Child psychiatry

This paper first summarizes the main findings of clinical studies conducted over the past two and a half decades on psychopathology (i.e., psychiatric diagnoses, behavior and emotional problems) in children with new onset and chronic epilepsy both with and without intellectual disability who are treated medically and surgically. Although impaired social relationships are core features of the psychiatric disorders found in pediatric epilepsy, few studies have examined social competence (i.e., social behavior, social adjustment, and social cognition) in these children. There also is a dearth of treatment studies on the frequent psychiatric comorbidities of pediatric epilepsy, attention deficit hyperactivity disorder, anxiety disorders, and depression. Drs. Hamiwka and Jones then describe their current and planned studies on social competence and cognitive behavioral treatment of anxiety disorders, respectively, in these children and how they might mitigate the poor long-term psychiatric and social outcome of pediatric epilepsy.     

Is an isolated ventricular septal defect detected before 24 weeks on ultrasound associated with fetal aneuploidy?

Objective: Whether the isolated VSD (i-VSD) is associated with aneuploidy to the same degree as a more severe heart anomaly is unclear. Our objective was to determine the likelihood of aneuploidy in pregnancies at a tertiary referral center when an i-VSD is detected before 24 weeks.

Methods: A retrospective chart review of all detailed anatomy ultrasounds before 24 weeks performed at the University of Kansas Medical Center from 08/23/2006 to 06/07/2012 was conducted. A complete evaluation of the fetal heart was accomplished using gray scale and spectral/color Doppler examinations. The outcomes of each pregnancy were reviewed for any diagnoses of aneuploidy. Odds ratios were calculated.

Results: A total of 4078 pregnancies with complete obstetric and neonatal data were reviewed. The prevalence of an i-VSD was 2.7% (112/4078). The odds ratio of aneuploidy when an i-VSD was present was (OR: 36.0, 95% CI: 5.0, 258.1). This odds ratio remained large when either an abnormal or unknown serum screen was present.

Conclusion: The presence of an i-VSD present before 24 weeks does increase the risk of fetal aneuploidy. Whether a normal serum screen or first trimester screen for aneuploidy negates the association of an i-VSD with aneuploidy still remains undetermined.     

The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma

The p110 isoforms of phosphoinositide 3-kinase (PI3K) are acutely regulated by extracellular stimuli. The class IA PI3K catalytic subunits (p110alpha, p110beta, and p110delta) occur in complex with a Src homology 2 (SH2) domain-containing p85 regulatory subunit, which has been shown to link p110alpha and p110delta to Tyr kinase signaling pathways. The p84/p101 regulatory subunits of the p110gamma class IB PI3K lack SH2 domains and instead couple p110gamma to G protein-coupled receptors (GPCRs). Here, we show, using small-molecule inhibitors with selectivity for p110beta and cells derived from a p110beta-deficient mouse line, that p110beta is not a major effector of Tyr kinase signaling but couples to GPCRs. In macrophages, both p110beta and p110gamma contributed to Akt activation induced by the GPCR agonist complement 5a, but not by the Tyr kinase ligand colony-stimulating factor-1. In fibroblasts, which express p110beta but not p110gamma, p110beta mediated Akt activation by the GPCR ligands stromal cell-derived factor, sphingosine-1-phosphate, and lysophosphatidic acid but not by the Tyr kinase ligands PDGF, insulin, and insulin-like growth factor 1. Introduction of p110gamma in these cells reduced the contribution of p110beta to GPCR signaling. Taken together, these data show that p110beta and p110gamma can couple redundantly to the same GPCR agonists. p110beta, which shows a much broader tissue distribution than the leukocyte-restricted p110gamma, could thus provide a conduit for GPCR-linked PI3K signaling in the many cell types where p110gamma expression is low or absent.     

Clinical experience with anticonvulsant medication in pediatric epilepsy and comorbid bipolar spectrum disorder

Anticonvulsant drugs are first-line treatments for both bipolar mood disorder and epilepsy; however, few studies have explored treatment options when these disorders co-occur. The aim of this study was to identify bipolar disorder symptoms common in pediatric epilepsy and to determine whether anticonvulsant monotherapy might be a practical treatment consideration. A retrospective chart review identified 38 children with bipolar spectrum disorder and epilepsy comorbidity. Two mental health clinicians independently assessed psychiatric diagnoses, symptoms, and assigned retrospective CGI-I ratings for psychiatric symptoms. Common bipolar symptoms included impulsivity, psychomotor agitation, and explosive rage. Forty-two medication trials with 11 different anticonvulsants were identified. Of the 30 instances in which anticonvulsant monotherapy was attempted, carbamazepine, divalproex sodium, lamotrigine, and oxcarbazepine were associated with better psychiatric CGI-I ratings than other monotherapies (P<0.01). Results suggest that in many cases, selected anticonvulsants appeared to simultaneously treat both epilepsy and mood disorder. Controlled trials are necessary to further ascertain optimal anticonvulsant usage.     

Pregnancy outcomes after cerclage placement in nulliparous women with a short cervix on transvaginal ultrasonography

Objective: Little is known about pregnancy outcomes associated with a short cervix and cerclage placement in nulliparous women.

Methods: An electronic query of our ultrasound database was used to identify patients whose cervical length measured <?25?mm between 16–24 weeks of gestation. Any nulliparous women, with no prior pregnancy lasting beyond 13 weeks 6 d gestational age, were included in the analysis. The primary outcome was the interval of time from the diagnosis of a short cervix (<25?mm) to the time of delivery.

Results: Our query identified 70 patients for analysis. The interval of time from diagnosis of a short cervix to delivery was observed to be 85 d (12.1 weeks) in the cerclage group and 116 d (16.6 weeks) in the expectantly managed group (p?=?0.02). In those women receiving a cerclage, there was a statistically significant risk of spontaneous preterm birth <32 weeks gestational age (R.R. 6.7 [95% CI 1.45–30.6]).

Conclusions: The impact of a short cervix is largely unknown in patients with an uncomplicated obstetrical history. Our investigation would suggest that in this subset of patients, cerclage would not be beneficial in preventing preterm delivery.     

Suicidality and epilepsy: a neuropsychobiological perspective

People with epilepsy (PWE) are at increased risk of experiencing suicidal ideation, displaying suicidal behavior, and committing suicide than the general population. The relationship between suicidality and epilepsy is complex and multifactorial in which operant pathogenic mechanisms include epilepsy-related variables, personal and familial psychiatric history, and iatrogenic effects. Furthermore, a bidirectional relationship between suicidality and epilepsy has suggested the existence of common neurobiological pathogenic mechanisms operant in both conditions and including disturbances of several neurotransmitters, in particular, serotonin (5HT), norepinephrine (NE), glutamate (GTE), and γ-aminobutyric acid (GABA), and disturbances of the hypothalamic–pituitary–adrenal axis (HPAA), which, in turn, can result in abnormal secretion of some of these neurotransmitters. The purpose of this article is to review these common neurobiological pathogenic mechanisms.