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Introduction Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). Method Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. Results 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298–7.642]) or decreasing group (OR = 3.137, [1.165–8.450]). In contrast, past (OR = .443, [.179–1.094]) or current (OR = .414, [.156–1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178–3.828]). Conclusion A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.

ObjectiveTo investigate the association between facial affect recognition (FAR) and type of adverse childhood experiences (ACEs) in a sample of clinical high risk (CHR) individuals and a matched sample of healthy controls (HCs).MethodsIn total, 309 CHR individuals and 51 HC were recruited as part of an European Union-funded multicenter study (EU-GEI) and included in this work. During a 2-year follow-up period, 65 CHR participants made a transition to psychosis (CHR-T) and 279 did not (CHR-NT). FAR ability was measured using a computerized version of the Degraded Facial Affect Recognition (DFAR) task. ACEs were measured using the Childhood Experience of Care and Abuse Questionnaire, the Childhood Trauma Questionnaire, and the Bullying Questionnaire. Generalized regression models were used to investigate the relationship between ACE and FAR. Logistic regressions were used to investigate the relationship between FAR and psychotic transition.ResultsIn CHR individuals, having experienced emotional abuse was associated with decreased total and neutral DFAR scores. CHR individuals who had experienced bullying performed better in the total DFAR and in the frightened condition. In HC and CHR, having experienced the death of a parent during childhood was associated with lower DFAR total score and lower neutral DFAR score, respectively. Analyses revealed a modest increase of transition risk with increasing mistakes from happy to angry faces.ConclusionsAdverse experiences in childhood seem to have a significant impact on emotional processing in adult life. This information could be helpful in a therapeutic setting where both difficulties in social interactions and adverse experiences are often addressed.

Background Individuals at clinical high risk (CHR) of psychosis have an approximately 20% probability of developing psychosis within 2 years, as well as an associated risk of non-psychotic disorders and functional impairment. People with subclinical psychotic experiences (PEs) are also at risk of future psychotic and non-psychotic disorders and decreased functioning. It is difficult to accurately predict outcomes in individuals at risk of psychosis on the basis of symptoms alone. Biomarkers for accurate prediction of outcomes could inform the clinical management of this group. Methods We conducted two nested case-control studies. We employed discovery-based proteomic methods to analyse protein expression in baseline plasma samples in EU-GEI and age 12 plasma samples in ALSPAC using liquid chromatography mass spectrometry. Differential expression of quantified proteomic markers was determined by analyses of covariance (with false discovery rate of 5%) comparing expression levels for each marker between those who did not and did not develop psychosis in Study 1 (adjusting for age, gender, body mass index and years in education), and between those who did and did not develop PEs in Study 2 (adjusting for gender, body mass index and maternal social class). Support vector machine algorithms were used to develop models for prediction of transition vs. non-transition (as determined by the Comprehensive Assessment of At Risk Mental States) and poor vs. good functional outcome at 2 years in Study 1 (General Assessment of Functioning: Disability subscale score 60). Similar algorithms were used to develop a model for prediction of PEs vs. no PEs at age 18 in Study 2 (as determined by the Psychosis Like Symptoms Interview). Results In Study 1, 35 of 166 quantified proteins were significantly differentially expressed between CHR participants who did and did not develop psychosis. Functional enrichment analysis provided evidence for particular implication of the complement and coagulation cascade (false discovery rate-adjusted Fisher’s exact test p=2.23E-21). Using 65 clinical and 166 proteomic features a model demonstrated excellent performance for prediction of transition status (area under the receiver-operating curve [AUC] 0.96, positive predictive value [PPV] 83.0%, negative predictive value [NPV] 93.8%). A model based on the ten most predictive proteins accurately predicted transition status in training (AUC 0.96, PPV 87.5%, NPV 95.8%) and withheld data (AUC 0.92, PPV 88.9%, NPV 91.4%). A model using the same 65 clinical and 166 proteomic features predicted 2-year functional outcome with AUC 0.72 (PPV 67.6%, NPV 47.6%). In Study 2, 5 of 265 quantified proteins were significantly differentially expressed between participants who did and did not report PEs at age 18. A model using 265 proteomic features predicted PEs at age 18 with AUC 0.76 (PPV 69.1%, NPV 74.2%). Discussion With external validation, models incorporating proteomic data may contribute to improved prediction of clinical outcomes in individuals at risk of psychosis.

Background As theorized by Abraham Maslow, a fundamental need of all humans is to seek a sense of belonging through meaningful social relationships. This universal process drives social identification, the incorporation of these important relationships into one’s own identity. Over the past several decades, social identity has been implicated in various studies of mental health for the protective role that it plays (Haslam et al. 2015). Paranoia is a core symptom of the schizotypy spectrum, a dynamic continuum that ranges from healthy personality traits to chronic schizophrenia. Paranoia is related to social identity in that it is thought to disrupt the ability to establish trusting social relationships. Over time, the association between social identification and paranoia has been indirectly investigated through various psychosocial factors such as self-esteem, which is thought to be directly influenced by social identity. Previous research has shown that a decrease in self-esteem precedes an immediate increase in paranoia (Myin-Germeys et al., 2008). Despite these findings, few studies have investigated whether social identification is associated with paranoia and the mechanisms by which this effect may emerge. The primary goal of this study was to investigate whether self-esteem mediates the effect of social identity on paranoia in a nonclinical sample. Based on scant previous studies (Bentall et al., 2017), this study hypothesized that self-esteem would mediate the pathway from social identity to paranoia. Methods The sample consisted of 168 Spanish nonclinical youngsters (mean age=28.01), belonging to the ongoing Barcelona Longitudinal Investigation of Schizotypy Study (BLISS). From a large pool of unselected college students, a selected subsample oversampled for schizotypy scores continues regular follow-up assessments. Social identity was measured using the Multidimensional Scale of Perceived Social Support (MSPSS; Landeta & Calvete, 2002), self-esteem was measured using the Rosenberg Self-Esteem Scale (RSES; Rosenberg, 1965), and paranoia was measured using the “suspiciousness” subscale of the Schizotypal Personality Questionnaire (SPQ; Raine, 1991). A simple mediation analysis of social identity and paranoia via self-esteem was conducted to examine the indirect effect of social identity on paranoia via self-esteem. Results Pearson’s correlations showed that social identity was correlated to self-esteem (r=0.311; p Discussion The finding that self-esteem mediates the pathway from social identity to paranoia provides an important connection between previous literature that has studied these relationships indirectly. This study concludes that meaningful social relationships may protect against paranoia and it highlights the relevance of tanking into account self-esteem in explaining the association between social identity and paranoia. Thus, it may provide a framework in which various forms of social interventions can be used to prevent and treat paranoid ideation. However, further steps are being taken to further establish this finding. It will be useful to look at various samples, both clinical and nonclinical, along the schizotypy spectrum in order to further investigate the mechanism of action underlying this environmental and psychological interaction.

Background Genetic vulnerability to psychosis is polygenic, involving multiple genes with small individual effects (Psychiatric Genomics Consortium (PGC), 2014). The risk of psychosis is also related to environmental factors, such as childhood trauma (Lardinois et al, 2011). Although the onset of psychosis is thought to result from the interaction of genetic and environmental risk factors (Walker & Diforio, 1997), the extent to which the influence of childhood trauma depends on genetic susceptibility remains unclear. We sought to address this issue in a large prospective study of people at clinical high risk (CHR) for psychosis. These individuals present with psychotic and affective symptoms, and are at increased risk of developing both schizophreniform and affective psychoses. Methods We studied subjects of European ancestry, drawn from EU-GEI, a large multi-centre prospective study of people at CHR for psychosis. At baseline, DNA was obtained from subjects who met the CAARMS criteria for the CHR state (n=266) and healthy controls (HC; n=42). Childhood trauma was assessed using the childhood trauma questionnaire (CTQ), which comprises 5 subdomains: emotional abuse, physical abuse, sexual abuse, physical neglect, and emotional neglect. Polygenic risk scores (PRSs) for schizophrenia (SCZ), bipolar disorder (BD) and major depressive disorder (MDD) were constructed separately, using results from meta-analyses by the corresponding Disorder Working Groups of the PGC. The CHR subjects were clinically monitored for up to 5 years and clinical outcomes were assessed in terms of transition to psychosis (as defined by the CAARMS), remission from the CHR state (subject no longer meets CAARMS inclusion criteria) and level of functioning (GAF Disability Scale). Logistic regression models were used to investigate the association between each PRSs and childhood trauma as predictors of transition and remission, adjusted by population stratification using the first 10 principal components, age, sex and site. All findings are reported at p Results Within the CHR sample, the onset of psychosis during follow up was related to interactions between the BD PRS and the total childhood trauma score (OR=0.959, 95% CI 0.930–0.988, p=0.006), and between the BD PRS and physical abuse (OR=0.787, 95% CI 0.689–0.900, p Discussion These data indicate that clinical outcomes in CHR subjects are related to interactions between the polygenic risk for psychotic disorders and childhood adversity. The measurement of interactions between genomic and environmental risk factors may help to predict individual outcomes in people at high risk in a clinical setting.

Background The traumagenic neurodevelopment model of psychosis poses that prolonged or severe stress exposure in critical developmental periods (i.e., childhood) disrupts psychobiological stress regulation mechanisms, increasing liability for the onset and persistence of psychotic symptoms after re-exposure to stressful events (Read et al., 2014). This disruption seems to result in a process of behavioral and biological sensitization by which the individual manifests an enhanced stress sensitivity to subsequent minor adversities in adulthood (Belda et al., 2015), which may cause an increased risk for psychosis. The behavioral manifestation of stress sensitization has been examined in samples at clinical risk for psychosis, but it has been scarcely studied in nonclinical populations. The first goal of the present study was to investigate whether the association between childhood trauma (CT) and perceived stress was moderated by the impact of recent life events in a nonclinical sample. The second goal was to test whether the association between CT and suspiciousness was mediated by perceived stress, and whether this mediation was moderated by the impact of life events. Following stress sensitization hypotheses, it was expected that the association between CT and suspiciousness would be mediated by higher levels of perceived stress. In turn, the impact of negative recent life events was expected to moderate the effect of CT on suspiciousness via increased levels of perceived stress. Methods The sample consisted of 168 Spanish nonclinical youngsters (mean age=28.01), belonging to the ongoing Barcelona Longitudinal Investigation of Schizotypy Study (BLISS). From a large pool of unselected college students, a selected subsample oversampled for schizotypy scores continues regular follow-up assessments. They were assessed for life events, perceived stress and suspiciousness at the concurrent assessment, whereas CT was assessed 7 years earlier at baseline. Linear regression and simple slope analyses were performed to test whether recent life events moderated the association between CT and suspiciousness. Moderated mediation analyses were conducted to examine the indirect effect of CT on suspiciousness via perceived stress moderated by the impact of recent life events. Results Recent life events significantly moderated the association between CT and perceived stress. Simple slope analyses indicated that this association was significant when subjects experienced negative or neutral life events, but not positive life events. Moderated mediation analyses revealed an indirect effect of CT on suspiciousness through perceived stress, which was moderated by the impact of recent life events. Thus, these mediational effects were significant for those subjects with a greater subjective appraisal of a negative or neutral impact of life events, but not for those experiencing a positive impact. The magnitude of the conditional indirect effect (as indicated by the Index of Moderated Mediation) was significantly different across levels of impact of recent life events (i.e., negative, neutral, positive). Discussion These findings provide further supporting evidence to the stress sensitization hypothesis for psychosis by showing its manifestation across both the clinical and nonclinical ranges of the hypothesized psychosis continuum. CT and perceived stress were associated when the impact of recent life events was negative or neutral, but not positive, suggesting that positive life events may play a protective role in the perception of stress and the role that stress shows in the mechanistic pathway to suspiciousness.

Elucidating schizotypal traits is important if we are to understand the various manifestations of psychosis spectrum liability and to reliably identify individuals at high risk for psychosis. The present study examined the network structures of (1) 9 schizotypal personality domains and (2) 74 individual schizotypal items, and (3) explored whether networks differed across gender and culture (North America vs China). The study was conducted in a sample of 27001 participants from 12 countries and 21 sites (M age = 22.12; SD = 6.28; 37.5% males). The Schizotypal Personality Questionnaire (SPQ) was used to assess 74 self-report items aggregated in 9 domains. We used network models to estimate conditional dependence relations among variables. In the domain-level network, schizotypal traits were strongly interconnected. Predictability (explained variance of each node) ranged from 31% (odd/magical beliefs) to 55% (constricted affect), with a mean of 43.7%. In the item-level network, variables showed relations both within and across domains, although within-domain associations were generally stronger. The average predictability of SPQ items was 27.8%. The network structures of men and women were similar (r = .74), node centrality was similar across networks (r = .90), as was connectivity (195.59 and 199.70, respectively). North American and Chinese participants networks showed lower similarity in terms of structure (r = 0.44), node centrality (r = 0.56), and connectivity (180.35 and 153.97, respectively). In sum, the present article points to the value of conceptualizing schizotypal personality as a complex system of interacting cognitive, emotional, and affective characteristics.

The schizotypy construct focuses attention on the liability to develop schizophrenia-spectrum disorders, yet traditionally, the schizotypy models have put more emphasis on stress-vulnerability interactions rather than developmental dynamics of emerging risk for psychopathology. Indeed, developmental accounts of this emerging personality trait have rarely been explicitly formulated. In this position article, we wish to convey some of the basic developmental tenets of schizotypy, and how they can inform high-risk research. Firstly, we tackle the state vs trait issue to outline the possible relationship between high-risk states and trait schizotypy. Second, we review the evidence suggesting that the consolidation of schizotypy, encompassing its 3 main dimensions, could be considered as a developmental mediator between very early risk factors and transition into high-risk states. Importantly, developmental dynamics between endophenotypes, as well as transactional and epigenetics mechanisms should enter modern conceptualizations of schizotypy. Finally, we present a developmental psychopathology perspective of schizotypy sensitive to both the multifinality and equifinality of schizophrenia-spectrum disorders. We conclude that schizotypy represents a crucial construct in a fully-developmental study of schizophrenia-spectrum disorders.