RESUMEN
SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.
RESUMEN
BACKGROUND: Bipolar disorder (BD) is a mental health condition that has one of the greatest risk of completed suicide (CS). Hospitalization in affective disorders is associated with increased illness severity and suicide risk, so the study of suicide after the first hospitalization is of special interest. METHOD: We studied a retrospective cohort consisting on all BD type I (BD-I) and II (BD-II) (according to DSM-IV criteria) admitted for the first time in their lives to the psychiatry unit of a general hospital between 1996 and 2016 from an area in Catalonia (Spain). All patients were also followed-up in a community center of mental health as outpatients until the end of 2017. Multiple variables were prospectively collected during the first hospital admission and were compared between patients who CS and those who did not. RESULTS: 14 of 313 (4.5%) bipolar patients included CS during the 11-year follow-up, and 93% used a violent method. In the univariate analysis we found that Bipolar II Disorder, treatment with antidepressants and/or with lamotrigine were associated with higher risk of CS, however, treatment with valproate and/or with antipsychotics were associated with lower risk of CS . After logistic regression multivariant analysis, only immediately previous violent suicide attempt and first-degree family history of CS remain significant risk factors of CS. A limitation is the relatively small sample from a local hospital and followed locally. CONCLUSION: Followed during an average of 11 years after the first hospital admission, Bipolar patients completed suicide at a rate 58 times higher than the general population and almost always performed through a violent method. Violent attempted suicide before admission and first- degree family history of CS, are clear and potent predictors of completed suicide.
