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ABSTRACT Introduction Methods Results Conclusions Adolescents with psychosis‐spectrum symptoms are at particularly high risk for suicide, however, little is known about how suicidal cognitions manifest in this population. Suicidal cognitions can occur as verbal thoughts and/or mental images of suicide, and mental images may be indicative of a higher risk for suicidal behaviours. Suicidal mental imagery could be a salient and important suicide‐related risk factor for adolescents with hallucinations in particular, however, the co‐occurrence of these phenomena has yet to be studied. In a sample of psychiatrically hospitalised adolescents, we hypothesize that hallucinations will be associated with increased suicidal mental imagery and suicide attempts.This chart review study included data from 219 adolescents admitted to a psychiatric inpatient unit. Adolescents completed an assessment battery probing hallucinations, suicidal cognitions, and suicide attempts.Adolescents with past‐month hallucinations had higher rates of past‐week suicidal verbal thoughts and suicidal mental imagery, but not suicide attempts, compared to those without hallucinations. Adolescents with hallucinations reported a younger onset of suicidal mental imagery, and they endorsed more frequent imagery. Past‐month hallucinations were significantly and positively associated with suicidal mental imagery, beyond the effects of internalising symptoms. Suicidal mental imagery was positively associated with past‐week suicide attempts, but past‐month hallucinations were not.Our findings indicate that hallucinations are linked to suicidal mental imagery, an important yet under‐studied risk factor for suicidal behaviour. These data highlight the need for more research exploring suicidal mental imagery among high‐risk adolescents experiencing hallucinations to inform suicide risk assessment and intervention. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Urbanicity is a well‐established risk factor for psychosis. Our recent multi‐national study found an association between urbanicity and clinical psychosis in Northern Europe but not in Southern Europe. In this study, we hypothesized that the effect of current urbanicity on variation of schizotypy would be greater in North‐western Europe countries than in Southern Europe ones.We recruited 1080 individuals representative of the populations aged 18–64 of 14 different sites within 5 countries, classified as either North‐western Europe (England, France, and The Netherlands) with Southern Europe (Spain and Italy). Our main outcome was schizotypy, assessed through the Structured Interview for Schizotypy‐Revised. Our main exposure was current urbanicity, operationalized as local population density. A priori confounders were age, sex, ethnic minority status, childhood maltreatment, and social capital. Schizotypy variation was assessed using multi‐level regression analysis. To test the differential effect of urbanicity between North‐western and Southern European, we added an interaction term between population density and region of recruitment.Population density was associated with schizotypy (β = 0.248,95%CI = 0.122–0.375;p < 0.001). The addition of the interaction term improved the model fit (likelihood test ratio:χ2 = 6.85; p = 0.009). The effect of urbanicity on schizotypy was substantially stronger in North‐western Europe (β = 0.620,95%CI = 0.362–0.877;p < 0.001) compared with Southern Europe (β = 0.190,95%CI = 0.083–0.297;p = 0.001).The association between urbanicity and both subclinical schizotypy and clinical psychosis, rather than being universal, is context‐specific. Considering that urbanization is a rapid and global process, further research is needed to disentangle the specific factors underlying this relationship. [ABSTRACT FROM AUTHOR]

Background: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. Methods: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. Results: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. Conclusions: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum. [ABSTRACT FROM AUTHOR]

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

Background: Neuropsychiatric disorders are common in 22q11.2 Deletion Syndrome (22q11DS) with about 25% of affected individuals developing schizophrenia spectrum disorders by young adulthood. Longitudinal evaluation of psychosis spectrum features and neurocognition can establish developmental trajectories and impact on functional outcome. Methods: 157 youth with 22q11DS were assessed longitudinally for psychopathology focusing on psychosis spectrum symptoms, neurocognitive performance and global functioning. We contrasted the pattern of positive and negative psychosis spectrum symptoms and neurocognitive performance differentiating those with more prominent Psychosis Spectrum symptoms (PS+) to those without prominent psychosis symptoms (PS−). Results: We identified differences in the trajectories of psychosis symptoms and neurocognitive performance between the groups. The PS+ group showed age associated increase in symptom severity, especially negative symptoms and general nonspecific symptoms. Correspondingly, their level of functioning was worse and deteriorated more steeply than the PS− group. Neurocognitive performance was generally comparable in PS+ and PS− groups and demonstrated a similar age-related trajectory. However, worsening executive functioning distinguished the PS+ group from PS− counterparts. Notably, of the three executive function measures examined, only working memory showed a significant difference between the groups in rate of change. Finally, structural equation modeling showed that neurocognitive decline drove the clinical change. Conclusions: Youth with 22q11DS and more prominent psychosis features show worsening of symptoms and functional decline driven by neurocognitive decline, most related to executive functions and specifically working memory. The results underscore the importance of working memory in the developmental progression of psychosis. [ABSTRACT FROM AUTHOR]

Psychosis spectrum disorders are conceptualized as neurodevelopmental disorders accompanied by disruption of large-scale functional brain networks. Dynamic functional dysconnectivity has been described in patients with schizophrenia and in help-seeking individuals at clinical high risk for psychosis. Less is known, about developmental aspects of dynamic functional network connectivity (dFNC) associated with psychotic symptoms (PS) in the general population. Here, we investigate resting state functional magnetic resonance imaging data using established dFNC methods in the Philadelphia Neurodevelopmental Cohort (ages 8-22 years), including 129 participants experiencing PS and 452 participants without PS (non-PS). Functional networks were identified using group spatial independent component analysis. A sliding window approach and k-means clustering were applied to covariance matrices of all functional networks to identify recurring whole-brain connectivity states. PS-associated dysconnectivity of default mode, salience, and executive networks occurred only in a few states, whereas dysconnectivity in the sensorimotor and visual systems in PS youth was more pervasive, observed across multiple states. This study provides new evidence that disruptions of dFNC are present even at the less severe end of the psychosis continuum in youth, complementing previous work on help-seeking and clinically diagnosed cohorts that represent the more severe end of this spectrum.

BackgroundPsychosis onset typically occurs in adolescence, and subclinical psychotic experiences peak in adolescence. Adolescence is also a time of critical neural and cognitive maturation. Using cross-sectional data from the Philadelphia Neurodevelopmental Cohort, we examined whether regional white matter (WM) development is disrupted in youths with psychosis spectrum (PS) features and whether WM maturation mediates the relationship between age and cognition in typically developing (TD) youths and youths with PS features.MethodsWe examined WM microstructure, as assessed via diffusion tensor imaging, in 670 individuals (age 10-22 years; 499 TD group, 171 PS group) by using tract-based spatial statistics. Multiple regressions were used to evaluate age × group interactions on regional WM indices. Mediation analyses were conducted on four cognitive domains-executive control, complex cognition, episodic memory, and social cognition-using a bootstrapping approach.ResultsThere were age × group interactions on fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and retrolenticular internal capsule. Follow-up analyses revealed these effects were significant in both hemispheres. Bilateral SLF FA mediated the relationship between age and complex cognition in the TD group, but not the PS group. Regional FA did not mediate the age-associated increase in any of the other cognitive domains.ConclusionsOur results showed aberrant age-related effects in SLF and retrolenticular internal capsule FA in youths with PS features. SLF development supports emergence of specific higher-order cognitive functions in TD youths, but not in youths with PS features. Future mechanistic explanations for these relationships could facilitate development of earlier and refined targets for therapeutic interventions.

Introduction:Converging evidence suggests that hippocampal subregions subserve different functions, and are differentially affected by psychosis illness progression. Despite this fact, studies have not often studied subregions cross-sectionally across the psychosis spectrum. Furthermore, little is known about associations between subregion volumes and hippocampus-mediated cognition. Methods:A total of 222 participants (61 ultra high risk [UHR], 91 schizophrenia [SCZ], and 70 healthy volunteers) underwent a 3T MRI scan, as well as structured clinical interviews and a cognitive battery. Hippocampal subfield analysis was conducted with Freesurfer. We compared subregion volumes across groups, controlling for age, gender, and intracranial volume. We also examined associations in the UHR and SCZ groups between hippocampal subregion volumes and verbal learning, visual learning, and working memory. Results:We found a dose-dependent relationship such that the SCZ group showed significantly greater subfield volume reductions than the UHR group, which in turn showed significantly greater subfield volume reductions than the healthy volunteer group. We also found associations between subregion volume and cognitive performance in the visual memory, verbal memory, and working memory domains. Discussion:Our study examined hippocampal subregion volumes cross-sectionally in a large sample across the psychosis spectrum, as well as links with hippocampus-mediated cognitive function. Our findings suggest that hippocampal abnormalities emerge before first psychosis episode onset, and may be etiologically informative.

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Background: Assessment of risks of illnesses has been an important part of medicine for decades. We now have hundreds of 'risk calculators' for illnesses, including brain disorders, and these calculators are continually improving as more diverse measures are collected on larger samples. Methods: We first replicated an existing psychosis risk calculator and then used our own sample to develop a similar calculator for use in recruiting 'psychosis risk' enriched community samples. We assessed 632 participants age 8–21 (52% female; 48% Black) from a community sample with longitudinal data on neurocognitive, clinical, medical, and environmental variables. We used this information to predict psychosis spectrum (PS) status in the future. We selected variables based on lasso, random forest, and statistical inference relief; and predicted future PS using ridge regression, random forest, and support vector machines. Results: Cross-validated prediction diagnostics were obtained by building and testing models in randomly selected sub-samples of the data, resulting in a distribution of the diagnostics; we report the mean. The strongest predictors of later PS status were the Children's Global Assessment Scale; delusions of predicting the future or having one's thoughts/actions controlled; and the percent married in one's neighborhood. Random forest followed by ridge regression was most accurate, with a cross-validated area under the curve (AUC) of 0.67. Adjustment of the model including only six variables reached an AUC of 0.70. Conclusions: Results support the potential application of risk calculators for screening and identification of at-risk community youth in prospective investigations of developmental trajectories of the PS. [ABSTRACT FROM AUTHOR]

Abstract Background Affective lability is elevated and associated with increased clinical burden in psychosis spectrum disorders. The extent to which the level, structure and dispersion of affective lability varies between the specific disorders included in the psychosis spectrum is however unclear. To have potential value as a treatment target, further characterization of affective lability in these populations is necessary. The main aim of our study was to investigate differences in the architecture of affective lability in different psychosis spectrum disorders, and if putative differences remained when we controlled for current symptom status. Methods Affective lability was measured with The Affective Lability Scale Short Form (ALS-SF) in participants with schizophrenia (SZ, n = 76), bipolar I disorder (BD-I, n = 105), bipolar II disorder (BD-II, n = 68) and a mixed psychosis-affective group (MP, n = 48). Multiple analyses of covariance were conducted to compare the ALS-SF total and subdimension scores of the diagnostic groups, correcting for current psychotic, affective and anxiety symptoms, substance use and sex. Double generalized linear models were performed to compare the dispersion of affective lability in the different groups. Results Overall group differences in affective lability remained significant after adjusting for covariates (p = .001). BD-II had higher affective lability compared to SZ and BD-I (p = .004), with no significant differences between SZ and BD-I. There were no significant differences in the contributions of ALS-SF dimensions to the total affective lability or in dispersion of affective lability between the groups. Conclusions This study provides the construct of affective lability in psychosis spectrum disorders with more granular details that may have implications for research and clinical care. It demonstrates that despite overlap in core symptom profiles, BD-I is more similar to SZ than it is to BD-II concerning affective lability and the BD groups should consequently be studied apart. Further, affective lability appears to be characterized by fluctuations between depressive- and other affective states across different psychosis spectrum disorders, indicating that affective lability may be related to internalizing problems in these disorders. Finally, although the level varies between groups, affective lability is evenly spread and not driven by extremes across psychosis spectrum disorders and should be assessed irrespective of diagnosis.

Aim: Psychosis is characterized by both alterations in emotional functioning and environmental stressors including bullying victimization. Recent evidence suggests that some alterations in emotional functioning (e.g., blunted positive facial expressions) are already present in the psychosis risk period. Yet, some clinically relevant facial emotions have not been investigated such as genuine smiles (thought to reflect genuine positive emotions) and non‐genuine smiles (thought to fake positive or mask negative emotions) in individuals meeting criteria for a clinical high‐risk (CHR) syndrome. Further, despite a compelling conceptual basis to suggest a link between affective expression and exposure to environmental stress, to date, no investigations have sought to examine this association. Here, we aim to assess differences between a sample of CHR (N = 65) and control (N = 67) individuals in genuine and non‐genuine smiles and associations with bullying victimization. Methods: Smiles (i.e., genuine; non‐genuine) were objectively coded on a second‐by‐second basis using the Facial Action Coding System during a digitally recorded clinical interview segment. Bullying victimization was measured via parent report. Results: Findings revealed that the CHR group (1) showed blunted genuine (but not non‐genuine) smiles compared to controls. Moreover, (2) bullying victimization was related to blunted genuine smiles, but not non‐genuine smiles. Conclusion: These findings expand our understanding of emotional alterations in this group with implications for diagnosis (highlighting blunted genuine smiles as a specific marker) and etiology (underscoring the role of bullying victimization in the etiology of emotional dysfunction). [ABSTRACT FROM AUTHOR]

Negative symptoms in the psychosis continuum are linked to impairments in reward processing and cognitive function. Processes at the interface of reward processing and cognition and their relation to negative symptoms remain little studied, despite evidence suggestive of integration in mechanisms and neural circuitry. Here, we investigated brain activation during reward-dependent modulation of working memory (WM) and their relationship to negative symptoms in subclinical and early stages of the psychosis continuum. We included 27 persons with high schizotypal personality traits and 23 patients with first episode psychosis as well as 27 healthy controls. Participants underwent functional magnetic resonance imaging while performing an established 2-back WM task with two reward levels (5 CHF vs. no reward), which allowed us to assess common reward-cognition regions through whole-brain conjunction analyses and to investigate relations with clinical scores of negative symptoms. As expected for behavior, reward facilitated performance while cognitive load diminished it. At the neural level, the conjunction of high reward and high cognitive load contrasts across the psychosis continuum showed increased hemodynamic activity in the thalamus and the cerebellar vermis. During high cognitive load, more severe apathy but not diminished expression in the psychosis continuum was associated with reduced activity in right lateral orbitofrontal cortex, midbrain, posterior vermal cerebellum, caudate and lateral parietal cortex. Our results suggest that hypoactivity in the cerebellar vermis and the cortical-striatal-midbrain-circuitry in the psychosis continuum relates to apathy possibly via impaired flexible cognitive resource allocation for effective goal pursuit. [ABSTRACT FROM AUTHOR]

Clinical interviews and laboratory-based emotional induction paradigms provide consistent evidence that facial affect is blunted in many individuals with schizophrenia. Although it is clear that blunted facial affect is not a by-product of diminished emotional experience in schizophrenia, factors contributing to blunted affect remain unclear. The current study used a combination of ambulatory video recordings that were evaluated via computerized facial affect analysis and concurrently completed ecological momentary assessment surveys to assess whether blunted affect reflects insufficient reactivity to affective or contextual factors. Specifically, whether individuals with schizophrenia require more intense affective experiences to produce expression, or whether they are less reactive to social factors (i.e. being in the presence of others, social motivation). Participants included outpatients with schizophrenia (n = 33) and healthy controls (n = 31) who completed six days of study procedures. Multilevel linear models were evaluated using both Null-Hypothesis Statistical Testing and Bayesian analyses. Individuals with schizophrenia displayed comparable expression of positive and negative emotion to controls during daily life, and no evidence was found for a different intensity of experience required for expression in either group. However, social factors differentially influenced facial expression in schizophrenia compared to controls, such that individuals with schizophrenia did not modulate their expressions based on social motivation to the same extent as controls. These findings suggest that social motivation may play an important role in determining when blunting occurs. [ABSTRACT FROM AUTHOR]

Background and Hypothesis: Impaired speech-gesture matching has repeatedly been shown in patients with schizophrenia spectrum disorders. Here, we tested the hypothesis that schizotypal traits in the general population are related to reduced speech-gesture matching performance and reduced self-reports about gesture perception. We further explored the relationships between facets of schizotypy and gesture processing in a network model., Study Design: Participants (1094 mainly healthy adults) were presented with concrete or abstract sentences accompanied with videos showing related or unrelated gestures. For each video, participants evaluated the alignment between speech and gesture. They also completed self-rating scales about the perception and production of gestures (Brief Assessment of Gesture scale) and schizotypal traits (Schizotypal Personality Questionnaire-Brief 22-item version). We analyzed bivariate associations and estimated a non-regularized partial Spearman correlation network. We characterized the network by analyzing bridge centrality and controllability metrics of nodes., Study Results: We found a negative relationship between both concrete and abstract gesture-speech matching performance and overall schizotypy. In the network, disorganization had the highest average controllability and it was negatively related to abstract speech-gesture matching. Bridge centralities indicated that self-reported production of gestures to enhance communication in social interactions connects self-reported gesture perception, schizotypal traits, and gesture processing task performance., Conclusion: The association between impaired abstract speech-gesture matching and disorganization supports a continuum between schizophrenia and schizotypy. Using gestures to facilitate communication connects subjective and objective aspects of gesture processing and schizotypal traits. Future interventional studies in patients should test the potential causal pathways implied by this network model., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Affective lability is elevated and associated with increased clinical burden in psychosis spectrum disorders. The extent to which the level, structure and dispersion of affective lability varies between the specific disorders included in the psychosis spectrum is however unclear. To have potential value as a treatment target, further characterization of affective lability in these populations is necessary. The main aim of our study was to investigate differences in the architecture of affective lability in different psychosis spectrum disorders, and if putative differences remained when we controlled for current symptom status. Methods: Affective lability was measured with The Affective Lability Scale Short Form (ALS-SF) in participants with schizophrenia (SZ, n = 76), bipolar I disorder (BD-I, n = 105), bipolar II disorder (BD-II, n = 68) and a mixed psychosis-affective group (MP, n = 48). Multiple analyses of covariance were conducted to compare the ALS-SF total and subdimension scores of the diagnostic groups, correcting for current psychotic, affective and anxiety symptoms, substance use and sex. Double generalized linear models were performed to compare the dispersion of affective lability in the different groups. Results: Overall group differences in affective lability remained significant after adjusting for covariates (p =.001). BD-II had higher affective lability compared to SZ and BD-I (p =.004), with no significant differences between SZ and BD-I. There were no significant differences in the contributions of ALS-SF dimensions to the total affective lability or in dispersion of affective lability between the groups. Conclusions: This study provides the construct of affective lability in psychosis spectrum disorders with more granular details that may have implications for research and clinical care. It demonstrates that despite overlap in core symptom profiles, BD-I is more similar to SZ than it is to BD-II concerning affective lability and the BD groups should consequently be studied apart. Further, affective lability appears to be characterized by fluctuations between depressive- and other affective states across different psychosis spectrum disorders, indicating that affective lability may be related to internalizing problems in these disorders. Finally, although the level varies between groups, affective lability is evenly spread and not driven by extremes across psychosis spectrum disorders and should be assessed irrespective of diagnosis. [ABSTRACT FROM AUTHOR]

Background: Childhood attention deficit-hyperactivity disorder (ADHD) is common in psychotic disorders. However, prevalence estimates vary widely and the impact of ADHD on the severity of psychotic symptoms and associated features is unclear. We used the Philadelphia Neurodevelopmental Cohort (PNC; n = 9498 youth age 8-21), which includes a comprehensive structured interview of clinical symptoms and the Penn Computerized Neurocognitive Battery (CNB), to clarify the prevalence of ADHD in psychosis spectrum (PS) youth and determine if comorbid ADHD is associated with severity of psychotic symptoms and cognitive impairment.Methods: Prevalence of ADHD among PS youth was established by comparing PS youth to all other youth in the PNC cohort. Cognition was compared between four groups: typically developing (TD), ADHD, PS without ADHD (PS-ADHD), and PS with ADHD (PS+ADHD). To evaluate the impact of ADHD on psychosis symptomatology, severity of positive and negative psychotic symptoms was compared between PS-ADHD and PS+ADHD groups.Results: ADHD was more prevalent in PS youth compared to non-PS youth (45% vs. 20%). Cognition was significantly impaired in PS youth compared to TD youth, but the presence of ADHD in PS youth was not associated with greater cognitive impairment. Co-morbid ADHD was, however, associated with more severe psychosis symptoms in PS youth.Conclusion: ADHD is more common among PS youth compared to youth without PS symptoms and is associated with more severe psychotic symptoms, but not severity of cognitive impairment. The association between ADHD and psychotic disorders may be mediated by psychosis symptoms in youth and may manifest a more stable cognitive impairment. [ABSTRACT FROM AUTHOR]

The thalamus is composed of multiple nuclei densely connected with the cortex in an organized manner, forming parallel thalamocortical networks critical to sensory, motor, and cognitive functioning. Thalamocortical circuit dysfunction has been implicated in multiple neurodevelopmental disorders, including schizophrenia, which also often exhibit sex differences in prevalence, clinical characteristics, and neuropathology. However, very little is known about developmental and sex effects on thalamocortical networks in youth. The present study characterized the effects of age, sex and psychosis symptomatology in anatomically constrained thalamocortical networks in a large community sample of youth (n = 1100, aged 8–21) from the Philadelphia Neurodevelopmental Cohort (PNC). Cortical functional connectivity of seven anatomically defined thalamic nuclear groups were examined: anterior, mediodorsal, ventral lateral, ventral posterolateral, pulvinar, medial and lateral geniculate nuclear groups. Age and sex effects were characterized using complementary thalamic region-of-interest (ROI) to cortical ROI and voxel-wise analyses. Effects of clinical symptomatology were analyzed by separating youth into three groups based on their clinical symptoms; typically developing youth (n = 298), psychosis spectrum youth (n = 320), and youth with other psychopathologies (n = 482). As an exploratory analysis, association with PRIME scores were used as a dimensional measure of psychopathology. Age effects were broadly characterized by decreasing connectivity with sensory/motor cortical areas, and increasing connectivity with heteromodal prefrontal and parietal cortical areas. This pattern was most pronounced for thalamic motor and sensory nuclei. Females showed greater connectivity between multiple thalamic nuclear groups and the visual cortex compared to males, while males showed greater connectivity with the inferior frontal and orbitofrontal cortices. Youth with psychosis spectrum symptoms showed a subtle decrease in thalamic connectivity with the premotor and prefrontal cortices. Across all youth, greater PRIME scores were associated with lower connectivity between the prefrontal cortex and mediodorsal thalamus. By characterizing typical development in anatomically constrained thalamocortical networks, this study provides an anchor for conceptualizing disruptions to the integrity of these networks observed in neurodevelopmental disorders.

The psychosis spectrum (PS) is associated with structural dysconnectivity concentrated in transmodal cortex. However, understanding of this pathophysiology has been limited by an overreliance on examining direct interregional connectivity. Using network control theory, we measured variation in both direct and indirect connectivity to a region to gain new insights into the pathophysiology of the PS. We used psychosis symptom data and structural connectivity in 1068 individuals from the Philadelphia Neurodevelopmental Cohort. Applying a network control theory metric called average controllability, we estimated each brain region's capacity to leverage its direct and indirect structural connections to control linear brain dynamics. Using nonlinear regression, we determined the accuracy with which average controllability could predict PS symptoms in out-of-sample testing. We also examined the predictive performance of regional strength, which indexes only direct connections to a region, as well as several graph-theoretic measures of centrality that index indirect connectivity. Finally, we assessed how the prediction performance for PS symptoms varied over the functional hierarchy spanning unimodal to transmodal cortex. Average controllability outperformed all other connectivity features at predicting positive PS symptoms and was the only feature to yield above-chance predictive performance. Improved prediction for average controllability was concentrated in transmodal cortex, whereas prediction performance for strength was uniform across the cortex, suggesting that indexing indirect connections through average controllability is crucial in association cortex. Examining interindividual variation in direct and indirect structural connections to transmodal cortex is crucial for accurate prediction of positive PS symptoms. [ABSTRACT FROM AUTHOR]

Background Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics. Method This work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined. Results An inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis–stress models. Conclusions Adversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling. [ABSTRACT FROM AUTHOR]

Impaired emotional processing and cognitive functioning are common in schizophrenia, schizoaffective disorder, and bipolar disorders, causing significant socioemotional disability. While a large body of research demonstrates abnormal cognition/emotion interactions in these disorders, previous studies investigating abnormalities in the emotional scene response using event-related potentials (ERPs) have yielded mixed findings, and few studies compare findings across psychiatric diagnoses. The current study investigates the effects of emotion and repetition on ERPs in a large, well-characterized sample of participants with schizophrenia-bipolar syndromes. Two ERP components that are modulated by emotional content and scene repetition, the early posterior negativity (EPN) and late positive potential (LPP), were recorded in healthy controls and participants with schizophrenia, schizoaffective disorder, bipolar disorder with psychosis, and bipolar disorder without psychosis. Effects of emotion and repetition were compared across groups. Results displayed significant but small effects in schizophrenia and schizoaffective disorder, with diminished EPN amplitudes to neutral and novel scenes, reduced LPP amplitudes to emotional scenes, and attenuated effects of scene repetition. Despite significant findings, small effect sizes indicate that emotional scene processing is predominantly intact in these disorders. Multivariate analyses indicate that these mild ERP abnormalities are related to cognition, psychosocial functioning, and psychosis severity. This relationship suggests that impaired cognition, rather than diagnosis or mood disturbance, may underlie disrupted neural scene processing in schizophrenia-bipolar syndromes. [ABSTRACT FROM AUTHOR]

Schizotypy refers to a multidimensional construct that spans a range of cognitive, behavioral, and personality features, representing liability to psychosis on a continuum between health and illness. Schizotypy has been associated with functional and structural brain alterations as potential intermediate phenotypes on the developmental path to psychosis. We scanned the literature between February 2019 and August 1, 2020 using PubMed, Medline, APA PsycINFO, and ProQuest. We identified eligible articles conducted on participants assessed with psychometric schizotypy across the health-illness spectrum and reporting a direct statistic between schizotypy and a structural, task-related, or functional magnetic resonance imaging brain measure. Articles not peer-reviewed and not written in English were excluded. We systematically reviewed 84 studies that determined the changes in gray matter, brain activation, and connectivity associated with schizotypy in both healthy and clinical cohorts. Morphological and functional changes in the default and the frontoparietal networks, specifically frontal and temporal cortices, were most frequently associated with schizotypy. Yet, we were unable to identify consistent patterns of morphological or functional brain aberration associated with schizotypy, due to methodological differences between studies in the conceptualization and measurement of schizotypy. Efforts toward greater methodological concordance in future neuroimaging research of schizotypy are needed to improve the identification of brain-based endophenotypes for schizophrenia. Public Significance Statement: This systematic review indicates that schizotypy is associated with structural and functional changes in frontal and temporal brain regions, extending to several additional regions. [ABSTRACT FROM AUTHOR]

Several trends intersecting over the past two decades have generated increasing debate as to how the concepts of schizophrenia, the schizophrenia spectrum, and the psychotic disorders spectrum should be regarded. These trends are reflected in various areas of research such as genomics, neuroimaging, and data-driven computational studies of multiple response systems. Growing evidence suggests that schizophrenia represents a broad and heterogenous syndrome, rather than a specific disease entity, that is part of a multi-faceted psychosis spectrum. Progress in explicating these various developments has been hampered by the dependence upon sets of symptoms and signs for determining a diagnosis, and by the reliance on traditional diagnostic categories in reviewing clinical research grants. To address these concerns, the U.S. National Institute of Mental Health initiated the Research Domain Criteria (RDoC) project, a translational research program that calls for studies designed in terms of empirically-based functions (such as cognitive control or reward learning) rather than diagnostic groups. RDoC is a research framework rather than an alternative diagnostic system, intended to provide data that can inform future nosological manuals. This commentary includes a brief summary of RDoC as it pertains to schizophrenia and psychotic spectra, examples of recent data that highlight the utility of the approach, and conclusions regarding the implications for evolving conceptualizations of serious mental illness.

Several trends intersecting over the past two decades have generated increasing debate as to how the concepts of schizophrenia, the schizophrenia spectrum, and the psychotic disorders spectrum should be regarded. These trends are reflected in various areas of research such as genomics, neuroimaging, and data-driven computational studies of multiple response systems. Growing evidence suggests that schizophrenia represents a broad and heterogenous syndrome, rather than a specific disease entity, that is part of a multi-faceted psychosis spectrum. Progress in explicating these various developments has been hampered by the dependence upon sets of symptoms and signs for determining a diagnosis, and by the reliance on traditional diagnostic categories in reviewing clinical research grants. To address these concerns, the U.S. National Institute of Mental Health initiated the Research Domain Criteria (RDoC) project, a translational research program that calls for studies designed in terms of empirically-based functions (such as cognitive control or reward learning) rather than diagnostic groups. RDoC is a research framework rather than an alternative diagnostic system, intended to provide data that can inform future nosological manuals. This commentary includes a brief summary of RDoC as it pertains to schizophrenia and psychotic spectra, examples of recent data that highlight the utility of the approach, and conclusions regarding the implications for evolving conceptualizations of serious mental illness. [ABSTRACT FROM AUTHOR]

Introduction: Approximately 10% of patients with psychotic disorders receive the diagnosis “Psychotic disorder not otherwise specified” (PNOS). However, there is a lack of knowledge about the clinical presentations captured by this diagnosis in the mental health services. Therefore, we examined the symptom profiles of participants with PNOS compared to participants with bipolar disorder (BD) and schizophrenia spectrum disorder (SZ) diagnoses.Methods: We here included 1,221 participants from the Thematically Organized Psychosis-study at Oslo University Hospital; 792 with SZ, 283 with BD, and 146 with PNOS, assessed with SCID-I for DSM-IV. The participants with PNOS were categorized into subgroups based on SCID information. The GAF, PANSS, Alcohol Use Disorders Identification Test (AUDIT), and Drug Use Disorders Identification Test (DUDIT) were used to assess function, clinical symptoms, and substance use.Results: In the PNOS group, 44% did not meet the criteria for any specific psychotic disorder, 35.5% had contradictory information making a specific diagnosis difficult, and 20.5% had inadequate information to make a specific diagnosis. The most frequent reason for a PNOS diagnosis was difficulty ruling out a substance-induced psychotic disorder (n = 41, 28%). Participants with PNOS were younger and more often first-episode than participants with BD and SZ. They were intermediate between BD and SZ for GAF scores (BD>PNOS>SZ) and PANSS scores (BD

Introduction: Approximately 10% of patients with psychotic disorders receive the diagnosis " Psychotic disorder not otherwise specified" (PNOS). However, there is a lack of knowledge about the clinical presentations captured by this diagnosis in the mental health services. Therefore, we examined the symptom profiles of participants with PNOS compared to participants with bipolar disorder (BD) and schizophrenia spectrum disorder (SZ) diagnoses. Methods: We here included 1,221 participants from the Thematically Organized Psychosis-study at Oslo University Hospital; 792 with SZ, 283 with BD, and 146 with PNOS, assessed with SCID-I for DSM-IV. The participants with PNOS were categorized into subgroups based on SCID information. The GAF, PANSS, Alcohol Use Disorders Identification Test (AUDIT), and Drug Use Disorders Identification Test (DUDIT) were used to assess function, clinical symptoms, and substance use. Results: In the PNOS group, 44% did not meet the criteria for any specific psychotic disorder, 35.5% had contradictory information making a specific diagnosis difficult, and 20.5% had inadequate information to make a specific diagnosis. The most frequent reason for a PNOS diagnosis was difficulty ruling out a substance-induced psychotic disorder (n = 41, 28%). Participants with PNOS were younger and more often first-episode than participants with BD and SZ. They were intermediate between BD and SZ for GAF scores (BD>PNOS>SZ) and PANSS scores (BD

The Prodromal Questionnaire-Brief Child Version (PQ-BC) has been developed as a tool for identifying psychotic-like experiences (PLEs) in school-age children. The current study examined the psychometric properties of the PQ-BC, examined how well the PQ-BC estimates the latent construct of PLEs (θ̂), and began the process of developing a screening form informed by item response theory (IRT). Utilizing the baseline (N = 11,129) sample from the Adolescent Brain Cognitive Development study, we examined which PQ-BC items provide the most information and best discriminate individuals experiencing PLEs. Using hierarchical linear models (HLMs), we found that θ̂ scores were significantly associated with several previously identified predictors of psychosis spectrum symptoms (i.e., history of psychosis, internalizing symptoms, cognitive impairments, developmental milestone delays, and resting-state functional connectivity impairments) at baseline and Year 1 (n = 5,532). Using item-level information and discrimination parameters of the PQ-BC from the baseline sample, we created a 7-item screening form. HLMs generally found significant associations between screening form scores for both baseline and Year 1 with the aforementioned predictors. The analyses provide evidence for the validity of a screening form derived from the PQ-BC using IRT-derived parameters. This screening form could prove useful when the full measure is not feasible. (PsycInfo Database Record (c) 2020 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

Current diagnostic systems mainly focus on symptoms needed to classify patients with a specific mental disorder and do not take into account the variation in co-occurring symptoms and the interaction between the symptoms themselves. The innovative network approach aims to further our understanding of mental disorders by focusing on meaningful connections between individual symptoms of a disorder and has thus far proven valuable insights to psychopathology. The aims of current study were to I) construct a symptom network and investigate interactions between a wide array of psychotic symptoms; II) identify the most important symptoms within this network and III) perform an explorative shortest pathway analysis between depressive and delusional symptoms. We analyzed interview data from n=408 male patients with non-affective psychosis using the Comprehensive Assessment of Symptoms and History (CASH). A network structure of 79 symptoms was computed to explore partial correlations between positive, negative, catatonia and affective symptoms. The resulting network showed strong connectivity between individual symptoms of the CASH, both within- and between-domains. Most central symptoms included 'loss of interest', 'chaotic speech', 'inability to enjoy recreational interest in activities', 'inability to form or maintain relationships with friends' and 'poverty of content of speech'. The shortest pathway analysis between depressive and delusional symptoms displayed an important role for 'persecutory delusions'. In conclusion, this study showed that individual psychotic symptoms are meaningfully related to each other not only within their own cluster, but also between different clusters and that important information may be acquired by investigating interactions at a symptom level. [ABSTRACT FROM AUTHOR]

BackgroundCurrent group-average analysis suggests quantitative but not qualitative cognitive differences between schizophrenia (SZ) and bipolar disorder (BD). There is increasing recognition that cognitive within-group heterogeneity exists in both disorders, but it remains unclear as to whether between-group comparisons of performance in cognitive subgroups emerging from within each of these nosological categories uphold group-average findings. We addressed this by identifying cognitive subgroups in large samples of SZ and BD patients independently, and comparing their cognitive profiles. The utility of a cross-diagnostic clustering approach to understanding cognitive heterogeneity in these patients was also explored.MethodHierarchical clustering analyses were conducted using cognitive data from 1541 participants (SZ n = 564, BD n = 402, healthy control n = 575).ResultsThree qualitatively and quantitatively similar clusters emerged within each clinical group: a severely impaired cluster, a mild-moderately impaired cluster and a relatively intact cognitive cluster. A cross-diagnostic clustering solution also resulted in three subgroups and was superior in reducing cognitive heterogeneity compared with disorder clustering independently.ConclusionsQuantitative SZ–BD cognitive differences commonly seen using group averages did not hold when cognitive heterogeneity was factored into our sample. Members of each corresponding subgroup, irrespective of diagnosis, might be manifesting the outcome of differences in shared cognitive risk factors. [ABSTRACT FROM PUBLISHER]

Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach. We also computed group comparisons of protein expressions between patients and controls, and between SZ and BD patients, as well. Potential associations of protein levels with cognitive functioning (psychomotor speed, executive functioning, crystallised intelligence) as well as underlying brain volume in the hippocampus were explored, using bivariate correlation analyses. The main finding of this study was that apolipoprotein expression differed between patients and controls and that these alterations in both disease groups were putatively related to cognitive impairments as well as to hippocampus volumes. However, none of the protein level differences were related to clinical symptom severity. In summary, altered apolipoprotein expression in BD and SZ was linked to cognitive decline and underlying morphological changes in both disorders. Our results suggest that the detection of molecular patterns in association with cognitive performance and its underlying brain morphology is of great importance for understanding of the pathological mechanisms of SZ and BD, as well as for supporting the diagnosis and treatment of both disorders. [ABSTRACT FROM AUTHOR]

Keywords: schizophrenia; early psychosis; nosology; extended psychosis phenotype; psychosis spectrum The extended psychosis phenotype is trans-nosographic in nature, implying that it is not restricted to any specific psychotic disorder but rather represents both a continuous expression across the psychosis spectrum and an extreme expression of continuously distributed quantitative traits in the general population. The transition rate to psychosis from a CHR state is approximately 20% over 1 year and 36% within three years; among those who convert, about 60% of diagnostic outcomes develop towards the schizophrenia spectrum and the remaining 40% towards mood-related and atypical forms of psychosis ([7]). Schizophrenia, early psychosis, nosology, extended psychosis phenotype, psychosis spectrum. [Extracted from the article]

The article presents the discussion on recent research studies showing negative associations between conspiracy beliefs and adherence to epidemiological safety guidelines. Topics include controlling for conspiracy beliefs and coronavirus-related anxiety and internal motivation to isolation; and using paranoia-like and conspiracy beliefs and internal motivation isolation and coronavirus-related anxiety from T1 as predictors in the created model.

Cognitive impairments have been linked to structural and functional alterations in frontal and subcortical brain regions, ultimately leading to fronto-thalamic connectivity disturbances. We hypothesized that such neuronal disruptions in frontal and subcortical structures may account for neuropsychological deficits in schizophrenia (SZ), schizophrenia relatives and bipolar disorder (BD). We acquired T1-weighted anatomical MRI sequences in 209 participants: 57 SZ patients, 47 first-degree relatives of SZ patients, 48 BD I patients and 57 healthy controls. We computed group comparisons of gray matter (GM) volume in frontal and basal ganglia regions-of-interest, followed by correlation analysis between psychomotor speed, executive functioning and learning and GM volumes in candidate regions. Several frontal GM volume reductions as well as GM increases in the thalamus and the putamen were exhibited in SZ patients as compared to controls. The same finding was observed - less pronounced - when comparing SZ relatives and controls. BD patients presented GM volume increases in the basal ganglia in comparison to controls. In SZ patients, increases in bilateral thalamus GM volume and decreases in left middle and superior frontal gyrus volume were significantly associated with worse cognitive performance. In summary, our results indicate distinct imbalances across frontal-subcortical circuits in BD, SZ relatives and SZ. The functional relevance of the findings were mainly limited to the SZ patients group: in this group, abnormalities were directly associated with cognitive performance. This result is in line with the finding that the volume alterations were strongest in SZ patients and followed by BD patients and SZ relatives. [ABSTRACT FROM AUTHOR]

Patients with psychotic disorders appear to exhibit greater impulsivity-related behaviors relative to healthy controls. However, the neural underpinning of this impulsivity remains uncertain. Furthermore, it remains unclear how impulsivity might differ or be conserved between psychotic disorder diagnoses in mechanism and manifestation. In this study, self-reported impulsivity, measured by Barratt Impulsiveness Scale (BIS), was compared between 305 controls (HC), 139 patients with schizophrenia (SZ), 100 with schizoaffective disorder (SZA), and 125 with psychotic bipolar disorder (PBP). In each proband group, impulsivity was associated with regional cortical volumes (using FreeSurfer analysis of T1 MRI scans), suicide attempt history, Global Assessment of Functioning (GAF), and Social Functioning Scale (SFS). BIS scores were found to differ significantly between participant groups, with SZA and PBP exhibiting significantly higher impulsivity than SZ, which exhibited significantly higher impulsivity than HC. BIS scores were significantly related to suicide attempt history, and they were inversely associated with GAF, SFS, and bilateral orbitofrontal cortex (OFC) volume in both SZA and PBP, but not SZ. These findings indicate that psychotic disorders, particularly those with prominent affective symptoms, are characterized by elevated self-reported impulsivity measures. Impulsivity's correlations with suicide attempt history, GAF, and SFS suggest that impulsivity may be a mediator of clinical outcome. The observed impulsivity-OFC correlations corroborate the importance of OFC deficits in impulsivity. These correlations' presence in SZA and PBP but not in SZ suggests that impulsivity may have different underlying mechanisms in affective and non-affective psychotic disorders. [ABSTRACT FROM AUTHOR]

Introduction: Since the early description of paranoia, the nosology of delusional disorder has always been controversial. The old idea of unitary psychosis has now gained some renewed value from the dimensional continuum model of psychotic symptoms.Aims: 1. To study the psychopathological dimensions of the psychosis spectrum; 2. to explore the association between psychotic dimensions and categorical diagnoses; 3. to compare the different psychotic disorders from a psychopathological and functional point of view.Material and Methods: This is an observational study utilizing a sample of some 550 patients with a psychotic disorder. 373 participants had a diagnosis of schizophrenia, 137 had delusional disorder and 40 with a diagnosis of schizoaffective disorder. The PANSS was used to elicit psychopathology and global functioning was ascertained using the GAF measure. Both exploratory and confirmatory factor analyses of the PANSS items were performed to extract psychopathological dimensions. Associations between diagnostic categories and dimensions were subsequently studied using ANOVA tests.Results: 5 dimensions - manic, negative symptoms, depression, positive symptoms and cognitive - emerged. The model explained 57.27% of the total variance. The dimensional model was useful to explained differences and similarities between all three psychosis spectrum categories. The potential clinical usefulness of this dimensional model within and between clinical psychosis spectrum categories is discussed. [ABSTRACT FROM AUTHOR]

Objective Schizophrenia ( SZ) and bipolar disorder ( BD) are heritable, polygenic disorders with shared clinical characteristics and genetic risk indicating a psychosis continuum. This is the first study using polygenic risk score ( PGRS) to investigate the localization of diagnostic subcategories along the entire psychosis spectrum. Method Based on results from the Psychiatric Genomics Consortium ( PGC), we assigned a SZ and BD PGRS to each individual in our independent sample [ N = 570 BD spectrum cases, 452 SZ spectrum cases and 415 healthy controls ( CTR)]. Potential differences in mean SZ and BD PGRS across diagnostic spectrums and subcategories were explored. Results SZ and BD PGRSs were significantly associated with both SZ and BD spectrums compared with CTR. For the subcategories, SZ PGRS was significantly associated with SZ, schizoaffective disorder, psychosis not otherwise specified, and BD1, while BD PGRS was significantly associated with BD1 and BD2. There were no significant differences between any of the diagnostic spectrums or subgroups for neither the SZ nor BD PGRS. Lifetime psychosis was significantly associated with SZ PGRS but not with BD PGRS. Conclusion These findings further support the psychosis continuum model and provide molecular polygenetic validation of the localization of diagnostic subcategories within this continuum. [ABSTRACT FROM AUTHOR]