Subclinical Psychotic Experiences Research Articles

Psychometric evaluation of the Subjective Well-being Under Neuroleptic Treatment Scale (SWN) in patients with schizophrenia, their relatives and controls

The objective of this study was to evaluate the psychometric properties of the 20-item version of the Subjective Well-being Under Neuroleptic Treatment Scale (SWN) in patients, their siblings and parents and in healthy controls. In order to study heritability of subjective well-being, assessment in unaffected relatives and healthy controls is necessary. Data were obtained from the Dutch GROUP study (Genetic Risk and Outcome of Psychosis), a large cohort study on non-affective psychotic disorders incorporating patients, their relatives and healthy controls. The SWN scale and other relevant assessments were completed by 545 schizophrenia patients, 541 siblings, 75 parents, and 280 healthy controls. Reliability within the four groups ranged between Cronbach's alpha 0.88 and 0.92. Factor analysis indicated a single factor structure of the SWN scale, which makes only SWN total scores relevant.The WHO-Quality of Life psychological domain correlated highly with SWN total scores in all groups. Subclinical psychotic experiences were found to be associated with SWN total scores in relatives and healthy controls, supporting the psychosis continuum concept. The 20-item SWN scale is a reliable measure for subjective well-being that can also be used in relatives and healthy controls to investigate genetic and psychological dispositions of subjective well-being.

Evidence that the wider social environment moderates the association between familial liability and psychosis spectrum outcome

Familial liability to both severe and common mental disorder predicts psychotic disorder and psychotic symptoms, and may be used as a proxy in models examining interaction between genetic risk and the environment at individual and contextual levels. In a representative general population sample (n=4011) in Izmir, Turkey, the full spectrum of expression of psychosis representing (0) no symptoms, (1) subclinical psychotic experiences, (2) low-impact psychotic symptoms, (3) high-impact psychotic symptoms and (4) full-blown clinical psychotic disorder was assessed in relation to mental health problems in the family (proxy for familial liability) and the wider social environment. Quality of the wider social environment was assessed in an independent sample using contextual measures of informal social control, social disorganization, unemployment and low income, aggregated to the neighbourhood level. The association between familial liability to severe mental illness and expression of psychosis spectrum was stronger in more deprived neighbourhoods [e.g. this association increased from β=0.33 (p=0.01) in low-unemployment neighbourhoods to β=0.92 (p<0.001) in high-unemployment neighbourhoods] and in neighbourhoods high in social control, while neighbourhood variables did not modify the association between familial liability to common mental disorder and the psychosis outcome. Neighbourhood variables mediated urbanicity effects. Contextual effects may be important in moderating the expression of psychosis liability in populations, representing a specific pathway independent of the link between common mental disorder and psychosis.

14:15 PERSISTENCE OF THE EXTENDED PSYCHOSIS PHENOTYPE IN YOUNG PEOPLE: LINK BETWEEN VULNERABILITY AND CLINICAL NEED

Psychosis is one of the most severe psychiatric conditions, in terms of both individual and societal burden. The pathway from the earliest and mildest expressions of psychosis to clinical disorder is highly variable and heterogeneous. A better understanding of the psychosis phenotype and its development into clinical states is important, since this offers opportunities for early intervention of psychotic disorders, with the ultimate goal to delay, attenuate or even prevent transition to clinical disorder. Psychosis is currently conceptualized as an extended, or continuous, phenotype, ranging from normal functioning at one end, through eccentricity and subclinical psychotic experiences, to florid psychotic disorder at the other end. The manifestation of this (liability to) psychotic psychopathology is represented by a continuous distribution of psychotic symptom severity/intensity in the general population. The studies in this thesis showed that many adolescents reported incidental subclinical psychotic experiences, underlining the high level of psychosis proneness in this developmental life phase. This psychosis proneness decreased with age, demonstrated by the lower levels of psychotic experiences reported by the young adult female sample compared to the adolescent samples. A model with five subdimensions, labeled Hallucinations, Delusions, Paranoia, Grandiosity and Paranormal beliefs, was shown to describe these experiences well in two large adolescent samples from the general population and was furthermore replicated in young adulthood, suggesting life-long stability of this underlying structure. Only some of these subdimensions (i.e. Hallucinations, Delusions and Paranoia) may tap into the extended psychosis phenotype in their continuity with mental illness. Psychosis proneness was shown to be very dynamic, particularly during adolescence. Many (biological, psychological and sociological) factors play a role in its development, such as trauma, cannabis use, depression, coping and genetic liability for psychosis; thus, it demonstrates that the development of psychosis over time takes place in a developmental and psychopathological context. Subclinical psychotic experiences are thought to be predictive for later clinical psychosis, as is, more strongly, Ultra High Risk (UHR) status. In other words, it is assumed that there is a dose-response function of risk between psychotic experiences/symptoms and later psychotic disorder. There is, however, a gap in the conceptualization of the psychosis continuum between subclinical psychosis at the level of the general population and UHR status for psychosis: there is no clear phenotype on the hypothesized psychosis continuum connecting individuals from the general population and individuals who are seeking help for their psychotic experiences. Studying the persistence of subclinical psychotic experiences over time may form the bridge between general population samples and UHR samples in the study of (the development of) psychosis, because this paradigm offers the possibility to study the extended psychosis phenotype at the level of the general population while focusing on a more specific phenotype that may be indicative for later psychotic development. Studying this phenotype of persisting subclinical psychotic experiences that can be seen as intermediate between general population and clinical population may thus be a fruitful paradigm for identifying individuals at increased risk for the development of psychosis.

Replication of the five-dimensional structure of positive psychotic experiences in young adulthood

Previous work has examined the structure of subclinical positive psychotic experiences. The current study, using confirmatory factor analysis in a general population sample of young adult females, replicated a five-dimensional model, which showed excellent model fit. The results suggest stability of the five-dimensional model across adolescent and young adult life.

Schizophrenia Candidate Gene ERBB4: Covert Routes of Vulnerability to Psychosis Detected at the Population Level

Prior genetic and functional evidence established ERBB4 as a probable schizophrenia susceptibility gene that may confer risk via modulating brain information processing dependent on the integrity of frontotemporal brain circuitry. Utilizing retrospective data drawn from the cross-sectional population-based Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS) (n = 1127), we attempted to independently replicate and further extend previous findings by examining the effects of ERBB4 gene variants on 3 broad population-based psychosis-related phenotypes: verbal working memory (VWM), trait schizotypy, and stress-induced subclinical psychotic experiences (PE). Three common ERBB4 single nucleotide polymorphisms that were previously associated with schizophrenia and impaired frontotemporal-related information processing (rs7598440, rs839523, and rs707284), their haplotypes, and corresponding diplotypes were tested. VWM performance was significantly associated with rs839523 and rs707284 markers even after correction for multiple testing, thus validating reported findings that have implicated ERBB4 gene variation on working memory. No associations were detected between these ERBB4 variants and trait schizotypy. However, we were able to detect a significant effect of rs7598440 marker on PE expressed under stressful environmental conditions. Combined haplotype analysis of the above 3 markers, identified a "yin-yang" pattern of association, confirmed at the diplotype level. While GGG haplotype homozygotes were associated with "protective" effects on VWM performance and PE, AAA "risk" haplotype carriers were associated with worse VWM performance and simultaneously exhibited significantly elevated PE. This dual, possibly pleiotropic, impact on frontotemporal circuitry and increased sensitivity to psychosocial stress may represent subtle manifestations of ERBB4-related vulnerability to psychosis, expressed at the population level.

Cannabis use and subclinical positive psychotic experiences in early adolescence: findings from a Dutch survey

To investigate the association between early cannabis use and subclinical psychotic experiences, distinguishing between five levels of use: never used, discontinued use (life-time users who did not use in the preceding year), experimental use, regular use and heavy use. Cross-sectional observational study. Dutch Health Behaviour in School-aged Children (HBSC) study, 2005 wave. A total of 4552 secondary school children aged 12-16 years. Cannabis use, Community Assessment of Psychic Experiences (CAPE) positive scale, confounding factors: age, gender, family affluence, household composition, social support, alcohol use, cigarette smoking, ethnicity and urbanicity. The association between cannabis use and subclinical positive symptoms was confirmed, and remained significant after extensive adjustment for potential confounders. Associations were found for all user groups, with strongest associations for the discontinued use group (β = 0.061, P = 0.000) and for the heavy use group (β = 0.065, P = 0.000). There is an enduring association between cannabis use at an early age and subclinical positive psychotic experiences, even after abstaining from cannabis for at least 1 year.

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

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. 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. 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). Poor interpersonal functioning in adolescence may reflect the earliest expression of neurodevelopmental alterations preceding expression of psychotic experiences in a symptom-specific fashion.

Reduced sensitivity to experimental pain in individuals with subclinical psychotic experiences

The 15th Biennial Winter Workshop in Psychoses, 15–18 November 2009, Barcelona, Spain: EPIDEMIOLOGY, DIAGNOSIS AND PHENOMENOLOGY

The relationship between coping and subclinical psychotic experiences in adolescents from the general population – a longitudinal study – CORRIGENDUM

The relationship between coping and subclinical psychotic experiences in adolescents from the general population – a longitudinal study – CORRIGENDUM

The relationship between coping and subclinical psychotic experiences in adolescents from the general population – a longitudinal study

Subclinical psychotic experiences during adolescence may represent liability for developing psychotic disorder. Both coping style and the degree of persistence of psychotic experiences may play a role in the progression to clinical psychotic disorder, but little is known about the causal relationship between the two. Path modelling was used to examine longitudinal relationships between subclinical positive psychotic experiences and three styles of coping (task-, emotion- and avoidance-oriented) in an adolescent general population sample (n=813) assessed three times in 3 years. Distinct developmental trajectories of psychotic experiences, identified with growth mixture modelling, were compared on the use of these coping styles. Over time, emotion-oriented coping in general was bi-directionally related to psychotic experiences. No meaningful results were found for task- or avoidance-oriented coping. Females reported using a wider range of coping styles than males, but the paths between coping and psychotic experiences did not differ by gender. Persistence of psychotic experiences was associated with a greater use of emotion-oriented coping, whereas a decrease in experiences over time was associated with an increased use of task-orientated coping. Emotion-oriented coping is the most important coping style in relation to psychotic experiences, as it may contribute to a 'vicious cycle' and is associated with persistence of experiences. In addition, more task-oriented coping may result in a decrease in psychotic experiences. Results suggest that opportunities for intervention may already be present at the level of subclinical psychosis.

Testing the Psychosis Continuum: Differential Impact of Genetic and Nongenetic Risk Factors and Comorbid Psychopathology Across the Entire Spectrum of Psychosis

A growing number of studies demonstrate high rates of subthreshold psychotic experiences, but there is considerable heterogeneity in rates due to study cohort and design factors, obscuring how prevalent psychotic experiences may or may not relate to rare psychotic disorders. In a representative general population sample (n = 4011) in Izmir, Turkey, the full spectrum of expression of psychosis was categorized across 5 groups representing (1) absence of psychosis, (2) subclinical psychotic experiences, (3) low-impact psychotic symptoms, (4) high-impact psychotic symptoms, and (5) full-blown clinical psychotic disorder and analyzed for continuity and discontinuity in relation to (1) other symptom dimensions associated with psychotic disorder and (2) proxies of genetic and nongenetic etiology. Results were tested for linear and extralinear contrasts between clinical and nonclinical and between disorder and nondisorder expression of psychosis. Demographic variables, indexing premorbid social adjustment and socioeconomic status, impacted mostly linearly; proxy variables of genetic loading (more or more severely affected relatives) impacted in a positive extralinear fashion; environmental risk factors sometimes impacted linearly (urbanicity and childhood adversity) and sometimes extralinearly (cannabis), occasioning a disproportional shift in risk at the clinical disorder end of the spectrum. Affective symptoms were associated with a disproportionally higher risk below the disorder threshold, whereas a disproportionally higher risk above the threshold was associated with psychotic symptom load, negative symptoms, disorganization, and visible signs of mental illness. Liability associated with respectively affective and nonaffective symptom domains, in interaction with environmental risks, may operate by impacting differentially over a quasi-continuous extended psychosis phenotype in the population.

Evidence for a persistent, environment-dependent and deteriorating subtype of subclinical psychotic experiences: a 6-year longitudinal general population study

Research suggests that subclinical psychotic experiences during adolescence represent the behavioral expression of liability for psychosis. Little is known, however, about the longitudinal trajectory of liability in general population samples. Growth mixture modeling was used to examine longitudinal trajectories of self-reported positive psychotic experiences in the Youth Self Report (YSR), completed three times over a period of 6 years by a general population cohort of adolescents aged 10-11 years at baseline (n=2230). Four groups with distinct developmental trajectories of low, decreasing, increasing and persistent levels of mild positive psychotic experiences were revealed. The persistent trajectory was associated strongly with cannabis use, childhood trauma, developmental problems and ethnic minority status, and consistently displayed strong associations with factors known to predict transition from subclinical psychotic experience to clinical psychotic disorder (severity of and secondary distress due to psychotic experiences, social and attentional problems and affective dysregulation) and also with high levels of parental-reported psychotic experiences and use of mental health care at the end of the follow-up period. Progressively weaker associations were found for the increasing, decreasing and low trajectories respectively. The results suggest that the outcome of early developmental deviation associated with later expression of psychotic experiences is contingent on the degree of later interaction with environmental risks inducing, first, persistence of psychotic experiences and, second, progression to onset of need for care and service use. Insight into the longitudinal dynamics of risk states in representative samples may contribute to the development of targeted early intervention in psychosis.

A twin study of genetic and environmental determinants of abnormal persistence of psychotic experiences in young adulthood

Evidence suggests that subclinical psychotic experiences are more likely to cause transition to psychotic disorder if their expression becomes persistent. The study of longitudinal patterns of subclinical psychotic experiences may help to distinguish subgroups with transient and persistent psychotic symptoms, who may differ in risk of later psychosis. The current study investigated patterns of developmental course of subclinical psychotic experiences in a general population sample of 566 female twins, aged 18-45 years. The positive symptoms subscale of the Community Assessment of Psychic Experiences (CAPE), completed three times in 2 years, was analyzed with growth modeling. Using Latent Class Analysis, two developmental courses were distinguished: a Persistent and a Low (expression of subclinical psychotic experiences) group. The Persistent group reported significantly higher levels of depressive and negative symptoms and worse functioning in daily life. Childhood trauma (OR: 3.26, P < 0.0001) and stressful life events over the study period (OR: 3.15, P = 0.031) predicted membership of the Persistent group. Of the monozygotic (MZ) twins with their co-twin in the Persistent group, 49% also were in the Persistent group themselves (OR: 9.32, P < 0.0001), compared to only 14% in the dizygotic (DZ) co-twins (OR: 1.56, P = 0.42) (χ(2)(2) = 22.97; P < 0.001). The findings suggest that persistence of subclinical psychosis is influenced by both genetic and environmental factors, providing the possibility to study the (possibly modifiable) etiology underlying the longitudinal process of persistence of the early expression of psychosis liability.

Subclinical psychosis and depression: Co-occurring phenomena that do not predict each other over time

BackgroundThe path from subclinical psychotic experiences to clinical disorder is thought to be mediated by the persistence of subclinical psychotic experiences. One of the factors that is likely associated with this persistence is depression. Although commonly viewed as interrelated concepts, the exact relationship between subclinical psychosis and depression is not clear. MethodsCross-lagged path modeling was used to explore the relationship between subclinical psychosis and depression across and over time in an adolescent population seeking assistance for non-psychotic disorders (N=138), measured at four occasions over a two-year period. ResultsSubclinical psychosis and depression were related to each other at every cross-sectional measurement, but did not predict each other over time. Subclinical psychotic experiences and depressive symptom levels were highest at baseline, when participants presented to the clinical service for help. In addition, the relationship between them was also strongest at baseline and decreased significantly over time. ConclusionThe results suggest that psychosis and depression are interrelated phenomena that strongly co-occur in time, but longitudinally, one does not predict change in the other. Both psychopathological dimensions should be addressed when treatment is provided to adolescent help-seekers.

A Population Based Analysis of Subclinical Psychosis and Help-Seeking Behavior

Clinically defined psychosis is recognizable and distinguishable from nonclinical or subclinical psychosis by virtue of its clinical relevance (ie, its associated distress and its need for care and/or treatment). According to the continuum hypothesis, subclinical psychosis is merely quantitatively different from more extreme phenotypic expressions and as such should also be indicative of distress and help-seeking behavior but to a lesser extent. Using data from the Adult Psychiatric Morbidity Survey, the current study focused on self-reported psychosis and help-seeking experiences in a general population sample free from clinically defined psychosis (N = 7266). After statistically controlling for the effects of a series of potential help-seeking correlates the findings showed that subclinical psychosis symptom experience was significantly associated with various forms of help-seeking behavior. Individuals who reported subclinical experiences of thought control, paranoia, and strange experiences were on average 2 times more likely to attend their general practitioner for emotional problems compared with those individuals who reported no psychosis. Individuals who reported subclinical experiences of paranoia were 3 times more likely to be in receipt of counseling/therapy compared with those with no experience of paranoia. Multiple subclinical psychotic experiences also predicted elevated help-seeking behavior. These findings may have a positive impact on the detection of individuals who are at increased risk of psychological distress and aid in the design and implementation of more effective treatments at both clinical and subclinical levels.

Evidence That Onset of Clinical Psychosis Is an Outcome of Progressively More Persistent Subclinical Psychotic Experiences: An 8-Year Cohort Study

This study examined the hypothesis that developmental expression of psychometric risk in the form of subclinical psychotic experiences in the general population is usually transitory but in some instances may become abnormally persistent and progress to a clinical psychotic state. A prospective cohort study was conducted in a general population sample of 845 adolescents, aged 14-17 years, in Munich, Germany (Early Developmental Stages of Psychopathology Study). Expression of psychosis was assessed 4 times (T0-T3) over a period of 8.4 years. Transition from subclinical psychosis at T0-T2 to clinical psychosis in terms of impairment at T3 was examined as a function of the level of prior persistence of subclinical psychosis (present never, once, twice, or thrice). The more the subclinical psychosis persisted over the period T0-T2, the greater the risk of transition to clinical psychosis at T3 in a dose-response fashion (subclinical psychosis expression once over T0-T2: odds ratio [OR] = 1.5 [95% confidence interval {CI} = 0.6-3.7], posttest probability [PP] = 5%; twice: OR = 5.0 [95% CI = 1.6-15.9], PP = 16%; at all 3 measurements: OR = 9.9 [95% CI = 2.5-39.8], PP = 27%). Of all clinical psychosis at T3, more than a third (38.3%) was preceded by subclinical psychotic experiences at least once and a fifth (19.6%) at least twice. Consequently, a significant proportion of psychotic disorder may be conceptualized as the rare poor outcome of a common developmental phenotype characterized by persistence of psychometrically detectable subclinical psychotic experiences. This may be summarized descriptively as a psychosis proneness-persistence-impairment model of psychotic disorder.

Psychosis: A Category or a Dimension?

Can J Psychiatry. 2009;54(3): 137-139. The diagnostic entity of schizophrenia creates a loose boundary around a heterogeneous collection of interrelated and relatively distinct phenotypes. The Diagnostic and Statistical Manual of Mental Disorders (DSM)-V planning process is currently under way and it has once again ignited the debate about the boundaries of this diagnosis. One question concerns whether psychotic symptoms can occur in healthy people. A recent quantitative review of all reported incidence and prevalence studies of population rates of subclinical psychotic experiences revealed a median prevalence rate of around 5% and a median incidence rate of around 3%.1 Many people who hear voices can cope with them and even view them as a positive part of their lives. I remember one of my own patients who had been hallucinating for 25 years. The month after I prescribed clozapine, he began to complain about the absence of auditory hallucinations. He was feeling lonely, bored, and sad. I decided to decrease the dosage of clozapine so he could hear his voices momentarily during the day. This clinical situation was new to me because it encouraged me, for the first time, to let the voices resurface gradually to increase my patient's quality of life, instead of trying to eradicate them. This prompted me to review literature and make connections with groups of people who consider that hearing voices is not automatically something negative but may actually be positive. In a more personal and provocative book entitled Is It Normal to be Psychotic?,2 I described subjective experiences and discussions with colleagues concerning these dimensional aspects of psychosis. For instance, in the case of psychoticlike symptoms during an exposure to cannabis in a nonpatient, what makes a person experience psychotic symptoms? One hypothesis is that individual differences may reflect a genetic psychotic vulnerability (for example, for carriers of the valine allele of the COMT Val 158Met polymorphism i3,4) so that cannabis use may have no adverse influence on people with 2 copies of the methionine allele. Given that psychosis results from the interaction of many genes, it could be a continuous phenotype with mild forms present in the general population. Currently, 114 combinations of symptoms can lead to establishing the DSM-PV definition of schizophrenia, and different populations of patients are defined by different diagnostic systems (that is, DSM-III-R, DSM-IV, International Classification of Diseases, 10th edition, and Research Diagnostic Criteria). This raises questions about the validity of the current definition. Some clinicians lean toward a categorical approach, whereas others consider psychosis a dimensional phenomenon. In the 2 following In Review articles,5,6 the authors illustrate the debate between the dimensional and categorical approaches. In the first article,5 Dr Genevieve Letourneau and I review the literature about what could be considered as psychotic phenomena in the healthy or nonclinical population. Having attended some European meetings and symposia organized by the International Network for Training, Education and Research into Hearing Voices, I observed that this phenomenon can be considered either as a purely pathological or as a completely normal phenomenon. On another occasion, during a meeting with several members of our team (nurses and doctors), I mentioned that I was writing an article on auditory hallucinations in healthy people. Surprisingly, 8 out of 10 members of the team admitted (in certain cases, with details) that they had heard voices at some point during their life. It did not prevent them from being health professionals, working in psychiatry, and, for the majority, taking charge of psychotic people suffering from auditory hallucinations. This discussion reflected epidemiologic findings showing that nonclinical subjects can experience temporary or durable psychotic phenomena. …

Does reactivity to stress cosegregate with subclinical psychosis? A general population twin study

This study assessed the relationship between stress reactivity (trait 1) and psychosis (trait 2) across genetically related persons (cross-twin, cross-trait design) to examine whether stress reactivity is an uncontaminated and unconfounded familial marker of psychosis risk. Reactivity to stress and subclinical psychotic experiences were assessed in 289 female, general population twin-pairs. Cross-trait, within-twin associations investigating the association between stress reactivity and subclinical psychotic experiences in each person, were calculated. In addition, cross-trait, cross-twin associations were calculated to assess whether stress reactivity in one twin was moderated by subclinical psychotic experiences in the co-twin. Cross-trait, within-twin analyses showed significant associations between stress reactivity and subclinical psychotic experiences in each person. In addition, the cross-trait cross-twin analyses showed that stress reactivity in twin 1 was significantly moderated by subclinical experiences in the co-twin. The results suggest that the psychosis phenotype cosegregates with increased emotional reactivity to stress in daily life.

A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness–persistence–impairment model of psychotic disorder

A systematic review of all reported incidence and prevalence studies of population rates of subclinical psychotic experiences reveals a median prevalence rate of around 5% and a median incidence rate of around 3%. A meta-analysis of risk factors reveals associations with developmental stage, child and adult social adversity, psychoactive drug use, and also male sex and migrant status. The small difference between prevalence and incidence rates, together with data from follow-up studies, indicates that approximately 75-90% of developmental psychotic experiences are transitory and disappear over time. There is evidence, however, that transitory developmental expression of psychosis (psychosis proneness) may become abnormally persistent (persistence) and subsequently clinically relevant (impairment), depending on the degree of environmental risk the person is additionally exposed to. The psychosis proneness-persistence-impairment model considers genetic background factors impacting on a broadly distributed and transitory population expression of psychosis during development, poor prognosis of which, in terms of persistence and clinical need, is predicted by environmental exposure interacting with genetic risk.

Does the Concept of "Sensitization" Provide a Plausible Mechanism for the Putative Link Between the Environment and Schizophrenia?

Previous evidence reviewed in Schizophrenia Bulletin suggests the importance of a range of different environmental factors in the development of psychotic illness. It is unlikely, however, that the diversity of environmental influences associated with schizophrenia can be linked to as many different underlying mechanisms. There is evidence that environmental exposures may induce, in interaction with (epi)genetic factors, psychological or physiological alterations that can be traced to a final common pathway of cognitive biases and/or altered dopamine neurotransmission, broadly referred to as "sensitization," facilitating the onset and persistence of psychotic symptoms. At the population level, the behavioral phenotype for sensitization may be examined by quantifying, in populations exposed to environmental risk factors associated with stress or dopamine-agonist drugs, (1) the increased rate of persistence (indicating lasting sensitization) of normally transient developmental expressions of subclinical psychotic experiences and (2) the subsequent increased rate of transition to clinical psychotic disorder.