p.L1612P, a novel voltage-gated sodium channel Nav1.7 mutation inducing a cold sensitive paroxysmal extreme pain disorder.

BACKGROUND: Mutations in the SCN9A gene cause chronic pain and pain insensitivity syndromes. We aimed to study clinical, genetic, and electrophysiological features of paroxysmal extreme pain disorder (PEPD) caused by a novel SCN9A mutation. METHODS: Description of a 4-generation family suffering from PEPD with clinical, genetic and electrophysiological studies including patch clamp experiments assessing response to drug and temperature. RESULTS: The family was clinically comparable to those reported previously with the exception of a favorable effect of cold exposure and a lack of drug efficacy including with carbamazepine, a proposed treatment for PEPD. A novel p.L1612P mutation in the Nav1.7 voltage-gated sodium channel was found in the four affected family members tested. Electrophysiologically the mutation substantially depolarized the steady-state inactivation curve (V1/2 from -61.8 ± 4.5 mV to -30.9 ± 2.2 mV, n = 4 and 7, P < 0.001), significantly increased ramp current (from 1.8% to 3.4%, n = 10 and 12) and shortened recovery from inactivation (from 7.2 ± 5.6 ms to 2.2 ± 1.5 ms, n = 11 and 10). However, there was no persistent current. Cold exposure reduced peak current and prolonged recovery from inactivation in wild-type and mutated channels. Amitriptyline only slightly corrected the steady-state inactivation shift of the mutated channel, which is consistent with the lack of clinical benefit. CONCLUSIONS: The novel p.L1612P Nav1.7 mutation expands the PEPD spectrum with a unique combination of clinical symptoms and electrophysiological properties. Symptoms are partially responsive to temperature but not to drug therapy. In vitro trials of sodium channel blockers or temperature dependence might help predict treatment efficacy in PEPD.

Observational study of suicide in Switzerland: comparison between psychiatric in- and outpatients.

AIMS OF THE STUDY: In Switzerland, suicide is a major cause of years of potential life lost. Among people who died by suicide, a significant number suffered from mental illness and were treated by psychiatric care institutions. Psychiatric patients are thus a specific target for suicide prevention. Based on data from a clinical committee reviewing every death by suicide of psychiatric patients in the Canton of Vaud (Switzerland), this observational study aimed to gain knowledge on sociodemographic and clinical characteristics of psychiatric patients who died by suicide by comparing in- and outpatients. METHODS: Sociodemographic and clinical characteristics of patients who died by suicide in our department from January 2007 to December 2019 were analysed. In- and outpatients were compared. RESULTS: The sample included 153 patients (64.7% males, n = 99). Three quarters (76.4%, n = 81) of the patients had at least one previous suicide attempt. In- and outpatients did not differ significantly in terms of sociodemographics data, psychiatric diagnosis or method of suicide. Almost all (97.2%) of the outpatients had at least one past psychiatric hospitalisation. We found gender disparities for several variables and a lower male/female suicide ratio than in the general Swiss population. Seventy-two percent of the outpatients (n = 49) had a last personal contact with clinicians less than a week before their suicide and 38.8 % of those less than 24 hours (28% of outpatients, n = 19). CONCLUSIONS: Patients dying by suicide present most of the time a serious psychiatric history. In- and outpatients seem to have a similar clinical and sociodemographic profile and suicide prevention should thus not be addressed differently in these two groups. The time between death of outpatients and last contact with a therapist was shorter than expected.