GFAP expression and social deficits in transgenic mice overexpressing human sAPPα.

Autistic individuals display impaired social interactions and language, and restricted, stereotyped behaviors. Elevated levels of secreted amyloid precursor protein-alpha (sAPPα), the product of α-secretase cleavage of APP, are found in the plasma of some individuals with autism. The sAPPα protein is neurotrophic and neuroprotective and recently showed a correlation to glial differentiation in human neural stem cells (NSCs) via the IL-6 pathway. Considering evidence of gliosis in postmortem autistic brains, we hypothesized that subsets of patients with autism would exhibit elevations in CNS sAPPα and mice generated to mimic this observation would display markers suggestive of gliosis and autism-like behavior. Elevations in sAPPα levels were observed in brains of autistic patients compared to controls. Transgenic mice engineered to overexpress human sAPPα (TgsAPPα mice) displayed hypoactivity, impaired sociability, increased brain glial fibrillary acidic protein (GFAP) expression, and altered Notch1 and IL-6 levels. NSCs isolated from TgsAPPα mice, and those derived from wild-type mice treated with sAPPα, displayed suppressed ß-tubulin III and elevated GFAP expression. These results suggest that elevations in brain sAPPα levels are observed in subsets of individuals with autism and TgsAPPα mice display signs suggestive of gliosis and behavioral impairment.

Improving child and adolescent psychiatry education for medical students: an inter-organizational collaborative action plan.

OBJECTIVE: A new Child and Adolescent Psychiatry in Medical Education (CAPME) Task Force, sponsored by the Association for Directors of Medical Student Education in Psychiatry (ADMSEP), has created an inter-organizational partnership between child and adolescent psychiatry (CAP) educators and medical student educators in psychiatry. This paper outlines the task force design and strategic plan to address the long-standing dearth of CAP training for medical students. METHOD: The CAPME ADMSEP Task Force, formed in 2010, identified common challenges to teaching CAP among ADMSEP's CAPME Task Force members, utilizing focus-group discussions and a needs-assessment survey. The Task Force was organized into five major sections, with inter-organizational action plans to address identified areas of need, such as portable modules and development of benchmark CAP competencies. RESULTS/CONCLUSION: The authors predict that all new physicians, regardless of specialty, will be better trained in CAP. Increased exposure may also improve recruitment into this underserved area.

Adolescent Polypharmacy and Serotonin Syndrome.

OBJECTIVES: The objective of this study was to present a case and review serotonin syndrome and the risk of occurrence in children and adolescents on multiple psychotropic medications. METHODS: The clinical history of a patient in the University of South Florida's child and adolescent psychiatry clinic is presented. Literature review on serotonin syndrome, attention-deficit/hyperactivity disorder (ADHD), and psychostimulants was conducted through PubMed. RESULTS/DISCUSSION: We have presented a case of possible serotonin-related abnormal movements in an adolescent girl prescribed stimulants and multiple serotonergic medications. Serotonin syndrome may be precipitated through drug interactions that increase serum levels of psychotropic medications. Patients with ADHD often have comorbid psychiatric illness requiring treatment with medication. Amphetamine salts are an often-overlooked agent that potentiates serotonin through monoamine oxidase inhibitor (MAO) inhibition and neurotransmitter release. Children and adolescents on multiple psychotropic medications should be closely monitored for the triad of altered mental status, neuromuscular abnormalities, and autonomic hyperactivity. CONCLUSIONS: Patients with ADHD often have comorbid psychiatric illness and are treated with multiple psychotropic medications. Given the effects of drug-drug interactions and the serotonergic effects of psychostimulants, clinicians should remain vigilant for the triad of altered mental status, neuromuscular abnormalities, and autonomic hyperactivity seen in serotonin syndrome.

Practice parameter for the assessment and treatment of children and adolescents with depressive disorders.

This practice parameter describes the epidemiology, clinical picture, differential diagnosis, course, risk factors, and pharmacological and psychotherapy treatments of children and adolescents with major depressive or dysthymic disorders. Side effects of the antidepressants, particularly the risk of suicidal ideation and behaviors are discussed. Recommendations regarding the assessment and the acute, continuation, and maintenance treatment of these disorders are based on the existent scientific evidence as well as the current clinical practice.

A stitch in time saves nine: intervention strategies for the remediation of competency.

The mission of medical educators in all fields is to perfect the science and the art of training competent physicians and the next generation of leaders. To do this, outcomes research regarding effective training and supervision techniques and curricula, the optimal educational environment, assessment, and remediation of competency is needed. It is incumbent upon training directors to continue to provide the primary leadership for the field of training. The areas that are ripe for research and development include effective curricula, effective evaluation and remediation of competency, and leadership skill development. As medicine becomes more complex, so does the task of training physicians. Joint monitoring and outcomes research of the training enterprise are the scholarly and academic missions of the present and the future.

Common Factors in Pediatric Psychiatry: A Review of Essential and Adjunctive Mechanisms of Treatment Outcome.

OBJECTIVE: The purpose of this article is to review the literature on hypothesized behavioral correlates of pharmacotherapy treatment response. A particular focus is placed on what have been referred to as "common factors" across mental health treatments, including medication adherence, therapeutic alliance, motivation for behavior change, and expectancies for positive treatment outcomes. These understudied factors may provide unique explanations for mechanisms of symptom change, patient risk as a result of protocol deviation, and attenuated treatment outcomes. METHOD: A literature search was conducted to evaluate the relationship between treatment processes in pediatric psychiatry and medication adherence, therapeutic alliance, motivation for behavior change, and expectancies for positive treatment outcomes. RESULTS: Substantial variability and room for improvement was identified for each common factor. Behavioral protocols have already been developed to address many aspects of common factors in pediatric psychiatric treatment, but are not yet a part of many practice parameters. CONCLUSION: Interventions to improve common factors can be used immediately in tandem with psychopharmacological interventions to provide increased symptom relief and reduce patient risk. Furthermore, incorporating instruction in common factors interventions can positively affect training of future providers and enhance understanding of the mechanisms of effect of medications. An increased focus on common factors, with a particular emphasis on quantifying the magnitude and mechanisms of their effects on psychopharmacological interventions stand to benefit child patients, their families, treatment providers, training facilities, and pharmaceutical manufacturers.

Syndrome of inappropriate antidiuretic hormone associated with escitalopram therapy.

Escitalopram is the selective serotonin reuptake inhibitor (SSRI) most recently approved for use in the United States. It is structurally related to citalopram, but is felt to have a more tolerable side-effect profile than its parent compound. Side effects are not generally serious and include headache, diarrhea, and nausea. While hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) have been associated with treatment with other SSRIs, there has only been one case of escitalopram-induced SIADH reported in the literature to date. We now report another case of a patient who developed SIADH after being treated with escitalopram for 4 weeks. The patient's hyponatremia improved following the discontinuation of escitalopram. Clinicians should be aware of this uncommon but significant side effect of SSRIs and monitor high-risk patients for the development of SIADH.

Practice parameter for the assessment and treatment of children and adolescents with substance use disorders.

This practice parameter describes the assessment and treatment of children and adolescents with substance use disorders and is based on scientific evidence and clinical consensus regarding diagnosis and effective treatment as well as on the current state of clinical practice. This parameter considers risk factors for substance use and related problems, normative use of substances by adolescents, the comorbidity of substance use disorders with other psychiatric disorders, and treatment settings and modalities.

Practice parameter for use of electroconvulsive therapy with adolescents.

Electroconvulsive therapy (ECT) may be an effective treatment for adolescents with severe mood disorders and other Axis I psychiatric disorders when more conservative treatments have been unsuccessful. ECT may be considered when there is a lack of response to two or more trials of pharmacotherapy or when the severity of symptoms precludes waiting for a response to pharmacological treatment. The literature on ECT in adolescents, including studies and case reports, was reviewed and then integrated into clinically relevant guidelines for practitioners. Mood disorders have a high rate of response to ECT (75%-100%), whereas psychotic disorders have a lower response rate (50%-60%). Consent of the adolescent's legal guardian is mandatory, and the patient's consent or assent should be obtained. State legal guidelines and institutional guidelines must be followed. ECT techniques associated with the fewest adverse effects and greatest efficacy should be used. The presence of comorbid psychiatric disorder is not a contraindication. Systematic pretreatment and posttreatment evaluation, including symptom and cognitive assessment, is recommended.

Practice parameter for the assessment and treatment of children and adolescents with enuresis.

Enuresis is a symptom that is frequently encountered in child psychiatric evaluations. Careful assessment is required to identify specific urologic, developmental, psychosocial, and sleep-related etiologies. For most children with enuresis, however, a specific etiology cannot be determined. Treatment then involves supportive approaches, conditioning with a urine alarm, or medications--imipramine or desmopressin acetate. The psychosocial consequences of the symptom must be recognized and addressed with sensitivity during the evaluation and treatment of enuresis.

Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults.

This practice parameter describes treatment with stimulant medication. It uses an evidence-based medicine approach derived from a detailed literature review and expert consultation. Stimulant medications in clinical use include methylphenidate, dextroamphetamine, mixed-salts amphetamine, and pemoline. It carries FDA indications for treatment of attention-deficit/hyperactivity disorder and narcolepsy.

Practice parameter for the prevention and management of aggressive behavior in child and adolescent psychiatric institutions, with special reference to seclusion and restraint.

This parameter reviews the current state of the prevention and management of child and adolescent aggressive behavior in psychiatric institutions, with particular reference to the indications and use of seclusion and restraint. It also presents guidelines that have been developed in response to professional, regulatory, and public concern about the use of restrictive interventions with aggressive patients with regard to personal safety and patient rights. The literature on the use of seclusion, physical restraint, mechanical restraint, and chemical restraint is reviewed, and procedures for carrying out each of these interventions are described. Clinical and regulatory agency perspectives on these interventions are presented. Effectiveness, indications, contraindications, complications, and adverse effects of seclusion and restraint procedures are addressed. Interventions are presented to provide more opportunities to promote patient independence and satisfaction with treatment while diminishing the necessity of using restrictive procedures.

Potential Autoepitope within the Extracellular Region of Contactin-Associated Protein-like 2 in Mice.

AIMS: Implicated in autoimmune encephalitis, neuromyotonia and genetic forms of autism, here we report that contactin-associated protein-like 2 (CNTNAP2) contains a potential autoepitope within the extracellular region. METHODOLOGY: CNTNAP2 sequence-similar regions (CSSRs) from human pathogens were identified. Sera from autistic and control children were obtained and analyzed for the presence of antibodies able to bind CSSRs. One such candidate CSSR was evaluated for evidence of autoimmune responses to CNTNAP2 in a mouse model of acute infection. RESULTS: Autistic and control children sera contained antibodies able to discrete regions of CNTNAP2. In a murine model of acute infection, a CSSR derived from the N-terminal extracellular region of CNTNAP2 resulted in anti-CNTNAP2 antibody production, proinflammatory cytokine elevation, cerebellar and cortical white matter T-cell infiltration as well as motor dysfunction. CONCLUSION: Taken together, these data suggest that CNTNAP2 contains a potential autoepitope within the extracellular region.

Practice parameter for the assessment and treatment of children and adolescents with schizophrenia.

This Practice Parameter reviews the literature on the assessment and treatment of children and adolescents with schizophrenia. Early-onset schizophrenia is diagnosed using the same criteria as in adults and appears to be continuous with the adult form of the disorder. Clinical standards suggest that effective treatment includes antipsychotic medications combined with psychoeducational, psychotherapeutic, and educational interventions. Since this Practice Parameter was last published in 2001, several controlled trials of atypical antipsychotic agents for early-onset schizophrenia have been conducted. However, studies suggest that many youth with early-onset schizophrenia do not respond adequately to available agents and are vulnerable to adverse events, particularly metabolic side effects. Further research is needed to develop more effective and safer treatments.

Practice parameter for the assessment and treatment of children and adolescents with tic disorders.

Tic disorders, including Tourette's disorder, present with a wide range of symptom severity and associated comorbidity. This Practice Parameter reviews the evidence from research and clinical experience in the evaluation and treatment of pediatric tic disorders. Recommendations are provided for a comprehensive evaluation to include common comorbid disorders and for a hierarchical approach to multimodal interventions.

Practice parameter for child and adolescent forensic evaluations.

This Parameter addresses the key concepts that differentiate the forensic evaluation of children and adolescents from a clinical assessment. There are ethical issues unique to the forensic evaluation, because the forensic evaluator's duty is to the person, court, or agency requesting the evaluation, rather than to the patient. The forensic evaluator clarifies the legal questions to be answered and structures the evaluation to address those issues. The forensic examination may include a review of collateral information, interviews and other assessments of the child or adolescent, and interviews with other relevant informants. The principles in this Parameter suggest the general approach to the forensic evaluation of children and adolescents and are relevant to delinquency, child custody, child maltreatment, personal injury, and other court-ordered and noncourt-ordered evaluations.

Reliability and validity of the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).

OBJECTIVE: To investigate the concurrent validity and reliability of the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), a short structured diagnostic interview for DSM-IV and ICD-10 psychiatric disorders in children and adolescents. METHOD: Participants were 226 children and adolescents (190 outpatients and 36 controls) aged 6 to 17 years. To assess the concurrent validity of the MINI-KID, participants were administered the MINI-KID and the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) by blinded interviewers in a counterbalanced order on the same day. Participants also completed a self-rated measure of disability. In addition, interrater (n = 57) and test-retest (n = 83) reliability data (retest interval, 1-5 days) were collected, and agreement between the parent version of the MINI-KID and the standard MINI-KID (n = 140) was assessed. Data were collected between March 2004 and January 2008. RESULTS: Substantial to excellent MINI-KID to K-SADS-PL concordance was found for syndromal diagnoses of any mood disorder, any anxiety disorder, any substance use disorder, any ADHD or behavioral disorder, and any eating disorder (area under curve [AUC] = 0.81-0.96, kappa = 0.56-0.87). Results were more variable for psychotic disorder (AUC = 0.94, kappa = 0.41). Sensitivity was substantial (0.61-1.00) for 15/20 individual DSM-IV disorders. Specificity was excellent (0.81-1.00) for 18 disorders and substantial (> 0.73) for the remaining 2. The MINI-KID identified a median of 3 disorders per subject compared to 2 on the K-SADS-PL and took two-thirds less time to administer (34 vs 103 minutes). Interrater and test-retest kappas were substantial to almost perfect (0.64-1.00) for all individual MINI-KID disorders except dysthymia. Concordance of the parent version (MINI-KID-P) with the standard MINI-KID was good. CONCLUSIONS: The MINI-KID generates reliable and valid psychiatric diagnoses for children and adolescents and does so in a third of the time as the K-SADS-PL.

Practice parameter for the assessment and treatment of children and adolescents with posttraumatic stress disorder.

This Practice Parameter reviews the evidence from research and clinical experience and highlights significant advances in the assessment and treatment of posttraumatic stress disorder since the previous Parameter was published in 1998. It highlights the importance of early identification of posttraumatic stress disorder, the importance of gathering information from parents and children, and the assessment and treatment of comorbid disorders. It presents evidence to support trauma-focused psychotherapy, medications, and a combination of interventions in a multimodal approach.