Suicide and Suicide Risk in Adolescents.

Suicide is the second leading cause of death for 10- to 24-year-olds in the United States and is a global public health issue, with a recent declaration of a National State of Emergency in Children's Mental Health by the American Academy of Pediatrics, American Academy of Child and Adolescent Psychiatry, and Children's Hospital Association. This clinical report is an update to the previous American Academy of Pediatrics clinical report, "Suicide and Suicide Attempts in Adolescents." Because pediatricians and pediatric health care providers are at the front line of care for adolescents amid a child and adolescent mental health crisis, and because of the chronic and severe shortage of mental health specialists, it is important that pediatric health care providers become facile with recognizing risk factors associated with suicidality and at-risk populations, screening and further assessment of suicidality as indicated, and evidence-based interventions for patients with suicidal ideation and associated behaviors. Suicide risk can be mitigated by appropriate screening, bolstering of protective factors, indicated treatment, community resources, and referrals to mental health providers when available.

Integration of Substance Use Disorder Treatment Into a Traditional Community Mental Health Treatment System.

In response to the opioid crisis, Catholic Charities of Baltimore sought to integrate substance use disorder treatment into their outpatient community mental health clinics. The agency developed a systematic practice improvement strategy that included a competency-based curriculum and supervision plan for psychiatric providers and therapists. Psychiatric providers developed competency with medications used to treat substance use disorders, and therapists developed competency in therapeutic modalities to treat substance use disorders, all of which were gradually integrated into outpatient clinics. This column demonstrates that integration of substance use disorder treatment into outpatient community mental health care is feasible and beneficial.

Collaborative Care in the Identification and Management of Psychosis in Adolescents and Young Adults.

Pediatricians are often the first physicians to encounter adolescents and young adults presenting with psychotic symptoms. Although pediatricians would ideally be able to refer these patients immediately into psychiatric care, the shortage of child and adolescent psychiatry services may sometimes require pediatricians to make an initial assessment or continue care after recommendations are made by a specialist. Knowing how to identify and further evaluate these symptoms in pediatric patients and how to collaborate with and refer to specialty care is critical in helping to minimize the duration of untreated psychosis and to optimize outcomes. Because not all patients presenting with psychotic-like symptoms will convert to a psychotic disorder, pediatricians should avoid prematurely assigning a diagnosis when possible. Other contributing factors, such as co-occurring substance abuse or trauma, should also be considered. This clinical report describes psychotic and psychotic-like symptoms in the pediatric age group as well as etiology, risk factors, and recommendations for pediatricians, who may be among the first health care providers to identify youth at risk.

Psychosocial functioning, familiality, and psychiatric comorbidity in bipolar youth with and without psychotic features.

OBJECTIVE: Few studies have examined the correlates of psychosis in children and adolescents with bipolar disorder (BPD). We examined psychiatric comorbidity, familiality, and psychosocial functioning in multiple domains in BPD children and adolescents with and without psychotic features. METHOD: As part of 2 ongoing family-based studies of children and adolescents with DSM-IV-defined BPD, we compared youth and their families with psychotic symptoms (BPD+P) and without psychotic symptoms (BPD-P). All youth and family members were assessed using indirect and direct structured psychiatric interviews (Kiddie Schedule for Affective Disorders-Epidemiologic Version and DSM-IV Structured Clinical Interview) in a blinded manner. One study was conducted from January 2000 through December 2004, and the other study was conducted from February 1997 through September 2006. RESULTS: Of the 226 youth with BPD, 33% manifested psychotic symptoms, as defined by the presence of hallucinations or delusions. We found that BPD+P youth had a greater number of BPD episodes (P < .01), more psychiatric hospitalizations (P < .01), and significantly higher rates of psychiatric comorbidity compared to BPD-P youth (all P values < .05). Additionally, a higher percentage of BPD+P youth had a family history of psychosis (P = .01). There was a lower processing speed (P = .03) and lower arithmetic scaled score (P = .04) in BPD+P youth, but no other meaningful differences in cognitive variables were identified between the 2 BPD groups. Psychosis in BPD was also associated with decreased family cohesion (P = .04) and poorer overall global functioning (P < .01). CONCLUSIONS: In children and adolescents with BPD, those who manifest psychotic features have higher rates of comorbid psychopathology, family history of psychosis, and poorer overall functioning in multiple domains than BPD children without psychosis. Future studies should examine neuroimaging correlates, medication response, and longitudinal course of children and adolescents with BPD who manifest psychosis as part of their clinical picture.

The diagnosis and treatment of attention deficit-hyperactivity disorder in children and adolescents with cystic fibrosis: a retrospective study.

BACKGROUND: There has been minimal study of the impact of attention deficit-hyperactivity disorder (ADHD) in cystic fibrosis (CF) or other chronic illness. OBJECTIVE: To examine patterns of ADHD diagnosis and treatment in CF. METHOD: Retrospective chart review of all pediatric patients in the Massachusetts General Hospital (MGH) CF Program referred from 8/05-12/08 for outpatient child psychiatric consultation and diagnosed with ADHD. The medication trial resulting in the best improvement in ADHD symptoms with the most tolerable side effects was designated the Best Regimen for each patient. RESULTS: Of the 188 patients aged 5-18 followed in the MGH CF Program during this time, 18 (9.6%) were referred to the liaison psychiatrist and diagnosed with ADHD. Eleven (61%) had CF treatment non-adherence as a presenting problem. Psychopharmacologic treatment of ADHD was attempted in 13 of the 18 cases. In eight cases the Best Regimen achieved a Clinical Global Impression improvement rating of much or very much improved. In three cases, the Best Regimen consisted of stimulant monotherapy; two consisted of nonstimulant monotherapy; two used a combination of two nonstimulants; and one used a combination of a stimulant and a nonstimulant. CONCLUSION: ADHD is common and treatable in pediatric patients with CF. Stimulants, nonstimulants, and combination therapies are viable treatment options. The presence of ADHD or other psychiatric disorders should be considered when behavior is interfering with adherence to medical care. Further research is needed into the prevalence and treatment of ADHD in CF and its impact on medical adherence and outcomes.

Modulation of astrocyte inducible nitric oxide synthase and cytokine expression by interferon beta is associated with induction and inhibition of interferon gamma-activated sequence binding activity.

Although interferon (IFN)-beta is firmly established as a therapeutic agent for multiple sclerosis, information regarding its role in astrocyte cytokine production is limited. In primary cultures of human astrocytes, we determined the effects of IFN-beta on astrocyte cytokine [tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6] and inducible nitric oxide synthase (iNOS) expression by ribonuclease protection assay and ELISA. We found that IFN-beta inhibited astrocyte cytokine/iNOS induced by IL-1 plus IFN-gamma, but in the absence of IFN-gamma, IFN-beta enhanced IL-1-induced cytokine/iNOS expression. Electrophoretic mobility shift analysis (EMSA) demonstrated that IFN-gamma induced sustained IFN-gamma-activated sequence (GAS) binding, while IFN-beta induced transient GAS binding. When used together, IFN-beta inhibited IFN-gamma-induced GAS binding activity. Nuclear factor-kappa B (NF-kappaB) activation was not altered by either IFNs, whereas IFN stimulated response element (ISRE) was only activated by IFN-beta and not IFN-gamma. These results suggest that IFN-beta can both mimic and antagonize the effect of IFN-gamma by modulating induction of nuclear GAS binding activity. Our results demonstrating differential regulation of astrocyte cytokine/iNOS induction by IFN-beta are novel and have implications for inflammatory diseases of the human CNS.

Role of mitogen-activated protein kinases in inducible nitric oxide synthase and TNFalpha expression in human fetal astrocytes.

Astrocytes are important sources of proinflammatory mediators such as iNOS and TNFalpha in the diseased central nervous system. In previous studies, we showed that the cytokine IL-1 plays a critical role in the activation of human astrocytes to express TNFalpha and the inducible form of nitric oxide synthase (iNOS). In the present study, we have addressed the role of the MAP-kinase pathway in the signaling events leading to the induction of these genes. Treatment with SB203580, a specific inhibitor of p38 mitogen-activated protein kinases (MAPK), potently inhibited IL-1-mediated induction of iNOS and TNFalpha in cultures of human fetal astrocytes. In contrast, PD98059, an upstream inhibitor of the extracellular regulated kinase (ERK)1/2 pathway, had little or no effect. Interestingly, SB203580 reduced the mRNA expression for iNOS, TNFalpha, and IL-6, indicating inhibition prior to translation. Transfection of astrocytes with a dominant-negative Jun-NH(2)-terminal kinase (JNK) construct also reduced iNOS expression. Western blot analysis showed phosphorylated p38 and JNK in IL-1-activated astrocytes, and phosphorylated ERK in both resting and activated cells. Electrophoretic mobility shift assay (EMSA) showed that IL-1 induced NF-kappaB and AP-1 DNA complex formation in astrocytes, and that SB203580 inhibited AP-1 complex formation. Taken together, these results demonstrate the differential roles played by the three MAP kinases in human astrocyte inflammatory gene activation and point to a crucial function of p38 and JNK MAP kinases in IL-1-mediated astrocyte activation.