The experience sampling method as an mHealth tool to support self-monitoring, self-insight, and personalized health care in clinical practice.

BACKGROUND: The experience sampling method (ESM) builds an intensive time series of experiences and contexts in the flow of daily life, typically consisting of around 70 reports, collected at 8-10 random time points per day over a period of up to 10 days. METHODS: With the advent of widespread smartphone use, ESM can be used in routine clinical practice. Multiple examples of ESM data collections across different patient groups and settings are shown and discussed, varying from an ESM evaluation of a 6-week randomized trial of mindfulness, to a twin study on emotion dynamics in daily life. RESULTS: Research shows that ESM-based self-monitoring and feedback can enhance resilience by strengthening the capacity to use natural rewards. Personalized trajectories of starting or stopping medication can be more easily initiated and predicted if sensitive feedback data are available in real time. In addition, personalized trajectories of symptoms, cognitive abilities, symptoms impacting on other symptoms, the capacity of the dynamic system of mental health to "bounce back" from disturbance, and patterns of environmental reactivity yield uniquely personal data to support shared decision making and prediction in clinical practice. Finally, ESM makes it possible to develop insight into previous implicit patterns of thought, experience, and behavior, particularly if rapid personalized feedback is available. CONCLUSIONS: ESM enhances clinical practice and research. It is empowering, providing co-ownership of the process of diagnosis, treatment evaluation, and routine outcome measurement. Blended care, based on a mix of face-to-face and ESM-based outside-the-office treatment, may reduce costs and improve outcomes.

Evidence that childhood urban environment is associated with blunted stress reactivity across groups of patients with psychosis, relatives of patients and controls.

PURPOSE: Psychosis is associated with urban upbringing, and increased emotional reactivity is associated with psychosis. The aim of this study was to examine to what degree urban upbringing impacts emotional reactivity, and how this may be relevant for psychotic disorder and familial risk of psychotic disorder. METHODS: Patients with a diagnosis of non-affective psychotic disorder (n = 57), 59 first degree relatives of patients and 75 healthy comparison subjects were studied with the experience sampling method (a random time sampling technique to assess affective experience in relation to fluctuating stressors in the flow of daily life), to measure a change in negative affect in relation to subjective stress. Urban exposure was defined at 5 levels, considering the population density and the number of moves between birth and the 15th birthday, using data from the Dutch Central Bureau of Statistics and the equivalent database in Belgium. RESULTS: Multilevel random regression analyses showed that urban upbringing was consistently and strongly associated with a reduced increase in negative affect in relation to SS in adulthood in a dose-response fashion in all three groups. Regression coefficients in the patient group decreased from 0.148 (p < 0.001) in the lowest urbanicity level to 0.094 (p < 0.001) in the highest urbanicity level. CONCLUSION: The findings suggest that urban upbringing may occasion "habituation" rather than "sensitization" across groups, which may or may not be relevant for the onset of psychotic disorder.

FKBP5 as a possible moderator of the psychosis-inducing effects of childhood trauma.

BACKGROUND: FK506 binding protein 5 (FKBP5) has repeatedly been shown to be a critical determinant of post-traumatic stress disorder (PTSD) and depression following childhood trauma. AIMS: To examine the role of FKBP5-trauma interactions in the partly stress-related psychosis phenotype. METHOD: In 401 general population twins, four functional polymorphisms were examined in models of psychosis and cortisol, and followed up in models of psychosis in three samples at different familial liability (175 controls, 200 unaffected siblings and 195 patients with a psychotic disorder). RESULTS: The most consistent finding was an interaction between childhood trauma and rs9296158/rs4713916 on psychotic symptoms and cortisol in the twin sample, combined with a directionally similar interaction in siblings (rs4713916) and patients (rs9296158), A-allele carriers at both polymorphisms being most vulnerable to trauma. CONCLUSIONS: Trauma may increase the risk of psychosis through enduring changes in the cortisol feedback loop, similar to that for PTSD, suggesting comparable biological mechanisms for psychosis across diagnostic boundaries.

Temporal dynamics of suspiciousness and hallucinations in clinical high risk and first episode psychosis.

The objective of the current study is to elucidate the temporal dynamics of suspiciousness and hallucinations as they occur in daily life in the early stages of psychosis. Their prevalence and co-occurrence, as well as their temporal relation to affect and delusions, were compared between patients with a first psychotic episode (FEP) and individuals at clinical high risk for psychosis (CHRp). The Experience Sampling Method was used to investigate suspiciousness and hallucinatory experiences, delusions, and affect at semi-random moments throughout six days in 33 CHRp and 34 FEP. Overall, 91% of CHRp and 59% of FEP reported suspiciousness, and 24% and 39% reported hallucinations, respectively. Hallucinations almost always co-occurred with suspiciousness, whereas suspiciousness was often present without hallucinations. Suspicious episodes in CHRp occurred with marked increases in delusional intensity, while hallucinatory experiences were mostly absent. In FEP, a decrease of positive affect preceded suspicious episodes, while an increase of negative affect preceded hallucinatory episodes. Our results indicated the presence of a delusional mood (atmosphere) in CHRp as an experience in itself, without co-occurring or following hallucinations, thus refuting the anomalous experience hypothesis of psychosis. The co-occurrence of hallucinations, on the other hand, indicates a more severe stage of symptomatology.

Are women better mindreaders? Sex differences in neural correlates of mentalizing detected with functional MRI.

BACKGROUND: The ability to mentalize, i.e. develop a Theory of Mind (ToM), enables us to anticipate and build a model of the thoughts, emotions and intentions of others. It has long been hypothesised that women differ from men in their mentalizing abilities. In the present fMRI study we examined the impact of (1) gender (women vs. men) and (2) game partner (human vs. computer) on ToM associated neural activity in the medial prefrontal cortex. Groups of men (n = 12) and women (n = 12) interacted in an iterated classical prisoner's dilemma forced choice situation with alleged human and computer partners who were outside the scanner. RESULTS: Both the conditions of playing against putative human as well as computer partners led to activity increases in mPFC, ACC and rTPJ, constituting the classic ToM network. However, mPFC/ACC activity was more pronounced when participants believed they were playing against the alleged human partner. Differences in the medial frontal lobe activation related to the sex of the participants could be demonstrated for the human partner > computer partner contrast. CONCLUSION: Our data demonstrate differences in medial prefrontal brain activation during a ToM task depending on both the gender of participants and the game partner.

Evidence that self-reported psychotic experiences represent the transitory developmental expression of genetic liability to psychosis in the general population.

It has been suggested that self-reported, common, non-clinical psychotic experiences may represent the transitory developmental expression of distributed genetic risk for psychosis. In a sample of female MZ (176 pairs) and DZ twins (113 pairs), cross-twin, cross-trait analyses were conducted to investigate the association between repeated continuous measures of self-reported psychotic experiences (PE-three measures over 18 months), assessed with the CAPE, in one twin and clinical interview categorical measures of psychotic symptoms (PS), assessed with SCID-I, in the other twin. The results showed that in MZ but not DZ pairs (interaction: chi(2) = 7.9, df = 1, P = 0.005), the cross-twin association between PE and PS was large and significant (standardized effect size: 0.26, 95% CI: 0.10-0.42) and of similar magnitude as the within-twin PE-PS association (standardized effect size: 0.28, 95% CI: 0.10-0.45), demonstrating both PE validity and genetic effects. In addition, the cross-twin association between PE and PS was significantly larger (interaction: chi(2) = 20.3, df = 1, P < 0.0001) for younger MZ twins (standardized effect size: 0.67, 95% CI: 0.44-0.90) than older MZ twins (standardized effect size: -0.05, 95% CI: -0.26 to 0.16), demonstrating developmental effects. This study indicates that self-reported psychotic experiences in the general population may represent the developmental expression of population genetic risk for psychosis.

Recovery from daily-life stressors in early and chronic psychosis.

Initial affective and psychotic reactivity to daily stressors is altered in psychosis, and most notably in early psychosis. In addition to altered initial stress reactivity, results from studies using Experience Sampling Methodology (ESM) and psychophysiological measures indicate that impaired recovery from mild stressors may also be a risk factor for mental illness. The current ESM study investigated affective recovery from daily stressors in chronic psychosis patients (CP; n = 162), individuals at early stages of psychosis (EP; n = 127), and healthy volunteers (HV; n = 220) assessing fluctuations in negative affect (NA), tension, and suspiciousness ten times a day on six consecutive days. Recovery was operationalized for all three variables as the return to baseline (i.e., level at t-1) following the first stressful event of a day (i.e., t0). The EP group showed a delayed recovery of NA (t1-t3: B = 0.185; p = .007 and B = 0.228; p = .002) and suspiciousness (t1: B = 0.223; p = .010 and B = 0.291; p = .002) compared to HV and CP, respectively. Delayed recovery was detected for tension as well (t1-t2: EP > HV: B = 0.242; p = .040 and EP > CP: B = 0.284; p = .023), but contrary to both other momentary states, this effect disappeared when controlling for subsequent stressful events. There were no significant differences in recovery between HV and CP. These results suggest that in EP, stressful daily events have longer-lasting effects on overall negative affect and subclinical psychotic-like experiences. Future studies should incorporate physiological and endocrine measures in order to integrate recovery patterns of the different stress systems.

Subjective quality of life in psychosis: Evidence for an association with real world functioning?

Subjective quality of life (SQOL) is an established patient-reported outcome in psychosis. However, current self-report measures of SQOL may be affected by recall bias and may not fully capture dynamic changes in SQOL over time. This study aimed to examine the ecological validity of self-reported and momentary assessment measures of SQOL, and their association with emotional experience, social interaction and activity in real life, in both patients with psychotic disorder (n = 56) and controls (n = 71). Self-reported QOL was assessed with the WHO-QOL, momentary QOL and real life experiences were assessed with the Experience Sampling Method (ESM). Results show that both measures were significantly associated in patients and controls, and associations with emotional experience were most relevant, momentary QOL being a stronger predictor than self-reported QOL. The association between momentary QOL and negative affect was stronger in patients than in controls. Overall, momentary QOL was more consistently associated with affect, social interaction and activity, while self-reported QOL displayed a more narrow association with mostly affect. Concluding, concurrent assessment of self-reported QOL and momentary QOL showed that momentary QOL may enhance the ecological validity of SQOL measurement. Experience sampling research may broaden our perspective on SQOL and its associations with real life functioning.

Developmental course of subclinical positive and negative psychotic symptoms and their associations with genetic risk status and impairment.

The proneness-persistence-impairment (PPI) model states that psychotic experiences are more likely to lead to impairment if their expression becomes persistent. Higher genetic risk for psychosis is known to affect proneness and persistence of subclinical positive symptoms. Less is known about potential effects of genetic risk on the course of subclinical negative symptoms, impairment, and their subsequent associations. The current study examined these issues in a large sample (n=1131), consisting of individuals with higher genetic risk (siblings of patients with psychotic disorders, n=703) and lower genetic risk (controls without a family member with lifetime psychosis, n=428). Psychotic experiences were assessed with the CAPE questionnaire, at two time points three years apart. Participants were allocated to one of four groups representing developmental course: stable low, decreasing, increasing or persisting subclinical positive/negative symptoms. Lifetime clinical psychosis was an exclusion criterion at baseline. Higher genetic risk status was found to be associated with a persisting course of both subclinical positive and negative symptoms, symptom-related distress and functional impairment. There is no evidence for an effect of genetic risk status on the association between developmental course and impairment. The results of the current study underline the importance of assessing psychotic experiences in the context of genetic risk, multidimensional and over time. Additionally, the current findings both underscore and contribute to the PPI model: psychotic experiences are more likely to lead to impairment if their expression becomes persistent, both in individuals with higher and lower genetic risk for psychosis.

Evidence that environmental and genetic risks for psychotic disorder may operate by impacting on connections between core symptoms of perceptual alteration and delusional ideation.

BACKGROUND: Relational models of psychopathology propose that symptoms are dynamically connected and hypothesize that genetic and environmental influences moderate the strength of these symptom connections. Previous findings suggest that the interplay between hallucinations and delusions may play a crucial role in the development of psychotic disorder. The current study examined whether the connection between hallucinations and delusions is impacted by proxy genetic and environmental risk factors. METHODS: Hallucinations and delusions at baseline and at 3-year follow-up were assessed in a sample of 1054 healthy siblings and 918 parents of 1109 patients with psychosis, and in 589 healthy controls (no familial psychosis risk). Environmental factors assessed were cannabis use, childhood trauma, and urbanicity during childhood. Logistic regression analyses tested whether familial psychosis risk predicted increased risk of delusions, given presence of hallucinations. Moderating effects of environmental factors on the hallucination-delusion association were tested in a similar fashion, restricted to the control and sibling groups. RESULTS: The risk of delusions, given hallucinations, was associated with proxy genetic risk: 53% in parents, 47% in siblings, and 36% in controls. The hallucination-delusion association was stronger in those reporting cannabis use (risk difference: 32%) and childhood trauma (risk difference: 15%) although not all associations were statistically conclusive (respectively: p = .037; p = .054). A directionally similar but nonsignificant effect was found for urb anicity during childhood (risk difference: 14%, p =.357). CONCLUSION: The strength of the connection between delusions and hallucinations is associated with familial and environmental risks for psychotic disorder, suggesting that specific symptom connections in the early psychosis psychopathology network are informative of underlying mechanisms.

Evidence that a psychopathology interactome has diagnostic value, predicting clinical needs: an experience sampling study.

BACKGROUND: For the purpose of diagnosis, psychopathology can be represented as categories of mental disorder, symptom dimensions or symptom networks. Also, psychopathology can be assessed at different levels of temporal resolution (monthly episodes, daily fluctuating symptoms, momentary fluctuating mental states). We tested the diagnostic value, in terms of prediction of treatment needs, of the combination of symptom networks and momentary assessment level. METHOD: Fifty-seven patients with a psychotic disorder participated in an ESM study, capturing psychotic experiences, emotions and circumstances at 10 semi-random moments in the flow of daily life over a period of 6 days. Symptoms were assessed by interview with the Positive and Negative Syndrome Scale (PANSS); treatment needs were assessed using the Camberwell Assessment of Need (CAN). RESULTS: Psychotic symptoms assessed with the PANSS (Clinical Psychotic Symptoms) were strongly associated with psychotic experiences assessed with ESM (Momentary Psychotic Experiences). However, the degree to which Momentary Psychotic Experiences manifested as Clinical Psychotic Symptoms was determined by level of momentary negative affect (higher levels increasing probability of Momentary Psychotic Experiences manifesting as Clinical Psychotic Symptoms), momentary positive affect (higher levels decreasing probability of Clinical Psychotic Symptoms), greater persistence of Momentary Psychotic Experiences (persistence predicting increased probability of Clinical Psychotic Symptoms) and momentary environmental stress associated with events and activities (higher levels increasing probability of Clinical Psychotic Symptoms). Similarly, the degree to which momentary visual or auditory hallucinations manifested as Clinical Psychotic Symptoms was strongly contingent on the level of accompanying momentary paranoid delusional ideation. Momentary Psychotic Experiences were associated with CAN unmet treatment needs, over and above PANSS measures of psychopathology, similarly moderated by momentary interactions with emotions and context. CONCLUSION: The results suggest that psychopathology, represented as an interactome at the momentary level of temporal resolution, is informative in diagnosing clinical needs, over and above traditional symptom measures.

Psychopathological mechanisms linking childhood traumatic experiences to risk of psychotic symptoms: analysis of a large, representative population-based sample.

BACKGROUND: Different psychological models of trauma-induced psychosis have been postulated, often based on the observation of "specific" associations between particular types of childhood trauma (CT) and particular psychotic symptoms or the co-occurrence of delusions and hallucinations. However, the actual specificity of these associations remains to be tested. METHODS: In 2 population-based studies with comparable methodology (Netherlands Mental Health Survey and Incidence Study-1 [NEMESIS-1] and NEMESIS-2, N = 13 722), trained interviewers assessed CT, psychotic symptoms, and other psychopathology. Specificity of associations was assessed with mixed-effects regression models with multiple outcomes, a statistical method suitable to examine specificity of associations in case of multiple correlated outcomes. RESULTS: Associations with CT were strong and significant across the entire range of psychotic symptoms, without evidence for specificity in the relationship between particular trauma variables and particular psychotic experiences (PEs). Abuse and neglect were both associated with PEs (OR abuse: 2.12, P < .001; OR neglect: 1.96, P < .001), with no large or significant difference in effect size. Intention-to-harm experiences showed stronger associations with psychosis than CT without intent (χ(2) = 58.62, P < .001). Most trauma variables increased the likelihood of co-occurrence of delusions and hallucinations rather than either symptom in isolation. DISCUSSION: Intention to harm is the key component linking childhood traumatic experiences to psychosis, most likely characterized by co-occurrence of hallucinations and delusions, indicating buildup of psychotic intensification, rather than specific psychotic symptoms in isolation. No evidence was found to support psychological theories regarding specific associations between particular types of CT and particular psychotic symptoms.

Epigenetic genes and emotional reactivity to daily life events: a multi-step gene-environment interaction study.

Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs) in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR), moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM). In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i) 85 unaffected siblings of patients with psychosis, (ii) 110 patients with psychotic disorders, and iii) 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825) and 1 SNP of MTHFR (rs1801131) moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery.

Emotional experience in negative symptoms of schizophrenia--no evidence for a generalized hedonic deficit.

BACKGROUND: Deficits in emotion processing are thought to underlie the key negative symptoms flat affect and anhedonia observed in psychotic disorders. This study investigated emotional experience and social behavior in the realm of daily life in a sample of patients with schizophrenia and schizoaffective disorder, stratified by level of negative symptoms. METHODS: Emotional experience and behavior of 149 patients with schizophrenia and schizoaffective disorder and 143 controls were explored using the Experience Sampling Method. RESULTS: Patients reported lower levels of positive and higher levels of negative affect compared with controls. High negative symptom patients reported similar emotional stability and capacity to generate positive affect as controls, whereas low negative symptom patients reported increased instability. All participants displayed roughly comparable emotional responses to the company of other people. However, in comparison with controls, patients showed more social withdrawal and preference to be alone while in company, particularly the high negative symptom group. CONCLUSIONS: This study revealed no evidence for a generalized hedonic deficit in patients with psychotic spectrum disorders. Lower rather than higher levels of negative symptoms were associated with a pattern of emotional processing which was different from healthy controls.

Altered transfer of momentary mental states (ATOMS) as the basic unit of psychosis liability in interaction with environment and emotions.

Psychotic disorders are thought to represent altered neural function. However, research has failed to map diagnostic categories to alterations in neural networks. It is proposed that the basic unit of psychotic psychopathology is the moment-to-moment expression of subtle anomalous experiences of subclinical psychosis, and particularly its tendency to persist from moment-to-moment in daily life, under the influence of familial, environmental, emotional and cognitive factors.In a general population twin sample (n = 579) and in a study of patients with psychotic disorder (n = 57), their non-psychotic siblings (n = 59) and unrelated controls (n = 75), the experience sampling paradigm (ESM; repetitive, random sampling of momentary mental states and context) was applied. We analysed, in a within-person prospective design, (i) transfer of momentary anomalous experience at time point (t-1) to time point (t) in daily life, and (ii) moderating effects of negative affect, positive affect, daily stressors, IQ and childhood trauma. Additionally, (iii) familial associations between persistence of momentary anomalous experience and psychotic symptomatology were investigated. Higher level of schizotypy in the twins (but not higher level of psychotic symptoms in patients) predicted more persistence of momentary anomalous experience in daily life, both within subjects and across relatives. Persistence of momentary anomalous experience was highest in patients, intermediate in their siblings and lowest in controls. In both studies, persistence of momentary anomalous experience was moderated by higher levels of negative affect, daily stressors and childhood trauma (only in twins), and by lower levels of positive affect. The study of alterations in the moment-to-moment transfer of subtle anomalous experience of psychosis, resulting in their persistence, helps to explain why psychotic and emotional dysregulation tend to cluster in a single phenotype such as schizophrenia, and how familial and environmental risks increase the risk of expression of psychosis from, first, subtle momentary anomalous experience to, second, observable clinical symptoms.

Mobile assessment in schizophrenia: a data-driven momentary approach.

In this article, a data-driven approach was adopted to demonstrate how real-life diary techniques [ie, the experience sampling method (ESM)] could be deployed for assessment purposes in patients with psychotic disorder, delivering individualized and clinically relevant information. The dataset included patients in an acute phase of psychosis and the focus was on paranoia as one of the main psychotic symptoms (30 patients with high levels of paranoia and 34 with low levels of paranoia). Based on individual cases, it was demonstrated how (1) symptom and mood patterns, (2) patterns of social interactions or activities, (3) contextual risk profiles (eg, is being among strangers, as opposed to family, associated with higher paranoia severity?), and (4) temporal dynamics between mood states and paranoia (eg, does anxiety precipitate or follow the onset of increased paranoia severity?) substantially differ within individual patients and across the high vs low paranoid patient group. Most striking, it was shown that individual findings are different from what is found on overall group levels. Some people stay anxious after a paranoid thought came to mind. For others, paranoia is followed by a state of relaxation. It is discussed how ESM, surfacing the patient's implicit knowledge about symptom patterns, may provide an excellent starting point for person-tailored psychoeducation and for choosing the most applicable therapeutic intervention.

Temporal dynamics of visual and auditory hallucinations in psychosis.

BACKGROUND: Hallucinations are a core feature of psychosis, often causing considerable distress. Reported prevalence ranges from 70% for auditory hallucinations (AHs) to 30% for visual hallucinations (VHs) and 4% for hallucinations in the tactile domain. AHs have been studied extensively but studies on VHs are scarce. The current study investigated the phenomenology of VHs and AHs in the realm of daily life, by analyzing their prevalence, course and co-occurrence over a 6-day period and their temporal relation to emotions and delusions. METHODS: The ESM, a structured diary technique, was used to investigate hallucinatory experiences in the context of daily life in a pooled data-set of 184 participants (71% males) with psychosis spectrum disorders, which were recruited from mental health facilities in the south of the Netherlands and Belgium. All self-assessments were rated on 7-point Likert scales. VHs were defined using participants' scores on the item "I see phenomena". AHs were measured using the item "I hear voices". RESULTS: Overall, 73 participants (40%) reported hallucinations. Ten participants reported VHs only, 38 reported both VHs and AHs, and 25 participants reported AHs only. AHs co-occurred with VHs in 40% of the hallucinatory moments. Patients with both VHs and AHs reported higher levels of negative affect, lower levels of positive affect and higher delusional intensity than non-hallucinating patients. Increased delusional intensity preceded the onset of hallucinatory episodes, whereas increases in positive or negative affect did not. DISCUSSION: These results show that VHs are common in patients with psychosis spectrum disorders and often co-occur with AHs in time. Furthermore delusional ideation may precede hallucinatory episodes in the realm of daily life, rather than result from a hallucination and affective dysregulation might not play a primary role in hallucination onset.

Evidence that onset of psychosis in the population reflects early hallucinatory experiences that through environmental risks and affective dysregulation become complicated by delusions.

OBJECTIVE: To examine the hypothesis that the "natural" combination of delusions and hallucinations in psychotic disorders in fact represents a selection of early subclinical hallucinatory experiences associated with delusional ideation, resulting in need for care and mental health service use. METHODS: In the Early Developmental Stages of Psychopathology study, a prospective, 10-year follow-up of a representative cohort of adolescents and young adults in Munich, Germany (n = 2524), clinical psychologists assessed hallucinations and delusions at 2 time points (T2 and T3). Analyses compared differences in psychopathology, familial liability for nonpsychotic disorder, nongenetic risk factors, persistence, and clinical outcome between groups characterized by: (1) absence of positive psychotic symptoms, (2) presence of isolated hallucinations, (3) isolated delusions, and (4) both hallucinations and delusions. RESULTS: Delusions and hallucinations occurred together much more often (T2: 3.1%; T3: 2.0%) than predicted by chance (T2: 1.0%; T3: 0.4%; OR = 11.0; 95% CI: 8.1, 15.1). Content of delusions was contingent on presence of hallucinations but modality of hallucinations was not contingent on presence of delusions. The group with both hallucinations and delusions, compared to groups with either delusions or hallucinations in isolation, displayed the strongest associations with familial affective liability and nongenetic risk factors, as well as with persistence of psychotic symptoms, comorbidity with negative symptoms, affective psychopathology, and clinical need. CONCLUSIONS: The early stages of psychosis may involve hallucinatory experiences that, if complicated by delusional ideation under the influence of environmental risks and (liability for) affective dysregulation, give rise to a poor prognosis hallucinatory-delusional syndrome.

Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective- and cross-sectional cohort studies.

Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41,803) and 8 population-based cross-sectional studies (n = 35,546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34-3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90-3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12-4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17-3.47]). The estimated population attributable risk was 33% (16%-47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis.

Affectively salient meaning in random noise: a task sensitive to psychosis liability.

Stable differences in the tendency to attribute meaning and emotional value to experience may represent an indicator of liability to psychosis. A brief task was developed assessing variation in detecting affectively meaningful speech (speech illusion) in neutral random signals (white noise) and the degree to which this was associated with psychometric and familial vulnerability for psychosis. Thirty patients, 28 of their siblings, and 307 controls participated. The rate of speech illusion was compared between cases and controls. In controls, the association between speech illusion and interview-based positive schizotypy was assessed. The hypothesis of a dose-response increase in rate of speech illusion across increasing levels of familial vulnerability for psychosis (controls, siblings of patients, and patients) was examined. Patients were more likely to display speech illusions than controls (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.4-11.7), also after controlling for neurocognitive variables (OR = 3.8, 95% CI = 1.04-14.1). The case-control difference was more accentuated for speech illusion perceived as affectively salient (positively or negatively appraised) than for neutrally appraised speech illusions. Speech illusion in the controls was strongly associated with positive schizotypy but not with negative schizotypy. In addition, the rate of speech illusion increased with increasing level of familial risk for psychotic disorder. The data suggest that the white noise task may be sensitive to psychometric and familial vulnerability for psychosis associated with alterations in top-down processing and/or salience attribution.