Quantification of HPV16 E7 Oncoproteins in Urine Specimens from Women with Cervical Intraepithelial Neoplasia.

We present the validity of using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) for quantifying high-risk human papillomavirus (HPV) 16 E7 oncoproteins in urine specimens as a noninvasive method of analyzing the oncogenic activity of HPV. Some reports claim that the oncogenic activity of HPV is a more relevant clinical indicator than the presence of HPV DNA for estimating malignant potential. In the present study, urine containing HPV16 and related types were selected by uniplex E6/E7 polymerase chain reaction and classified according to the pathologic diagnosis of cervical intraepithelial neoplasia (CIN) in cervical biopsy specimens. Our ultrasensitive ELISA was able to detect attomole levels of HPV16 E7 oncoproteins, and it detected HPV16-positive SiHa cells at >500 cells/mL without detecting HPV18-positive cells. Our ELISA results showed E7 oncoproteins in 80% (4/5) of urine specimens from women with HPV16-positive CIN1, 71% (5/7) of urine specimens from CIN2 patients, and 38% (3/8) of urine specimens from CIN3 patients. Some urine specimens with undetectable E7 oncoproteins were thought to be negative for live HPV 16-positive cells or in an inactivated state of infection. These results provide the basis for assessing oncogenic activity by quantifying E7 oncoproteins in patient urine.

The Mental Health Toll of the COVID-19 Pandemic on Adolescents Receiving Inpatient Psychiatric Treatment.

Objective: During the COVID-19 pandemic, the prevalence of depression and anxiety among children and adolescents significantly increased, along with the number of visits to emergency departments due to suicidality and/or suicide attempts. Relatedly, health care workers experienced significant burnout and symptoms of anxiety, depression, and posttraumatic stress disorder during this time. However, the corresponding impact on psychiatric inpatient treatment has not yet been researched. We hypothesized that during the pandemic, adolescents hospitalized in an acute care psychiatric inpatient unit had increased incidents of suicide attempts and nonsuicidal self-injurious behaviors and of aggressive behaviors toward others, resulting in greater use of constant observation and restraints. Method: This study was a retrospective chart review based on electronic medical record data examining use of restraints and constant observation one year before the pandemic (March 2019 to February 2020) and 1 year following the onset of the pandemic (March 2020 to February 2021) in an acute-care adolescent (12 to 17 years old) psychiatric inpatient unit. Results: There were 571 admissions during the year before the pandemic and 500 admissions during the pandemic. The number of patients who were restrained (χ2 = 7.86, p = 0.005), number of patients who were placed on constant observation (χ2 = 13.41, p < 0.001), and number of constant observation orders per patient (χ2 = 91.90, p < 0.001) were all significantly greater during the pandemic. Conclusion: Psychiatrically hospitalized adolescents during the pandemic received more intensive interventions such as restraints and constant observation. Severe patient psychopathology and staff shortages, as well as limitations of and decreases to the dialectical behavior therapy program, may have been the contributing factor.

Race-Based Disparities in the Frequency and Duration of Restraint Use in a Psychiatric Inpatient Setting.

OBJECTIVE: Patients' race and age have each been identified as risk factors for experiencing restraint events during psychiatric hospitalization. Restraint duration is also an important variable in determining disparities in treatment. To the authors' knowledge, no studies to date have examined the effect of the interaction of race and age on restraint use and duration in inpatient psychiatric settings. This retrospective chart review of electronic medical records of patients admitted between 2012 and 2019 sought to examine whether race and age interacted in predicting differences in the use and duration of restraints in a psychiatric inpatient setting. METHODS: Logistic and hierarchical regression analyses were conducted on data from a sample of 29,739 adolescent (ages 12-17 years) and adult (ages ≥18 years) inpatients to determine whether the interaction of race and age group (adolescent or adult) significantly predicted a restraint event or differences in restraint duration. RESULTS: Black (adjusted OR [AOR]=1.85) and multiracial (AOR=1.36) patients were more likely to experience a restraint event than were their White peers. Black race was also significantly (p=0.001) associated with longer restraint duration. No significant interaction was detected between race and age in predicting restraint events or duration. CONCLUSIONS: Although the interaction between race and age did not predict restraint events or duration, the findings indicate racial disparities in the frequency and duration of restraint events among Black and multiracial individuals and may inform efforts to reduce these events.

Racial and ethnic inequities in psychiatric inpatient building and unit assignment.

Racism is a social determinant of mental health which has a disproportionally negative impact on the experiences of psychiatric inpatients of color. Distinct differences in the physical space and clinical settings of two inpatient buildings at a hospital system in the tristate (New York, New Jersey, Connecticut) area of the United States led to the present investigation of racial inequities in the assignment of patients to specific buildings and units. Archival electronic medical record data were analyzed from over 18,000 unique patients over a period of six years. Hierarchical logistic regression analyses were conducted with assigned building (old vs. new building) as the binary outcome variable. Non-Hispanic White patients were set as the reference group. Black, Hispanic/Latinx, and Asian patients were significantly less likely to be assigned to better resourced units in the new building. When limiting the analysis to only general adult units, Black and Hispanic/Latinx patients were significantly less likely to be assigned to units in the new building. These results suggest ethnoracial inequities in patient assignment to buildings which differed in clinical and physical conditions. The findings serve as a call to action for hospital systems to examine the ways in which structural racism impact clinical care.

Symptoms and Characteristics of Youth Hospitalized for Depression: Subthreshold Manic Symptoms Can Help Differentiate Bipolar from Unipolar Depression.

Background: Most people who have major depressive disorder (MDD) or bipolar disorder (BD) will have their first episode of depression in adolescence. However, in the absence of significant [hypo]manic symptoms, there are no clear guidelines for distinguishing bipolar from unipolar depression, which can lead to misdiagnosis and ineffective/harmful treatment. We aimed to compare phenomenological differences among youth with MDD or BD hospitalized for an acute episode of depression. Methods: A retrospective electronic chart review of adolescents hospitalized in an acute care inpatient unit who had a discharge diagnosis of MDD, MDD with mixed or psychotic features (MDD+), BD-I-current episode depressed, or BD-II-current episode depressed, was performed. Results: Altogether, 598 patients (mean age = 15.1 ± 1.5 years, female = 71%, and White = 46%) met study inclusion criteria, i.e., BD-I: n = 39, BD-II: n = 84, MDD: n = 422, and MDD+: n = 53 patients. The admission Hamilton Depression Rating Scale (HAMD) total score was significantly higher in the BD-I (29.3 ± 9.1) and MDD+ (31.2 ± 9.3) groups versus the MDD group (24.3 ± 9.7) (p < 0.05). Although there were some group differences in the severity of individual depression symptoms, these did not line up neatly across BD and MDD groups. At admission, Young Mania Rating Scale (YMRS) total scores were significantly higher in the BD-I (14.4 ± 7.4), BD-II (13.8 ± 6.5), and MDD+ groups (14.3 ± 6.6) versus the MDD group (8.2 ± 4.6, p < 0.05). Additionally, 9 of 11 and 4 of 11 YMRS items scored significantly higher in the BD-II and BD-I groups versus the MDD group, respectively. The motor activity and hypersexuality items, in particular, were scored consistently higher in the BD groups than MDD groups. Limitations: All diagnoses were made based on a clinical interview and not a structured diagnostic interview, and some of the subgroup sample sizes were relatively modest, limiting the power for group comparisons. Conclusion: The presence of subsyndromal manic symptoms during an episode of MDD currently offers the clearest way by which to differentiate bipolar depression from unipolar depression.

Efficacy and sustainability of dialectical behaviour therapy for inpatient adolescents: a follow-up study.

BACKGROUND: Dialectical behaviour therapy (DBT) is an evidence-based treatment for adolescents targeting suicidal and non-suicidal self-injurious behaviours. Research supports DBT's efficacy in inpatient settings, but implementation and sustainability are understudied. AIMS: This study is a follow-up of a previous study by Tebbett-Mock et al and examines the efficacy and sustainability of an adolescent DBT inpatient unit within a psychiatric hospital in the Northeast. We hypothesised that adolescents who received DBT in our follow-up group (DBT Group 2) would not have statistical difference (ie, greater or fewer) of the following compared with the first group of patients who received DBT on the unit the year prior (DBT Group 1) and would have significantly fewer of the following compared with the treatment as usual (TAU) group: (1) constant observation hours for suicidal ideation, self-injury and aggression; (2) incidents of suicide attempts, self-injury and aggression; (3) restraints; (4) seclusions; (5) days hospitalised; (6) times readmitted to the unit within 30 days of discharge. METHODS: We conducted a retrospective chart review for adolescents receiving inpatient DBT (DBT Group 1, n=425; DBT Group 2, n=393) and a historical control group (TAU, n=376). The χ2 tests and one-way analysis of variance were conducted as preliminary analyses to examine group differences on diagnosis, gender and age. Kruskal-Wallis H tests were conducted to examine group differences on outcomes. Mann-Whitney U tests were used as post hoc analyses. RESULTS: Patients in DBT Group 2 were comparable to DBT Group 1 for the number of constant observation hours for self-injury (U=83 432.50, p=0.901), restraints (U=82 109, p=0.171) and days hospitalised (U=83 438.5, p=0.956). Patients in DBT Group 2 had a significantly greater number of incidents of suicide attempts compared with DBT Group 1 (U=82 662.5, p=0.037) and of self-injury compared with patients in DBT Group 1 (U=71724.5, p<0.001) and TAU (U=65649.0, p<0.001). CONCLUSIONS: Results provide support for adolescent inpatient DBT compared with TAU and highlight staff turnover and lack of training as potential barriers to sustainability and efficacy.

First case of molecularly identified and genetically characterized human T-cell leukemia virus type 2 infection in a pregnant woman in non-endemic Japan.

Human T-cell leukemia virus type 2 (HTLV-2) is non-endemic in Japan unlike the related HTLV type 1. Previously, although HTLV-2-seropositivity was identified via western blotting in one male blood donor in Japan, there have been no reports of HTLV-2 provirus detection by nucleic acid testing. In this report, one Japanese pregnant woman was clinically diagnosed as being HTLV-2-infected with a line immunoassay for specific antibodies after primary testing through prenatal screening in Japan. In genomic DNA of her peripheral blood mononuclear cells, HTLV-2 proviral genome was detected by nucleic acid testing (three methods) with quantitative polymerase chain reaction. The full-genome sequence of this strain was successfully determined. The identified virus was interestingly characterized as a presumed progenitor of subtypes a and c by recombination region and phylogenetic tree analyses. In conclusion, the present infection is, to our knowledge, the first case of molecularly identified and genetically characterized HTLV-2 infection found via prenatal screening in non-endemic Japan.

Lessons Learned From a Mental Health Hospital: Managing COVID-19.

Congregate settings such as psychiatric units have an increased risk of disease transmission because of the milieu setting and the inability to isolate patients. Interventions to prevent infection and cross-contamination are discussed including monitoring of patient temperatures, personal protective equipment, remote care, monitoring of human resources, and reinforcement of infection prevention strategies. We discuss the effectiveness of those interventions and the lessons learned, including implications for psychiatric clinical care, during future pandemics or a next wave of COVID-19.

Dialectical Behavior Therapy Decreases Depressive Symptoms Among Adolescents in an Acute-Care Inpatient Unit.

Objective: Research has shown that dialectical behavior therapy (DBT) is an effective treatment modality to decrease suicidal ideation, incidents of nonsuicidal self-injurious behavior, and suicide attempts in an adolescent outpatient population. However, research on the impact of DBT on depressive and manic symptoms for adolescents and within an inpatient setting is limited. The purpose of this study is to examine whether DBT significantly decreases depressive and manic symptoms compared with treatment as usual (TAU) for inpatient adolescents. Method: We conducted a retrospective chart review for adolescents receiving inpatient DBT and for a historical control group on the same unit before DBT (i.e., TAU). Group differences for continuous outcomes were analyzed using analysis of covariance (ANCOVA), where discharge scores for Hamilton Depression Rating Scale (HAMD), Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity for Symptoms (CGI-S), and Dynamic Appraisal of Situational Aggression (DASA) were predicted by treatment condition (i.e., DBT and TAU) while co-varying for admission scores and using a t test for CGI-Improvement (CGI-I) in functioning, which was administered upon discharge. Results: Patients who received DBT had significantly lower HAMD scores, F(1, 409) = 5.272, p = 0.022, ηp2 = 0.013, and lower CGI-I scores, t(596) = 2.50, p = 0.00 upon discharge when controlling for admission scores, compared with patients who received TAU. ANCOVAs showed no significant differences on the YMRS, CGI-S, or DASA between the DBT and TAU groups. Conclusion: DBT on an acute-care inpatient unit for adolescents seems to significantly decrease depressive symptoms during a relatively short period of time compared with TAU. DBT may be an effective treatment modality to decrease depressive symptoms for acute-care inpatient units for adolescents.

Efficacy of Dialectical Behavior Therapy Versus Treatment as Usual for Acute-Care Inpatient Adolescents.

OBJECTIVE: Dialectical behavior therapy (DBT) is an evidence-based treatment that targets suicidal behavior and nonsuicidal self-injury (NSSI) and has been adapted for adolescents. Given the seriousness of these behaviors, many adolescents are psychiatrically hospitalized, but minimal research has been conducted on specific interventions during hospitalization. The goal of this study was to evaluate DBT versus treatment as usual (TAU) for adolescents on an acute-care psychiatric inpatient unit. METHOD: We conducted a retrospective chart review for adolescents receiving inpatient DBT (n = 425) and for a historical control group treated on the same unit before DBT (ie, TAU, n = 376). Both χ2 and t tests were conducted as preliminary analyses to examine differences between groups on diagnosis, sex, and age. Mann-Whitney U tests were conducted to examine differences between groups on outcome variables. The potential benefit of cost savings was analyzed. RESULTS: Patients who received DBT had significantly fewer constant observation (CO) hours for self-injury; incidents of suicide attempts and self-injury; restraints; and days hospitalized compared to patients who received TAU. Statistically significant differences were not found between DBT and TAU groups for number of CO hours for aggression, incidents of aggression toward patients or staff, seclusions, or readmissions. A cost analysis determined that $251,609 less was spent on staff time for CO hours with DBT compared to TAU. CONCLUSION: Results provide support for the implementation of DBT in an acute-care adolescent psychiatric inpatient unit for adolescents. Clinical implications, study limitations, and future research directions are discussed.

Pro Re Nata Medication Use in Acute Care Adolescent Psychiatric Unit.

Objective: Evidence to support the use of pro re nata (PRN) medication is limited, and the details of PRN use (indication, frequency of administration, patient characteristics) are rarely reported, particularly in youth populations. The goal of this study was to report on the pattern of PRN use over 6 years in an acute care psychiatric unit for adolescents. Methods: A retrospective chart review of patients' records from November 2012 to October 2018 was conducted. Variables extracted from electronic medical records included age, gender, race/ethnicity, clinical rating scores at admission (on a subset of patients), length of stay, psychotropic and nonpsychotropic PRN medication administration, timing of administration, discharge diagnosis, and discharge medication. Results: Records from 2961 individuals with a total 3937 admissions were analyzed. A total of 62% of admissions had at least one PRN medication administration. Severity of symptoms, as indicated by higher scores on clinical rating scales at admission, longer length of stay, and readmission were related to high PRN use. Patients with bipolar spectrum disorders received more psychotropic and nonpsychotropic PRN medications than other patients. Patients who were high psychotropic PRN users were also high nonpsychotropic PRN users. Conclusion: Despite the lack of clear evidence in support of the efficacy of PRN medications, they commonly used to control symptoms in acute care inpatient settings. Youth with severe symptoms utilized not only psychotropic PRN medication but also nonpsychotropic PRN more frequently, suggesting a possible role of systemic disorder among youth with serious mental illness. More research is necessary to examine the efficacy of PRN medications for managing targeted symptoms.

Changes in white matter microstructure predict lithium response in adolescents with bipolar disorder.

OBJECTIVES: To investigate whether response to lithium treatment in pediatric bipolar disorder can be predicted by changes in white matter microstructure in key cortico-limbic tracts involved in emotion regulation. METHODS: Eighteen clinically referred lithium-naive patients (mean age 15.5 years) were administered clinical rating scales and diffusion tensor imaging (DTI) examinations at baseline and following 4 weeks of lithium treatment. Clinical ratings were repeated following 8 weeks of treatment. Patients with Clinical Global Impressions (CGI) ratings of 1 ("very much improved") or 2 ("much improved") were classified as responders. Ten healthy volunteers received baseline and follow-up DTI examinations. Using the ENIGMA pipeline, we investigated the relationship between changes in fractional anisotropy (FA) in the cingulum hippocampus (CGH) and clinical response to lithium. RESULTS: Patients demonstrated significantly lower FA compared to healthy volunteers in the left and right CGH white matter at baseline. Following 4 weeks of lithium treatment, FA in the left CGH increased in patients, but no significant changes in FA were observed among the untreated healthy volunteers. Lithium responders had a significantly greater increase in FA compared to non-responders. Moreover, baseline (pre-treatment) FA in the left CGH white matter significantly predicted week 8 overall CGI severity score, with post hoc analyses indicating that these effects were evident for both severity of depression and mania. CONCLUSIONS: Our findings suggest that response to lithium treatment in pediatric bipolar disorder is associated with normalization of white matter microstructure in regions associated with emotion processing.

Correlates of Subjective Caregiver Strain in Caregivers of Youth Evaluated in a Pediatric Psychiatric Emergency Room.

BACKGROUND: Although caregiver burden is relevant to the outcome for psychiatrically ill youth, most studies have focused on caregiver burden in the community or research settings. Therefore, we aimed at evaluating the subjective caregiver strain (SCS) at the time of presentation of youth to a pediatric psychiatric emergency room (PPER), assessing potential correlates to provide leads for improvements in formal support systems. METHODS: In this retrospective cohort study, the internalized, externalized, and total SCS were assessed in caregivers of youth <18 years of age consecutively evaluated at a PPER during a 1 year period using the Caregiver Strain Questionnaire. Sociodemographic and a broad range of clinical data were collected during the PPER visit using a 12-page semistructured institutional evaluation form. The Appropriateness of Pediatric Psychiatric Emergency Room Contact scale, incorporating acuity, severity and harm potential, was used to rate appropriateness of the visit. RESULTS: In caregivers of 444 youth, the internalized SCS was significantly higher than the externalized SCS (p < 0.001). Multivariable analyses indicated that higher total and externalized SCS were associated with disruptive behavior or substance abuse/dependent disorder diagnosis, presenting complaint of aggression, and discharge plan to the police. Higher total and internalized SCS were associated with lower child functioning, whereas total and internalized SCS were lower in adopted children. In addition, higher externalized SCS was associated with investigator-rated inappropriateness of the emergency visit, presenting complaint of defiance, and a lack of prior psychiatric ER visits. CONCLUSIONS: High levels of CS in PPER highlight the necessity to adhere to existing guidelines regarding the inclusion of caregivers' perceptions into comprehensive psychiatric assessments. The particularly high strain in caregivers of children with externalizing disorders and in families with low-functioning youth may need to prompt PPER staff to provide efficient information on appropriate treatment options for these children and on support facilities for the parents.

Activating and Tranquilizing Effects of First-Time Treatment with Aripiprazole, Olanzapine, Quetiapine, and Risperidone in Youth.

OBJECTIVE: To assess activating and tranquilizing effects of second-generation antipsychotics (SGAs) in youth. METHODS: As part of the naturalistic inception cohort study, "Second-generation Antipsychotic Treatment Indication, Effectiveness and Tolerability in Youth (SATIETY)," subjective ratings of activating and tranquilizing symptoms were obtained monthly for 3 months from antipsychotic-naïve youth initiating SGAs using the Treatment Emergent Symptoms Scale (TESS). Discontinuation rates, and TESS-reported symptom rates, and severity were related to clinical and treatment parameters. Two compound measures of TESS were defined: presence of any daytime activating (ACTIVATION+) and sedating symptoms (SEDATION+). RESULTS: In 327 antipsychotic-naïve youth originally initiating the four studied SGAs, discontinuation due to sedation was marginally highest with quetiapine (13.0%) followed by olanzapine (7.3%), risperidone (4.2%), and aripiprazole (2.0%) (p = 0.056). Two hundred fifty-seven antipsychotic-naïve youth (13.8 ± 3.6 years, male = 57.8%) initiated aripiprazole (n = 40), olanzapine (n = 45), quetiapine (n = 36), or risperidone (n = 135) and completed ≥1 postbaseline follow-up visit. Baseline prevalence of ACTIVATION+ (39.9%) or SEDATION+ (54.1%) did not differ between SGAs. Rates of both compound measures changed significantly over time (decrease for ACTIVATION+, p = 0.0002; increase for SEDATION+, p < 0.0001) with slight differences between SGAs, explained by lower rates of ACTIVATION+ with olanzapine (p = 0.002) and slightly higher rates of ACTIVATION+ with aripiprazole (p = 0.018) during follow-up, and lower rates of SEDATION+ with aripiprazole (p = 0.018). All four SGAs reduced insomnia (p = 0.001) and increased hypersomnia (p < 0.001). Postbaseline prevalence of drowsiness, the most frequent, but mild TESS complaint was 85%, without SGA differences. Younger age was associated with activating symptoms, higher age with sedating symptoms, and lower baseline functioning increased both. Psychomotor retardation rates were high in subjects with schizophrenia-spectrum disorders, whereas stimulant comedication was associated with psychomotor activation, regardless of diagnosis. CONCLUSIONS: Although small SGA-specific differences in activating/sedating compound side effect measures were noted, independent predictors of single TESS ratings included clinical parameters, rather than specific SGAs, suggesting a need for carefully individualized treatment strategies.

Frequency and correlates of DSM-5 attenuated psychosis syndrome in a sample of adolescent inpatients with nonpsychotic psychiatric disorders.

OBJECTIVES: DSM-5 conceptualized attenuated psychosis syndrome (APS) as self-contained rather than as a risk syndrome, including it under "Conditions for Further Study," but also as a codable/billable condition in the main section. Since many major mental disorders emerge during adolescence, we assessed the frequency and characteristics of APS in adolescent psychiatric inpatients. METHODS: Consecutively recruited adolescents hospitalized for nonpsychotic disorders (September 2009-May 2013) were divided into APS youth versus non-APS youth, based on the Structured Interview of Prodromal Syndromes (SIPS) and according to DSM-5 criteria, and compared across multiple characteristics. RESULTS: Of 89 adolescents (mean ± SD age = 15.1 ± 1.6 years), 21 (23.6%) had APS. Compared to non-APS, APS was associated with more comorbid disorders (2.7 ± 1.0 vs 2.2 ± 1.3), major depressive disorder (61.9% vs 27.9%), oppositional defiant disorder/conduct disorder (52.4% vs 25.0%), and personality disorder traits (57.1% vs 7.4%, the only diagnostic category surviving Bonferroni correction). APS youth were more severely ill, having higher SIPS total positive, negative, and general symptoms; Brief Psychiatric Rating Scale total and positive scores; depression and global illness ratings; and lower Global Assessment of Functioning (GAF). Conversely, Young Mania Rating Scale scores, suicidal behavior, prescribed psychotropic medications, and mental disorder awareness were similar between APS and non-APS groups. In multivariable analysis, lowest GAF score in the past year (odds ratio [OR] = 51.15; 95% confidence interval [CI], 2.46-2,439.0) and social isolation (OR = 27.52; 95% CI, 3.36-313.87) were independently associated with APS (r(2) = 0.302, P < .0001). Although psychotic disorders were excluded, 65.2% (APS = 57.1%, non-APS = 67.7%, P = .38) received antipsychotics. CONCLUSION: One in 4 nonpsychotic adolescent inpatients met DSM-5 criteria for APS. APS youth were more impaired, showing a complex entanglement with a broad range of psychiatric symptoms and disorders, including depression, impulse-control, and, especially, emerging personality disorders. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01383915.

Outcome of Youth with Early-Phase Schizophrenia-Spectrum Disorders and Psychosis Not Otherwise Specified Treated with Second-Generation Antipsychotics: 12 Week Results from a Prospective, Naturalistic Cohort Study.

OBJECTIVES: The purpose of this study was to assess differences in the outcomes of youth with schizophrenia-spectrum disorders (SCZ-S) and psychotic disorder not otherwise specified (PsyNOS) during early antipsychotic treatment. METHODS: The study was a prospective, naturalistic, inception cohort study of youth ≤19 years old with SCZ-S (schizophrenia, schizoaffective disorder, schizophreniform disorder) or PsyNOS (PsyNOS, brief psychotic disorder) and ≤24 months of lifetime antipsychotic treatment receiving clinician's choice antipsychotic treatment. Baseline demographic, illness and treatment variables, and effectiveness outcomes were compared at 12 weeks last-observation-carried-forward across SCZ-S and PsyNOS patients, adjusting for significantly different baseline variables. RESULTS: Altogether, 130 youth with SCZ-S (n=42) or PsyNOS (n=88), mostly antipsychotic naïve (76.9%), were prescribed risperidone (47.7%), olanzapine (19.2%), aripiprazole (14.6%), quetiapine (11.5%), or ziprasidone (6.9%). Compared with those with PsyNOS, SCZ-S youth were older (16.4±2.1 vs. 14.8±3.2, p=0.0040), and less likely to be Caucasian (19.1% vs. 42.5%, p=0.009). At baseline, SCZ-S patients had significantly higher Clinical Global Impressions-Severity (CGI-S) scores (6.0±0.9 vs. 5.5±0.8, p=0.0018) and lower Children's Global Assessment Scale (CGAS) scores (29.6±9.2 vs. 36.1±8.9, p=0.0002) and were more likely to be in the severely ill CGAS group (i.e., CGAS≤40). SCZ-S and PsyNOS patients did not differ regarding all-cause discontinuation (40.5 vs. 40.3%. p=0.49), discontinuation because of adverse effects (12.2% vs. 12.4%, p=0.97), or nonadherence (29.3% vs. 30.9%, p=0.88), but somewhat more SCZ-S patients discontinued treatment for inefficacy (19.5% vs. 7.4%, p=0.063). CGI-S and CGAS scores improved significantly in both diagnostic groups (p=0.0001, each). Adjusting for baseline differences, PsyNOS patients experienced significantly better CGI-I improvement (CGI-I) scores (p=0.012) and more frequently reached higher categorical CGAS group status (p=0.021) than SCZ-S patients. CONCLUSIONS: Both youth with SCZ-S and those with PsyNOS experienced significant improvements with clinician's choice antipsychotic treatment. However, treatment discontinuation was common within 12 weeks, with greater inefficacy-related discontinuation in the SCZ-S group, whereas CGI-I and CGAS score-based improvements were greater in the PsyNOS group.

Neuromotor Adverse Effects in 342 Youth During 12 Weeks of Naturalistic Treatment With 5 Second-Generation Antipsychotics.

OBJECTIVE: Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS. METHOD: Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS. RESULTS: In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS. CONCLUSION: In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.

Suicidality and hospitalization as cause and outcome of pediatric psychiatric emergency room visits.

The aim of this study was to identify predictors of suicidality in youth presenting to a pediatric psychiatric emergency room service (PPERS). To this end, we conducted a retrospective cohort study of youth aged <18 years consecutively assessed by a PPERS 01.01.2002-12.31.2002, using a 12-page semi-structured institutional evaluation form and the Columbia Classification Algorithm for Suicide Assessment. Multivariate regression analyses were conducted to identify correlates of suicidal thoughts and attempts/preparation and their relationship to outpatient/inpatient disposition. Of 1,062 youth, 265 (25.0%) presented with suicidal ideation (16.2%) or attempt/preparation (8.8%). Suicidal ideation was associated with female sex, depression, adjustment disorder, absent referral by family/friend/self, school referral, precipitant of peer conflict, and no antipsychotic treatment (p < 0.0001). Suicidal attempt/preparation was associated with female sex, depression, lower GAF score, past suicide attempt, precipitant of peer conflict, and no stimulant treatment (p < 0.0001). Compared to suicidal attempt/preparation, suicidal ideation was associated with school referral, and higher GAF score (p < 0.0001). Of the 265 patients with suicidality, 58.5% were discharged home (ideation = 72.1% vs. attempt/preparation = 33.7%, p < 0.0001). In patients with suicidal ideation, outpatient disposition was associated with higher GAF score, school referral, and adjustment disorder (p < 0.0001). In patients with suicidal attempt/preparation, outpatient disposition was associated with higher GAF score, lower acuity rating, and school referral (p < 0.0001). Suicidality is common among PPERS evaluations. Higher GAF score and school referral distinguished suicidal ideation from suicidal attempt/preparation and was associated with outpatient disposition in both presentations. Increased education of referral sources and establishment of different non-PPERS evaluation systems may improve identification of non-emergent suicidal presentations and encourage more appropriate outpatient referrals.

Type and duration of subsyndromal symptoms in youth with bipolar I disorder prior to their first manic episode.

OBJECTIVES: The aim of the present study was to systematically evaluate the prodrome to mania in youth. METHODS: New-onset/worsening symptoms/signs of ≥ moderate severity preceding first mania were systematically assessed in 52 youth (16.2 ± 2.8 years) with a research diagnosis of bipolar I disorder (BD-I). Youth and/or caregivers underwent semi-structured interviews, using the Bipolar Prodrome Symptom Scale-Retrospective. RESULTS: The mania prodrome was reported to start gradually in most youth (88.5%), with either slow (59.6%) or rapid (28.8%) deterioration, while a rapid-onset-and-deterioration prodrome was rare (11.5%). The manic prodrome, conservatively defined as requiring ≥ 3 symptoms, lasted 10.3 ± 14.4 months [95% confidence interval (CI): 6.3-14.4], being present for ≥ 4 months in 65.4% of subjects. Among prodromal symptoms reported in ≥ 50% of youth, three were subthreshold manic in nature (irritability: 61.5%, racing thoughts: 59.6%, increased energy/activity: 50.0%), two were nonspecific (decreased school/work functioning: 65.4%, mood swings/lability: 57.7%), and one each was depressive (depressed mood: 53.8%) or subthreshold manic/depressive (inattention: 51.9%). A decreasing number of youth had ≥ 1 (84.6%), ≥ 2 (48.1%), or ≥ 3 (26.9%) 'specific' subthreshold mania symptoms (i.e., elation, grandiosity, decreased need for sleep, racing thoughts, or hypersexuality), lasting 9.5 ± 14.9 months (95% CI: 5.0-14.0), 3.5 ± 3.5 months (95% CI: 2.0-4.9), and 3.0 ± 3.2 months (95% CI: 1.0-5.0) for ≥ 1, ≥ 2, or ≥ 3 specific symptoms, respectively. CONCLUSIONS: In youth with BD-I, a relatively long, predominantly slow-onset mania prodrome appears to be common, including subthreshold manic and depressive psychopathology symptoms. This suggests that early clinical identification and intervention may be feasible in bipolar disorder. Identifying biological markers associated with clinical symptoms of impending mania may help to increase chances for early detection and prevention before full mania.

Prevalence and correlates of antipsychotic polypharmacy in children and adolescents receiving antipsychotic treatment.

Antipsychotic polypharmacy (APP), which is common in adults with psychotic disorders, is of unproven efficacy and raises safety concerns. Although youth are increasingly prescribed antipsychotics, little is known about APP in this population. We performed a systematic PubMed search (last update 26 January 2013) of studies reporting the prevalence of APP in antipsychotic-treated youth. Summary statistics and statistical tests were calculated at the study level and not weighted by sample size. Fifteen studies (n = 58 041, range 68-23 183) reported on APP in youth [mean age = 13.4 ± 1.7 yr, 67.1 ± 10.2% male, 77.9 ± 27.4% treated with second-generation antipsychotics (SGAs)]. Data collected in these studies covered 1993-2008. The most common diagnoses were attention-deficit hyperactivity disorder (ADHD; 39.9 ± 23.5%) and conduct disorder/oppositional defiant disorder (CD/ODD; 33.6 ± 24.8). In studies including predominantly children (mean age = <13 yr, N = 5), the most common diagnosis were ADHD (50.6 ± 25.4%) and CD/ODD (39.5 ± 27.5%); while in studies with predominantly adolescents (mean age = ⩾13 yr, N = 7) the most common diagnoses were schizophrenia-spectrum disorders (28.6 ± 23.8%), anxiety disorders (26.9 ± 14.9%) and bipolar-spectrum disorders (26.6 ± 7.0%), followed closely by CD/ODD (25.8 ± 17.7). The prevalence of APP among antipsychotic-treated youth was 9.6 ± 7.2% (5.9 ± 4.5% in child studies, 12.0 ± 7.9% in adolescent studies, p = 0.15). Higher prevalence of APP was correlated with a bipolar disorder or schizophrenia diagnosis (p = 0.019) and APP involving SGA+SGA combinations (p = 0.0027). No correlation was found with APP definition [⩾1 d (N = 10) vs. >30-⩾90 d (N = 5), p = 0.88]. Despite lacking safety and efficacy data, APP in youth is not uncommon, even in samples predominantly consisting of non-psychotic patients. The duration, clinical motivations and effectiveness of this practice require further study.