High Probability of Gene-Drug Interactions Associated with Medication Side Effects in Adolescent Depression: Results from a Randomized Controlled Trial of Pharmacogenetic Testing.

Introduction: Combinatorial pharmacogenetic testing panels are widely available in clinical practice and often separate medications into columns/bins associated with low, medium, or high probability of gene-drug interactions. The objective of the Adolescent Management of Depression (AMOD) study was to determine the clinical utility of combinatorial pharmacogenetic testing in a double-blind, randomized, controlled effectiveness study by comparing patients who had genetic testing results at time of medication initiation to those that did not have results until week 8. The objective of this post hoc analysis was to assess and report additional outcomes with respect to significant gene-drug interactions (i.e., a medication in the high probability gene-drug interaction bin as defined by a proprietary algorithm) compared with patients taking a medication with minimal to moderate gene-drug interactions (i.e., a medication from the low or medium probability gene-drug interaction bin, respectively). Methods: Adolescents 13-18 years (N = 170) with moderate to severe major depressive disorder received pharmacogenetic testing. Symptom improvement and side effects were assessed at baseline, week 4, week 8, and 6 months. Patients were grouped into three categories based on whether the medication they were prescribed was associated with low, medium, or high risk for gene-drug interactions. Patients taking a medication from the low/medium gene-drug interaction bin were compared with patients taking a medication from the high gene-drug interaction bin. Results: Patients taking a medication from the high gene-drug interaction bin were more likely to endorse side effects compared with patients taking a medication in the low/medium gene-drug interaction bin at week 8 (p = 0.001) and 6 months (p < 0.0001). Depressive symptom severity scores did not differ significantly across the medication bins. Conclusions: This study demonstrates the utility of gene-drug interaction testing to guide medication decisions to minimize side effect burden rather than solely prioritizing the search for the most efficacious medication. (Clinical Trials Registration Identifier: NCT02286440).

The Virtual Couch: a Curriculum on the Question of the Fundamentals of Remote Psychotherapy-Pilot Study.

OBJECTIVE: With a rise in remote clinical practice related to the COVID-19 pandemic, a novel remote psychotherapy curriculum was presented to psychiatry residents and fellows to address the urgent need to teach trainees how to adapt traditional psychotherapy skills to telepsychiatry settings. METHODS: Trainees completed a survey before and after receiving the curriculum to assess remote psychotherapy skills and areas for growth. RESULTS: Eighteen trainees (24% fellows, 77% residents) completed the pre-curriculum survey, and 28 trainees (26% fellows, 74% residents) completed the post-curriculum survey. Thirty-five percent of pre-curriculum participants indicated no experience with remote psychotherapy. Technology (24%) and patient engagement (29%) were identified as the greatest challenges in providing teletherapy pre-curriculum. Content related to patient care (69%) and technology (31%) was of most interest to pre-curriculum participants and identified as most helpful post-curriculum (53% and 26%, respectively). After receiving the curriculum, most trainees planned to make internal, provider-related changes to their remote teletherapy practice. CONCLUSIONS: The remote psychotherapy curriculum was well received by psychiatry trainees who had limited experience with remote clinical practice prior to the pandemic.

Machine Learning Identifies Smartwatch-Based Physiological Biomarker for Predicting Disruptive Behavior in Children: A Feasibility Study.

Objective: Parents frequently purchase and inquire about smartwatch devices to monitor child behaviors and functioning. This pilot study examined the feasibility and accuracy of using smartwatch monitoring for the prediction of disruptive behaviors. Methods: The study enrolled children (N = 10) aged 7-10 years hospitalized for the treatment of disruptive behaviors. The study team completed continuous behavioral phenotyping during study participation. The machine learning protocol examined severe behavioral outbursts (operationalized as episodes that preceded physical restraint) for preparing the training data. Supervised machine learning methods were trained with cross-validation to predict three behavior states-calm, playful, and disruptive. Results: The participants had a 90% adherence rate for per protocol smartwatch use. Decision trees derived conditional dependencies of heart rate, sleep, and motor activity to predict behavior. A cross-validation demonstrated 80.89% accuracy of predicting the child's behavior state using these conditional dependencies. Conclusion: This study demonstrated the feasibility of 7-day continuous smartwatch monitoring for children with severe disruptive behaviors. A machine learning approach characterized predictive biomarkers of impending disruptive behaviors. Future validation studies will examine smartwatch physiological biomarkers to enhance behavioral interventions, increase parental engagement in treatment, and demonstrate target engagement in clinical trials of pharmacological agents for young children.

Association between early childhood sleep difficulties and subsequent psychiatric illness.

STUDY OBJECTIVES: Chronic disruptions to sleep in childhood are associated with increased prevalence of psychiatric disease later in development. When sleep disruptions remit before adolescence, the increased prevalence of psychiatric disease is no longer observed, highlighting the importance of early detection and intervention. Clinicians typically rely on caregivers' reports for diagnosis and management of childhood sleep challenges. We examined whether findings on polysomnogram (PSG) can offer similar insight into childhood sleep difficulties and the risk of subsequent psychiatric illness. METHODS: A cohort was identified of 348 children ages 5 years 11 months and younger with sleep difficulties rising to the level of formal clinical workup. A retrospective review of caregiver-reported sleep concerns, PSG results, and subsequent psychiatric illness was completed. PSG findings were compared to presence of psychiatric illness later in life as well as caregivers' reported concerns. Chi-squared and Fisher's exact tests were completed to evaluate correlations and Cohen's kappa was used to evaluate agreement. RESULTS: With only a few exceptions, comparisons between clinician findings on PSG and subsequent psychiatric diagnoses were statistically nonsignificant. Similarly, the relationship between caregivers' subjective reports about sleep and clinicians' findings on PSG demonstrated only slight to fair agreement, suggesting reported concerns were not predictive of PSG results. CONCLUSIONS: Parental reports of subjective sleep concerns are indicative of different sleep pathologies compared to sleep pathologies detected on PSG. The addition of PSG to caregiver-reported data appears to have limited clinical utility in understanding sleep concerns associated with the risk of subsequent psychiatric illness in young children. CITATION: Pease E, Shekunov J, Savitz ST, et al. Association between early childhood sleep difficulties and subsequent psychiatric illness. J Clin Sleep Med. 2023;19(12):2059-2063.

Event-Related Potential Markers of Suicidality in Adolescents.

BACKGROUND: Implicit cognitive markers may assist with the prediction of suicidality beyond clinical risk factors. The aim of this study was to investigate neural correlates associated with the Death/Suicide Implicit Association Test (DS-IAT) via event-related potentials (ERP) in suicidal adolescents. METHODS: Thirty inpatient adolescents with suicidal ideations and behaviors (SIBS) and 30 healthy controls from the community were recruited. All participants underwent 64-channel electroencephalography, DS-IAT, and clinical assessments. Hierarchical generalized linear models with spatiotemporal clustering were used to identify significant ERPs associated with the behavioral outcome of DS-IAT (D scores) and group differences. RESULTS: Behavioral results (D scores) showed that the adolescents with SIBS had stronger implicit associations between "death" and "self" than the healthy group (P = .02). Within adolescents with SIBS, participants with stronger implicit associations between "death" and "self" reported more difficulty in controllability of suicidal ideation in the past 2 weeks based on the Columbia-Suicide Severity Rating Scale (P = .03). For the ERP data, the D scores and N100 component over the left parieto-occipital cortex had significant correlations. Significant group differences without behavioral correlation were observed for a second N100 cluster (P = .01), P200 (P = .02), and late positive potential (5 clusters, all P ≤ .02). Exploratory predictive models combining both neurophysiological and clinical measures distinguished adolescents with SIBS from healthy adolescents. CONCLUSIONS: Our results suggest that N100 may be a marker of attentional resources involved in the distinction of stimuli that are congruent or incongruent to associations between death and self. Combined clinical and ERP measures may have utility in future refinements of assessment and treatment approaches for adolescents with suicidality.

Sequential bilateral accelerated theta burst stimulation in adolescents with suicidal ideation associated with major depressive disorder: Protocol for a randomized controlled trial.

BACKGROUND: Suicide is a leading cause of death in adolescents worldwide. Previous research findings suggest that suicidal adolescents with depression have pathophysiological dorsolateral prefrontal cortex (DLPFC) deficits in γ-aminobutyric acid neurotransmission. Interventions with transcranial magnetic stimulation (TMS) directly address these underlying pathophysiological deficits in the prefrontal cortex. Theta burst stimulation (TBS) is newer dosing approach for TMS. Accelerated TBS (aTBS) involves administering multiple sessions of TMS daily as this dosing may be more efficient, tolerable, and rapid acting than standard TMS. MATERIALS AND METHODS: This is a randomized, double-blind, sham-controlled trial of sequential bilateral aTBS in adolescents with major depressive disorder (MDD) and suicidal ideation. Three sessions are administered daily for 10 days. During each session, continuous TBS is administered first to the right DPFC, in which 1,800 pulses are delivered continuously over 120 seconds. Then intermittent TBS is applied to the left DPFC, in which 1,800 pulses are delivered in 2-second bursts and repeated every 10 seconds for 570 seconds. The TBS parameters were adopted from prior research, with 3-pulse, 50-Hz bursts given every 200 ms (at 5 Hz) with an intensity of 80% active motor threshold. The comparison group will receive 3 daily sessions of bilateral sham TBS treatment for 10 days. All participants will receive the standard of care for patients with depression and suicidal ideation including daily psychotherapeutic skill sessions. Long-interval intracortical inhibition (LICI) biomarkers will be measured before and after treatment. Exploratory measures will be collected with TMS and electroencephalography for biomarker development. DISCUSSION: This is the first known randomized controlled trial to examine the efficacy of sequential bilateral aTBS for treating suicidal ideation in adolescents with MDD. Results from this study will also provide opportunities to further understand the neurophysiological and molecular mechanisms of suicidal ideation in adolescents. TRIAL REGISTRATION: Investigational device exemption (IDE) Number: G200220, ClinicalTrials.gov (ID: NCT04701840). Registered August 6, 2020. https://clinicaltrials.gov/ct2/show/NCT04502758?term=NCT04701840&draw=2&rank=1.

PISTACHIo (PreemptIon of diSrupTive behAvior in CHIldren): real-time monitoring of sleep and behavior of children 3-7 years old receiving parent-child interaction therapy augment with artificial intelligence - the study protocol, pilot study.

BACKGROUND: Emotional behavior problems (EBP) are the most common and persistent mental health issues in early childhood. Early intervention programs are crucial in helping children with EBP. Parent-child interaction therapy (PCIT) is an evidence-based therapy designed to address personal difficulties of parent-child dyads as well as reduce externalizing behaviors. In clinical practice, parents consistently struggle to provide accurate characterizations of EBP symptoms (number, timing of tantrums, precipitating events) even from the week before in their young children. The main aim of the study is to evaluate feasibility of the use of smartwatches in children aged 3-7 years with EBP. METHODS: This randomized double-blind controlled study aims to recruit a total of 100 participants, consisting of 50 children aged 3-7 years with an EBP measure rated above the clinically significant range (T-score ≥ 60) (Eyberg Child Behavior Inventory-ECBI; Eyberg & Pincus, 1999) and their parents who are at least 18 years old. Participants are randomly assigned to the artificial intelligence-PCIT group (AI-PCIT) or the PCIT-sham biometric group. Outcome parameters include weekly ECBI and Pediatric Sleep Questionnaire (PSQ) as well as Child Behavior Checklist (CBCL) obtained weeks 1, 6, and 12 of the study. Two smartphone applications (Garmin connect and mEMA) and a wearable Garmin smartwatch are used collect the data to monitor step count, sleep, heart rate, and activity intensity. In the AI-PCIT group, the mEMA application will allow for the ecological momentary assessment (EMA) and will send behavioral alerts to the parent. DISCUSSION: Real-time predictive technologies to engage patients rely on daily commitment on behalf of the participant and recurrent frequent smartphone notifications. Ecological momentary assessment (EMA) provides a way to digitally phenotype in-the-moment behavior and functioning of the parent-child dyad. One of the study's goals is to determine if AI-PCIT outcomes are superior in comparison with standard PCIT. Overall, we believe that the PISTACHIo study will also be able to determine tolerability of smartwatches in children aged 3-7 with EBP and could participate in a fundamental shift from the traditional way of assessing and treating EBP to a more individualized treatment plan based on real-time information about the child's behavior. TRIAL REGISTRATION: The ongoing clinical trial study protocol conforms to the international Consolidated Standards of Reporting Trials (CONSORT) guidelines and is registered in clinicaltrials.gov (ID: NCT05077722), an international clinical trial registry.

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents.

OBJECTIVES: Theta burst stimulation (TBS) is often used in clinical practice and research protocols for adults with neuropsychiatric disorders. There are substantial knowledge gaps related to the application of TBS in children and adolescents. This systematic review examined the safety and tolerability of TBS in children and adolescents. MATERIALS AND METHODS: A systematic review of human TBS studies in children and adolescents was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following inclusion criteria were applied: 1) articles in English language only; 2) studies that included child and adolescent participants (up to 21 years of age); 3) studies that administered intermittent TBS or continuous TBS or both to participants; 4) studies that had an outcome measure; and 5) availability of full text material. The primary outcome measures were tolerability and safety. When feasible, the clinical effects were reviewed. RESULTS: Twenty relevant articles met the criteria for inclusion. The reported adverse events were mild and similar to what is noted in adult studies. The most common symptom was headache. One case report described a seizure induced by TBS. Collectively, the studies were heterogeneous but the methodologic quality of randomized trials was high. CONCLUSIONS: TBS interventions in children may have similar safety, tolerability, and feasibility as compared to adults. However, long-term, follow-up studies of TBS are lacking. Future dose-ranging studies with systematic assessment of adverse events will be important in the translation of findings with TBS from adults to youth.

Delayed Signs and Symptoms of Extended Release Guanfacine Overdose in Two Adolescent Patients: Implications of Monitoring on the Psychiatry Unit.

Guanfacine is a selective alpha-2a adrenoreceptor agonist that with overdose can cause symptoms ranging from mild sedation to coma, respiratory depression, hyporeflexia, hypotonia, bradycardia, and hypotension. Despite a well-defined and predictable toxidrome, variations can be seen based on multiple factors including age, quantity ingested, organ functions, coingestions, time since ingestion, and specific dosage form. Here, we describe two cases of delayed presentation of extended release guanfacine toxicity and highlight the variations encountered in the toxidrome presentation. These cases bring to attention the importance of maintaining a high suspicion for such atypical presentations, keeping in mind the limitations of managing these complications on an inpatient psychiatric unit.

Evidence for machine learning guided early prediction of acute outcomes in the treatment of depressed children and adolescents with antidepressants.

BACKGROUND: The treatment of depression in children and adolescents is a substantial public health challenge. This study examined artificial intelligence tools for the prediction of early outcomes in depressed children and adolescents treated with fluoxetine, duloxetine, or placebo. METHODS: The study samples included training datasets (N = 271) from patients with major depressive disorder (MDD) treated with fluoxetine and testing datasets from patients with MDD treated with duloxetine (N = 255) or placebo (N = 265). Treatment trajectories were generated using probabilistic graphical models (PGMs). Unsupervised machine learning identified specific depressive symptom profiles and related thresholds of improvement during acute treatment. RESULTS: Variation in six depressive symptoms (difficulty having fun, social withdrawal, excessive fatigue, irritability, low self-esteem, and depressed feelings) assessed with the Children's Depression Rating Scale-Revised at 4-6 weeks predicted treatment outcomes with fluoxetine at 10-12 weeks with an average accuracy of 73% in the training dataset. The same six symptoms predicted 10-12 week outcomes at 4-6 weeks in (a) duloxetine testing datasets with an average accuracy of 76% and (b) placebo-treated patients with accuracies of 67%. In placebo-treated patients, the accuracies of predicting response and remission were similar to antidepressants. Accuracies for predicting nonresponse to placebo treatment were significantly lower than antidepressants. CONCLUSIONS: PGMs provided clinically meaningful predictions in samples of depressed children and adolescents treated with fluoxetine or duloxetine. Future work should augment PGMs with biological data for refined predictions to guide the selection of pharmacological and psychotherapeutic treatment in children and adolescents with depression.

A Randomized Controlled Trial of Combinatorial Pharmacogenetics Testing in Adolescent Depression.

OBJECTIVE: Numerous commercial pharmacogenetics panels are now widely available for clinical use in psychiatric practice. However, there is a paucity of literature evaluating the use of combinatorial pharmacogenetics panels to enhance outcomes in the treatment of adolescents with depression. This study sought to prospectively evaluate the clinical impact of combinatorial pharmacogenetics testing in a double-blind, randomized, controlled effectiveness study for the pharmacologic treatment of adolescents with depression. METHOD: Adolescents aged 13 to 18 years (N = 176) with moderate to severe major depressive disorder (MDD) were randomized to treatment arm guided by testing in which pharmacogenetic testing results were available at the baseline visit (GENE arm, n = 84) or a treatment-as-usual arm (TAU arm, n = 92) in which testing results were not available until an 8-week visit. Raters, participants, and families were blinded to group allocation. Symptom improvement, side effects, and satisfaction were assessed throughout the study at 4 weeks, 8 weeks, and 6 months. RESULTS: There were no differences between the GENE and TAU arms at 8 weeks or 6 months for symptom improvement, side effect burden, or satisfaction. Selective serotonin reuptake inhibitors were prescribed at higher rates in the TAU arm compared to the GENE arm (p = .024). CONCLUSION: Combinatorial pharmacogenetics-guided treatment did not demonstrate improved outcomes compared to TAU in adolescents with MDD. Future research should examine how specific medication-gene pairs may affect clinical outcomes in the treatment of adolescents with depression and how best to integrate pharmacogenetics into clinical practice. CLINICAL TRIAL REGISTRATION INFORMATION: A PK/PD Genetic Variation Treatment Algorithm Versus Treatment As Usual for Adolescent Management Of Depression; https://www.clinicaltrials.gov; NCT02286440.

Childhood psychiatric outcomes in the context of suspected neglect and abuse reports related and unrelated to parental substance use.

BACKGROUND: Child maltreatment is prevalent in the United States and carries long-term consequences. Parental substance use may have associations with child maltreatment. It is unclear whether co-occurring parental substance use aggravates childhood psychiatric outcomes related to suspected maltreatment. OBJECTIVE: To compare psychiatric and healthcare utilization outcomes in children with suspected abuse reports, with and without documented parental substance use. PARTICIPANTS AND SETTING: Retrospective cohort study (n = 2831) of children with suspected abuse/neglect (SANC) reports filed in the electronic health record between January 1, 2000 and January 1, 2016. Children who had SANC reports referencing parental substance use (n = 458) were compared with those who had SANC reports that did not reference substance use (n = 2346). METHODS: Outcome data included ICD-10 coded medical and psychiatric diagnoses and healthcare utilization. RESULTS: Compared to children who had a SANC report filed without parental substance use, children with parental substance use in a SANC showed significantly lower age-adjusted odds of anxiety disorder, mood disorder and externalizing disorder, and higher odds of a substance use disorder diagnosis. They were also less likely to present to an emergency department visit for any reason in the year prior to the report. CONCLUSIONS: Children with exposure to parental substance use in a household where parental abuse or neglect was suspected had lower odds of adverse psychiatric outcomes as compared to children with suspected report of abuse or neglect unrelated to parental substance use. The present findings highlight the complex interplay of psychosocial factors associated with outcomes of childhood maltreatment.

A Retrospective Examination of the Impact of Pharmacotherapy on Parent-Child Interaction Therapy.

Objective: Parent-child interaction therapy (PCIT) is an evidence-based approach for children aged 2-7 years with disruptive behavior problems. This study examined the effectiveness of PCIT with and without concurrent pharmacotherapy. Methods: A convenience sample was collected from a retrospective chart review of preschool-aged children treated with PCIT at the Mayo Clinic Young Child Clinic between 2016 and 2020. Quantitative and qualitative data were abstracted from all patients. The sample was divided into two groups based on psychotropic medications status (medicated and unmedicated) at the initiation of PCIT. Effectiveness of treatment was assessed with the change in Eyberg Child Behavior Inventory (ECBI) score. The change over time in ECBI score was compared between the two PCIT groups with and without concurrent pharmacotherapy using a linear mixed model. Results: Of the 62 youth, 38.71% were females. Mean age was 4.71 ± 1.17 years. The mean baseline ECBI score was 148.74 ± 30.86, indicating clinically significant disruptive behaviors. The mean number of PCIT sessions was 6.59 ± 3.82. There was no statistically significant difference in ECBI scores between the two groups at pre-PCIT (medication group: 149.68, standard error [SE] = 11.61 vs. unmedicated group: 147.92, SE = 10.93, p = 0.8904) and at post-PCIT (medication group: 116.27 [SE = 11.89] vs. unmedicated group: 128.86 [SE = 11.57], p = 0.3464). There was a statistically significant improvement in ECBI scores for both groups after completing therapy (medication group = -33.41 [-22.32%], SE = 6.27, p < 0.0001; d = 1.144; unmedicated group = -19.06 [-12.88%], SE = 5.78, p = 0.0022; d = 1.078). Conclusions: PCIT reduced disruptive behaviors in this sample of young children regardless of concurrent pharmacotherapy. Future prospective studies should consider one particular pharmacological agent and long-term outcomes of treatment. PCIT and certain pharmacological treatments could have complex and important bidirectional priming effects for both treatments.

Preliminary Evidence for Anhedonia as a Marker of Sexual Trauma in Female Adolescents.

INTRODUCTION: Major depressive disorder (MDD) is a common condition with heterogeneous presentations that often include predominant anhedonia. Previous studies have revealed that childhood trauma is a potent risk factor for the development of MDD; however, the clinical implications of this finding are not fully understood. METHODS: Participants were adolescents (age 13-21 years) with a diagnosis of moderate-to-severe major depressive disorder and healthy controls. We used generalized linear models to assess the relationship between anhedonia severity and trauma severity in a cross-sectional dataset. RESULTS: This cross-sectional analysis of an adolescent sample that underwent clinical evaluations and a trauma assessment, suggested that anhedonia was associated with historical trauma severity. The association between anhedonia and sexual abuse was greater in female participants compared to male participants. DISCUSSION: Our results were partially in line with the reported literature in adult samples. Future studies aiming to characterize the trauma-anhedonia relationship in adolescents should utilize scales designed specifically to measure these constructs in young populations, and scales that assess specific subtypes of anhedonia.

The Negative Impact of Maternal Perinatal Opioid Use on Neonatal Outcomes.

Objective: To compare outcomes among newborns of opioid-using and nonopioid drug-using mothers with those of control mothers who did not report substance use.Methods: Using the Rochester Epidemiology Project, newborns diagnosed with drug withdrawal syndrome (per ICD-9 or ICD-10 codes) from January 2010 through June 2017 were identified. For mothers, data collected included age, race, drug use, number of prenatal visits, and results of the urinary drug abuse survey, meconium test, and self-report survey. Demographic and perinatal data collected for newborns included birth date; sex; Apgar scores at 1, 5, and 10 minutes; neonatal intensive care stay; and vital status. Controls (n = 771) were similarly selected in regard to sex, birth date, and county.Results: Of 328 infants identified, 168 were born with opioid neonatal abstinence syndrome and 160 with a nonopioid withdrawal syndrome. Control mothers had more prenatal visits than mothers in the nonopioid and opioid groups. Newborns of control mothers had higher Apgar scores at 1 and 5 minutes than both substance-using groups. Opioid-using mothers were almost twice as likely to have newborns requiring intensive care and 3 times as likely to use benzodiazepines compared to the other substance-using mothers. Substance-using mothers had more premature babies than controls.Conclusions: Prenatal opioid use is a substantial risk factor for prematurity. Newborns diagnosed with neonatal abstinence syndrome are at risk of perinatal complications. Mothers using opioids during pregnancy also tend to use other substances. Longitudinal research should clarify how prenatal substance use interacts with other risk factors during a child's first years.

Clinical Characteristics, Outcomes, Disposition, and Acute Care of Children and Adolescents Treated for Acetaminophen Toxicity.

OBJECTIVE: Acetaminophen is a common cause of intentional and inadvertent overdoses among children and adolescents worldwide. Little is known about characteristics and clinical outcomes of these youths. The primary goal of this naturalistic study was to describe the psychiatric characteristics, medical management, outcomes, and dispositions of children and adolescents evaluated for excessive acetaminophen exposure. METHODS: The Rochester Epidemiology Project database was searched for all patients ages 0-18 treated for excessive acetaminophen exposure in Olmsted County, Minnesota, during a 7-year period (2004-2010). Demographic factors, overdose intentionality, medical and psychiatric treatment, mental health and addiction history, and disposition from the emergency department (ED) were documented. RESULTS: Of 110 cases of acetaminophen overdose (89 female patients and 21 male patients), 97 (88%) were intentional and 13 (12%) were unintentional. Fifteen patients (14%) were discharged from the ED, and 69 (63%) required admission to a medical unit. Sixty-four (59%) received N-acetylcysteine. Ninety-eight (89%) were evaluated by psychiatry, and 80 (73%) were admitted for psychiatric hospitalization. Most had at least one psychiatric diagnosis, most commonly depression (55%); 22 (20%) had a prior suicide attempt. Substance use was common, notably alcohol dependence (N=16, 15%), alcohol abuse (N=18, 16%), and cannabis abuse (N=18, 16%). All survived and recovered without liver transplant. CONCLUSIONS: Among pediatric patients with acetaminophen overdoses, psychiatric comorbidities and substance use were common. Most received both inpatient medical and psychiatric treatment. Interventions that restrict acetaminophen access are needed for this population, as are suicide risk reduction interventions for delivery in emergency settings.

A pilot spectroscopy study of adversity in adolescents.

Background: Childhood adversity is a global health problem affecting 25-50% of children worldwide. Few prior studies have examined the underlying neurochemistry of adversity in adolescents. This cross-sectional study examined spectroscopic markers of trauma in a cohort of adolescents with major depressive disorder (MDD) and healthy controls. We hypothesized that historical adversity would have a negative relationship with spectroscopic measures of glutamate metabolites in anterior cingulate cortex. Methods: Adolescent participants (aged 13-21) underwent a semi-structured diagnostic interview and clinical assessment, which included the self-report Childhood Trauma Questionnaire (CTQ), a 28-item assessment of childhood adversity. Proton magnetic resonance spectroscopy (1H-MRS) scans at 3 Tesla of an anterior cingulate cortex (ACC) voxel (8 cm3) encompassing both hemispheres were collected using a 2-dimensional J-averaged sequence to assess N-acetylaspartate (NAA), Glx (glutamate+glutamine) and [NAA]/[Glx] concentrations. Generalized linear models assessed the relationships between CTQ scores and metabolite levels in ACC. Results: Thirty-nine participants (17 healthy controls, 22 depressed participants) underwent 1H-MRS and completed the CTQ measures. There were decrements in [NAA]/[Glx] ratio in the ACC of participants with childhood adversity while no significant relationship between CTQ total score and any of the ACC metabolites was found in the combined sample. Exploratory results revealed a positive association between Glx levels and CTQ scores in depressed participants. Conversely the [NAA]/[Glx] ratio had a negative association with total CTQ scores in the depressed participants. Emotional Abuse Scale showed a significant negative relationship with [NAA]/[Glx] ratio in the combined sample when adjusted for depression severity. Conclusions: Our findings suggest that childhood adversity may impact brain neurochemical profiles. Further longitudinal studies should examine neurochemical correlates of childhood adversity throughout development and in populations with other psychiatric disorders.

The Role of Parental Capacity for Medical Decision-Making in Medical Ethics and the Care of Psychiatrically Ill Youth: Case Report.

Introduction: Parents/legal guardians are medical decision-makers for their minor children. Lack of parental capacity to appreciate the implications of the diagnosis and consequences of refusing recommended treatment may impede pediatric patients from receiving adequate medical care. Child and adolescent psychiatrists (CAPs) need to appreciate the ethical considerations relevant to overriding parental medical decision-making when faced with concerns for medical neglect. Methods: Two de-identified cases illustrate the challenges inherent in clinical and ethical decision-making reflected in concerns for parental capacity for medical decision-making. Key ethical principles are reviewed. Case 1: Treatment of an adolescent with an eating disorder ethically complex due to the legal guardian's inability to adhere with treatment recommendations leading to the patient's recurrent abrupt weight loss. Case 2: Questions of parental decisional capacity amid treatment of an adolescent with schizoaffective disorder raised due to parental mistrust of diagnosis, disagreement with treatment recommendations, and lack of appreciation of the medical severity of the situation with repeated discharges against medical advice and medication nonadherence. Discussion: Decisions to question parental capacity for medical decision-making when risk of imminent harm is low but concern for medical neglect exists are controversial. Systematic review of cases concerning for medical neglect benefits from the assessment of parental decisional capacity, review of ethical standards and principles. Conclusion: Recognition of the importance of parental decision-making capacity as relates to parental autonomy and medical neglect and understanding key ethical principles will enhance the CAP's capacity in medical decision-making when stakes are high and absolute recommendations are lacking.

Immune mediated pediatric encephalitis - need for comprehensive evaluation and consensus guidelines.

BACKGROUND: Autoimmune encephalitis is characterized by neuropsychiatric symptoms associated with brain inflammation. The differential is usually broad and Psychiatry often collaborates with Neurology in diagnostic clarification and symptom management. At least 40% of neuroencephalitis cases are of unknown etiology which adds to difficulties in making the right diagnosis and deciding on the appropriate treatment (Granerod et al., Lancet Infect Dis 10:835-44, 2010). The aim of this case series was to present four cases with complicated psychiatric symptomatology and isolated neurologic signs and symptoms, evaluated at a large tertiary medical center and treated for suspected autoimmune encephalitis, demonstrating the complexity of diagnosis and treatment. CASE PRESENTATION: Four diagnostically challenging and heterogeneous cases displayed clinical symptomatology suggestive of autoimmune encephalitis. All cases presented with neurologic and psychiatric symptoms, but had negative autoantibody panels, normal or inconclusive magnetic resonance imaging results and non-specific cerebrospinal fluid changes. All were challenged with immunosuppressive/immunomodulatory treatments with overall poor response rates. CONCLUSIONS: There is a heterogeneous presentation of autoimmune encephalitis in pediatric populations. In the absence of positive findings on testing, individuals who do not meet proposed criteria for seronegative encephalitis may be misdiagnosed, and/or may not respond adequately to treatment. In those cases, comprehensive evaluation and stringent application of consensus guidelines is necessary.

Evidence Based Dyadic Therapies for 0- to 5-Year-Old Children With Emotional and Behavioral Difficulties.

As many as one in four preschool-aged children are estimated to struggle with psychosocial stress and social-emotional issues; yet, interventions are often postponed until older ages when change is actually more difficult. Reasons for this include limited interventions, paucity of FDA approved medications for young children, as well as the dearth of clinicians adequately trained in psychotherapeutic approaches for young children. This commentary outlines indications of the four most commonly used evidence-based dyadic psychotherapies for young children: Child-Parent Psychotherapy (CPP) and Trauma-Focused Cognitive Behavioral Therapy (TF-CBT), used primarily for young children with trauma, and Parent-Child Interaction Therapy (PCIT) and Child Parent Relationship Therapy (CPRT), used mostly for children with behavioral issues. Rooted in attachment theory and further supported by the premise that the quality of the child-caregiver dyad is paramount to psychological wellbeing, these therapies focus on strengthening this relationship. Literature indicates that insecure or disorganized early attachments adversely affect an individual's lifelong trajectory. These therapies have demonstrated efficacy leading to positive behavioral changes and improved parent-child interactions. The major challenges of clinical practice focused on young children and their families include proper diagnosis and determining the best therapeutic strategy, especially for families who have not benefited from prior interventions. At this time, it is still unclear which therapy is best indicated for which type of patients and it mostly has been driven by convenience and provider preference or training. Further research is required to tailor treatments more successfully to the child's needs.