Delayed neuropathy due to organophosphate insecticide injection in an attempt to commit suicide.
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ABSTRACT:
SUBMITTER: Ergun SS
PROVIDER: S-EPMC2654942 | biostudies-other | 2009 Mar
REPOSITORIES: biostudies-other
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Project description:The organophosphate-induced delayed neuropathy (OPIDN), often leads to paresthesias, ataxia and paralysis, occurs in the late-stage of acute poisoning or after repeated exposures to organophosphate (OP) insecticides or nerve agents, and may contribute to the Gulf War Syndrome. The acute phase of OP poisoning is often attributed to acetylcholinesterase inhibition. However, the underlying mechanism for the delayed neuropathy remains unknown and no treatment is available. Here we demonstrate that TRPA1 channel (Transient receptor potential cation channel, member A1) mediates OPIDN. A variety of OPs, exemplified by malathion, activates TRPA1 but not other neuronal TRP channels. Malathion increases the intracellular calcium levels and upregulates the excitability of mouse dorsal root ganglion neurons in vitro. Mice with repeated exposures to malathion also develop local tissue nerve injuries and pain-related behaviors, which resembles OPIDN. Both the neuropathological changes and the nocifensive behaviors can be attenuated by treatment of TRPA1 antagonist HC030031 or abolished by knockout of Trpa1 gene. In the classic hens OPIDN model, malathion causes nerve injuries and ataxia to a similar level as the positive inducer tri-ortho-cresyl phosphate (TOCP), which also activates TRPA1 channel. Treatment with HC030031 reduces the damages caused by malathion or tri-ortho-cresyl phosphate. Duloxetine and Ketotifen, two commercially available drugs exhibiting TRPA1 inhibitory activity, show neuroprotective effects against OPIDN and might be used in emergency situations. The current study suggests TRPA1 is the major mediator of OPIDN and targeting TRPA1 is an effective way for the treatment of OPIDN.
| S-EPMC5537602 | biostudies-literature
Project description:An 89-year-old man attempted suicide by ingesting a pesticide (trichlorfon). After surviving the initial critical period in the intensive care unit, he developed rapidly progressive distal weakness and sensory disturbance. Electrophysiological examinations revealed sensory motor axonal polyneuropathy. Delayed polyneuropathy is a rare manifestation of organophosphate poisoning. Nerve conduction studies play an important role in the diagnosis of this rare clinical condition.
| S-EPMC5548687 | biostudies-other
Project description:BackgroundHow does genetic liability to suicide attempt (SA), suicide death (SD), major depression (MD), bipolar disorder (BD), schizophrenia (SZ), alcohol use disorder (AUD), and drug use disorder (DUD) impact on risk for SA and SD?MethodsIn the Swedish general population born 1932-1995 and followed through 2017 (n = 7 661 519), we calculate family genetic risk scores (FGRS) for SA, SD, MD, BD, SZ, AUD, and DUD. Registration for SA and SD was assessed from Swedish national registers.ResultsIn univariate and multivariate models predicting SA, FGRS were highest for SA, AUD, DUD, and MD. In univariate models predicting SD, the strongest FGRS were AUD, DUD, SA, and SD. In multivariate models, the FGRS for SA and AUD were higher in predicting SA while the FGRS for SD, BD, and SZ were higher in predicting SD. Higher FGRS for all disorders significantly predicted both younger age at first SA and frequency of attempts. For SD, higher FGRS for MD, AUD, and SD predicted later age at SD. Mediation of FGRS effects on SA and SD was more pronounced for SD than SA, strongest for AUD, DUD, and SZ FGRS and weakest for MD.ConclusionsFGRS for both SA and SD and for our five psychiatric disorders impact on risk for SA and SD in a complex manner. While some of the impact of genetic risk factors for psychiatric disorders on risk for SA and SD is mediated through developing the disorders, these risks also predispose directly to suicidal behaviors.
| S-EPMC10916711 | biostudies-literature
Project description:Blunted neurohormonal responses to serotonergic agents are found in major depression and suicidal behavior, but there have been no prospective studies of their relationship to later suicide attempt. In this study, healthy volunteers and depressed subjects were administered a fenfluramine (FEN) and placebo challenge test at baseline and then followed for 2 years. Seven subjects made suicide attempts within the follow-up period. Healthy volunteers, depressed non-attempters, depressed past suicide attempters, and depressed future attempters were compared on plasma prolactin and cortisol responses, as well as on mood (Profile of Mood States; POMS) and behavioral measures that were assessed at baseline and at the end of each challenge testing day. Both past and future attempters had lower total prolactin output (area under the curve) in response to FEN relative to non-patients. Future attempters had lower cortisol response relative to all other groups. All subject groups reported a decrease in POMS Fatigue subscale score and increase in finger tapping rate after receiving FEN. Depressed subjects reported a significant decline in POMS Total, Depression, and Tension/Anxiety scores, but future attempters' did not, showing a slight mean increase. Lower cortisol response correlated with greater suicidal ideation 3 months and 1 year post-study. Logistic regression revealed that blunting of cortisol response and worsening of mood after FEN, and younger age could be used to predict later suicide attempt in the majority of cases (4/7). Results suggest that blunted cortisol and unfavorable acute mood response to serotonergic challenge, in the context of the general activating effects of these drugs, may be a risk factor for later suicide attempt.
| S-EPMC3055397 | biostudies-other
Project description:OBJECTIVES:Organophosphate (OP) pesticides inhibit both red blood cell (RBC) and plasma cholinesterases (ChEs). Oximes, especially pralidoxime (2-PAM), are widely used as antidotes to treat OP poisoning. In addition, N-acetylcysteine (NAC) is sometimes used as an adjuvant antidote. The current study aimed to assess the feasibility of using NAC as a single therapeutic agent for OP poisoning in comparison to in vitro 2-PAM. METHODS:This study was carried out at the Razi Drug Research Center of Iran University of Medical Sciences, Tehran, Iran, between April and September 2014. A total of 22 healthy human subjects were recruited and 8 mL citrated blood samples were drawn from each subject. Dichlorvos-inhibited blood samples were separately exposed to low and high doses (final concentrations of 300 and 600 μmol.L-1, respectively) of 2-PAM, NAC and cysteine. Plasma and RBCs were then separated by centrifugation and their ChE activity was measured using spectrophotometry. RESULTS:Although cysteine-and not NAC-increased the ChE activity of both plasma and RBCs over those of dichlorvos, it did not increase them over those of a high dose of 2-PAM. CONCLUSION:These results suggest that the direct reactions of 2-PAM and cysteine with dichlorvos and the reactivation of phosphorylated ChEs occurr via an associative stepwise addition-elimination process. High therapeutic blood concentrations of cysteine are needed for the elevation of ChE activity in plasma and RBCs; however, both this agent and NAC may still be effective in the reactivation of plasma and RBC ChEs.
| S-EPMC5642358 | biostudies-other
Project description:Suicide accounts for nearly 800,000 deaths per year worldwide with rates of both deaths and attempts rising. Family studies have estimated substantial heritability of suicidal behavior; however, collecting the sample sizes necessary for successful genetic studies has remained a challenge. We utilized two different approaches in independent datasets to characterize the contribution of common genetic variation to suicide attempt. The first is a patient reported suicide attempt phenotype asked as part of an online mental health survey taken by a subset of participants (n = 157,366) in the UK Biobank. After quality control, we leveraged a genotyped set of unrelated, white British ancestry participants including 2433 cases and 334,766 controls that included those that did not participate in the survey or were not explicitly asked about attempting suicide. The second leveraged electronic health record (EHR) data from the Vanderbilt University Medical Center (VUMC, 2.8 million patients, 3250 cases) and machine learning to derive probabilities of attempting suicide in 24,546 genotyped patients. We identified significant and comparable heritability estimates of suicide attempt from both the patient reported phenotype in the UK Biobank (h2SNP = 0.035, p = 7.12 × 10-4) and the clinically predicted phenotype from VUMC (h2SNP = 0.046, p = 1.51 × 10-2). A significant genetic overlap was demonstrated between the two measures of suicide attempt in these independent samples through polygenic risk score analysis (t = 4.02, p = 5.75 × 10-5) and genetic correlation (rg = 1.073, SE = 0.36, p = 0.003). Finally, we show significant but incomplete genetic correlation of suicide attempt with insomnia (rg = 0.34-0.81) as well as several psychiatric disorders (rg = 0.26-0.79). This work demonstrates the contribution of common genetic variation to suicide attempt. It points to a genetic underpinning to clinically predicted risk of attempting suicide that is similar to the genetic profile from a patient reported outcome. Lastly, it presents an approach for using EHR data and clinical prediction to generate quantitative measures from binary phenotypes that can improve power for genetic studies.
| S-EPMC6609505 | biostudies-literature
Project description:BackgroundDespite a reported high rate of mental disorders in refugees, scientific knowledge on their risk of suicide attempt and suicide is scarce. We aimed to investigate (1) the risk of suicide attempt and suicide in refugees in Sweden, according to their country of birth, compared with Swedish-born individuals and (2) to what extent time period effects, socio-demographics, labour market marginalisation (LMM) and morbidity explain these associations.MethodsThree cohorts comprising the entire population of Sweden, 16-64 years at 31 December 1999, 2004 and 2009 (around 5 million each, of which 3.3-5.0% refugees), were followed for 4 years each through register linkage. Additionally, the 2004 cohort was followed for 9 years, to allow analyses by refugees' country of birth. Crude and multivariate hazard ratios (HRs) with 95% confidence intervals (CIs) were computed. The multivariate models were adjusted for socio-demographic, LMM and morbidity factors.ResultsIn multivariate analyses, HRs regarding suicide attempt and suicide in refugees, compared with Swedish-born, ranged from 0.38-1.25 and 0.16-1.20 according to country of birth, respectively. Results were either non-significant or showed lower risks for refugees. Exceptions were refugees from Iran (HR 1.25; 95% CI 1.14-1.41) for suicide attempt. The risk for suicide attempt in refugees compared with the Swedish-born diminished slightly across time periods.ConclusionsRefugees seem to be protected from suicide attempt and suicide relative to Swedish-born, which calls for more studies to disentangle underlying risk and protective factors.
| S-EPMC7893509 | biostudies-literature
Project description:BackgroundSeveral original studies have investigated the effect of alcohol use disorder (AUD) on suicidal thought and behavior, but there are serious discrepancies across the studies. Thus, a systematic assessment of the association between AUD and suicide is required.MethodsWe searched PubMed, Web of Science, and Scopus until February 2015. We also searched the Psycinfo web site and journals and contacted authors. We included observational (cohort, case-control, and cross-sectional) studies addressing the association between AUD and suicide. The exposure of interest was AUD. The primary outcomes were suicidal ideation, suicide attempt, and completed suicide. We assessed heterogeneity using Q-test and I2 statistic. We explored publication bias using the Egger's and Begg's tests and funnel plot. We meta-analyzed the data with the random-effects models. For each outcome we calculated the overall odds ratio (OR) or risk ratio (RR) with 95% confidence intervals (CI).ResultsWe included 31 out of 8548 retrieved studies, with 420,732 participants. There was a significant association between AUD and suicidal ideation (OR=1.86; 95% CI: 1.38, 2.35), suicide attempt (OR=3.13; 95% CI: 2.45, 3.81); and completed suicide (OR=2.59; 95% CI: 1.95, 3.23 and RR=1.74; 95% CI: 1.26, 2.21). There was a significant heterogeneity among the studies, but little concern to the presence of publication bias.ConclusionsThere is sufficient evidence that AUD significantly increases the risk of suicidal ideation, suicide attempt, and completed suicide. Therefore, AUD can be considered an important predictor of suicide and a great source of premature death.
| S-EPMC4439031 | biostudies-literature
Project description:Suicide has been associated with smoking/tobacco use but its association of and change in smoking/tobacco use status with suicide attempt (SA) is not well established.We investigated whether persistent, former tobacco use, initiation, quitting tobacco use, relapse to tobacco use, and DSM-IV nicotine dependence predict independently SA using Wave 1 and 2 data of the National Epidemiologic Survey of Alcohol and Related Conditions. Data from 34,653 US adults interviewed at Wave 1 (2001-02) and Wave 2 (2004-05) were analyzed. The main outcome measure was SA between Wave 1 and Wave 2 as reported at Wave 2.Among the 1,673 respondents reporting lifetime SA at Wave 2, 328 individuals reported SA between Wave 1 and Wave 2. Current and former tobacco use at Wave 1 predicted Wave 2 SA independently of socio-demographic characteristics, psychiatric history, and prior SA (Adjusted Odds Ratio (AOR): 1.49; 95% CI: 1.13-1.95, AOR: 1.31; 95% CI:1.01-1.69, respectively versus never tobacco users). The strongest association with SA was observed among former tobacco users who relapsed after Wave 1 (AOR: 4.66; 95% CI: 3.49-6.24) and among tobacco use initiators after Wave 1 (AOR: 3.16; 95% CI: 2.23-4.49). Persistent tobacco use (current tobacco use at both Wave 1 and Wave 2) also had an increased risk of SA (AOR: 1.89; 95% CI: 1.47-2.42). However, former tobacco users in both Waves 1 and 2 did not show a significantly elevated risk for SA in Wave 2 (AOR:1.09, 95% CI: 0.78-1.52) suggesting that the risk resided mainly in Wave 1 former tobacco users who relapsed to tobacco use by Wave 2. DSM-IV nicotine dependence did not predict SA at Wave 2.In a representative sample of US adults, relapse, tobacco use initiation, and persistent tobacco use, which are amenable to intervention, were associated with risk of SA.
| S-EPMC4388646 | biostudies-other
Project description:ImportanceMental health of soldiers is adversely affected by the death and injury of other unit members, but whether risk of suicide attempt is influenced by previous suicide attempts in a soldier's unit is unknown.ObjectiveTo examine whether a soldier's risk of suicide attempt is influenced by previous suicide attempts in that soldier's unit.Design, setting, and participantsUsing administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (STARRS), this study identified person-month records for all active-duty, regular US Army, enlisted soldiers who attempted suicide from January 1, 2004, through December 31, 2009 (n = 9650), and an equal-probability sample of control person-months (n = 153 528). Data analysis was performed from August 8, 2016, to April 10, 2017.Main outcomes and measuresLogistic regression analyses examined the number of past-year suicide attempts in a soldier's unit as a predictor of subsequent suicide attempt, controlling for sociodemographic features, service-related characteristics, prior mental health diagnosis, and other unit variables, including suicide-, combat-, and unintentional injury-related unit deaths. The study also examined whether the influence of previous unit suicide attempts varied by military occupational specialty (MOS) and unit size.ResultsOf the final analytic sample of 9512 enlisted soldiers who attempted suicide and 151 526 control person-months, most were male (86.4%), 29 years or younger (68.4%), younger than 21 years when entering the army (62.2%), white (59.8%), high school educated (76.6%), and currently married (54.8%). In adjusted models, soldiers were more likely to attempt suicide if 1 or more suicide attempts occurred in their unit during the past year (odds ratios [ORs], 1.4-2.3; P < .001), with odds increasing as the number of unit attempts increased. The odds of suicide attempt among soldiers in a unit with 5 or more past-year attempts was more than twice that of soldiers in a unit with no previous attempts (OR, 2.3; 95% CI, 2.1-2.6). The association of previous unit suicide attempts with subsequent risk was significant whether soldiers had a combat arms MOS or other MOS (ORs, 1.4-2.3; P < .001) and regardless of unit size, with the highest risk among those in smaller units (1-40 soldiers) (ORs, 2.1-5.9; P < .001). The population-attributable risk proportion for 1 or more unit suicide attempts in the past year indicated that, if this risk could be reduced to no unit attempts, 18.2% of attempts would not occur.Conclusions and relevanceRisk of suicide attempt among soldiers increased as the number of past-year suicide attempts within their unit increased for combat arms and other MOSs and for units of any size but particularly for smaller units. Units with a history of suicide attempts may be important targets for preventive interventions.
| S-EPMC5674988 | biostudies-literature