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

OBJECTIVE: Widespread 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. METHODS: 38 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. RESULTS: Participants 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. CONCLUSION: CHR-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.

Burden Experienced by Primary Caregivers of Children With Psychotic Disorders and at Clinical High Risk for Psychosis.

BACKGROUND: Despite the existing research exploring caregiver burden in adult psychosis, few studies have examined the experience of providing care to children diagnosed with psychotic disorders (PDs) and those identified as having clinical high risk for psychosis (CHR-P). OBJECTIVE: This study measured the level of burden in caregivers of children with PD and CHR-P and examined associated risk factors, including social support, caregiver-child relationship, severity of illness, and frequency of psychiatric hospitalizations. METHODS: A total of 56 caregivers completed validated measures and provided demographic information. Measures included the Zarit Burden Interview, the Multidimensional Scale of Perceived Social Support, the Behavior Assessment System for Children, Third Edition, Parenting Relationship Questionnaire-Child and Adolescent Form (BASC-3 PRQ-CA), and the Clinical Global Impression-Severity scale. RESULTS: The majority of caregivers were women (86%), mothers (84%), White (63%), married (66%), working full-time (50%), college-educated (79%), and whose mean age was 45.7 years (SD = 8.09). Nearly half of the caregivers (45%) reported a high level of caregiver burden, 39% rated their burden in the mild to moderate range, and 16% reported little to no burden. There was no significant difference in mean burden between PD and CHR-P groups. Higher caregiver burden was associated with lower levels of social support (r = -.408, p = .002), lower levels of parenting confidence (r = -.514, p < .001), higher levels of relational frustration (r = .612, p < .001), and higher severity of illness (r = .316 p = .025). CONCLUSIONS: These findings underscore the critical unmet need for support for caregivers of children with PD and CHR-P. Applications to clinical practice are discussed.

Similar Rates of Deleterious Copy Number Variants in Early-Onset Psychosis and Autism Spectrum Disorder.

OBJECTIVE: Copy number variants (CNVs) are strongly associated with neurodevelopmental and psychotic disorders. Early-onset psychosis (EOP), where symptoms appear before 18 years of age, is thought to be more strongly influenced by genetic factors than adult-onset psychotic disorders. However, the prevalence and effect of CNVs in EOP is unclear. METHODS: The authors documented the prevalence of recurrent CNVs and the functional impact of deletions and duplications genome-wide in 137 children and adolescents with EOP compared with 5,540 individuals with autism spectrum disorder (ASD) and 16,504 population control subjects. Specifically, the frequency of 47 recurrent CNVs previously associated with neurodevelopmental and neuropsychiatric illnesses in each cohort were compared. Next, CNV risk scores (CRSs), indices reflecting the dosage sensitivity for any gene across the genome that is encapsulated in a deletion or duplication separately, were compared between groups. RESULTS: The prevalence of recurrent CNVs was significantly higher in the EOP group than in the ASD (odds ratio=2.30) and control (odds ratio=5.06) groups. However, the difference between the EOP and ASD groups was attenuated when EOP participants with co-occurring ASD were excluded. CRS was significantly higher in the EOP group compared with the control group for both deletions (odds ratio=1.30) and duplications (odds ratio=1.09). In contrast, the EOP and ASD groups did not differ significantly in terms of CRS. CONCLUSIONS: Given the high frequency of recurrent CNVs in the EOP group and comparable CRSs in the EOP and ASD groups, the findings suggest that all children and adolescents with a psychotic diagnosis should undergo genetic screening, as is recommended in ASD.

Multi-informant reports of depressive symptoms and suicidal ideation among adolescent inpatients.

OBJECTIVE: Suicide is a leading cause of death among adolescents, and suicidal thoughts represent key predictors to suicidal behavior. Yet, suicidal thoughts can be challenging to accurately assess. Symptoms that commonly co-occur with suicidal thoughts, such as depressive symptoms, may provide valuable information for predicting these thoughts. Although clinicians commonly collect multi-informant reports about adolescent depressive symptoms, these reports often yield discrepant findings as individual predictors of adolescents' suicidal thoughts. METHOD: We tested the ability of specific patterns of multi-informant reports to predict adolescents' suicidal thoughts. Ninety adolescent inpatients and their parents (i.e., "dyads") reported on adolescent depressive symptoms, and adolescents completed self-report assessments of suicidal thoughts at baseline and three-month follow-up. RESULTS: Dyads displayed variability in reporting patterns, and these patterns uniquely predicted suicidal thoughts. Adolescents reporting elevated depressive symptoms displayed increased concurrent suicidal thoughts relative to adolescents reporting subthreshold depressive symptoms, regardless of parent report. Yet, only adolescents who reported elevated depressive symptoms and whose parents reported subthreshold adolescent depressive symptoms displayed increased future suicidal thoughts. CONCLUSIONS: Identifying patterns of multiple informants' reports about adolescent depressive symptoms may improve the prediction of suicidal thoughts. These findings have important implications for assessing adolescents at risk for suicide.

Depressive symptom screening and endorsement of psychosis risk-related experiences in a diverse adolescent and young adult outpatient clinic in the US.

BACKGROUND: Early identification and intervention is a gold standard for psychotic disorders, for which delays in care can have serious consequences. Screening for psychosis in primary care may circumvent barriers related to stigma and facilitate shorter pathways to care. Yet, there is debate regarding the benefit-risk balance for psychosis screening in general adolescent populations. METHODS: Primary care patients of an adolescent/young adult medical clinic in the US ages 14-21 self-administered surveys assessing age, sex, receipt of psychotherapy, and occurrence, frequency (1-5), and distress (0-3) for 23 psychosis risk (PR) symptoms, including 6 general/nonspecific items and 17 psychosis-specific items. Participants also completed the 9-item Patient Health Questionnaire (PHQ-9); scores of ≥10 suggested clinically significant depressive symptoms. Analyses characterized PR symptoms and examined associations of PR symptom distress with current therapy and depressive symptom severity. RESULTS: Of 212 patients who completed the survey, 75% endorsed ≥1 PR symptom and 27% rated ≥3 on distress for psychosis-specific items. Those with high PHQ-9 scores reported higher PR distress overall (t = -6.1, df = 52.3, p < 0.001) but not on psychosis-specific items such as hallucinations and suspiciousness. One in 9 participants reported heightened PR distress without being in therapy or having high depressive symptoms. CONCLUSIONS: Most adolescents in this primary care sample endorsed symptoms associated with PR. Distress related to these symptoms was less common but occurred even in the absence of depressive symptoms. PR screening only in youth with high depressive symptom screens or in mental health care may miss youth needing further assessment for psychosis.

RCL1 copy number variants are associated with a range of neuropsychiatric phenotypes.

Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants having a large effect, offering opportunities for genetic discoveries and early therapeutic interventions. Here, the index case is an 18-year-old boy, who at 14 years of age had a decline in cognitive functioning over the course of a year and subsequently presented with catatonia, auditory and visual hallucinations, paranoia, aggression, mood dysregulation, and disorganized thoughts. Exome sequencing revealed a stop-gain mutation in RCL1 (NM_005772.4:c.370 C > T, p.Gln124Ter), encoding an RNA 3'-terminal phosphate cyclase-like protein that is highly conserved across eukaryotic species. Subsequent investigations across two academic medical centers identified eleven additional cases of RCL1 copy number variations (CNVs) with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1 contributes to a range of neurological and clinical phenotypes.

Implementing Evidence-Based Treatments for Youth in Acute and Intensive Treatment Settings.

Evidence-based treatments (EBTs) have been well studied in outpatient and research settings to address a myriad of mental health concerns. Research studies have found benefits and challenges when implementing these interventions. However, less is known about the implementation of EBTs in acute and intensive treatment settings such as inpatient psychiatric hospitalization (IPH) units, partial hospitalization programs (PHPs), or intensive outpatient programs (IOPs). As a result, the specific benefits and challenges of providing EBTs in these settings are less clear. For example, challenges of implementing EBTs in IPHs, PHPs, and IOPs can include working within a multi-disciplinary team setting and sustaining trained staff. The current article provides an overview of implementing EBTs in IPHs PHPs, and IOPs. Current PHP, IOP, and IPH models of implementing evidence-based interventions along with strategies for engaging stakeholders, program development and implementation, and measurement are reviewed. Further considerations for sustainability and practice consideration are also provided.

Does function predict persistence? Nonsuicidal self-injury among adolescents during and after hospitalization.

Nonsuicidal self-injury (NSSI) is a prevalent, concerning behavior among adolescents. Importantly, NSSI can serve a variety of functions. Some adolescents engage in NSSI to fulfill automatic or self-oriented functions (e.g., cutting to avoid internal negative states), whereas others engage in NSSI to serve social functions (e.g., cutting to communicate with others). This study tests whether self-reported reasons for engaging in NSSI, hereafter referred to as NSSI functions, predict NSSI thoughts and behaviors during and after hospitalization among adolescent psychiatric inpatients. Endorsement of both automatic and social NSSI functions, as well as positive and negative reinforcement subtypes, was assessed at hospital admission. Results showed that endorsement of overall automatic function predicted which adolescents engaged in NSSI behavior during hospitalization. Moreover, automatic and social functions showed distinct predictive patterns, such that automatic functions corresponded to greater likelihood of NSSI-related thoughts and behaviors whereas social functions mainly corresponded to reduced likelihood of NSSI-related outcomes. Of note, NSSI functions were less predictive of NSSI-related outcomes after hospital discharge. These findings suggest that identifying adolescent inpatients' reasons for NSSI engagement may meaningfully distinguish those at higher risk (and those at lower risk) of NSSI persistence during their hospital stay.

P300 amplitude attenuation in high risk and early onset psychosis youth.

Little research has investigated the use of electrophysiological biomarkers in childhood and adolescence to distinguish early onset psychosis and the clinical high risk state. The P300 evoked potential is a robust neurophysiological marker of schizophrenia that is dampened in patients with schizophrenia and, less consistently, in those with affective psychoses and those at clinical high risk for psychosis (CHR). How it may differ between patients with psychotic disorders (PS) and CHR is less studied, especially in youth. The current study compared P300 activity among children and adolescents, aged 5-18 years, at CHR (n = 43), with PS (n = 28), and healthy controls (HC; n = 24). Participants engaged in an auditory event-related potential (ERP) task to elicit a P300 response and completed clinical interviews to verify symptoms and diagnoses. Linear regression analyses revealed a decrease in P300 amplitude with increased severity of psychotic symptoms. PS participants showed a diminished P300 response compared to those at CHR and HC, particularly among adolescents aged 13-18. This response was most evident at centroparietal and parietal locations in the right hemisphere. The findings suggest that high risk and psychotic symptomatology is linked to attenuated parietal P300 activity in youth as young as 13 years. Further exploration of the P300 as a biomarker for psychosis in very young patients could inform tailored, appropriate interventions at early stages of disease progression. Future research should evaluate whether specific phenotypic and genotypic characteristics are differentially associated with neurophysiological biomarkers and whether P300 attenuation in CHR youth can predict later symptom severity.

Implicit Cognitions as a Behavioral Marker of Suicide Attempts in Adolescents.

Using self-harm Implicit Association Tests (IATs), we sought to test whether (1) suicidal adolescents show implicit identification with self-harm and whether (2) IATs are reliable and sensitive to psychiatric change and (3) predict future suicide attempts. We administered 6 self-harm IATs to 71 adolescents from a psychiatric inpatient unit and assessed suicidal behaviors at admission, discharge and 3 months after discharge. Results were in the expected direction for each IAT but not statistically significant. After aggregating trials across IATs, suicide attempters showed increased implicit identification with self-harm, compared with non-suicidal controls. IATs showed good reliability and sensitivity to psychiatric change but did not prospectively predict suicide attempts. Adolescent suicide attempters may have stronger implicit associations with self-harm than non-suicidal controls.

Potentially traumatic events in youth with and at clinical high risk for psychosis.

AIM: Previous research has demonstrated a strong association between early trauma exposure and the development of psychotic symptoms. However, few of these studies have included young adolescents and children. This study investigated rates and number of potentially traumatic experiences (PTEs) among typically developing youth (TD; n = 21), youth at clinical high risk for psychosis (CHR; n = 38), and youth with a psychotic disorder (PD; n = 28) between 7 and 18 years of age. CHR participants were further evaluated to determine whether a history of PTEs was associated with prodromal symptom severity. METHODS: Study group inclusion was determined by structured interviews. Trauma history was assessed using the post-traumatic stress disorder module of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. CHR participants with vs without a history of PTEs were compared on severity of prodromal symptoms. RESULTS: CHR and PD participants reported significantly higher rates and numbers of PTEs than TD participants. Contrary to expectations and prior research, CHR participants with vs without a history of PTEs did not differ in prodromal symptom severity. Explanations and implications for the findings are discussed. CONCLUSIONS: These findings suggest that the relationship between trauma and the development of psychotic symptoms extends to children and adolescents as young as 7 years of age. This study underscores the importance of screening for trauma exposure among youth seeking treatment for psychotic symptoms.

Social impairment and social language deficits in children and adolescents with and at risk for psychosis.

INTRO: One of the more debilitating functional outcomes of schizophrenia-spectrum disorders is social impairment. Previous studies have identified impaired social functioning both in the prodromal phase of psychosis and after acute symptoms abate, suggesting that social impairment represents a core deficit in psychosis not directly linked to psychotic episodes or symptom severity. To date, research in this area has focused primarily on adult populations rather than children, and has not directly assessed social language in individuals across the psychosis continuum. METHODS: 81 youth ages 7-18 (N = 24 Typically Developing [TD], N = 36 Clinical High Risk [CHR], N = 21 Psychotic Disorder [PD]) were recruited. Youth participants were administered the Social Language Development Test (SLDT), and parent(s)/guardian(s) completed the Social Responsiveness Scale-II (SRS-II). RESULTS: Social language ability was not associated with social impairment. PD participants performed significantly worse on the SLDT than TD participants. CHR and PD participants were both rated as having experienced significantly greater social impairment than TD participants on every subscale of the SRS-II. DISCUSSION: Deficits in social language ability and social functioning are strong candidates for phenotypic markers of psychosis, and may be evident earlier in development than previous work has demonstrated. Additionally, the severity of social impairment did not differ between CHR and PD participants, further supporting that social cognitive deficits and social impairment, while related to symptom severity, are discrete deficits in individuals with and at risk for psychosis. These results highlight the importance of addressing social skills for individuals presenting in clinical settings with psychotic symptoms, including children.

De novo variant of TRRAP in a patient with very early onset psychosis in the context of non-verbal learning disability and obsessive-compulsive disorder: a case report.

BACKGROUND: TRRAP encodes a multidomain protein kinase that works as a genetic cofactor to influence DNA methylation patterns, DNA damage repair, and chromatin remodeling. TRRAP protein is vital to early neural developmental processes, and variants in this gene have been associated with schizophrenia and childhood disintegrative disorder. CASE PRESENTATION: Here, we report on a patient with a de novo nonsynonymous TRRAP single-nucleotide variant (EST00000355540.3:c.5957G > A, p.Arg1986Gln) and early onset major depression accompanied by a psychotic episode (before age 10) that occurred in the context of longer standing nonverbal learning disability and a past history of obsessions and compulsions. CONCLUSIONS: The de novo variant and presentation of very early onset psychosis indicate a rare Mendelian disorder inheritance model. The genotype and behavioral abnormalities of this patient are reviewed.

Young children with psychotic symptoms and risk for suicidal thoughts and behaviors: a research note.

OBJECTIVE: Suicidal thoughts and behaviors (STBs) are prevalent among youth with psychotic disorders (PD) relative to the general population. Recent research now suggests that STBs may present during the prodromal phase of the disease, or the clinical high risk (CHR) state. While this knowledge is important for the development of suicide prevention strategies in adolescent and adult populations, it remains unclear whether risk for suicide extends to children with or at risk for psychosis. The current study is an extension of previous work assessing STBs in youth across the psychosis continuum. We examine STBs in 37 CHR and PD children ages 7-13 years old, and further explore the prodromal symptom correlates of STB severity among CHR children. RESULTS: CHR and PD children endorsed STBs with a frequency and severity similar to what is observed in older CHR and PD populations. A number of children had never previously vocalized their suicidal plans or intent. Among CHR children, Social Anhedonia and Odd Behavior or Appearance were significantly correlated with STB severity. These findings underscore the importance of screening for STBs even in young children presenting with psychotic symptoms.

De novo ATP1A3 and compound heterozygous NLRP3 mutations in a child with autism spectrum disorder, episodic fatigue and somnolence, and muckle-wells syndrome.

Complex phenotypes may represent novel syndromes that are the composite interaction of several genetic and environmental factors. We describe an 9-year old male with high functioning autism spectrum disorder and Muckle-Wells syndrome who at age 5  years of age manifested perseverations that interfered with his functioning at home and at school. After age 6, he developed intermittent episodes of fatigue and somnolence lasting from hours to weeks that evolved over the course of months to more chronic hypersomnia. Whole exome sequencing showed three mutations in genes potentially involved in his clinical phenotype. The patient has a predicted pathogenic de novo heterozygous p.Ala681Thr mutation in the ATP1A3 gene (chr19:42480621C>T, GRCh37/hg19). Mutations in this gene are known to cause Alternating Hemiplegia of Childhood, Rapid Onset Dystonia Parkinsonism, and CAPOS syndrome, sometimes accompanied by autistic features. The patient also has compound heterozygosity for p.Arg490Lys/p.Val200Met mutations in the NLRP3 gene (chr1:247588214G>A and chr1:247587343G>A, respectively). NLRP3 mutations are associated in an autosomal dominant manner with clinically overlapping auto-inflammatory conditions including Muckle-Wells syndrome. The p.Arg490Lys is a known pathogenic mutation inherited from the patient's father. The p.Val200Met mutation, inherited from his mother, is a variant of unknown significance (VUS). Whether the de novoATP1A3mutation is responsible for or plays a role in the patient's episodes of fatigue and somnolence remains to be determined. The unprecedented combination of two NLRP3 mutations may be responsible for other aspects of his complex phenotype.

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

BACKGROUND: Previous 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. METHODS: Eighty-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). RESULTS: Findings 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. CONCLUSION: Suicidal 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.

Social cognitive impairment in 22q11 deletion syndrome: A review.

Individuals with 22q11.2 deletion syndrome (22q11DS) exhibit a broad array of physical and psychiatric features, of which impaired social cognition and poor social functioning are common. This review seeks to (1) characterize the current understanding of impairment across social cognitive domains in the context of 22q11DS, and (2) synthesize the relevant literature on social cognition and psychosis, given that the prevalence of psychosis in 22q11DS is especially high compared to the general population. A total of 16 papers examining social cognition in 22q11DS were identified through a comprehensive literature search conducted using electronic databases such as PubMed and PSYCInfo. Results suggest that individuals with 22q11DS exhibit impaired emotion processing and complex theory of mind relative to their typically developing peers, though some findings were accounted for by neurocognitive and intellectual abilities. Further, no studies have examined the domains of attribution bias or social perception in 22q11DS, highlighting a critical gap in the extant literature. More research is needed to better elucidate the trajectory of how and why social cognitive impairment develops in 22q11DS, and to explore possible relationships to psychiatric comorbidities like psychosis. Treatment implications and future steps are considered.

A Developmental Perspective on Social-Cognition Difficulties in Youth at Clinical High Risk for Psychosis.

LEARNING OBJECTIVES: After participating in this activity, learners should be better able to:• Evaluate the evolution of social cognitive abilities as a developmental process• Assess the evidence regarding social cognition difficulties in youth at clinical high risk for psychosisIndividuals at clinical high risk (CHR) for psychosis exhibit a broad range of difficulties, including impaired social cognition, which may represent a target for early identification and intervention. Several studies have examined various domains of social cognition in CHR individuals. Most focus on adolescent and young adult populations, but given the accumulating evidence that impairment exists before the onset of psychotic disorders, it is critically important to begin to look for these risk markers in younger children. The present article reviews 25 studies on CHR that examine any of the following four domains of social cognition: emotion processing, theory of mind, social perception, or attribution bias. Eligible studies were identified through a comprehensive literature search, conducted using electronic databases, including PubMed/MEDLINE and PsycINFO, and combinations of key social-cognition and CHR search terms. Despite some mixed results, the existing literature establishes that CHR individuals display social-cognitive impairment, though it remains unclear as to how and when that impairment develops. Thus, by using the literature on social cognition in typically developing children as a model and reference, and by looking at the evolution of social-cognitive abilities as a developmental process, our review presents a valuable new perspective that indicates the necessity of further investigation in younger, at-risk populations. Implications for treatment and future research are discussed.