A history of childhood trauma in patients with psychosis is associated with increased stress reactivity later in life, suggestive for an underlying process of behavioural sensitization.     

Subclinical psychotic experiences and cognitive functioning as a bivariate phenotype for genetic studies in the general population

OBJECTIVE: Cognitive deficits may be vulnerability markers for the development of schizophrenia. This study examined whether cognitive deficits are related to specific dimensions of subclinical psychotic experiences and whether associations between these variables are caused by additive genetic, common environmental and/or individual-specific environmental factors. METHOD: A general population sample of 298 female twin pairs completed the Community Assessment of Psychic Experiences and a neuropsychological test battery. Associations between subclinical positive and negative psychotic dimensions and neuropsychological factors (episodic memory and information processing speed) were examined. Univariate correlation and structural equation analyses were performed to explore the role of genetic and environmental factors in the phenotypes separately. Bivariate correlation and structural equation analyses were applied to examine the causes of association. RESULTS: There were significant correlations between information processing speed and both the positive (r=.11; p<.05) and the negative dimension (r=.10; p<.05). For the negative dimension and for speed of processing, the data suggested a model that included genetic factors. The observed phenotypic correlation between the negative dimension and information processing speed could be solely explained in terms of additive genetic factors. Although the comparison of the correlations for MZ and DZ pairs did not give a clear indication as to the underlying causes of the association, structural equation modelling suggested that the observed phenotypic correlation between the negative dimension and information processing speed could be solely explained in terms of additive genetic factors. CONCLUSION: Negative symptoms and information processing speed are associated at the subclinical level and this association appears to be influenced by genetic factors exclusively. Bivariate psychosis phenotypes may represent suitable candidates for molecular genetic studies in the general population.     

Deconstructing the familiality of the emotive component of psychotic experiences in the general population

OBJECTIVE: Genetic and environmental influences on variation in distress associated with subclinical psychotic experiences were examined. METHOD: A total of 289 twin pairs filled in the Community Assessment of Psychic Experiences, a self-report instrument assessing subclinical positive and negative psychotic experiences and associated distress (distresspos and distressneg). Using structural equation modelling, univariate and bivariate models were fitted. RESULTS: Univariate model fitting showed genetic and non-shared environmental influences on both distresspos and distressneg. Bivariate model fitting showed that 52% of the correlation between the two phenotypes (r=0.46) was because of shared genes and that non-shared environmental factors accounted for 48% of the correlation. CONCLUSION: Liability to psychosis not only refers to the development of psychosis per se, but also to the liability to develop dysfunctional emotional appraisals. The emotive component of psychosis liability involves genetic transmission of a general, non-symptom-specific distress factor that may be a target for molecular genetic research.     

Data Gathering: Biased in Psychosis?

This study examined whether the probabilistic reasoning bias referred to as a "jumping-to-conclusions" (JTC) style of reasoning, which, according to previous research, is associated with particular psychotic symptoms such as delusions, represents a trait that can also be detected in nonpsychotic relatives of patients with schizophrenia and in nonpsychotic individuals with a high level of psychotic experiences. Participants were, in order of level of psychosis liability, 40 patients with schizophrenia or a schizoaffective disorder, 40 first-degree nonpsychotic relatives, 41 participants from the general population with above average expression of psychotic experiences, and 53 participants from the general population with an average level of psychotic experiences. A "jumping-to-conclusions" bias was assessed using the beads task. A dose-response relationship was found in the association between level of psychosis liability and JTC (defined as needing only a single bead to complete the beads task) (odds ratio [OR] linear trend = 1.59, 95% CI: 1.13-2.24), and, independently, alinear association was apparent between JTC and level of delusional ideation (OR linear trend = 2.59, 95% CI: 1.18-5.69). In addition, the association between psychosis liability and JTC was generally much stronger as the level of delusional ideation was higher. JTC is associated with liability to psychosis (trait), in particular if the psychosis phenotype is characterized by delusional ideation (state).     

Relationships between trauma and psychosis: an exploration of cognitive and dissociative factors

OBJECTIVE: There is a growing awareness of the relationship between trauma and psychosis. Studies have found associations between traumatic life experiences and the development of psychosis. METHOD: This study examined the prevalence of trauma exposure and post-traumatic stress disorder (PTSD) in 32 people with psychotic diagnoses and investigated associations between specific traumas and psychotic symptoms. The role of dissociation and cognitive factors was also explored. RESULTS: The prevalence of lifetime trauma was high (94% of the sample reported at least one traumatic event). The prevalence of current PTSD was 53%. Severity of trauma was associated with severity of PTSD and psychotic experiences. Physical abuse was associated with positive psychotic symptoms and sexual abuse was specifically related to hallucinations. Dissociative processes and negative beliefs formed as a result of trauma were associated with psychotic experiences (particularly hallucinations). CONCLUSION: These findings are consistent with the suggestion that psychosis may be trauma-induced, and other implications are considered.     

Investigating the association between neurocognition and psychosis in bipolar disorder: further evidence for the overlap with schizophrenia

Objectives: In schizophrenia, a distinction is made between psychosis with developmental and cognitive impairment on the one hand and psychosis without developmental impairment and positive symptoms on the other. In this study, we investigated whether this model can be extended to bipolar disorder by testing the hypothesis that neurocognitive functioning is inversely related to positive psychotic symptoms in bipolar disorder. Methods: Neurocognitive functioning and psychopathology were assessed in (i) 76 patients with bipolar disorder, (ii) 39 of their healthy first‐degree relatives, and (iii) 61 healthy controls. Cognitive performance of bipolar patients and their first‐degree relatives was investigated, taking into account the possible moderating effect of the level of expression of psychosis in patients and relatives. Results: Bipolar patients showed impaired cognitive performance on multiple cognitive domains, whereas performance of their relatives was comparable to that of controls. A history of psychotic symptoms in patients was suggestive of less likelihood of cognitive alterations in relatives, and the presence of subclinical psychotic symptoms within the group of relatives predicted better cognitive performance. Conclusions: The finding of similar psychosis‐cognition associations in bipolar disorder as implied by the two pathways leading to nonaffective psychotic disorders suggests that this model might be extended to the continuum spanning affective and nonaffective psychosis. This is in line with the idea of a partially overlapping vulnerability to bipolar disorder and schizophrenia and provides an explanation for the apparent differences in cognitive alterations in those at risk for the two disorders.     

Life events and high-trait reactivity together predict psychotic symptom increases in schizophrenia

Psychotic symptoms are exacerbated by stressful life events in schizophrenia patients as a group. Some individuals appear to be more vulnerable than others in this regard. This study tested whether schizophrenia patients are highly emotionally reactive compared with controls and whether the level of trait emotional reactivity in patients influences the degree to which they respond to life stressors with exacerbations of psychosis. Schizophrenic outpatients and nonpsychiatric controls were assessed for levels of trait emotional reactivity, arousability, and trait anxiety. Severity of symptoms was also rated in the patients. Patients were then followed up 9 months later, assessed for independent stressful life events occurring during the month before the follow-up session, and reassessed for symptom levels. The patients scored higher than the control subjects on all 3 measures of reactivity at the initial assessment. At follow-up, the occurrence of potentially stressful life events predicted increases in psychotic symptoms in patients, and there was a significant interaction between level of initial trait reactivity and the occurrence of life events in the prediction of these increases. High-trait-reactive patients showed increases in psychotic symptoms in response to life stressors, whereas low-trait-reactive patients did not. These findings support the idea that patients as a group have higher than normal levels of trait reactivity and also that patients with very high levels of trait reactivity are at elevated risk of psychotic relapse under stress. Such patients might benefit particularly from interventions designed to assist them in coping with potentially stressful life events and circumstances.     

Sex differences in psychosis: normal or pathological?

BACKGROUND: Schizophrenia first appears in adolescence, in boys at an earlier age than girls. The interpretation of this key epidemiological finding crucially depends on whether similar age-related sex differences exist in the expression of associated, subclinical psychosis-like experiences. METHODS: Findings are based on a population sample of 2548 adolescents and young adults aged 17-28. Subjects were assessed with the core psychosis sections on delusions and hallucinations of the Munich-Composite International Diagnostic Interview. RESULTS: The risk of subclinical psychotic experiences was significantly higher for males in the younger half of the cohort (17-21 years), but similar in the older half (22-28 years). CONCLUSIONS: These findings suggest that normal maturational changes in adolescence with differential age of onset in boys and girls cause the expression of psychosis, the extreme of which is schizophrenia.     

COMT Val158Met-stress interaction in psychosis: role of background psychosis risk

Background: The interplay between the catechol‐O‐methyltransferase (COMT) Val158Met polymorphism and environmental stress may have etiological relevance for psychosis, but differential effects have been reported in healthy control and patient groups, suggesting that COMT Val158Met interactions with stress may be conditional on background genetic risk for psychotic disorder. Methods: Patients with a nonaffective psychotic disorder (n = 86) and control participants (n = 109) were studied with the experience sampling method (a structured diary technique) in order to assess stress, negative affect and momentary psychotic symptoms in the flow of daily life. Results: Multilevel analyses revealed significant three‐way interactions between group status (patient or control), COMT genotype and stress in the model of negative affect (χ²(2) = 13.26, P < 0.01) as well as in the model of momentary psychotic symptoms (χ²(2) = 6.92, P < 0.05). Exploration of the three‐way interaction revealed that in patients, COMT genotype moderated the association between stress and negative affect (χ²(4) = 11.50, P < 0.005), as well as the association between stress and momentary psychosis (χ²(4) = 12.79, P < 0.005). Met/Met genotype patients showed significantly increased psychotic and affective reactivity to stress in comparison to the Val/Met and Val/Val genotypes. In contrast, healthy controls did not display large or significant COMT Val158Met X stress interactions. Conclusions: Important differences exist in the effect of COMT Val158Met on stress reactivity, which may depend on background risk for psychotic disorder. Differential sensitivity to environmental stress occasioned by COMT Val158Met may be contingent on higher order interactions with genetic variation underlying psychotic disorder.     

The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings From the Multinational EU-GEI Study

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment–environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (β for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E × E interactions.     

Dynamic Association Between Interpersonal Functioning and Positive Symptom Dimensions of Psychosis Over Time: A Longitudinal Study of Healthy Adolescents

Background: Cross-sectional studies have indicated that alterations in social functioning, particularly interpersonal functioning, are associated with the occurrence of psychotic symptoms and experiences at different levels of the extended psychosis phenotype (ranging from population psychometric expression of liability to overt psychotic disorder). However, more research is needed on the development of this association over time. Methods: Cross-lagged path modeling was used to analyze bidirectional, longitudinal associations between 4 dimensions of subclinical psychotic experiences (persecutory ideation, bizarre experiences, perceptual abnormalities, and magical thinking) and interpersonal functioning in an adolescent general population sample (N = 881 at T1, N = 652 at T2, and N = 512 at T3) assessed 3 times in 3 years. Results: All symptom dimensions showed some association with interpersonal functioning over time, but only bizarre experiences and persecutory ideation were consistently and longitudinally associated with interpersonal functioning. Poorer interpersonal functioning predicted higher levels of bizarre experiences and persecutory ideation at later measurement points (both T1 to T2 and T2 to T3). Conclusions: Poor interpersonal functioning in adolescence may reflect the earliest expression of neurodevelopmental alterations preceding expression of psychotic experiences in a symptom-specific fashion.     

The interplay of psychosis and victimisation across the life course: a prospective study in the general population

Purpose

Psychosis has been associated with adult victimisation. However, it remains unclear whether psychosis predicts incident adult victimisation, or whether adult victimisation predicts incident psychosis. Furthermore, a moderating effect of childhood victimisation on the association between psychosis and adult victimisation has not been investigated.

Methods

The longitudinal association between baseline psychotic experiences and six-year incidence of adult victimisation was assessed in a prospective general population cohort of 6646 adults using logistic regression analysis. The association between baseline adult victimisation and six-year incidence of psychotic experiences was examined as well. Furthermore, the moderating effect of childhood victimisation on these bidirectional associations was analysed.

Results

Psychotic experiences and childhood victimisation were both associated with an increased risk of incident adult victimisation. However, this was through competing pathways, as suggested by a negative interaction between psychotic experiences and childhood victimisation. Baseline adult victimisation and childhood victimisation both independently increased the risk of incident psychotic experiences, but there was no interaction between adult victimisation and childhood victimisation.

Conclusions

Psychosis and victimisation are interconnected throughout the life course. Childhood victimisation is connected to psychosis through two pathways: one direct and one indirect through adult victimisation. In individuals without childhood victimisation, psychosis and adult victimisation bidirectionally impact on each other.

     

Familial Liability to Psychosis Is Associated With Attenuated Dopamine Stress Signaling in Ventromedial Prefrontal Cortex

Objective: Patients diagnosed with a psychotic disorder and their first-degree relatives display increased reactivity to stress. Theory predicts that experience of psychosocial stress is associated both with ventromedial prefrontal and mesolimbic dopamine neurotransmission. However, while there is evidence of aberrant striatal dopamine processing in psychotic disorder, the role of the prefrontal cortex remains under-researched. This study aimed at investigating stress-induced in vivo dopamine release in ventromedial prefrontal cortex (vmPFC) of individuals at familial risk for psychosis. Method: Fourteen healthy first-degree relatives of patients with a diagnosis of psychotic disorder and 10 control subjects underwent a single dynamic positron emission tomography (PET) scanning session after intravenous administration of 183.2 (SD = 7.6) MBq [¹⁸F]fallypride. Psychosocial stress was initiated at 100min postinjection using a computerized mental arithmetic task with social evaluative threat components. PET data were analyzed using the linearized simplified reference region model. Regression analyses were performed to compare the spatial extent of task-related ligand displacement between control subjects and relatives and to find how it related to self-rated experiences of psychosocial stress and psychosis. Results: First-degree relatives displayed hyporeactive dopamine signaling in the vmPFC in response to stress. Increased levels of subjectively rated stress were associated with increased intensity of psychotic experiences. This effect was particularly pronounced in first-degree relatives. Conclusion: Although previous studies have hypothesized a role for prefrontal dopamine dysfunction in psychosis, this study, to our knowledge, is the first in vivo human imaging study showing attenuated (ie, hyporeactive) dopamine stress neuromodulation in vmPFC of individuals at familial risk for psychosis.Key words: schizophrenia, positron emission tomography, neuromodulation, relatives, mesolimbic, salience