The impact of self-efficacy, alexithymia and multiple traumas on posttraumatic stress disorder and psychiatric co-morbidity following epileptic seizures: A moderated mediation analysis

This study investigated the incidence of posttraumatic stress disorder (PTSD) and psychiatric co-morbidity following epileptic seizure, whether alexithymia mediated the relationship between self-efficacy and psychiatric outcomes, and whether the mediational effect was moderated by the severity of PTSD from other traumas. Seventy-one (M=31, F=40) people with a diagnosis of epilepsy recruited from support groups in the United Kingdom completed the Posttraumatic Stress Diagnostic Scale, the Hospital Anxiety and Depression Scale, the Toronto Alexithymia Scale-20 and the Generalized Self-Efficacy Scale. They were compared with 71 people (M=29, F=42) without epilepsy. For people with epilepsy, 51% and 22% met the diagnostic criteria for post-epileptic seizure PTSD and for PTSD following one other traumatic life event respectively. For the control group, 24% met the diagnostic criteria for PTSD following other traumatic life events. The epilepsy group reported significantly more anxiety and depression than the control. Partial least squares (PLS) analysis showed that self-efficacy was significantly correlated with alexithymia, post-epileptic seizure PTSD and psychiatric co-morbidity. Alexithymia was also significantly correlated with post-epileptic seizure PTSD and psychiatric co-morbidity. Mediation analyses confirmed that alexithymia mediated the path between self-efficacy and post-epileptic seizure PTSD and psychiatric co-morbidity. Moderated mediation also confirmed that self-efficacy and PTSD from one other trauma moderated the effect of alexithymia on outcomes. To conclude, people can develop posttraumatic stress disorder symptoms and psychiatric co-morbidity following epileptic seizure. These psychiatric outcomes are closely linked with their belief in personal competence to deal with stressful situations and regulate their own functioning, to process rather than defend against distressing emotions, and with the degree of PTSD from other traumas. © 2013 Elsevier Ireland Ltd

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK

Imipramine Treatment of Children with Separation Anxiety Disorder

The efficacy of imipramine was investigated in 20 children (ages 6 to 15) with separation anxiety disorder. Children were treated for a month with vigorous behavioral treatment. If they did not respond, they entered a double-blind, randomized, 6-week trial of imipramine or placebo. Of 45 children accepted, 21 (47%) entered the trial. About half the children improved with either treatment, and no superiority for imipramine was obtained. There was no instance of clinically significant EKG changes. This small study failed to replicate previous findings of imipramine efficacy in a similar, but larger, clinical population. J. Am. Acad. Child Adolesc. Psychiatry, 1992, 31, 1:21–28

Use of Imipramine in Children with Intractable Asthma and Psychiatric Disorders: A Warning

Imipramine is an established treatment for anxiety in adults. Some evidence also exists that it may be beneficial in children. Because of the frequent co-occurrence of anxiety and affective symptomatology in asthmatic children, a pilot study was undertaken to obtain clinical observations on the effects of imipramine on symptoms of asthma as well as those of separation anxiety and depression in children suffering from intractable asthma. The pilot trial was terminated because of medical complications after 6 patients participated

High prevalence of hepatitis B virus susceptibility among persons undergoing community-based hepatitis C virus treatment

BackgroundDue to shared modes of transmission, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is common, and HBV vaccination is recommended for all persons with HCV who remain susceptible to HBV. To identify potential gaps in HBV vaccination among this high-risk population, we aimed to determine the patterns of HBV susceptibility in persons undergoing community-based HCV treatment.MethodsWe performed a cross-sectional study within two community-based HCV treatment programs in an urban US setting. Participants were identified for HCV screening and confirmatory testing via street-outreach recruitment directed at persons experiencing homelessness and currently using drugs. Participants were excluded if HBsAg was reactive. Cohort characteristics were obtained via intake surveys and descriptive analysis was performed by exposure status.ResultsAmong 150 participants without chronic HBV receiving community-based HCV treatment, 43% had evidence of prior HBV infection, 26% were immune from vaccination, and 31% were non-immune. Among the subset of the cohort reporting current injection drug use (IDU) (N = 100), 31% (n = 10) of those aged 24-40 and 47% (n = 23) of those aged 41-57 remained susceptible to HBV infection. By contrast only two participants aged 58-74 were HBV non-immune (11%), with 84% immune due to prior exposure.ConclusionsOur data reflect a high prevalence of HBV susceptibility among persons undergoing community-based HCV treatment. Although younger patients were more likely to be immune due to vaccination, a high proportion remained non-immune to HBV, particularly among those reporting current IDU. Our data reflect a gap in HBV vaccination among younger persons with HCV and suggest a potential role for co-localizing HBV vaccination with community-based HCV screening and treatment

High prevalence of hepatitis B virus susceptibility among persons undergoing community-based hepatitis C virus treatment

Abstract Background Due to shared modes of transmission, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is common, and HBV vaccination is recommended for all persons with HCV who remain susceptible to HBV. To identify potential gaps in HBV vaccination among this high-risk population, we aimed to determine the patterns of HBV susceptibility in persons undergoing community-based HCV treatment. Methods We performed a cross-sectional study within two community-based HCV treatment programs in an urban US setting. Participants were identified for HCV screening and confirmatory testing via street-outreach recruitment directed at persons experiencing homelessness and currently using drugs. Participants were excluded if HBsAg was reactive. Cohort characteristics were obtained via intake surveys and descriptive analysis was performed by exposure status. Results Among 150 participants without chronic HBV receiving community-based HCV treatment, 43% had evidence of prior HBV infection, 26% were immune from vaccination, and 31% were non-immune. Among the subset of the cohort reporting current injection drug use (IDU) (N = 100), 31% (n = 10) of those aged 24–40 and 47% (n = 23) of those aged 41–57 remained susceptible to HBV infection. By contrast only two participants aged 58–74 were HBV non-immune (11%), with 84% immune due to prior exposure. Conclusions Our data reflect a high prevalence of HBV susceptibility among persons undergoing community-based HCV treatment. Although younger patients were more likely to be immune due to vaccination, a high proportion remained non-immune to HBV, particularly among those reporting current IDU. Our data reflect a gap in HBV vaccination among younger persons with HCV and suggest a potential role for co-localizing HBV vaccination with community-based HCV screening and treatment