Diagnostic Yield of Epilepsy-Genes Sequencing and Chromosomal Microarray in Pediatric Epilepsy.

BACKGROUND: Around 40% of individuals with epilepsy have an underlying identifiable genetic etiology. Common methods for epilepsy genetic testing are chromosomal microarray (CMA) and epilepsy-genes sequencing (EGS). Historically, CMA was the first-line test for patients with epilepsy, but recent studies have shown that EGS has a superior diagnostic yield. To further optimize testing algorithms for epilepsy, we compared these tests' diagnostic yields and explored how they are influenced by age of onset and phenotype complexity. METHODS: Genetic test results from a cohort of patients with epilepsy were used to determine the diagnostic yield of CMA (n = 366) versus EGS (n = 370) for genetic epilepsy etiologies. Further analysis examined the probability of diagnostic results based on age of seizure onset and patients' phenotype complexity. RESULTS: For patients who underwent CMA, causative variants were found in 28 of 366 cases (7.7%), and 60 of 366 patients (16.4%) had at least one variant of uncertain significance (VUS). For EGS, 65 of 370 (17.6%) cases had causative variants, whereas 155 of 370 (41.9%) had at least one VUS. EGS had a significantly higher diagnostic yield than CMA (odds ratio [OR] = 2.63, P < 0.001). This difference in diagnostic yield was further pronounced among patients with infantile seizure onset (OR = 4.69, P < 0.001) and patients with additional neurological findings (OR = 2.99, P < 0.001). CONCLUSION: To minimize the time and resources required to reach a diagnosis, clinicians and insurers alike should consider using EGS as an initial diagnostic tool.

Don't Ditch the Laptop Just Yet: A Direct Replication of Mueller and Oppenheimer's (2014) Study 1 Plus Mini Meta-Analyses Across Similar Studies.

In this direct replication of Mueller and Oppenheimer's (2014) Study 1, participants watched a lecture while taking notes with a laptop (n = 74) or longhand (n = 68). After a brief distraction and without the opportunity to study, they took a quiz. As in the original study, laptop participants took notes containing more words spoken verbatim by the lecturer and more words overall than did longhand participants. However, laptop participants did not perform better than longhand participants on the quiz. Exploratory meta-analyses of eight similar studies echoed this pattern. In addition, in both the original study and our replication, higher word count was associated with better quiz performance, and higher verbatim overlap was associated with worse quiz performance, but the latter finding was not robust in our replication. Overall, results do not support the idea that longhand note taking improves immediate learning via better encoding of information.

Persistent escalation of alcohol consumption by mice exposed to brief episodes of social defeat stress: suppression by CRF-R1 antagonism.

RATIONALE: Episodic bouts of social stress can precede the initiation, escalation, or relapse to disordered alcohol intake. Social stress may engender neuroadaptations in the hypothalamic-pituitary-adrenal (HPA) axis and in extrahypothalamic stress circuitry to promote the escalation of alcohol intake. OBJECTIVES: We aimed to (1) confirm a pattern of escalated drinking in socially defeated mice and to (2) test drugs that target distinct aspects of the HPA axis and extrahypothalamic neural substrates for their effectiveness in reducing murine, stress-escalated drinking. METHODS: Male C57BL/6J (B6) mice were socially defeated by resident Swiss-derived males for ten consecutive days receiving 30 bites/day. Ten days after the final defeat, cohorts of B6 mice received continuous or intermittent access to 20% EtOH (w/v) and water. After 4 weeks of drinking, mice were injected with weekly, systemic doses of the CRF-R1 antagonist, CP376395; the glucocorticoid receptor antagonist, mifepristone; the 11-beta-hydroxylase inhibitor, metyrapone; or the 5-alpha-reductase inhibitor, finasteride. RESULTS: Prior to drug treatments, defeated mice reliably consumed more EtOH than non-defeated controls, and mice given alcohol intermittently consumed more EtOH than those with continuous access. CP376395 (17-30 mg/kg) reduced continuous, but not intermittent EtOH intake (g/kg) in socially defeated mice. Mifepristone (100 mg/kg), however, increased drinking by defeated mice with intermittent access to alcohol while reducing drinking during continuous access. When administered finasteride (100 mg/kg) or metyrapone (50 mg/kg), all mice reduced their EtOH intake while increasing their water consumption. CONCLUSIONS: Mice with a history of episodic social defeat stress were selectively sensitive to the effects of CRF-R1 antagonism, suggesting that CRF-R1 may be a potential target for treating alcohol use disorders in individuals who escalate their drinking after exposure to repeated bouts of psychosocial stress. Future studies will clarify how social defeat stress may alter the expression of extrahypothalamic CRF-R1 and glucocorticoid receptors.