Structured Interview For Prodromal Symptoms Research Articles

Heterogeneity of clinical symptomatology in pediatric patients at clinical high risk for psychosis

ObjectiveWidespread use of diagnostic tools like the Structured Interview for Prodromal Symptoms (SIPS) has highlighted that youth at Clinical High Risk for Psychosis (CHR-P) present with heterogeneous symptomatology. This pilot study aims to highlight the range of clinical characteristics of CHR-P youth, investigate the role of the non-positive (negative, disorganization, and general) symptoms in risk assessment, and determine if specific profiles are associated with severe symptomatology.Methods38 participants aged 7–18 were administered the SIPS and designated as CHR-P. Descriptive statistics and mean difference t-tests were used to describe the range in prevalence and severity of SIPS symptoms and to identify symptoms associated with greater overall symptomatology.ResultsParticipants who had a greater number of positive symptoms also had significantly more negative, disorganization, and general symptoms. A number of SIPS symptoms were associated with greater number of positive symptoms.ConclusionCHR-P youth represent a heterogeneous group, presenting with a wide range in clinical presentation as reflected in both the number of SIPS symptoms and their severity. Though the severity and duration of positive SIPS symptoms determines the CHR-P classification, high ratings on several of the other SIPS negative, disorganization, and general items may be useful indicators of elevated symptomatology.

N400 event-related brain potential index of semantic processing and two-year clinical outcomes in persons at high risk for psychosis: A longitudinal study.

The N400 event-related brain potential (ERP) semantic priming effect reflects greater activation of contextually related versus unrelated concepts in long-term semantic memory. Deficits in this measure have been found in persons with schizophrenia and those at clinical high risk (CHR) for this disorder. In CHR patients, we previously found that these deficits predict poorer social functional outcomes after 1 year. In the present study, we tested whether these deficits predicted greater psychosis-spectrum symptom severity and functional impairment over 2 years. We measured N400 semantic priming effects at baseline in CHR patients (n = 47) who viewed prime words each followed by a related/unrelated target word at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured psychosis-spectrum symptoms using the Structured Interview for Prodromal Symptoms and role and social functioning with the Global Functioning: Role and Social scales, at baseline, 1 (n = 29) and 2 years (n = 25). There was a significant interaction between the N400 semantic priming effect at the 300-ms SOA and time on GF:Role scores, indicating that, contrary to expectations, smaller baseline N400 semantic priming effects were associated with more improvement in role functioning from baseline to Year 1, but baseline N400 priming effects did not predict role functioning at Year 2. N400 priming effects were not significantly associated with different trajectories in psychosis-spectrum symptoms or social functioning. Thus, CHR patients' N400 semantic priming effects did not predict clinical outcomes over 2 years, suggesting that this ERP measure may have greater value as a state or short-term prognostic neurophysiological biomarker.

Multivariate joint models for the dynamic prediction of psychosis in individuals with clinical high risk

This study attempted to construct and validate dynamic prediction via multivariate joint models and compare the prognostic performance of these models to both static and univariate joint models. Individuals with clinical high risk(CHR)(n=289) were recruited and re-assessed for positive symptoms, general functions, and conversion to psychosis at 2-months, 1-year, and 2-years to develop the dynamic models. A multivariate joint model of positive psychotic symptoms was assessed using the Structured Interview for Prodromal Symptoms(SIPSp) and general function assessed by global assessment of functioning scores(GAFs) with time-to-conversion to psychosis. The area under the receiver operating characteristic(ROC) curve(AUC) was used to test the accuracy of the models. Among 298 CHR individuals, 68 converted to psychosis within 2 years after the initial assessments. Multivariate joint models showed that declining GAFs and increasing SIPSp corresponded to significant and trending to significantly increased risk of psychosis onset and had much higher prognostic accuracy (cross-validated AUC=0.9) compared to the static model(AUC=0.6) and univariate joint models(cross-validated AUC=0.6-0.8). Our results showed that multivariate joint models could be highly efficient in forecasting psychosis onset for CHR individuals. Longitudinal assessments for psychopathology and general functions can be useful for dynamically predicting the prognosis of the pre-morbid phase of psychosis.

The non-specific nature of mental health and structural brain outcomes following childhood trauma.

Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure. We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry. (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found. These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.

T27. COGNITIVE RESERVE IN CHILD AND ADOLESCENT OFFSPRING OF PATIENTS DIANOSED WITH SCHIZOPHRENIA OR BIPOLAR DISORDER

BackgroundCognitive Reserve (CR) is defined as the ability of the brain to cope and deal with physiological or pathological brain injuries. In the field of psychiatry, higher levels of CR have been associated with lower levels of psychotic symptoms, higher psycho-social functioning and higher cognitive performance, suggesting that CR should be considered as a protective factor (Barnett et al., 2006; Amoretti et al., 2016). This study aims to compare CR levels in a sample of adolescents and young adult offspring of patients with schizophrenia or bipolar disorder who are at high risk of developing these disorders (HR) and compared them with a group of healthy controls (HC). We also assess the utility of CR in predicting clinical and cognitive variables.MethodsParticipants were 85 HR and 45 HC. A CR proxy was calculated based on premorbid IQ, socio-occupational attainment and social activities. Clinical assessment included: the Structured Interview for Prodromal Symptoms (SOPS), the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). Neuropsychological assessment included: Working Memory, Processing Speed, Verbal Memory, attention and executive functioning. A factorial analysis was conducted in order to obtain a single CR measure. Differences between groups in CR were assessed via MANCOVA and linear regressions were conducted to check the effectiveness of CR in predicting clinical and neuropsychological variables.ResultsNo significant differences were observed in age or gender between HR and HC groups. Socioeconomic status was lower in HR subjects (F=8.100, p=0.005).CR was significantly lower in the HR group than in the HC group (F=17.522; p<0.001). Moreover, the CR proxy was able to correctly classify 72.7% of the sample as either HR or HC. Our proxy was able to predict the following clinical variables in the HR group: negative (F=9.269; p=0.002), and total (F=7.290; p=0.009) prodromal symptoms, the YMRS (F=11.597; P<0.001) and the HDRS (F=12.761; p<0.001). In terms of neuropsychological variables, RC predicted WM (F=9.738; p=0.003), PS (F=4.557; p=0.037) and verbal memory [immediate (F=6.999; p=0.010) and delayed recall (F=10.990; P=0.002)] in the HR sample.DiscussionHR subjects have lower CR than controls. CR is associated with clinical and neuropsychological variables. To our knowledge no previous studies have assessed CR in high risk samples. Nevertheless, studies conducted in adult first episode psychotic samples have shown an association between CR and the severity of symptoms.

M26. CLINICAL CHARACTERISTICS OF CHILD AND ADOLESCENT OFFSPRING OF PATIENTS DIAGNOSED WITH SCHIZOPHERNIA: A COMPARATIVE STUDY WITH ADHD CHILDREN

BackgroundRecent studies have observed high rates of psychopathology in child and adolescent offspring of patients with schizophrenia (SZoff). Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent psychopathology in SZoff (Sanchez-Gistau, et al., 2015). The high prevalence of ADHD observed in SZoff can conceal the vulnerability characteristics specific to schizophrenia. The aim of this study is to analyze the clinical characteristics of a sample of child and adolescent SZoff diagnosed with ADHD (SZoff-ADHD) compared to a sample of children with ADHD without a family history of psychotic disorders and a sample of healthy controls. We hypothesize that SZoff-ADHD will show more psychopathology and more prodromal psychotic symptoms than the other two groups.Methodswe studied a sample of 22 SZoff-ADHD children, 15 children with ADHD with no familiar history of psychotic disorders and 40 healthy controls (HC) between 6 and 17 years old and we conducted a complete clinical assessment which included: Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Structured interview for Prodromal Symptoms (SOPS) and Global Assessment Functioning (GAF). In order to detect significant differences between groups, multilevel mixed-effect logistic regression models (categorical variables) or multilevel mixed-effect linear regression models (continuous variables) were performed with group as the fixed factor and the fact of having a sibling in the same study (identified by the family number) as the random variable.Resultssignificant differences between groups were found in socio-economic status which was lower in the SZoff-ADHD group than in the other two groups (F=15.886; p<0.001). Moreover the SZoff-ADHD also showed a higher percentage of males (90.9%) compared with the ADHD group (62.5%) and the HC (45%) (F=12.647; p=0.002). No significant age differences between groups were detected.Regarding clinical assessments, the SZoff-ADHD group showed a higher percentage of conduct disorders (F=3.720; p=0.039) than the ADHD group. No significant differences were observed in other psychopathological diagnoses. Furthermore the SZoff-ADHD group also obtained higher scores than the HC group on the following scales: YMRS, positive, negative, general and total sub-scales of the SOPS and lower scores in the GAF. The ADHD group obtained significantly higher scores than the HC group in the sub-scale of SOPS general prodromal symptoms and lower scores on the GAF. Significant differences were detected between SZoff-ADHD and ADHD in the YMRS and the positive and negative sub-scales of the SOPS where the SZoff-ADHD group showed higher scores than the ADHD group.DiscussionCompared with the HC group, the SZoff-ADHD displayed more manic, prodromal psychotic symptoms and worse psychosocial functioning. The ADHD group showed an intermediate pattern between the SZoff-ADHD and the HC group, with more general prodromal symptoms and lower psychosocial functioning than the HC group but lower scores than the SZoff-ADHD in the psychotic prodromal symptoms interview.

Efficacy of the Cooperative Assessment Method (COOPAS) to Improve the Psychiatric Care of Help-Seeking Adolescents.

ObjectiveEffective treatment of adolescents with psychopathological disorders is essential to reduce later morbidity and disability.To evaluate the clinical value of a new adolescent Cooperative Assessment scheme (COOPAS) as indicated by establishing therapeutic alliance, improving symptoms, and particularly by reducing dropouts.MethodConsecutive help-seeking adolescents (N=136) were recruited, evaluated with an 8-week COOPAS protocol and followed for 6 months to document dropouts during treatment. Clinical rating scales [Hamilton Depression and Anxiety scales (HAM-D, HAM-A), Global Functioning Role and Social Scales (GF-RS, GF-SS), Structured Interview for Prodromal Symptoms (SIPS), Clinical Global Impression (CGI), Working Alliance Inventory-Therapist version (WAI-T), Therapist Response Questionnaire (TRQ), Psychotherapy Relationship Questionnaire (PRQ)] were administered at intake, 4 weeks later, and at the end of COOPAS evaluation (8 weeks).ResultsFinal HAM-A and HAM-D scores improved by 25%; CGI, GF-SS and GF-RS also improved significantly. Similarly, WAI-T showed significant improvements in all three subscales, and patient-clinician relationships (PRQ) showed decreases in Anxious/Preoccupied and Avoidant/Counterdependent dimensions with increases of the Secure/Engaged measure. After 6 months, dropout rate was 8.82%.ConclusionsCOOPAS assessment was followed by reduced depressive and anxiety symptoms, good therapeutic alliance, and low dropout in adolescents.

Poor functional recovery is better predicted than conversion in studies of outcomes of clinical high risk of psychosis: insight from SHARP.

Few of the previous studies of clinical high risk of psychosis (CHR) have explored whether outcomes other than conversion, such as poor functioning or treatment responses, are better predicted when using risk calculators. To answer this question, we compared the predictive accuracy between the outcome of conversion and poor functioning by using the NAPLS-2 risk calculator. Three hundred CHR individuals were identified using the Chinese version of the Structured Interview for Prodromal Symptoms. Of these, 228 (76.0%) completed neurocognitive assessments at baseline and 199 (66.3%) had at least a 1-year follow-up assessment. The latter group was used in the NAPLS-2 risk calculator. We divided the sample into two broad categories based on different outcome definitions, conversion (n = 46) v. non-conversion (n = 153) or recovery (n = 138) v. poor functioning (n = 61). Interestingly, the NAPLS-2 risk calculator showed moderate discrimination of subsequent conversion to psychosis in this sample with an area under the receiver operating characteristic curve (AUC) of 0.631 (p = 0.007). However, for discriminating poor functioning, the AUC of the model increased to 0.754 (p < 0.001). Our results suggest that the current risk calculator was a better fit for predicting a poor functional outcome and treatment response than it was in the prediction of conversion to psychosis.

Prediction of psychosis in prodrome: development and validation of a simple, personalized risk calculator.

This study aim to derive and validate a simple and well-performing risk calculator (RC) for predicting psychosis in individual patients at clinical high risk (CHR). From the ongoing ShangHai-At-Risk-for-Psychosis (SHARP) program, 417 CHR cases were identified based on the Structured Interview for Prodromal Symptoms (SIPS), of whom 349 had at least 1-year follow-up assessment. Of these 349 cases, 83 converted to psychosis. Logistic regression was used to build a multivariate model to predict conversion. The area under the receiver operating characteristic (ROC) curve (AUC) was used to test the effectiveness of the SIPS-RC. Second, an independent sample of 100 CHR subjects was recruited based on an identical baseline and follow-up procedures to validate the performance of the SIPS-RC. Four predictors (each based on a subset of SIPS-based items) were used to construct the SIPS-RC: (1) functional decline; (2) positive symptoms (unusual thoughts, suspiciousness); (3) negative symptoms (social anhedonia, expression of emotion, ideational richness); and (4) general symptoms (dysphoric mood). The SIPS-RC showed moderate discrimination of subsequent transition to psychosis with an AUC of 0.744 (p < 0.001). A risk estimate of 25% or higher had around 75% accuracy for predicting psychosis. The personalized risk generated by the SIPS-RC provided a solid estimate of conversion outcomes in the independent validation sample, with an AUC of 0.804 [95% confidence interval (CI) 0.662-0.951]. The SIPS-RC, which is simple and easy to use, can perform in the same manner as the NAPLS-2 RC in the Chinese clinical population. Such a tool may be used by clinicians to counsel appropriately their patients about clinical monitor v. potential treatment options.

Translation and validation study of the prodromal questionnaire brief version into Indonesian language.

Psychosis is a mental disorder resulting in high disability impacts. Many studies show that early detection of prodromal symptoms may improve prognosis. Psychotic prodromal symptoms may mimic other mental health conditions such as depression, anxiety or learning difficulties. The aim of this study was to analyze validity, reliability, sensitivity and specificity of the Prodromal Questionnaire Brief Version (PQ-B) Indonesian version to detect psychotic prodromal symptoms. The PQ-B was translated into Indonesian then back-translated into English. Subjects included in this study were 50 children and adolescent psychiatric patients from Cipto Mangunkusumo National Hospital, aged 10-18 years old. Validity measurement was performed by comparing the total score and distress score of PQ-B with the categorical scale of Structured Interview for Prodromal Symptoms (SIPS) as the gold standard using Spearman correlation. Total scale and subscale reliability were examined using the Cronbach's Alpha. Analysis with Spearman correlation showed significant results of both PQ-B total score with diagnosis of SIPS (r = 0.374 and p = 0.007); and PQ-B distress score with diagnosis of SIPS (r = 0.400 and p = 0.004). Cronbach Alpha coefficient was equal to 0.853 for all scales. The sensitivity of the PQ-B in the Indonesian language is 70%, and the specificity is 72%, whereas, in the original language (English), the sensitivity and specificity is 88% and 68%. This study provides evidence of good validity, reliability, sensitivity, and specificity of PQ-B Indonesian language to detect prodromal symptoms of those who seek help in the psychiatric outpatient clinic.

S105. VALIDATING THE PREDICTIVE ACCURACY OF THE NAPLS-2 PSYCHOSIS RISK CALCULATOR IN A CLINICAL HIGH-RISK SAMPLE FROM THE SHARP (SHANGHAI AT RISK FOR PSYCHOSIS) PROGRAM

BackgroundThe present study aims to validate the predictive accuracy of the NAPLS-2 psychosis risk calculator in a clinical high-risk (CHR) sample from the SHARP (ShangHai At Risk for Psychosis) program in Shanghai, China using comparable inclusion/exclusion criteria and assessments.MethodsThree hundred CHR individuals were identified by the Chinese version of the Structured Interview for Prodromal Symptoms. Of these, 228 (76.0%) completed neuro-cognitive assessments at baseline and 199 (66.3%) had at least a one-year follow-up assessment. The latter group was used in risk calculation. Six key predictors (baseline age, unusual thoughts and suspiciousness, symbol coding and verbal learning test performance, functional decline and family history of psychosis) were entered into the NAPLS-2 model to generate a psychosis risk estimate for each case. The area under the receiver operating characteristic curve (AUC) was used to test the effectiveness of this discrimination.ResultsThe NAPLS risk calculator showed moderate discrimination of subsequent transition to psychosis in the SHARP sample with an AUC of 0.631 (p = 0.007). Whether discriminating either transition or poor treatment/clinical outcomes, the AUC of the model increased to 0.754 (p < 0.001). A risk estimate of 30% or higher had moderate sensitivity (53%) and excellent specificity (86%) for prediction of poor treatment/clinical outcome.DiscussionThe NAPLS-2 risk calculator largely generalizes to a Shanghai CHR sample but is meaningfully improved when predicting an individual’s poor clinical outcome as well as conversion. Our findings provide a critical step in the implementation of CHR risk calculation in China.

The interaction between neurocognitive functioning, subthreshold psychotic symptoms and pharmacotherapy in 22q11.2 deletion syndrome: A longitudinal comparative study

BackgroundThe 22q11.2 deletion syndrome (22q11DS) is the most common genetic syndrome associated with schizophrenia. The goal of this study was to evaluate longitudinally the interaction between neurocognitive functioning, the presence of subthreshold psychotic symptoms (SPS) and conversion to psychosis in individuals with 22q11DS. In addition, we attempted to identify the specific neurocognitive domains that predict the longitudinal evolution of positive and negative SPS, as well as the effect of psychiatric medications on 22q11DS psychiatric and cognitive developmental trajectories. MethodsForty-four participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically developing (TD) controls, age range 12–35years, were assessed at two time points (15.2±2.1months apart). Evaluation included the Structured Interview for Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn Computerized Neurocognitive Battery (CNB). Results22q11DS individuals with SPS had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in both WS and TD controls. Baseline levels of negative SPS were associated with global neurocognitive performance (GNP), executive function and social cognition deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS individuals treated with psychiatric medications showed significant improvement in GNP score between baseline and follow-up assessments, an improvement that was not seen in untreated 22q11DS. ConclusionsOur results highlight the time-dependent interplay among positive and negative SPS symptoms, neurocognition and pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS.

Interpersonal sensitivity and persistent attenuated psychotic symptoms in adolescence.

Interpersonal sensitivity defines feelings of inner-fragility in the presence of others due to the expectation of criticism or rejection. Interpersonal sensitivity was found to be related to attenuated positive psychotic symptom during the prodromal phase of psychosis. The aims of this study were to examine if high level of interpersonal sensitivity at baseline are associated with the persistence of attenuated positive psychotic symptoms and general psychopathology at 18-month follow-up. A sample of 85 help-seeking individuals (mean age=16.6, SD=5.05) referred an Italian early detection project, completed the interpersonal sensitivity measure and the structured interview for prodromal symptoms (SIPS) at baseline and were assessed at 18-month follow-up using the SIPS. Results showed that individuals with high level of interpersonal sensitivity at baseline reported high level of attenuated positive psychotic symptoms (i.e., unusual thought content) and general symptoms (i.e., depression, irritability and low tolerance to daily stress) at follow-up. This study suggests that being "hypersensitive" to interpersonal interactions is a psychological feature associated with attenuated positive psychotic symptoms and general symptoms, such as depression and irritability, at 18-month follow-up. Assessing and treating inner-self fragilities may be an important step of early detection program to avoid the persistence of subtle but very distressing long-terms symptoms.

Attenuated psychotic symptoms in children and adolescent offspring of patients with schizophrenia

ObjectiveTo compare the offspring of patients with SZ (SZoff) with those of a community control group (CC-off) to determine the variables associated with attenuated psychotic symptoms (APS), general symptomatology and functioning that may help to differentiate those at genetic risk for SZ. Methods41 SZ-off and 107 CC-off aged 6–17years were included. The Structured Interview for Prodromal Symptoms (SIPS), scored on the Scale of Prodromal Symptoms (SOPS), was administered by a child psychiatrist blinded to parental diagnoses, together with other clinical and functional scales. ResultsThe SZ-off group presented higher scores in positive (p=0.000), negative (p=0.012), and disorganized (p=0.009) subscale scores, as well as in the total score (p=0.001) on the SOPS when compared with the CC-off group. Other scales indicated significant emotional (p=0.028), behavioral (p=0.000) and peer-related problems (p=0.025), lower performance at school (p=0.025) and increased dysfunction score (p=0.005) in the SZ-off group. Logistic regression analysis revealed lower socioeconomic statuses (OR: 0.92, 95%CI: 0.87–0.97) and higher SOPS positive subscale scores (OR: 2.41, 95%CI: 1.31–4.42) in the SZ-off group. ConclusionsSZ-off presented significantly more APS and higher mean scores in psychopathological scales than CC-off, together with increased dysfunction scores. These early warning signs and follow-up for those at genetic high risk for schizophrenia will provide useful information about symptom progression, facilitating early intervention to improve short and long-term outcomes in youths with a positive family history.

Suicidal behaviors and their relationship with psychotic-like symptoms in children and adolescents at clinical high risk for psychosis

BackgroundPrevious research has demonstrated elevated rates of suicide attempts and ideation in individuals with psychosis. This study investigated rates and severity of suicidal behavior in youth with and at clinical high risk for psychosis, and examined the positive, negative, and disorganized symptoms associated with suicidal behaviors among the clinical high risk group. MethodsEighty-six youth ages 7–18 (n=21 non-clinical controls [NCC], n=40 clinical high risk [CHR], n=25 diagnosed psychotic disorder [PD]) were recruited. CHR and PD participants were identified using the Structured Interview for Prodromal Symptoms (SIPS) and Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version (KSADS-PL). All participants completed the Suicide Behaviors Questionnaire-Revised (SBQ-R). ResultsFindings indicated significantly higher levels of suicidal behavior among CHR and PD relative to NCC participants (F=7.64, p=0.001). 17.5% of CHR participants had previously attempted suicide. Dysphoric Mood and Odd Behavior or Appearance were significantly correlated with suicidal behavior severity among CHR youth. ConclusionSuicidal behavior was observed with greater frequency and severity in the CHR and PD groups than in the NCC group. CHR suicidal behavior severity was correlated most strongly with Dysphoric Mood and Odd Behavior or Appearance, a relationship which warrants further investigation.

Twelve Year Longitudinal Trajectories Of Neuroanatomy, Functional Connectivity And Neuropsychological Function In 22Q11.2 Deletion Syndrome: Prediction To Psychosis

We conducted a twelve-year longitudinal study of neuroanatomic, neurofunctional and neuropsychological development in youth with 22q11.2 deletion syndrome (22q11DS). Participants, consisting of 88 youth with 22q11DS, 33 unaffected siblings, and 32 community controls, were recruited to our academic medical center from throughout North America, and were followed every three years for four timepoints. Mean age in years at the first timepoint was 11.9; second timepoint, 15.1; third timepoint, 18.1; fourth timepoint, 21.2. High resolution MRI scans and standard neuropsychological measures were administered at all timepoints. Trajectories of cortical thickness and surface area were measured with FreeSurfer, V.5.1. Functional connectivity (at the fourth timepoint only) was measured with the Functional Connectivity Toolbox (CONN) in Matlab. Positive symptoms of psychosis were measured with the Positive Symptom Subscale of the Structured Interview for Prodromal Symptoms (SIPS). Longitudinal linear mixed model regression analyses were conducted, and results were corrected for multiple comparisons. Relative to controls, probands displayed significantly slower rates of longitudinal change in cortical thickness of the superior parietal lobule and precuneus (p-values <0.01). Moreover, functional connectivity between superior parietal lobule and temporal regions were disrupted in probands relative to controls (p < 0.02). Parietal lobe trajectories also predicted Time 4 positive prodromal symptoms (p<0.01) in the probands. Over time, probands also exhibited slower rates of improvement in scores on visual working memory (p=0.001) and auditory/verbal learning (p=0.002) relative to their peers. Decrements in auditory/verbal learning were associated with Time 4 positive prodromal symptoms (p=0.01), as were decrements in the executive skill of set-shifting (p=0.001) and in sustained attention (p=0.006). We conclude that aberrant longitudinal alterations in parietal cortical thickness / connectivity, as well as decrements in auditory/verbal learning, executive function and sustained attention may represent biomarkers for the eventual onset of prodromal psychosis in 22q11DS.

Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study

About one third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop schizophrenia. Notably, a full-blown psychotic disorder is usually preceded by subthreshold symptoms. Therefore, it is important to identify early signs of psychosis in this population, a task that is complicated by the intellectual disabilities typically seen in 22q11.2DS. We aimed to identify subthreshold psychotic symptoms that distinguish 22q11.2DS from other neurodevelopmental disorders. The study included two independent cohorts from Tel Aviv and Philadelphia. 22q11.2DS (N=171) and typically developing (TD; N=832) individuals were enrolled at both sites and further compared to two groups with intellectual disabilities: Williams syndrome (WS; N=21) in the Tel Aviv cohort and idiopathic developmental disabilities (IDD; N=129) in the Philadelphia cohort. Participants and their primary caregivers were interviewed with the Structured Interview for Prodromal Symptoms (SIPS) and psychopathologies were assessed using standardized tools; general cognitive abilities were assessed with the Computerized Neurocognitive Battery. Negative/disorganized subthreshold syndrome was significantly more common in the 22q11.2DS group than in the WS (OR=3.90, 95% CI=1.34–11.34) or IDD (OR=5.05, 95% CI=3.01–10.08) groups. The 22q11.2DS group had higher scores than the two intellectual disabilities groups on several SIPS negative items, including avolition and decreased expression of emotion. Overall, there were few significant correlations between level of cognitive deficits and severity of negative symptoms in 22q11.2DS and only in the Tel Aviv cohort. Our findings suggest that 22q11.2DS individuals at the age of risk for developing psychosis should be closely monitored for negative symptoms.

Longitudinal study of premorbid adjustment in 22q11.2 deletion (velocardiofacial) syndrome and association with psychosis.

Velocardiofacial syndrome, also known as 22q11.2 deletion syndrome (22q11DS), is associated with an increased risk of major psychiatric disorders, including schizophrenia. The emergence of psychotic symptoms in individuals with schizophrenia in the general population is often preceded by a premorbid period of poor or worsening social and/or academic functioning. Our current study evaluated premorbid adjustment (via the Cannon-Spoor Premorbid Adjustment Scale [PAS]) and psychotic symptoms (via the Structured Interview for Prodromal Symptoms and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version) in youth with 22q11DS (N = 96), unaffected siblings (N = 40), and community controls (N = 50). The PAS scores indicated greater maladjustment during all developmental periods in individuals with 22q11DS compared to the controls. Many participants with 22q11DS had chronically poor (n = 33) or deteriorating (n = 6) PAS scores. In 22q11DS, chronically poor PAS trajectories and poor childhood and early adolescence academic domain and total PAS scores significantly increased the risk of prodromal symptoms or overt psychosis. Taking into account the catechol-O-methyltransferase (COMT) genotype, the best predictor of (prodromal) psychosis was the early adolescence academic domain score, which yielded higher sensitivity and specificity in the subgroup of youth with 22q11DS and the high-activity (valine) allele. PAS scores may help identify individuals at higher risk for psychosis.

Screening schizotypal personality disorder for detection of clinical high risk of psychosis in Chinese mental health services

Schizotypal personality disorder (SPD) is viewed as a marker of prodromal psychosis. However, information regarding genetic risk (e.g. SPD) is often overlooked in the identification process. This study assessed whether SPD screening questionnaire help the prodromal psychosis (also widely applied “clinical high risk” (CHR) for clinical sample) detection in Chinese mental health service. This work also examined whether SPD had higher frequency in genetic risk population and CHR subjects. Two wave studies concerning the SPD identification was used for analysis. Wave 1 survey: 3075 subjects were assessed by Personality Diagnostic Questionnaire for SPD (PDQ-SPD) and Structured Clinical Interview for DSM-IV Axis II (SCID-II). Wave 2 survey: 2113 subjects screened with the prodromal questionnaire -brief version (PQ-B), PDQ-SPD, and interviewed by Structured Interview for Prodromal Symptoms (SIPS). Subjects with family history of mental disorders or with psychosis reported significantly higher scores in SPD. Receiver operating characteristic curves suggested that PDQ-SPD had moderate sensitivity and specificity for identifying CHR subjects. There was significant higher on SPD features in subjects with early stage (Course less than 1 year) of psychosis. Identifying SPD may be useful in early detection of psychosis especially in detecting the genetic risk syndromes and can be integrated with existing prodromal screen tools to improve its efficiency.

Family-focused treatment improves attenuated psychotic symptoms, but does not differ from brief treatment in negative symptoms and social functioning in ultra high risk patients aged 12–35 years

ABSTRACT FROM: Miklowitz DJ, O'Brien MP, Schlosser DA, et al . Family-focused treatment for adolescents and young adults at high risk for psychosis: results of a randomized trial. J Am...