Association between child psychiatric emergency room outcomes and dimensions of psychopathology.

OBJECTIVE: To determine the degree to which dimensional psychopathology predicts length of stay in an emergency department (ED) and need for hospital admission among children with psychiatric complaints. METHOD: Electronic health records of children age 4-17 years who presented to the ED of a large academic medical center were analyzed using a natural language processing tool to estimate Research Domain Criteria (RDoC) symptom scores. These scores' association with length of stay and probability of admission versus discharge to home were evaluated. RESULTS: We identified 3061 children and adolescents who presented to the ED and were evaluated by the psychiatry service between November 2008 and March 2015. Median length of stay was 7.8 h (interquartile range 5.2-14.3 h) and 1696 (55.4%) were admitted to the hospital. Higher estimated RDoC arousal, cognitive, positive, and social domain scores were associated with increased length of stay in multiple regression models, adjusted for age, sex, race, private insurance, voluntary admission, and diagnostic categories. In similarly adjusted models, odds of hospital admission were increased by higher RDoC arousal and cognitive domain scores and decreased by higher negative domain scores. CONCLUSIONS: A natural language processing tool to characterize dimensional psychopathology identified features associated with differential outcomes in children in the psychiatric ED, most notably symptoms reflecting arousal and cognitive function. Methodologically, this in silico approach to risk stratification should facilitate precision psychiatry in children within the emergency setting.

Norepinephrine and serotonin imbalance in the locus coeruleus in bipolar disorder.

OBJECTIVES: Abnormalities in norepinephrine (NE) and serotonin (5-HT) are implicated in bipolar disorder (BD). We examined 5-HT input and NE neurons in the locus coeruleus (LC, the NE nucleus that innervates the forebrain) in BD by quantifying immunoreactivity (IR) for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the biosynthetic enzymes for NE and 5-HT, respectively. METHODS: Six suicides with BD were compared to matched normal controls and unipolar major depression suicides, using immunocytochemistry with computer-assisted quantification of immunoreactivity. RESULTS: Depressed bipolar suicides had 26.7 +/- 1.3% of LC area occupied by the TH immunoreactive (TH-IR) process, while controls had 50.7 +/- 8% (p = 0.002) and unipolar depressed suicides had 50.3 +/- 2.5% (p = 0.003). In bipolars, these processes did not stain as darkly (1.9 +/- 0.5 x background) as controls (2.9 +/- 0.9 x background; p = 0.01) or unipolars (2.9 +/- 0.6 x background; p = 0.002). Bipolar suicides also had less TPH-IR processes in the LC (11.7 +/- 10%) compared with controls (32.8 +/- 8.8%; p = 0.01) or unipolar suicides (30.3 +/- 8%; p = 0.02). The TPH-IR intensity did not differ between groups. CONCLUSIONS: We found less TH-IR and TPH-IR in the LC in depressed bipolar suicides, but not unipolar suicides, suggesting that both NE and 5-HT activity is lower in BD. Studies during manic or euthymic states will determine whether these changes are mood state dependent.

Recurrent de novo mutations of SCN1A in severe myoclonic epilepsy of infancy.

Mutations in the voltage-gated sodium channel gene SCN1A are a major cause of severe myoclonic epilepsy of infancy (Dravet syndrome) and generalized epilepsy with febrile seizures plus. This study reports the identification of six de novo SCN1A mutations in patients with severe myoclonic epilepsy of infancy, including a tetranucleotide deletion in exon 26. The same deletion was previously observed in two unrelated patients and appears to result from slipped-strand mispairing of a direct repeat during deoxyribonucleic acid replication. Review of the literature indicates that recurrent mutations account for 25% of SCN1A mutations in severe myoclonic epilepsy of infancy, including six sites of deamination at CpG dinucleotides.

Addictions and their familiality in Iceland.

Here, we provide an overview of previous family studies of addiction and present a new family study based on clinical data for more than 19,000 individuals who have been treated for addiction in Iceland over the last three decades. Coupled with the extensive Icelandic genealogy information, this population-based sample provides a unique opportunity for family studies. The relative risk (RR) was determined for up to fifth-degree relatives of probands diagnosed with alcohol, cannabis, sedative, and amphetamine dependence. We observe highly significant RR values for all substances ranging from 2.27 for alcohol to 7.3 for amphetamine, for first-degree relatives, and RRs significantly above 1 for distant relations, where the effect of shared environmental factors is minimized. The magnitude of risk in psychostimulant dependence is particularly striking. These findings emphasize the role of genetics in the etiology of addiction and highlight the importance of substance-specific effects.