Structured Interview For Prodromal Syndromes Research Articles

Duration of Untreated Prodromal Psychosis and Cognitive Impairments

The possible association between the duration of untreated prodromal symptoms (DUPrS) and cognitive functioning in individuals at clinical high risk (CHR) for psychosis remains underexplored. To investigate the intricate interplay between DUPrS, cognitive performance, and conversion outcomes, shedding light on the potential role of DUPrS in shaping cognitive trajectories and psychosis risk in individuals at CHR for psychosis. This cohort study of individuals at CHR for psychosis was conducted at the Shanghai Mental Health Center in China from January 10, 2016, to December 29, 2021. Participants at CHR for psychosis typically exhibit attenuated positive symptoms; they were identified according to the Structured Interview for Prodromal Syndromes, underwent baseline neuropsychological assessments, and were evaluated at a 3-year clinical follow-up. Data were analyzed from August 25, 2021, to May 10, 2023. Duration of untreated prodromal symptoms and cognitive impairments in individuals at CHR for psychosis. The primary study outcome was conversion to psychosis. The DUPrS was categorized into 3 groups based on percentiles (33rd percentile for short [≤3 months], 34th-66th percentile for median [4-9 months], and 67th-100th percentile for long [≥10 months]). The DUPrS, cognitive variables, and the risk of conversion to psychosis were explored through quantile regression and Cox proportional hazards regression analyses. This study included 506 individuals (median age, 19 [IQR, 16-21] years; 53.6% [n = 271] women). The mean (SD) DUPrS was 7.8 (6.857) months, and the median (IQR) was 6 (3-11) months. The short and median DUPrS groups displayed poorer cognitive performance than the long DUPrS group in the Brief Visuospatial Memory Test-Revised (BVMT-R) (Kruskal-Wallis χ2 = 8.801; P = .01) and Category Fluency Test (CFT) (Kruskal-Wallis χ2 = 6.670; P = .04). Quantile regression analysis revealed positive correlations between DUPrS rank and BVMT-R scores (<90th percentile of DUPrS rank) and CFT scores (within the 20th-70th percentile range of DUPrS rank). Among the 506 participants, 20.8% (95% CI, 17.4%-24.5%) converted to psychosis within 3 years. Cox proportional hazards regression analysis identified lower educational attainment (hazard ratio [HR], 0.912; 95% CI, 0.834-0.998), pronounced negative symptoms (HR, 1.044; 95% CI, 1.005-1.084), and impaired performance on the Neuropsychological Assessment Battery: Mazes (HR, 0.961; 95% CI, 0.924-0.999) and BVMT-R (HR, 0.949; 95% CI, 0.916-0.984) tests as factors associated with conversion. The finding of this cohort study suggest the intricate interplay between DUPrS, cognitive performance, and conversion risk in individuals at CHR for psychosis. The findings emphasize the importance of considering both DUPrS and cognitive functioning in assessing the trajectory of these individuals.

Detecting at-risk mental states for psychosis (ARMS) using machine learning ensembles and facial features.

Our study aimed to develop a machine learning ensemble to distinguish "at-risk mental states for psychosis" (ARMS) subjects from control individuals from the general population based on facial data extracted from video-recordings. 58 non-help-seeking medication-naïve ARMS and 70 healthy subjects were screened from a general population sample. At-risk status was assessed with the Structured Interview for Prodromal Syndromes (SIPS), and "Subject's Overview" section was filmed (5-10min). Several features were extracted, e.g., eye and mouth aspect ratio, Euler angles, coordinates from 51 facial landmarks. This elicited 649 facial features, which were further selected using Gradient Boosting Machines (AdaBoost combined with Random Forests). Data was split in 70/30 for training, and Monte Carlo cross validation was used. Final model reached 83% of mean F1-score, and balanced accuracy of 85%. Mean area under the curve for the receiver operator curve classifier was 93%. Convergent validity testing showed that two features included in the model were significantly correlated with Avolition (SIPS N2 item) and expression of emotion (SIPS N3 item). Our model capitalized on short video-recordings from individuals recruited from the general population, effectively distinguishing between ARMS and controls. Results are encouraging for large-screening purposes in low-resource settings.

Serum Levels of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in the Subtypes of Clinical High Risk Individuals: A Prospective Cohort Study.

Numerous studies have established the roles of inflammation and angioneurins in the pathogenesis of schizophrenia (SCZ). This study aimed to compare the serum levels of tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) in patients at clinical high risk (CHR) for psychosis or SCZ at baseline and one year after treatment. A total of 289 CHR participants from the Shanghai At Risk for Psychosis Extended Program (SHARP) were tracked for a year. They were divided into two and four subtypes based on symptom severity according to the Structured Interview for Prodromal Syndromes (SIPS) and received standard medical care. At baseline and one-year follow-up, TNF-α and VEGF were detected using enzyme-linked immunosorbent assay, and pathological features were assessed using the Global Assessment of Function (GAF) score. Baseline TNF-α levels did not differ significantly, while VEGF levels were lower in patients with more severe symptoms. VEGF showed a negative correlation with negative features, both overall (r = -0.212, p = 0.010) and in the subgroup with higher positive scores (r = -0.370, p = 0.005). TNF-α was positively correlated with negative symptoms in the subgroup with higher negative scores (r = 0.352, p = 0.002). A three-way multivariate analysis of variance demonstrated that participants in Subtype 1 of positive or negative symptoms performed better than those in Subtype 2, with significant main effects and interactions of group and both cytokines. TNF-α and VEGF levels are higher and lower, respectively, in CHR patients with more severe clinical symptoms, particularly negative symptoms, which point to a worsening inflammatory and vascular status in the brain.

Effect of Shi-Zhen-An-Shen herbal formula granule in the treatment of young people at ultra-high risk for psychosis: a pilot study.

To date, there is no conclusive evidence for early interventions on ultra-high risk (UHR) for psychosis. The Chinese herbal medicine is confirmed to be beneficial in improving psychiatric symptoms and cognitive impairments for schizophrenia patients. However, the effect of Chinese herbal medicine on treating UHR patients remains unknown. Eighty UHR patients were recruited from the outpatient department. They were randomly assigned to receive either Shi-Zhen-An-Shen herbal formula granule (SZAS-HFG) combined with aripiprazole placebo or aripiprazole combined with SZAS-HFG placebo for a 12-week treatment. The psychiatric symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). The Trail Making Test part A (TMT-A), Brief Visuospatial Memory Test (BVMT), Hopkins Verbal Learning Test (HVLT), and Continuous Performance Test (CPT) were used to assess cognitive functions. we also employed the Global Assessment of Functioning (GAF) to evaluate social functioning. The linear mixed-effects models were performed to detect the difference in effectiveness between the two groups. After 12-week treatment, both groups showed significant effects of time on SIPS, TMT-A, HVLT, BVMT, and GAF. There was a significant effect of group only on CPT. Moreover, we also found a significant interaction effect on GAF. SZAS-HFG can effectively alleviate psychosis symptoms, and improve cognitive impairments and overall functioning as well as aripiprazole.Clinical trial registration: Chinese Clinical Trial Registry, ChiCTR-IOR-17013513.

Gesticulation in individuals with at risk mental states for psychosis

Nonverbal communication (NVC) is a complex behavior that involves different modalities that are impaired in the schizophrenia spectrum, including gesticulation. However, there are few studies that evaluate it in individuals with at-risk mental states (ARMS) for psychosis, mostly in developed countries. Given our prior findings of reduced movement during speech seen in Brazilian individuals with ARMS, we now aim to determine if this can be accounted for by reduced gesticulation behavior. Fifty-six medication-naïve ARMS and 64 healthy controls were filmed during speech tasks. The frequency of specifically coded gestures across four categories (and self-stimulatory behaviors) were compared between groups and tested for correlations with prodromal symptoms of the Structured Interview for Prodromal Syndromes (SIPS) and with the variables previously published. ARMS individuals showed a reduction in one gesture category, but it did not survive Bonferroni’s correction. Gesture frequency was negatively correlated with prodromal symptoms and positively correlated with the variables of the amount of movement previously analyzed. The lack of significant differences between ARMS and control contradicts literature findings in other cultural context, in which a reduction is usually seen in at-risk individuals. However, gesture frequency might be a visual proxy of prodromal symptoms, and of other movement abnormalities. Results show the importance of analyzing NVC in ARMS and of considering different cultural and sociodemographic contexts in the search for markers of these states.

A network analysis of anxiety, depressive, and psychotic symptoms and functioning in children and adolescents at clinical high risk for psychosis.

Youths at clinical high risk for psychosis (CHR-P) are characterized by a high prevalence of anxiety and depressive disorders. The present study aimed at developing and analyzing a network structure of CHR-P symptom domains (i.e., positive, negative, disorganization, and general subclinical psychotic symptoms), depressive and anxiety symptoms, and general functioning. Network analysis was applied to data on 111 CHR-P children and adolescents (M age = 14.1), who were assessed using the Structured Interview for Prodromal Syndromes, the Children's Depression Inventory, the Children's Global Assessment Scale, and the Multidimensional Anxiety Scale for Children. In the network, negative and disorganization symptoms showed the strongest association (r = 0.71), and depressive and anxiety symptoms showed dense within-domain connections, with a main bridging role played by physical symptoms of anxiety. The positive symptom cluster was not associated with any other node. The network stability coefficient (CS) was slightly below 0.25, and observed correlations observed ranged from 0.35 to 0.71. The lack of association between subclinical positive symptoms and other network variables confirmed the independent nature of subclinical positive symptoms from comorbid symptoms, which were found to play a central role in the analyzed network. Complex interventions should be developed to target positive and comorbid symptoms, prioritizing those with the most significant impact on functioning and the most relevance for the young individual, through a shared decision-making process. Importantly, the results suggest that negative and disorganization symptoms, as well as depressive and anxiety symptoms, may be targeted simultaneously.

Motion energy analysis during speech tasks in medication-naïve individuals with at-risk mental states for psychosis

Movement abnormalities are commonly observed in schizophrenia and at-risk mental states (ARMS) for psychosis. They are usually detected with clinical interviews, such that automated analysis would enhance assessment. Our aim was to use motion energy analysis (MEA) to assess movement during free-speech videos in ARMS and control individuals, and to investigate associations between movement metrics and negative and positive symptoms. Thirty-two medication-naïve ARMS and forty-six healthy control individuals were filmed during speech tasks. Footages were analyzed using MEA software, which assesses movement by differences in pixels frame-by-frame. Two regions of interest were defined—head and torso—and mean amplitude, frequency, and coefficient of variability of movements for them were obtained. These metrics were correlated with the Structured Interview for Prodromal Syndromes (SIPS) symptoms, and with the risk of conversion to psychosis—inferred with the SIPS risk calculator. ARMS individuals had significantly lower mean amplitude of head movement and higher coefficients of movement variability for both head and torso, compared to controls. Higher coefficient of variability was related to higher risk of conversion. Negative correlations were seen between frequency of movement and most SIPS negative symptoms. All positive symptoms were correlated with at least one movement variable. Movement abnormalities could be automatically detected in medication-naïve ARMS subjects by means of a motion energy analysis software. Significant associations of movement metrics with symptoms were found, supporting the importance of movement analysis in ARMS. This could be a potentially important tool for early diagnosis, intervention, and outcome prediction.

Reduced interpersonal neural synchronization in right inferior frontal gyrus during social interaction in participants with clinical high risk of psychosis: An fNIRS-based hyperscanning study

BackgroundClinical high risk (CHR) of psychosis is characterized by cognitive impairment in social interaction. However, research investigating the neurobiological underpinnings of social interactions and interpersonal relationships in CHR participants is sparse. Methods21 CHR and 54 healthy controls (HCs) participated in the study. Dyads were formed between one CHR, one sex-matched HC, and two sex-matched HCs comprising 19 CHR-HC dyads and 19 HC-HC dyads. The concentration changes of oxyhemoglobin and deoxyhemoglobin were examined during a two-block button-press “cooperation” and “competition” task using functional near-infrared spectroscopy(fNIRS) hyperscanning technology. CHR diagnosis and psychopathological assessments were performed by Structured Interview for Prodromal Syndromes (SIPS) and Scale of Prodromal Symptoms (SOPS). Neural synchronizations were compared between CHR-HC dyads and HC-HC dyads. Correlation analyses were performed to identify the relationship between neural synchronization, clinical syndrome and cognition. ResultsDuring the cooperation, but not the competition task, the CHR-HC dyads showed reduced inter-brain neural synchronization (INS) in the right inferior frontal gyrus (IFG) compared to the HC-HC dyads. INS also showed a positive correlation with the average cooperation rate. Moreover, the reduced INS in the CHR-HC group was significantly correlated with symptoms score of suspiciousness/persecutory ideas and movement disorders. ConclusionsThe decreased INS in right IFG during cooperation could account for CHR's cognitive impairment of social interaction. Our findings provide evidence that inter-brain neural synchronization potentially represents a biomarker of social interaction deficits of CHR.

Convergent and divergent gray matter volume abnormalities in unaffected first-degree relatives and ultra-high risk individuals of schizophrenia

High-risk populations of schizophrenia can be mainly identified as genetic high-risk based on putative endophenotypes or ultra-high-risk (UHR) based on clinically manifested symptoms. Previous studies have consistently shown brain structural abnormalities in both genetic high-risk and UHR individuals. In this study, we aimed to disentangle the convergent and divergent pattern of gray matter alterations between UHR and unaffected first-degree relatives from genetic high-risk individuals. We used structural MRI scans and voxel-based morphometry method to examine gray matter volume (GMV) differences among 23 UHR subjects meeting the Structured Interview for Prodromal Syndromes (SIPS) criteria, 18 unaffected first-degree relatives (UFDR), 26 first-episode schizophrenia patients (FES) and 54 healthy controls (CN). We found that a number of brain regions exhibited a monotonically decreasing trend of GMV from CN to UFDR to UHR to FES. Compared with CN, the UHR subjects showed significant decreases of GMV similar to the patients in the inferior temporal gyrus, fusiform gyrus, middle occipital gyrus, insula, and limbic regions. Moreover, the UHR transformed subgroup had significantly lower GMV than UHR non-transformed subgroup in the right inferior temporal/fusiform gyrus. On the other hand, the UFDR subjects only showed significant GMV decreases in the inferior temporal gyrus and fusiform. Moreover, we found GMV in the occipital lobe was negatively correlated with the UHR subjects’ composite positive symptom of SIPS, and GMV in the cerebellum was positively correlated with FES subjects’ symptom severity. Our results suggest that GMV deficits and regional dysfunction are evident prior to the onset of psychosis and are more prominent in the UHR than the UFDR individuals.

Antipsychotic prescription, assumption and conversion to psychosis: resolving missing clinical links to optimize prevention through precision

The current concept of clinical high-risk(CHR) of psychosis relies heavily on “below-threshold” (i.e. attenuated or limited and intermittent) psychotic positive phenomena as predictors of the risk for future progression to “above-threshold” positive symptoms (aka “transition” or “conversion”). Positive symptoms, even at attenuated levels are often treated with antipsychotics (AP) to achieve clinical stabilization and mitigate the psychopathological severity. The goal of this study is to contextually examine clinicians’ decision to prescribe AP, CHR individuals’ decision to take AP and psychosis conversion risk in relation to prodromal symptoms profiles. CHR individuals (n = 600) were recruited and followed up for 2 years between 2016 and 2021. CHR individuals were referred to the participating the naturalistic follow-up study, which research procedure was independent of the routine clinical treatment. Clinical factors from the Structured Interview for Prodromal Syndromes (SIPS) and global assessment of function (GAF) were profiled via exploratory factor analysis (EFA), then the extracted factor structure was used to investigate the relationship of prodromal psychopathology with clinicians’ decisions to AP-prescription, CHR individuals’ decisions to AP-taking and conversion to psychosis. A total of 427(71.2%) CHR individuals were prescribed AP at baseline, 532(88.7%) completed the 2-year follow-up, 377(377/532, 70.9%) were taken AP at least for 2 weeks during the follow-up. EFA identified six factors (Factor-1-Negative symptoms, Factor-2-Global functions, Factor-3-Disorganized communication & behavior, Factor-4-General symptoms, Factor-5-Odd thoughts, and Factor-6-Distorted cognition & perception). Positive symptoms (Factor-5 and 6) and global functions (Factor-2) factors were significant predictors for clinicians’ decisions to AP-prescription and CHR individuals’ decisions to assume AP, whereas negative symptoms (Factor-1) and global functions (Factor-2) factors predicted conversion. While decisions to AP-prescription, decisions to AP-taking were associated to the same factors (positive symptoms and global functions), only one of those was predictive of conversion, i.e. global functions. The other predictor of conversion, i.e. negative symptoms, did not seem to be contemplated both on the clinician and patients’ sides. Overall, the findings indicated that a realignment in the understanding of AP usage is warranted.

Reduced Expression of Emotion: A Red Flag Signalling Conversion to Psychosis in Clinical High Risk for Psychosis (CHR-P) Populations

Objective: In this hypothesis-testing study, which is based on findings from a previous atheoretical machine-learning study, we test the predictive power of baseline “reduced expression of emotion” for psychosis. Method: Study participants (N = 96, mean age 16.55 years) were recruited from the Prevention of Psychosis Study in Rogaland, Norway. The Structured Interview for Prodromal Syndromes (SIPS) was conducted 13 times over two years. Reduced expression of emotion was added to positive symptoms at baseline (P1–P5) as a predictor of psychosis onset over a two-year period using logistic regression. Results: Participants with a score above zero on expression of emotion had over eight times the odds of conversion (OR = 8.69, p < .001). Data indicated a significant dose–response association. A model including reduced expression of emotion at baseline together with the positive symptoms of the SIPS rendered the latter statistically insignificant. Conclusions: The study findings confirm findings from the previous machine-learning study, indicating that observing reduced expression of emotion may serve two purposes: first, it may add predictive value to psychosis conversion, and second, it is readily observable. This may facilitate detection of those most at risk within the clinical high risk of psychosis population, as well as those at clinical high risk. A next step could be including this symptom within current high-risk criteria. Future research should consolidate these findings.

Kraepelin and Bleuler were right: disorganised thinking and poverty of emotions, not delusions or hallucinations, are primary in psychoses

Background In psychotic patients, functional outcome is associated with several clinical, neuropsychological and developmental factors. In a prospective study design, we aimed to predict functional outcome in patients with first-episode psychosis (FEP) and clinical high risk to psychosis (CHR) by sociodemographic, clinical, neuropsychological and premorbid factors, as well as by follow-up symptomatology. Methods Altogether, 130 FEP and 60 CHR patients were recruited and their Global Assessment of Functioning (GAF) was assessed at baseline (T0) and when nine months (T1) and 18 months (T2) was elapsed from baseline examination. Sum of follow-up GAFT1 and GAFT2 (F-GAF) was predicted by background characteristics and factorised dimensions of the Structured Interview for Prodromal Syndromes (SIPS) symptoms, Premorbid Adjustment Scale (PAS), Trauma and Distress Scale items and neuropsychological tests, and by psychotic, depression and anxiety symptoms at T1 and T2. Results F-GAF was predicted by PAS Sociability and School Performance, SIPS Disorganised Thinking, work and marital status in FEP patients. In CHR patients, only SIPS Emotional Poverty predicted significantly F-GAF. In them, follow-up Depression/Anxiety symptomatology is associated strongly with poor F-GAF. The effects of PAS Sociability and School Performance on F-GAF were mediated via SIPS Emotional Poverty in both FEP and CHR patients. Conclusions In patients with FEP, poor premorbid adjustment, Disorganised Thinking, poor baseline work status and single marital status predict poor follow-up functioning. In both FEP and CHR patients, the effect of premorbid adjustment on follow-up functioning is mediated via Emotional Poverty. In patients with CHR, basic disturbances are affective disorders.

Cognitive Patterns and Conversion in a Representative Sample of Individuals at Risk for Psychosis.

Clinical high-risk (CHR) individuals belong to a heterogeneous group, of which only a few will cross the threshold for a clinical diagnosis. Cognitive disturbances are present in CHR subjects and may be indicative of transition. Our study aims to identify such deficits in a representative CHR for psychosis sample. Our sample comprised 92 CHR individuals and 54 controls from a representative cohort of the general population. They were followed up for a mean of 2.5 years, with 15 individuals converting to schizophrenia or other Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnoses. Neurocognitive assessment was performed with the University of Pennsylvania Computerized Neuropsychological Testing, and CHR status was assessed with the Structured Interview for Prodromal Syndromes (SIPS). Baseline scores were entered in a latent profile analysis model. Our study brought forward a four-class model on cognitive performance. One class displayed better performance, whereas the other three performed worse, all compared with controls. The class with lower executive function also had the highest score on disorganized communication (SIPS P5 = 1.36, p < 0.05), although unrelated to conversion. Among the low performers, the class significantly related to conversion (p = 0.023) had the highest score in decreased expression of emotion (SIPS N3 = 0.85, p < 0.05). Our study brings new and relevant data on non-help-seeking CHR individuals and the relationship between cognitive patterns and conversion. We have highlighted a specific cognitive signature, associated with negative symptoms, which represents a stable trait with presumed lower conversion to a psychiatric illness.

COX-2 pathway is upregulated in ultra-high risk individuals for psychosis

Background The identification of Ultra-High Risk (UHR) individuals is thought to be useful for early intervention to improve psychosis outcomes. However, transition rates vary widely, and there is an effort to make these criteria more specific and accurate. Neuroinflammation has been discussed in the pathophysiology of psychosis. The metabolism of eicosanoids is a key process in inflammatory states. Therefore, we investigated whether the study of the inflammatory COX-2 pathway through the quantification of the eicosanoid levels can be a useful approach for the characterisation of UHR individuals. Methods One hundred and twenty-two individuals were included in this study (67 UHR and 55 controls) based on performance on the Prodromal Questionnaire. UHR status was assessed by Structured Interview for Prodromal Syndromes (SIPS). We determined the levels of Prostaglandin F2α (PGF2α), Prostaglandin E2 (PGE2), and Thromboxane B2 (TxB2) in plasma using ELISA assays. Results Concentrations of PGE2 and TxB2 were increased in UHR compared to controls (p = 0.01 and p < 0.05, respectively). PGE2 and PGF2α levels were correlated to negative symptoms (p < 0.01 and p < 0.05), whereas TxB2 correlated with positive symptoms (p = 0.05) as assessed by the SIPS. Conclusions Our findings suggest that overactivation of the COX-2 pathway may be related to an increased risk for psychosis. However, our data do not allow us to draw conclusions related to the cause-effect mechanisms. Future studies should determine whether the levels of the eicosanoids have a predictive value for the transition of UHR to frank psychosis.

Further evidence that antipsychotic medication does not prevent long-term psychosis in higher-risk individuals.

Although existing guidelines have discouraged use of antipsychotics for general clinical high-risk (CHR) individuals, it is unclear if antipsychotics can prevent psychosis in higher-risk population. We aimed to study the comparative real-world effectiveness of antipsychotic treatments for preventing psychosis in higher-risk CHR individuals. A total of 300 CHR individuals were identified using the structured interview for prodromal syndromes (SIPS) and followed the participants for 3 years. In total, 228(76.0%) individuals completed baseline assessments using the NAPLS-2 risk calculator (NAPLS-2-RC), and 210(92.1%) completed the follow-up. The sample was further stratified according to risk level. "Higher-risk" was defined based on the NAPLS-2-RC risk score (≥ 20%) and SIPS positive symptom total scores (≥ 10). The main outcome was conversion to psychosis and poor functional outcomes, defined as a global assessment of function (GAF) score lower than 60 at follow-up. In higher-risk CHR individuals, we found no significant difference in the rate of conversion to psychosis or poor functional outcomes between the antipsychotic and no-antipsychotic groups. Low-risk individuals treated with antipsychotic drugs were more likely exhibit poor functional outcomes compared with the no-antipsychotics group(NAPLS-2-RC estimated risk: χ2 = 8.330, p = 0.004; Positive symptom severity: χ2 = 12.997, p < 0.001). No significant effective factors were identified for prevention of the conversion to psychosis; conversely, CHR individuals who were treated with high dose antipsychotics (olanzapine, aripiprazole) showed a significantly increased risk of poor functional outcomes. In CHR individuals, antipsychotic treatment should be provided with caution because of the risk of poor functional outcomes. Further, antipsychotic treatment does not appear to prevent onset of psychosis in real-world settings.

Elevated emotion reactivity and emotion regulation in individuals at clinical high risk for developing psychosis and those diagnosed with a psychotic disorder.

Disrupted affective processes are core features of psychosis; yet emotion reactivity and emotion regulation impairments have not been fully characterized in individuals at clinical high-risk for developing psychosis (CHR) or adolescents diagnosed with a psychotic disorder (AOP). Characterizing these impairments may provide a fuller understanding of factors contributing to psychosis risk and psychosis onset. Using cross-sectional and longitudinal data, we evaluated (1) group-level effects of emotion reactivity and regulation, (2) stability of group-level effects over time and age, (3) relationships between emotion reactivity and regulation, and (4) associations between these measures and psychosocial functioning and clinical symptomatology. Eighty-seven participants (CHR=32, TD=42, AOP=13; 12-25 years, 1-5 visits) completed the Emotion Reactivity Scale, Difficulties in Emotion Regulation Scale, and Emotion Regulation Questionnaire. We assessed psychotic symptoms with the Structured Interview for Prodromal Syndromes and measured real-world functioning with the Global Functioning: Social and Role Scales. We used analysis of variance to assess Aim 1 and linear mixed models to address Aims 2-4. CHR and AOP endorsed experiencing heightened levels of emotion reactivity and greater difficulty utilizing emotion regulation strategies compared to TD. These impairments were stable across time and adolescent development. Greater levels of emotion reactivity were associated with greater emotion regulation impairments. Greater impairments in emotion regulation were associated with lower social functioning and greater negative symptom severity. Therapeutic interventions designed to reduce emotion reactivity and improve one's ability to utilize emotion regulation strategies may be effective in reducing clinical symptomatology and improving real-world functioning in CHR and AOP.

Inter-rater reliability of subthreshold psychotic symptoms in individuals with 22q11.2 deletion syndrome

BackgroundPathways leading to psychosis in 22q11.2 deletion syndrome (22q11.2DS) have been the focus of intensive research during the last two decades. One of the common clinical risk factors for the evolution of psychosis in 22q11.2DS is the presence of positive and negative subthreshold psychotic symptoms. The gold standard for measuring subthreshold symptoms is the Structured Interview for Prodromal Syndromes (SIPS) and its accompanying Scale of Prodromal Symptoms (SOPS) ratings. Although the scale has been used by many centers studying 22q11.2DS, the inter-site reliability of the scale in this population has never been established.MethodsIn the present study, experienced clinical assessors from three large international centers studying 22q11.2DS independently rated video recordings of 18 adolescents and young adults with 22q11.2DS.ResultsThe intraclass correlations coefficients (ICCs) among three raters for the SOPS total scores, as well as for the positive, negative, and disorganization subscale scores, were good-to-excellent (ICCs range 0.73–0.93). The raters were also able to reliably determine the subjects’ subthreshold syndrome status (ICC = 0.71). The reliability of individual items was good-to-excellent for all items, ranging from 0.61 for motor disturbances [G3] to 0.95 for bizarre thinking.ConclusionsOur results show that trained clinicians can reliably screen for subthreshold psychotic symptoms in individuals with 22q11.2DS. To increase assessment reliability, we suggest specific clarifications and simplifications to the standard SIPS interview for future studies.

Screening of the college students at clinical high risk for psychosis in China: a multicenter epidemiological study

BackgroundTo investigate a 3-stage screening procedure and explore the clinical features of subjects at Clinical High Risk (CHR) for psychosis in a representative sample of Chinese college students.MethodsAn epidemiological survey of the prevalence of the CHR syndrome in Chinese college students that was selected by stratified random sampling from Shanghai, Nanjing and Nanchang cities was done following a 3-stage procedure. Participants were initially screened with the Prodromal Questionnaire-brief version (PQ-B), and whose distress score of PQ-B exceeded 24 would be invited to a telephone assessment using the subscale for positive symptoms of the Scale of Prodromal Symptoms (SOPS)/Structured Interview for Prodromal Syndromes (SIPS). Lastly, participants who scored 3 or higher in any item of the subscale would be administered with the SIPS interview conducted by trained researchers to confirm the diagnosis of CHR syndrome.ResultsTwenty-three thousand sixty-three college students completed the survey during September 2017 to October 2018. Seventy-two students were diagnosed as CHR subjects, and the detection rate in the total sample was 0.3%. The peak age range for the first diagnosis of CHR was 17 to 20 years. Thirteen and forty-six were set as the cutoff points of PQ-B total score and distress score to balance the greatest sensitivity and specificity. Binary logistic regression revealed that 8 items in PQ-B showed significant distinction for detecting CHR subjects.ConclusionsThe 3-stage screening method can be utilized in the detection of CHR subjects for psychosis in the general population, during which delusional ideas, perceptual abnormalities and suspiciousness deserve great attention.

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis

The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.

The relationship between self-disorders (SDS) and depressive/anxious symptoms in a clinical sample of adolescents

IntroductionSelf-disorders (SDs) have been described as a core feature of schizophrenia-spectrum disorders. Previous studies conducted on heterogeneous clinical adult and adolescents samples demonstrated that SDs aggregate selectively in the schizophrenia spectrum disorders compared to other disorders.ObjectivesTo examine the specificity of SDs for schizophrenia spectrum disorders in adolescent inpatient sample.MethodsFifty-five adolescent inpatients admitted to the Child Psychiatry Unit at the Sapienza University in Rome were assessed for psychopathology using Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL), Structured Interview for Prodromal Syndromes (SIPS/SOPS),Examination of Anomalous Self-Experiences (EASE), Multidimensional Anxiety Scale for Children (MASC), Calgary depression scale for schizophrenia (CDSS)ResultsPatients, aged 14-18 years, were divided in four diagnostic groups: schizophrenia spectrum disorders (5 pts.), mood disorders (19 pts.), anxiety disorders (27 pts.) and other disorders (4 pts.). Frequency of self-disorders was different among the 4 groups. Including patients schizotypal personality disorder in the schizophrenia-spectrum disorder group, the difference is still significant. Mann-Whitney U test shows no differences between EOP and UHR patients in SD. Furthermore, correlations between EASE total score and Calgary and MASC total scores were significant.ConclusionsOur results confirm the specificity of SDs for schizophrenia spectrum disorders and also the belonging of schizotypal personality disorder to schizophrenia-spectrum.