Pediatric suicide: Review of a preventable tragedy.

Concepts of suicide are explored in this issue with a focus on suicide in children and adolescents. The epidemiology of pediatric suicide in the United States is reviewed; also, risk and protective factors, as well as prevention strategies, are discussed. Suicide in the pediatric athlete and the potential protective effect of exercise are examined. In addition, this analysis addresses the beneficial role of psychological management as well as current research on pharmacologic treatment and brain stimulation procedures as part of comprehensive pediatric suicide prevention. Though death by suicide in pediatric persons has been and remains a tragic phenomenon, there is much that clinicians, other healthcare professionals, and society itself can accomplish in the prevention of pediatric suicide as well as the management of suicidality in our children and adolescents.

Genomic architecture of autism spectrum disorder in Qatar: The BARAKA-Qatar Study.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social and communication skills, restricted interests, and repetitive behaviors. The prevalence of ASD among children in Qatar was recently estimated to be 1.1%, though the genetic architecture underlying ASD both in Qatar and the greater Middle East has been largely unexplored. Here, we describe the first genomic data release from the BARAKA-Qatar Study-a nationwide program building a broadly consented biorepository of individuals with ASD and their families available for sample and data sharing and multi-omics research. METHODS: In this first release, we present a comprehensive analysis of whole-genome sequencing (WGS) data of the first 100 families (372 individuals), investigating the genetic architecture, including single-nucleotide variants (SNVs), copy number variants (CNVs), tandem repeat expansions (TREs), as well as mitochondrial DNA variants (mtDNA) segregating with ASD in local families. RESULTS: Overall, we identify potentially pathogenic variants in known genes or regions in 27 out of 100 families (27%), of which 11 variants (40.7%) were classified as pathogenic or likely-pathogenic based on American College of Medical Genetics (ACMG) guidelines. Dominant variants, including de novo and inherited, contributed to 15 (55.6%) of these families, consisting of SNVs/indels (66.7%), CNVs (13.3%), TREs (13.3%), and mtDNA variants (6.7%). Moreover, homozygous variants were found in 7 families (25.9%), with a sixfold increase in homozygous burden in consanguineous versus non-consanguineous families (13.6% and 1.8%, respectively). Furthermore, 28 novel ASD candidate genes were identified in 20 families, 23 of which had recurrent hits in MSSNG and SSC cohorts. CONCLUSIONS: This study illustrates the value of ASD studies in under-represented populations and the importance of WGS as a comprehensive tool for establishing a molecular diagnosis for families with ASD. Moreover, it uncovers a significant role for recessive variation in ASD architecture in consanguineous settings and provides a unique resource of Middle Eastern genomes for future research to the global ASD community.

Risk of suicide in children and adolescents in the emergency department-is universal screening the answer?

OBJECTIVE: Suicide is a leading cause of death among children and adolescents. Suicide risk screening tools can detect the risk of suicide among patients presenting to healthcare settings. The aim of this review was to describe the effectiveness of universal suicide risk screening (all patients) compared with selective screening (behavioural health patients only) in children and adolescents in emergency departments (EDs). METHOD: A literature search was conducted on PubMed for articles related to suicide risk screening in paediatric EDs between January 2016 and February 2022. RESULTS: 8 studies met the selection criteria. The review showed that 46%-93% of patients that screened positive for suicide risk had presented with a medical concern. These patients would have been missed without universal suicide risk screening. In both selective and universal screening scenarios, use of a suicide risk screening tool was better at detecting suicide risk compared with use of presenting problem alone. Suicide risk screening was found to be acceptable without increasing length of stay in the ED. CONCLUSION: Based on this review, using a suicide screening tool can help detect patients at risk who would otherwise have been missed.

International perspective on integrated care models in child and adult mental health.

The dearth of child and adolescent mental health services (CAMHS) is a global problem. Integrating CAMHS in primary care has been offered as a solution. We sampled integrated care perspectives from colleagues around the world. Our findings include various models of integrated care namely: the stepped care model in Australia; shared care in the United Kingdom (UK) and Spain; school-based collaborative care in Qatar, Singapore and the state of Texas in the US; collaborative care in Canada, Brazil, US, and Uruguay; coordinated care in the US; and, developing collaborative care models in low-resource settings, like Kenya and Micronesia. These findings provide insights into training initiatives necessary to build CAMHS workforce capacity using integrated care models, each with the ultimate goal of improving access to care. Despite variations and progress in implementing integrated care models internationally, common challenges exist: funding within complex healthcare systems, limited training mechanisms, and geopolitical/policy issues. Supportive healthcare policy, robust training initiatives, ongoing quality improvement and measurement of outcomes across programs would provide data-driven support for the expansion of integrated care and ensure its sustainability.

The environment contributes more than genetics to smaller hippocampal volume in Posttraumatic Stress Disorder (PTSD).

BACKGROUND: Studies using structural magnetic resonance imaging (MRI) volumetrics showed smaller hippocampal volume in patients with post-traumatic stress disorder (PTSD). These studies were cross-sectional and did not address whether smaller volume is secondary to stress-induced damage, or whether pre-existing factors account for the findings. The purpose of this study was to use a co-twin case control design to assess the relative contribution of genetic and environmental factors to hippocampal volume in PTSD. METHODS: Monozygotic (N = 13 pairs) and dizygotic (N = 21 pairs) twins with a history of Vietnam Era military service, where one brother went to Vietnam and developed PTSD, while his brother did not go to Vietnam or develop PTSD, underwent MR imaging of the brain. Structural MRI scans were used to manually outline the left and right hippocampus on multiple coronal slices, add the areas and adjust for slice thickness to determine hippocampal volume. RESULTS: Twins with Vietnam combat-related PTSD had a mean 11% smaller right hippocampal volume in comparison to their twin brothers without combat exposure or PTSD (p < .05). There was no significant interaction by zygosity, suggesting that this was not a predisposing risk factor or genetic effect. CONCLUSIONS: These findings are consistent with smaller hippocampal volume in PTSD, and suggest that the effects are primarily due to environmental effects such as the stress of combat.

Obsessive-compulsive disorder in children and adolescents: epidemiology, diagnosis and management.

Obsessive-compulsive disorder (OCD) can be found in about 4% of the general population and is characterized by various compulsions and obsessions that interfere with the person's quality of life from a mild to severe degree. The following discussion reflects on current concepts in this condition, including its epidemiology and etiologic underpinnings (behavioral, neurological, immunological, gastroenterological, as well as genetic). The interplay of PANS and PANDAS are included in this review. In addition, the core concepts of OCD diagnosis, differential diagnosis, and co-morbidities are considered. It is stressed that the quality of life for persons with pediatric OCD as well as for family members can be quite limited and challenged. Thus, principles of management are presented as a guide to improve the quality of life for these persons as much as possible.

Autism spectrum disorder.

Sources of data: This article is based on key recent published literature including international guidelines and relevant reviews and meta-analyses. Authors have also supplemented this material with their own clinical experience. Areas of agreement: There is an agreement that autism spectrum disorder (ASD) have a strong hereditary component. There is also a consensus that the reported prevalence estimates have increased in the last 5 years. There is strong support for using the broader spectrum disorder conceptualization of the DSM-5. Areas of controversy: Higher public awareness of ASD has generated several controversial theories of causation. We review a number of environmental risk factors receiving media attention including: vaccines, mercury, heavy metal exposure and Selective Serotonin Uptake Inhibitors (SSRIs). Popular yet controversial treatment interventions are discussed. Early diagnostic screening tools are also addressed. Growing points: There is increasing scientific interest in identifying biomarkers of autism with potential for early diagnosis, prognostic indicators and predictive treatment responses. We review evidence from genetics, neuroimaging and eye tracking as candidate biomarkers. Area timely for developing research: Family studies point to a strong hereditary component in the aetiology of autism. However these studies have not established 100% concordance rates, suggesting a role for environmental factors. The gene-environment interplay has not received enough attention in scientific research. This represents an important new avenue for research in ASD.

ADHD and adolescent athletes.

Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that affects the child and adolescent population. It is characterized by impairment in attention/concentration, hyperactivity, and impulsivity, all of which can impact performance of athletes. ADHD treatment within the athletic population is a unique challenge. The research in this field has been relatively limited. The National Collegiate Athletic Association and International Olympic Committee both regulate the use of psychostimulants for treatment of ADHD due to their performance-enhancing effects. In this article, authors have discussed the screening methods, pharmacological treatment, side effects, and behavioral approaches for the treatment of ADHD in adolescent athletes.

Autism spectrum disorders: clinical features and diagnosis.

The last decade has seen an increase of interest in autism spectrum disorders (ASD). With the prevalence now approaching 1%, children with ASD are usually first evaluated by clinicians working in primary care, such as pediatricians and family practitioners. Although classic autism is easy to recognize, differentiating autism from other spectrum disorders and comorbid conditions is not always simple.

Psychopharmacology of autistic spectrum disorders in children and adolescents.

This article provides an overview of the psychopharmacologic management of irritability, hyperactivity, and repetitive behaviors in children and adolescents with autism spectrum disorder. A review of the current literature on medications used to treat these conditions with emphasis on randomized controlled trials is presented.

Psychopharmacology of ADHD in pediatrics: current advances and issues.

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder found in 3% to 8% of children and adolescents. An important part of ADHD management is psychopharmacology, which includes stimulants, norepinephrine reuptake inhibitors, alpha-2 agonists, and antidepressants. Medications with the best evidence-based support for ADHD management are the stimulants methylphenidate and amphetamine. A number of newer, long-acting stimulants are now available and a number of new medications are considered that are under current research.

Effects of dexamethasone on declarative memory function in posttraumatic stress disorder.

Alterations in the hypothalamic-pituitary-adrenal (HPA) axis and hippocampal-based memory have been associated with posttraumatic stress disorder (PTSD), and the administration of exogenous glucocorticoids has been shown to result in a transient verbal declarative memory impairment in healthy human subjects. The purpose of this study was to assess the effects of the glucocorticoid dexamethasone on verbal declarative memory function in patients with PTSD. Forty-two men and women with (n=14) and without (n=28) PTSD received placebo or dexamethasone (1 and 2 mg on two successive days) in a double-blind, randomized fashion. Declarative memory was assessed with paragraph recall at baseline (day 1) and day 3. There was a significant interaction between diagnosis and drug (dexamethasone vs. placebo) on paragraph recall related to a relative detrimental effect of dexamethasone on memory function in healthy subjects, but not those with PTSD. These findings are consistent with an altered sensitivity of declarative memory function in PTSD to regulation by glucocorticoids, possibly explainable by alterations in glucocorticoid receptors in the hippocampus or other brain regions mediating declarative memory.

Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression.

CONTEXT: We previously used positron emission tomography (PET) measurement of brain metabolism with 18fluorodeoxyglucose to show that patients receiving selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan depletion-induced return of depressive symptoms have an acute decrease in metabolism in orbitofrontal cortex, dorsolateral prefrontal cortex, and thalamus. Many patients with depression in remission while taking norepinephrine reuptake inhibitors (NRIs) (but not SSRIs) experience a return of depressive symptoms with depletion of norepinephrine and dopamine using alpha-methylparatyrosine (AMPT). OBJECTIVE: To assess brain metabolic correlates of AMPT administration in patients with depression in remission while receiving NRIs. DESIGN, SETTING, AND PARTICIPANTS: Randomized, controlled, double-blind trial in which 18 patients recruited in 1997-2000 from the general community who had depression in remission while taking NRIs had PET imaging in a psychiatric research unit following AMPT and placebo administration. INTERVENTIONS: After initial medication with desipramine and follow-up until response, patients underwent active AMPT (five 1-g doses administered orally over 28 hours) and placebo (diphenhydramine hydrochloride, five 50- mg doses administered similarly) catecholamine depletion challenges in randomized order of assignment, after which PET imaging was performed on day 3 of each condition. Both study conditions were performed 1 week apart. MAIN OUTCOME MEASURES: Regional brain metabolism rates in patients with and without AMPT-induced return of depressive symptoms. RESULTS: AMPT-induced return of depressive symptoms was experienced by 11 of the 18 patients and led to decreased brain metabolism in a number of cortical areas, with the greatest magnitude of effects in orbitofrontal (P =.002) and dorsolateral prefrontal (P =.03) cortex and thalamus (P =.006). Increased resting metabolism in prefrontal and limbic areas predicted vulnerability to return of depressive symptoms. CONCLUSIONS: Different neurochemical systems that mediate depression may have effects on a common brain circuitry. Baseline metabolism in successfully treated depressed patients may predict vulnerability to future episodes of depression.

MRI and PET study of deficits in hippocampal structure and function in women with childhood sexual abuse and posttraumatic stress disorder.

OBJECTIVE: Animal studies have suggested that early stress is associated with alterations in the hippocampus, a brain area that plays a critical role in learning and memory. The purpose of this study was to measure both hippocampal structure and function in women with and without early childhood sexual abuse and the diagnosis of posttraumatic stress disorder (PTSD). METHOD: Thirty-three women participated in this study, including women with early childhood sexual abuse and PTSD (N=10), women with abuse without PTSD (N=12), and women without abuse or PTSD (N=11). Hippocampal volume was measured with magnetic resonance imaging in all subjects, and hippocampal function during the performance of hippocampal-based verbal declarative memory tasks was measured by using positron emission tomography in abused women with and without PTSD. RESULTS: A failure of hippocampal activation and 16% smaller volume of the hippocampus were seen in women with abuse and PTSD compared to women with abuse without PTSD. Women with abuse and PTSD had a 19% smaller hippocampal volume relative to women without abuse or PTSD. CONCLUSIONS: These results are consistent with deficits in hippocampal function and structure in abuse-related PTSD.

Genetic and nongenetic factors influencing substance use by adolescents.

Substance use by adolescents can lead to mortality, physical and social morbidity, and a brain disorder called substance dependence if allowed to progress to chronic, repetitive self-administration. Substance abuse and dependence can begin in adolescence or adulthood, but many of the attitudes and behaviors that affect risk become established during adolescence. Genetic risk factors have been identified for at least two distinct disorders and more are under active study to determine the cause and pathophysiology of addictive disorders. Although much remains to be done, a complex interplay of numerous genetic and environmental risk factors clearly is involved. An understanding of the most important environmental risk factors has led to effective primary prevention approaches; knowledge of the genetic risk factors and neuropharmacology of drugs of abuse in the brain is beginning to influence secondary prevention efforts and treatment, including better medications for addictive disorders. A large proportion of adolescents carry a genetic vulnerability that can be expressed when they accept peer and societal influences that promote experimentation with substances of abuse. At that point, the genetic factors take over, maintaining the drug self-administration pattern. Decay of social status results from association with drug-using peers and shifts in priorities supportive of drug use rather than education and productivity. More research into the genetic risk factors and applications of current knowledge to treatment is needed.

Reduced volume of orbitofrontal cortex in major depression.

BACKGROUND: Functional neuroimaging studies have implicated dysfunction of orbitofrontal cortex in the symptoms of depression, and a recent postmortem study of depressed patients found reduced density of neurons and glia in this area. The purpose of this study was to measure volume of orbitofrontal cortex and other frontal cortical subregions in patients with major depression. METHODS: Magnetic resonance imaging was used to measure volume of the orbitofrontal cortex and other frontal cortical regions in patients with major depression in remission (n = 15) and comparison subjects (n = 20). RESULTS: Patients with depression had a statistically significant 32% smaller medial orbitofrontal (gyrus rectus) cortical volume, without smaller volumes of other frontal regions including anterior cingulate Brodmann's area 24 (subgenual gyrus), anterior cingulate Brodmann's area 32, subcallosal gyrus (Brodmann's area 25), or whole brain volume. The findings were significant after statistically controlling for brain size. CONCLUSIONS: These findings are consistent with smaller orbitofrontal cortical volume in depression.