Individual prediction of symptomatic converters in youth offspring of bipolar parents using proton magnetic resonance spectroscopy.

Children of individuals with bipolar disorder (bipolar offspring) are at increased risk for developing mood disorders, but strategies to predict mood episodes are unavailable. In this study, we used support vector machine (SVM) to characterize the potential of proton magnetic resonance spectroscopy (1H-MRS) in predicting the first mood episode in youth bipolar offspring. From a longitudinal neuroimaging study, 19 at-risk youth who developed their first mood episode (converters), and 19 without mood episodes during follow-up (non-converters) were selected and matched for age, sex and follow-up time. Baseline 1H-MRS data were obtained from anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex (VLPFC). Glutamate (Glu), myo-inositol (mI), choline (Cho), N-acetyl aspartate (NAA), and phosphocreatine plus creatine (PCr + Cr) levels were calculated. SVM with a linear kernel was adopted to classify converters and non-converters based on their baseline metabolites. SVM allowed the significant classification of converters and non-converters across all regions for Cho (accuracy = 76.0%), but not for other metabolites. Considering all metabolites within each region, SVM allowed the significant classification of converters and non-converters for left VLPFC (accuracy = 76.5%), but not for right VLPFC or ACC. The combined mI, PCr + Cr, and Cho from left VLPFC achieved the highest accuracy differentiating converters from non-converters (79.0%). Our findings from this exploratory study suggested that 1H-MRS levels of mI, Cho, and PCr + Cr from left VLPFC might be useful to predict the development of first mood episode in youth bipolar offspring using machine learning. Future studies that prospectively examine and validate these metabolites as predictors of mood episodes in high-risk individuals are necessary.

An Atypical Presentation of Pediatric Acute Neuropsychiatric Syndrome Responding to Plasmapheresis Treatment.

Here we report a case of a 15-year-old female who had originally been diagnosed and treated unsuccessfully for schizophrenia, psychosis, severe anxiety, and depression. More in-depth history revealed an abrupt onset of her symptoms with remote acute infections and many exhibited characteristics of obsessive compulsive disorder with rituals. Work-up for underlying infectious, immunodeficiency, and autoimmune causes was unrevealing except for very high levels of anti-neuronal antibodies which have been linked to Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). Treatment options were discussed with the family and it was decided to use a course of plasmapheresis based on previous studies demonstrating efficacy and its safety profile. After course of therapy, there was a dramatic resolution of her psychosis, OCD traits, and anxiety. She was able to stop all of her antipsychotic and anxiety medications and resume many of her previous normal daily activities. The effect of this treatment has been sustained to the present time. This case emphasizes the importance of exploring nontraditional treatments for severe, treatment-resistant mental illness which requires a multidisciplinary approach. Further research is warranted in larger populations to investigate pathomechanisms and treatment of PANs/PANDAs.

The Generalized Anxiety Disorder 7-item scale in adolescents with generalized anxiety disorder: Signal detection and validation.

BACKGROUND: In pediatric patients with anxiety disorders, existing symptom inventories are either not freely available or require extensive time and effort to administer. We sought to evaluate a brief self-report scale-the Generalized Anxiety Disorder 7-item scale (GAD-7)-in adolescents with generalized anxiety disorder (GAD). METHODS: The Pediatric Anxiety Rating Scale (PARS) and the GAD-7 were administered to youth with GAD (confirmed by structured interview). Relationships between the measures were assessed, and sensitivity and specificity was determined with regard to a global symptom severity measure (Clinical Global Impression-Severity). RESULTS: In adolescents with GAD (N = 40; mean age, 14.8 ± 2.8), PARS and GAD-7 scores strongly correlated (R = 0.65, P ≤ .001) and a main effect for symptom severity was observed (P ≤ .001). GAD-7 scores ≥11 and ≥17 represented the optimum specificity and sensitivity for detecting moderate and severe anxiety, respectively. CONCLUSIONS: The PARS and GAD-7 similarly reflect symptom severity. The GAD-7 is associated with acceptable specificity and sensitivity for detecting clinically significant anxiety symptoms. GAD-7 scores may be used to assess anxiety symptoms and to differentiate between mild and moderate GAD in adolescents, and may be more efficient than the PARS.

Beyond DSM-5 and IQ Scores: Integrating the Four Pillars to Forensic Evaluations.

The current adult and child forensic psychiatrist is well trained, familiar, and comfortable with the use of the semi-structured Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, APA 2013 (DSM-5) [In APA, 2003] interview style. The author's assertion is not that this method is invalid or unreliable; rather, that it can be complemented by integrating elements of the defendant's four pillar assessment. Assessing the four pillars expands on the information provided by a semi-structured DSM-5-style interview in psychiatry. The four pillars are the foundation of a person's personality; temperament, cognition (learning abilities or weaknesses), cognitive flexibility (theory of mind) and internal working models of attachment, within the backdrop of the family and of the social and cultural environment in which they have lived. The importance of the study of four pillars is based on the understanding that human behavior and psychopathology as a complex and multifaceted process that includes the level of social-emotional maturity and cognitive abilities (In Delgado et al. Contemporary Psychodynamic Psychotherapy for Children and Adolescents: Integrating Intersubjectivity and Neuroscience. Springer, Berlin, 2015). The four pillars are not new concepts, rather they had been studied by separate non-clinical disciplines, and had not been integrated to the clinical practice. As far as we know, it wasn't until Delgado et al. (Contemporary Psychodynamic Psychotherapy for Children and Adolescents: Integrating Intersubjectivity and Neuroscience. Springer, Berlin, 2015) incorporated the four pillars in a user-friendly manner to clinical practice.

A Pilot Study on Developing a Standardized and Sensitive School Violence Risk Assessment with Manual Annotation.

School violence has increased over the past decade and innovative, sensitive, and standardized approaches to assess school violence risk are needed. In our current feasibility study, we initialized a standardized, sensitive, and rapid school violence risk approach with manual annotation. Manual annotation is the process of analyzing a student's transcribed interview to extract relevant information (e.g., key words) to school violence risk levels that are associated with students' behaviors, attitudes, feelings, use of technology (social media and video games), and other activities. In this feasibility study, we first implemented school violence risk assessments to evaluate risk levels by interviewing the student and parent separately at the school or the hospital to complete our novel school safety scales. We completed 25 risk assessments, resulting in 25 transcribed interviews of 12-18 year olds from 15 schools in Ohio and Kentucky. We then analyzed structured professional judgments, language, and patterns associated with school violence risk levels by using manual annotation and statistical methodology. To analyze the student interviews, we initiated the development of an annotation guideline to extract key information that is associated with students' behaviors, attitudes, feelings, use of technology and other activities. Statistical analysis was applied to associate the significant categories with students' risk levels to identify key factors which will help with developing action steps to reduce risk. In a future study, we plan to recruit more subjects in order to fully develop the manual annotation which will result in a more standardized and sensitive approach to school violence assessments.

Neurofunctional Differences Among Youth With and at Varying Risk for Developing Mania.

OBJECTIVE: To examine prefrontal and amygdala activation during emotional processing in youth with or at varying risk for developing mania to identify candidate central prodromal risk biomarkers. METHOD: Four groups of medication-free adolescents (10-20 years old) participated: adolescents with first-episode bipolar I disorder (BP-I; n = 32), adolescents with a parent with bipolar disorder and a depressive disorder (at-risk depressed [ARD]; n = 32), healthy adolescents with a parent with bipolar disorder (at-risk healthy [ARH]; n = 32), and healthy adolescents with no personal or family history of psychiatric illness (healthy comparison [HC]; n = 32). Participants underwent functional magnetic resonance imaging while performing a continuous performance task with emotional and neutral distracters. Region-of-interest analyses were performed for the bilateral amygdala and for subregions of the ventrolateral prefrontal cortex and anterior cingulate cortex. RESULTS: Overall, no group differences in bilateral amygdala and ventrolateral prefrontal cortex (Brodmann area [BA] 45/47) activation during emotional or neutral stimuli were observed. The BP-I group exhibited lower right pregenual anterior cingulate cortex activation compared with the HC group, and activation in the left BA 44 was greater in the ARH and ARD groups compared with the HC group. BP-I and ARD groups exhibited blunted activation in the right BA 10 compared with the ARH group. CONCLUSION: During emotional processing, amygdala and ventrolateral prefrontal cortex (BA 45/47) activation does not differ in youth with or at increasing risk for BP-I. However, blunted pregenual anterior cingulate cortex activation in first-episode mania could represent an illness biomarker, and greater prefrontal BA 10 and BA 44 activations in at-risk youth could represent a biomarker of risk or resilience warranting additional investigation in prospective longitudinal studies.

The impact of ADHD on morality development.

Attention deficit hyperactive disorder (ADHD) is one of the most commonly diagnosed childhood mental disorders. This pervasive disorder can affect all aspects of the child's life, including, but not limited to: peer relations, adult relations and intellectual development. As a direct result of ADHD, many of these deficiencies pervade through the child's life into adulthood. Although there is a growing number of literature focusing on the sequela of ADHD, especially social deviance, most of the literature's scope is limited to the connection between ADHD and criminality. This finite perspective provides little insight into the developmental characteristics which actually link ADHD to criminality. The most glaring example of an obscured developmental link is that of moral judgment. The following is an attempt to draw a meaningful connection between deficient moral development and ADHD, especially as it relates to attachment theory. Connecting previous research relevant to the topic as well as time-tested psychological theories on morality and attachment will serve to validate this claim.

Antidepressant tolerability in anxious and depressed youth at high risk for bipolar disorder: a prospective naturalistic treatment study.

OBJECTIVE: Depressive and anxiety disorders are common in youth who are at risk for bipolar disorder (i.e., youth who have at least one parent with bipolar disorder) and antidepressants are commonly prescribed as treatment. However, there are few data regarding the safety and tolerability of antidepressants in this population. Therefore, we sought to prospectively examine the effects of these medications in children and adolescents who are diagnosed with depressive or anxiety disorders and have a parent with bipolar I disorder. METHODS: Youth aged 9-20 years, with at least one parent with bipolar I disorder [high risk (HR)], were recruited (n = 118) and assessed using semi-structured diagnostic interviews. Participants were prospectively evaluated using a modified version of the Longitudinal Interval Follow-up Evaluation to assess changes in affective and anxiety symptoms and were treated naturalistically. RESULTS: Over the course of 43-227 weeks (mean duration of follow-up: 106 ± 55 weeks), 21% (n = 25) of youth had antidepressant exposure and, of these, 57% (n = 12) had an adverse reaction (e.g., irritability, aggression, impulsivity, or hyperactivity) that led to antidepressant discontinuation. Those patients who experienced an adverse reaction were significantly younger than those who did not (p = 0.02) and discontinuation of antidepressant therapy secondary to an adverse event occurred at an average of 16.7 ± 17.4 weeks (median: 11 weeks, range: 2-57 weeks). Cox proportional hazard analyses yielded a hazard ratio of 0.725 (p = 0.03), suggesting that there is a 27% decrease in the likelihood of an antidepressant-related adverse event leading to discontinuation with each one-year increase in age. CONCLUSIONS: Antidepressant medications may be poorly tolerated in youth with a familial risk for developing mania. Controlled studies further assessing treatments for depression and anxiety in HR youth are urgently needed.

The association between salivary hormone levels and children's inpatient aggression: a pilot study.

Aggression is a common management problem for child psychiatry hospital units. We describe an exploratory study with the primary objective of establishing the feasibility of linking salivary concentrations of three hormones (testosterone, dehydroepiandrosterone [DHEA], and cortisol) with aggression. Between May 2011 and November 2011, we recruited 17 psychiatrically hospitalized boys (age 7-9 years). We administered the Brief Rating of Aggression by Children and Adolescents (BRACHA) and Predatory-Affective Aggression Scale (PAAS) upon admission. Saliva samples were collected from the participants during a 24-h period shortly after admission: immediately upon awakening, 30 min later, and again between 3:45 and 7:45 P.M. Nursing staff recorded Overt Aggression Scale ratings twice a day during hospitalization to quantify aggressive behavior. The salivary cortisol concentrations obtained from aggressive boys 30 min after awakening trended higher than levels from the non-aggressive boys (p = 0.06), were correlated with the number of aggressive incidents (p = 0.04), and trended toward correlation with BRACHA scores (p = 0.06). The aggressive boys also showed greater morning-to-evening declines in cortisol levels (p = 0.05). Awakening levels of DHEA and testosterone were correlated with the severity of the nearest aggressive incident (p < 0.05 for both). The BRACHA scores of the aggressive boys were significantly higher than scores of the non-aggressive boys (p < 0.001). Our data demonstrate the feasibility of collecting saliva from children on an inpatient psychiatric unit, affirm the utility of the BRACHA in predicting aggressive behavior, and suggest links between salivary hormones and aggression by children who undergo psychiatric hospitalization.

Pharmacology and pharmacogenetics of pediatric ADHD with associated aggression: a review.

Attention deficit hyperactivity disorder (ADHD) is often associated with symptoms of aggression in children and adolescents. Clinically, this is complex because aggression can be from hyperactivity and impulsivity, or could be a distinct symptom from a comorbid diagnosis. Past research has recommended first treating the primary disorder of ADHD. Stimulants are the most common treatment for pediatric ADHD, which can be helpful in decreasing aggressive behaviors. Alpha-adrenergic agonists and atomoxetine (ATX) are non-stimulant medications for ADHD and aggression, but more research is necessary to compare these drugs to stimulants. If aggressive symptoms do not improve from treating the primary disorder, aggression can be treated separately. Risperidone, lithium, valproic acid, clonidine, and guanfacine have shown positive results in reducing aggression, but studies including children with aggression and ADHD are limited. The variability in treatment tolerability in patients has stimulated research in pharmacogenetics for ADHD. Although this field is still emerging, research has found evidence supporting a link between the response rate of methylphenidate and the dopamine transporter (DAT1) and a link between the metabolism rate of atomoxetine and hepatic cytochrome 450 isozymes. Pharmacogenetics may be relevant to ADHD and associated aggression. Further research in pharmacogenetics will strive to identify patterns of genetic variations that can tailor individual treatments.

The Missing Link between Juvenile Delinquency and Pediatric Posttraumatic Stress Disorder: An Attachment Theory Lens.

The present paper reviews pediatric posttraumatic stress disorder, emphasizing the relational basis of the disorder and highlighting the missing link between juvenile delinquency and trauma. The first part of the paper defines trauma and the diagnostic criteria for PTSD, noting child-specific features. The second part reviews the literature emphasizing the relational and attachment relevant nature of trauma. The third part explores psychological mechanisms for how attachment relations could affect trauma responses. Attachment relations (1) shape core schemas of the world, others, and the self and (2) foster emotional engagement or disengagement, both of which have been associated with traumatic responses. The most empirically supported pediatric trauma treatment, trauma-focused cognitive behavioral therapy (TF-CBT), acknowledges the attachment figure's influence and includes treating and training the parent and conjoint child-parent discussion. The next section reviews the noteworthy link between juvenile delinquency and trauma history. More awareness of trauma and PTSD in children and adolescents is recommended to effectively address juvenile delinquency. The review ends with a few helpful points for practicing pediatricians regarding childhood trauma.

Brief Rating of Aggression by Children and Adolescents (BRACHA): development of a tool for assessing risk of inpatients' aggressive behavior.

This study evaluated the Brief Rating of Aggression by Children and Adolescents-Preliminary Version (BRACHA 0.8), an actuarial method of assessing the risk of aggressive behavior by hospitalized children and adolescents. Licensed psychiatric social workers used a 16-item questionnaire to assess all patients seen in the emergency department (ED) of a major urban children's hospital. Over a six-month period, 418 patients (age range, 3.5-19.0 years) underwent psychiatric hospitalization after ED evaluation. The hospital nursing staff recorded the inpatients' behavior, with the Overt Aggression Scale (OAS). Inpatients were deemed aggressive if, during the first six days of their hospital stay, they scored one or higher on any OAS subscale. We evaluated questionnaire properties, items, and demographic covariates (e.g., age, sex, and living situation) by using factor analyses, logistic regression models, and receiver operating characteristic (ROC) methods. A total of 292 aggressive acts were committed by 120 (29% of 418) patients. Fourteen of the 16 items predicted (p < .007) inpatient aggression and showed good internal consistency (Cronbach's α = 0.837). Age was inversely related to probability of aggression and was incorporated into the final assessment instrument. Predictive power was comparable with other published risk assessment instruments (ROC areas of .75 for any aggression and .82 for aggression toward others). BRACHA 0.8 shows promise in rapidly assessing risk of inpatient aggression, but further studies are needed to establish the reliability and validity of the instrument.

Evidence-based recommendations for the treatment of aggression in pediatric patients with attention deficit hyperactivity disorder.

An evidence-based practice project was completed to develop best practice recommendations for the treatment of aggression in children and adolescents with attention deficit hyperactivity disorder (ADHD). Ovid Medline, PsychInfo, the National Guidelines Clearinghouse, and the Cochrane Database of Systematic Reviews were searched with limits set for English language, years 1996 to January 2010. A search of the pediatric literature was conducted for synthesized evidence in the form of meta-analyses, systematic reviews, or practice guidelines related to the treatment of aggression in children and adolescents with attention deficit hyperactivity disorder. Data were extracted using the LEGEND system. Three evidence-based care recommendations for the management of aggression in children and adolescents with ADHD were developed with an associated grade for the body of evidence. First-line pharmacotherapy for aggressive behavior in children and adolescents with ADHD should be ADHD medications. Additional research is needed to evaluate the efficacy of psychiatric medications on signs of aggression within the context of ADHD.

Neuroendocrine aspects of pediatric aggression: Can hormone measures be clinically useful?

Pediatric aggression is common in human societies, mainly presenting as impulsive aggression or predatory aggression. Numerous psychiatric disorders can contain aggression as a symptom, leading to difficulties in diagnosis and treatment. This review focuses on the biological systems that affect pediatric aggression. We review the hypothalamic-pituitary-adrenal (HPA) axis, the hypothalamic-pituitary-gonadal (HPG) axis, and the mechanisms by which these axes influence the body and mind of aggressive children and adolescents. Although this review focuses on the HPA and HPG axes, it is important to note that other biological systems have relationships with these two axes. Based on the results of the studies reviewed, elevated cortisol concentrations were associated with impulsive aggression, whereas, low levels of cortisol were associated with callous-unemotional traits similar to predatory aggression. Higher levels of dehydroepiandrosterone were correlated with higher levels of aggression as were higher levels of testosterone. However, there have been discrepancies in the results between various studies, indicating the need for more research on hormonal levels and pediatric aggression. In the future, hormonal levels may be useful in determining what treatments will work best for certain pediatric patients.

Pharmacological treatment of pathologic aggression in children.

Children with psychiatric illness may display pathologic aggression (PA) that is destructive, severe, chronic, and unresponsive to psychosocial and psychopharmacological treatment of their underlying condition(s) and psychosocial interventions specifically targeting PA. For this subset of children with PA, pharmacotherapy may be an appropriate treatment option to optimize their functioning. This article reviews pharmacological treatment studies for PA in children and the safety and efficacy of risperidone, olanzapine, lithium, divalproex sodium, methylphenidate, and typical antipsychotics in this patient population. While safety needs to be emphasized when prescribing medication for these patients, serious health and safety risks are also raised when PA is not effectively treated. Future research is needed to evaluate whether the long-term risks associated with the pharmacological treatment of PA outweigh the potential benefits to the child.

A retrospective chart review of intramuscular ziprasidone for agitation in children and adolescents on psychiatric units: prospective studies are needed.

OBJECTIVE: Our primary objective was to evaluate the effectiveness and tolerability of intramuscular ziprasidone for impulsivity and agitation in psychiatrically hospitalized children and adolescents. Our secondary objective was to examine demographic and clinical factors associated with treatment response. METHOD: We conducted a retrospective chart review of children and adolescents admitted to Cincinnati Children's Hospital Medical Center (CCHMC) psychiatric units between January 1, 2002, and July 11, 2005, who received intramuscular ziprasidone. Medical records were reviewed to determine demographic and clinical information as well as tolerability and effectiveness of ziprasidone. The Behavioral Activity Rating Scale (BARS) was used retrospectively to assess clinical response. Regression analyses were performed to evaluate the effect of demographic factors (age, gender, and ethnicity) and primary psychiatric diagnoses on treatment response. Electrocardiogram (ECG) data was inadequate. RESULTS: Fifty nine children and adolescents received a total of 77 injections of intramuscular ziprasidone for acute agitation. The mean +/- SD BARS score decreased from 6.5 +/- 0.7 to 3.1 +/- 1.3. The most common side effect was drowsiness or falling asleep (n = 46, 60%). Three (4%) could not be roused after the injection. CONCLUSIONS: Intramuscular ziprasidone may be helpful for agitation but often caused oversedation. Safety data, including ECGs, is needed in controlled prospective studies.

Body mass indexes and lipid profiles in hospitalized children and adolescents exposed to atypical antipsychotics.

OBJECTIVE: The purpose of this study was to examine body mass indexes (BMI) and lipid profiles of children and adolescents hospitalized for a psychiatric illness and exposed to an atypical antipsychotic. METHOD: Medical records of children and adolescents (ages of 5-18 years) with an inpatient psychiatric hospitalization between July 1, 2004, and June 30, 2005, were reviewed. Subjects were required to have been treated with at least one atypical antipsychotic during the month prior to admission. Height, weight, and fasting lipid values completed upon admission were collected. Prevalences of overweight (sex-specific BMI for age>or=the 95th percentile) and at risk for overweight (sex-specific BMI for age between the 85th and 94.9th percentiles) were determined and compared to estimates from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) data. The prevalence of abnormal lipid profiles was also evaluated using widely accepted criteria specific for pediatric patients. Exploratory multiple linear regression models were fit to examine relationships of demographic and clinical variables with BMI z-scores and lipid profiles. RESULTS: Of 95 inpatients (mean age 14 years, 43% female, and 60% white) evaluated, 16% (n=15) were at risk for overweight and 53% (n=50) were overweight. Fifty-one percent (n=48) and 48% (n=46) of the sample had elevated triglycerides (TG) levels and low high-density lipoprotein (HDL) levels, respectively. CONCLUSION: The prevalence of overweight among hospitalized children and adolescents with exposure to atypical antipsychotics is triple that of national norms. Dyslipidemia was also common in this inpatient sample. Future studies should assess the development of overweight, the factors contributing to it, and related comorbidities in youths with mental illness.

Rates, types, and psychosocial correlates of legal charges in adolescents with newly diagnosed bipolar disorder.

OBJECTIVES: To examine the rates, types, and psychosocial correlates of legal charges in adolescents with newly diagnosed bipolar disorder (BD). METHODS: Adolescents (n = 80), between the ages of 12 and 21 years (mean = 15.6, standard deviation = 2.3), hospitalized for their initial manic or mixed episode of BD, were evaluated for the incidence of prior juvenile offending (i.e., legal charges). We examined potential psychosocial correlates associated with legal charges using chi-square, t-tests, and discriminant function analyses to determine if there were differences between adolescents who did and did not offend prior to their first manic episode. RESULTS: Juvenile antisocial behaviors were common (55%) for adolescents with newly diagnosed BD. Discriminant function analysis revealed that older age at first treatment (p < 0.01), sexual activity over the previous month (p < 0.05), therapeutic use of stimulants (p < 0.05), and anxiety disorders were the most significant factors to differentiate between bipolar adolescents who offended and those who did not (Wilks' lambda = 0.80, p < 0.005). CONCLUSIONS: Our findings indicate that there are identifiable psychosocial correlates associated with antisocial behaviors in adolescents with newly diagnosed BD that may improve our understanding of juvenile antisocial behaviors.