Crime-scene and offender characteristics in conventional and nonconventional stranger homicides committed by male offenders in Sweden.

In Sweden, from 1990 to 2013, most homicides occurred between family members, friends or acquaintances: the annual rate of incidents between unacquainted offenders and victims ranged between 8% and 13%. In the majority of these "stranger homicides," three common motives, as defined by the precipitating event, could be identified: homicides resulting from a spontaneous altercation; homicides committed in the context of a robbery or burglary; and homicides committed in the context of a gangland conflict. The remaining minority-with uncommon or indiscernible motives-could, nonetheless, be categorized according to their nonconventional distinguishing feature: homicides characterized by the offender's ostensibly mentally aberrant behavior; homicides committed in the context of a hate offense or politically motivated offense; homicides committed in the context of a sexual offense; and homicides committed in the context of a mass killing or series of homicides. In this registry-based study of 224 incidents, "conventional" stranger homicides, defined by their commonplace motive, were compared with "nonconventional" stranger homicides, defined by their lack of such motive. The former were more often committed with an accomplice, against a male victim, whereas the latter were more often committed in a public place, after contact initiated by the offender. In the latter, offenders were less often intoxicated at the time of the offense and more often adjudged to suffer from a severe mental disorder. The subcategory of nonconventional stranger homicides characterized by the offender's ostensibly mentally aberrant behavior corresponded largely to both the archetypal stranger-homicide construct and the popular notion "act of madness."

Duration of forensic psychiatric care and subsequent criminal recidivism in individuals sentenced in Sweden between 2009 and 2019.

Background: The duration of forensic psychiatric care is in Sweden not determined at the time of sentencing; instead, offenders are regularly evaluated, often with regard to risk of criminal recidivism. The length and justifiability of such a sanction have been greatly debated; however, previous estimates of treatment duration based on datasets delimited to discharged patients-have provided an uncertain groundwork for these deliberations. The aim of this study was to use a more suitable approach to calculate average duration of forensic psychiatric care and to examine the relationship between length of treatment and subsequent recidivism after discharge. Methods: This retrospective cohort study focused on offenders sentenced to forensic psychiatric care in Sweden between 2009 and 2019 and registered in the Swedish National Forensic Psychiatric Register (n = 2064), with a follow-up period until May 2020. We used Kaplan-Meier estimator to calculate and visualize treatment duration including analyses comparing levels of relevant variables, and then evaluated criminal recidivism in patients discharged from treatment between 2009 and 2019 (n = 640), after stratification for the same variables and dichotomization by treatment duration. Results: The median duration of forensic psychiatric care was estimated to 89.7 months (95% CI 83.2-95.8). Treatment was longer in offenders who committed violent crimes, suffered from psychosis, or had a history of substance use disorder, and in offenders whose sentences included special court supervision. The cumulative incidence of recidivism in patients discharged from treatment was estimated to 13.5% at 12 months (95% CI 10.6-16.2) and 19.5% at 24 months (95% CI 16.0-22.8). Corresponding cumulative incidence of violent crime post discharge was 6.3% at 12 months (95% CI 4.3-8.3) and 9.9% at 24 months (95% CI 7.3-12.4). Among other findings, in patients without a history of substance use disorder and patients whose sentences did not include special court supervision, recidivism was significantly higher in those with a shorter treatment duration. Conclusion: Using the entirety of a suitable, contemporary, prospectively enrolled cohort of mentally ill offenders, we were able to estimate-with greater accuracy than previous studies-the average duration of Swedish forensic psychiatric care and rate of subsequent criminal recidivism.

Infection during childhood and the risk of violent criminal behavior in adulthood.

Infections during brain development appear to contribute to cognitive impairment and aggressive behavior, as well as to a number of developmental mental disorders closely associated with violent criminal behavior. Yet, no study has thus far ever investigated whether infections during brain development increases the risk of violent criminality later in life. In this population-based cohort study, about 2.2 million individuals born in Sweden between the years 1973 and 1995 were included in an effort to estimate the association between infections during childhood (registered ICD-10 diagnoses of infections incurred before the age of 14 years) and violent criminal behavior (registered convictions for a violent crime between the ages of 15 and 38 years, prior to December 31, 2011). After inclusion of several sociodemographic parameters, risks of violent criminal behavior conferred by childhood infections - expressed as hazard ratios (HRs) and 95% confidence intervals (CIs) - were calculated by means of Cox regression. Mediation analyses were performed to explore the effect of psychiatric disorders on the association between infections during childhood and violent criminality. Results revealed a modest, yet significant, association between an infection during childhood and violent criminality later in life (adjusted HR 1.14, 95% CI 1.12-1.16). Infections during the first year of life and infections in the central nervous system were associated with the highest risks of subsequent violent criminality (adjusted HR 1.20, 95% CI 1.18-1.23, and adjusted HR 1.17, 95% CI 1.08-1.26, respectively). The association was partly mediated by the presence of a psychiatric disorder. In summary, independent of a wide range of covariates, our results suggest that infections during brain development could be part of the genesis of violent criminal behavior.

Psychopathy-associated personality traits influence crime-scene behavior in male homicide offenders.

Purpose: We investigated whether psychopathy-associated personality traits and behavioral styles affect the manner in which homicides are committed or the motives underlying them. Materials and methods: Using three nationwide registries and an in-house homicide database based on court verdicts, we identified all cases of homicide in Sweden during the years 2007, 2008 and 2009. In 72 male offenders who had undergone assessment using the Psychopathy Checklist - Revised (PCL-R), the manner of homicide was categorized as instrumental or expressive, and the motive as belonging to one of five categories: (1) intimate-partner or family-related homicide; (2) homicide occurring during altercations, (3) robberies or burglaries, or (4) criminal conflicts; or (5) sexual homicide. Results and conclusions: Offenders who had committed homicide in an instrumental manner or with a sexual motive had higher scores on PCL-R factor 1 than offenders displaying an expressive manner or other motives, suggesting that partially adaptive personality traits influence the crime-scene behavior of the former type of offenders more than maladaptive behavioral styles.

Emergence of Huntington Disease in a Man With a Premorbid Criminal Lifestyle.

We present here a case in which Huntington disease (HD) was diagnosed upon forensic-psychiatric evaluation of a 34-year-old male repeat offender. Despite a family history of HD, as well as overt delusions and motor pathology, the disease had not been recognized at an earlier stage, and the patient was serving a prison sentence at the time of diagnosis. The case highlights difficulties court officials may face with regard to identifying severe psychiatric and neurological disorders in repeat offenders. Such offenders' gradually deteriorating status could be overlooked by the court, even in cases in which a tailored judicial process is warranted. Also, the present case highlights the risk of using antipsychotic medication to treat HD, since it may worsen sufferers' capacity to recognize emotions in others, thereby increasing the risk of altercations and criminal activity.

Adherence to psychotropic medication in completed suicide in Sweden 2006-2013: a forensic-toxicological matched case-control study.

OBJECTIVE: To investigate the influence of adherence to psychotropic medications upon the risk of completed suicide by comparing person-level prescriptions and postmortem toxicological findings among complete-suicide cases and non-suicide controls in Sweden 2006-2013. METHODS: Using national registries with full coverage on dispensed prescriptions, results of medico-legal autopsies, causes of death, and diagnoses from inpatient care, estimated continuous drug use for 30 commonly prescribed psychotropic medications was compared with forensic-toxicological findings. Subjects who had died by suicide (cases) were matched (1:2) with subjects who had died of other causes (controls) for age, sex, and year of death. Odds ratios were calculated using logistic regression to estimate the risk of completed suicide conferred by partial adherence and non-adherence to pharmacotherapy. Adjustments were made for previous inpatient care and the ratio of initiated and discontinued dispensed prescriptions, a measure of the continued need of treatment preceding death. RESULTS: In 5294 suicide cases and 9879 non-suicide controls, after adjusting for the dispensation ratio and other covariates, partial adherence and non-adherence to antipsychotics were associated with 6.7-fold and 12.4-fold risks of completed suicide, respectively, whereas corresponding risk estimates for antidepressant treatment were not statistically significant and corresponding risk increases for incomplete adherence to antidepressant treatment were lower (1.6-fold and 1.5-fold, respectively) and lacked statistical significance. CONCLUSION: After adjustment for the need of treatment, biochemically verified incomplete adherence to antipsychotic pharmacotherapy was associated with markedly increased risks of completed suicide.

Injury-Related Healthcare Use and Risk of Filicide Victimization: A Population-Based Case-Control Study.

Research on child-related risk factors for filicide is scant. We investigated whether prior healthcare use for injury (including poisoning) influences filicide risk. Victims (0-14 years; n = 71) were identified in a national autopsy database for the years 1994-2012 and compared to matched, general population controls (n = 355). Healthcare use data were retrieved from a national patient registry. Risks were estimated using odds ratios (ORs) and 95% confidence intervals (CIs). For females, prior inpatient care for injury conferred a statistically significant sevenfold risk (OR = 6.67 [95% CI: 1.49-29.79]), and any prior injury-related healthcare use conferred a statistically significant fourfold risk (OR = 3.57 [95% CI: 1.13-11.25]), of filicide victimization. No statistically significant risks were found for males. Healthcare personnel should be aware that children treated for injuries, especially females, may be at an elevated risk of filicide victimization. Nevertheless, the filicide base rate remains low, and parents may be stigmatized by unfounded alerts; thus, prudent reflection should precede reports to the authorities.

Selective serotonin re-uptake inhibitors and the risk of violent suicide: a nationwide postmortem study.

PURPOSE: We endeavored to investigate whether previous findings of an association between antemortem exposure to selective serotonin re-uptake inhibitors (SSRI) and method of suicide could be replicated. METHODS: Using the Swedish National Board of Forensic Medicine's toxicology database and the Swedish National Board of Health and Welfare's national registries of causes of death and prescriptions, 10,002 incidents of suicide were retrieved. Risks of violent suicide conferred by SSRIs, expressed as odds ratios (ORs) with 95% confidence intervals (CIs), were estimated using logistic regression. In accordance with previous work, suicide by violent means-cases-were defined as death attributable to causes designated by ICD-10 codes X70-X83 and Y20-Y33; and suicide by non-violent means-controls-by codes X60-X69 and Y10-Y19. RESULTS: Our results imply that SSRI exposure confers a risk of violent suicide for shorter treatment durations; and that antemortem exposure to other substances (including illegal drugs) confounds estimates of risk. After adjustment for age, sex, and other substances, SSRIs treatment not exceeding 28 days conferred an almost fourfold risk of violent suicide (OR 3.6 [95% CI 1.9-6.8]), a finding partly in line with a recent Swedish study that employed a case-crossover design. CONCLUSIONS: Although risks associated with shorter treatment duration may reflect latencies to onset of therapeutic effect, it is unclear how latencies would influence the choice of suicide method, unless conditions for which SSRIs are prescribed are themselves associated with violent suicide. Finally, in the total dataset, SSRIs were not associated with an increased risk of violent suicide; however, by adjusting for other substances, we avoided the spurious conclusion that the effect of medications in this regard is protective.

Pre-offense alcohol intake in homicide offenders and victims: A forensic-toxicological case-control study.

BACKGROUND AND AIM: Alcohol is associated with violent behavior, although little is known regarding to what extent alcohol increases homicide risk. We aimed to estimate risks of homicide offending and victimization conferred by the presence of ethanol in blood by using toxicological data from homicide victims and offenders and from controls who had died in vehicle-related accidents. METHODS: From nationwide governmental registries and databases, forensic-toxicological results were retrieved for victims (n = 200) and offenders (n = 105) of homicides committed during the years 2007-2009 and individuals killed in vehicle-related accidents (n = 1629) during the years 2006-2014. Ethanol levels in blood exceeding 0.01 g/100 ml were considered positive. RESULTS: Using logistic regression, we found that the presence of ethanol in blood conferred a significantly increased risk of homicide offending (age-adjusted odds ratio [aOR] = 3.6, 95% confidence interval [95% CI] = 2.3-5.6) and homicide victimization (aOR = 2.1, 95% CI = 1.4-3.0). After stratification by sex, risk estimates in females were about 3-fold greater than in males for both homicide offending ([aOR = 11.0, 95% CI = 2.4-49.8] versus [aOR = 3.1, 95% CI = 1.9-4.9]) and victimization ([aOR = 5.4, 95% CI = 2.4-12.2] versus [aOR = 1.7, 95% CI = 1.1-2.8]). Sensitivity analyses yielded similar estimates. CONCLUSIONS: The results of the present study are consistent with prior findings suggesting alcohol to be an important risk factor for homicide offending and victimization. Surprisingly, however, associations were more pronounced in females, although additional studies that control for potential confounders are warranted to facilitate speculations about causality.

Comparison of dispensed medications and forensic-toxicological findings to assess pharmacotherapy in the Swedish population 2006 to 2013.

PURPOSE: To investigate person-level agreement between medication exposure as predicted using the PRE2DUP (a prescription-based design to estimate continuous drug use) method and postmortem toxicological findings, in the Swedish population during the years 2006 to 2013. METHODS: Using the Swedish National Board of Forensic Medicine's toxicology database and the Swedish National Board of Health and Welfare's registries on causes of death, dispensed medications, and in-patient care, forensic-toxicological findings were compared with prescription-based estimates of drug use for 27 medications. We modeled expected drug-use periods with the PRE2DUP using an algorithm of demonstrated high validity that evaluates personal drug-purchasing patterns with consideration to possible stockpiling of drugs and package information. Excluding criteria included self-inflicted death and recent in-patient care. RESULTS: In data from 18 627 performed autopsies, as well as 10 160 instances of dispensed drug use, the agreement between PRE2DUP drug-use periods and forensic toxicology was, overall, moderate (Cohen's kappa: 0.56 [95% confidence interval {CI}: 0.55-0.57]) with a positive predictive value, or predicted adherence rate, of 46.0%. The group-level predicted adherence and agreement were highest for antidepressants, at 71.0% (Cohen's kappa: 0.74 [CI: 0.73-0.76]), and lowest for cardiovascular drugs, at 21.5% (Cohen's kappa: 0.33 [CI: 0.31-0.36]). Predicted recreational use (negative predictive value) was low for all investigated drugs (0.0%-1.4%). The biological half-life explained 29% (P = 0.003) of the variability of the false-positive rate. CONCLUSIONS: Measured agreement between PRE2DUP-based drug-use estimates and forensic-toxicological findings is dependent upon a number of factors, including true continuous drug use and postmortem detectability of the investigated drugs, as well as the occurrence of unconventional dosing and true non-adherence.

Psychotropic Medications in Swedish Homicide Victims and Offenders: A Forensic-Toxicological Case-Control Study of Adherence and Recreational Use.

OBJECTIVE: We aimed to assess the extent to which adherence to, and recreational use of, psychotropic medications influence the risk of homicide offending and victimization. METHODS: We conducted a population-based case-control study by way of linking a nationwide registry of dispensed prescriptions with a forensic-toxicological database. Homicide victims (n = 200) and offenders (n = 105) were identified for the years 2007-2009 and vehicle-accident controls (n = 1,643) for the years 2006-2013. The occurrence of congruence and incongruence between dispensed prescriptions and toxicology was used as a measure of adherence and recreational use. RESULTS: For antidepressants, incongruence-but not congruence-between dispensed prescriptions and toxicology was associated with a significantly increased risk of homicide offending (odds ratio adjusted for age and sex [aOR] = 6.2; 95% confidence interval [CI], 3.3-11.6) but not homicide victimization (aOR = 0.8; 95% CI, 0.3-2.0). For antipsychotics and mood stabilizers, a significantly increased risk of homicide offending was associated with incongruence between prescriptions and toxicology (aOR = 7.0; 95% CI, 2.8-17.7), whereas risk estimates for congruence were not significantly elevated for either homicide offending or victimization. For GABAergic hypnotics, congruence and incongruence were significantly associated with increased risks of both homicide offending (aOR = 5.4; 95% CI, 2.6-11.0 and aOR = 4.9; 95% CI, 2.6-9.3, respectively) and homicide victimization (aOR = 2.1; 95% CI, 1.1-4.2 and aOR = 3.2; 95% CI, 1.7-6.1, respectively). Sensitivity analyses with a subset of controls yielded similar estimates. CONCLUSIONS: Nonadherence to medications used to treat affective and psychotic disorders appears to elevate the risk of homicide offending. Both medicinal and recreational use of GABAergic hypnotics appears to elevate the risk of homicide offending and victimization. In summary, vigilance regarding adherence to medications prescribed for mood disorders and psychosis, as well as restrictiveness regarding licit and illicit access to addictive hypnotics, might contribute to a reduction of homicidal violence.

Glucose metabolism in completed suicide: a forensic-pathological pilot study.

AIM: To determine whether antemortem blood levels of glycated hemoglobin (HbA1c) and glucose predict completed suicide and, by extension, whether markers of glucose metabolism might be associated with a prosuicidal trait or state. METHOD: From consecutively performed autopsies, samples of blood and vitreous humor from 17 suicide victims and 27 non-suicide controls were compared with regard to levels of glucose, lactate, and HbA1c. RESULTS: Mean HbA1c was higher, and mean estimated blood glucose lower, among suicide victims, although tests revealed no significant differences (P=0.171 and P=0.395, respectively). HbA1c levels exceeding 48.0 mmol/mol, which were indicative of persistent hyperglycemia, were twice as common in suicide victims (59% vs 30%; P=0.068). CONCLUSION: The finding of this pilot study suggest that deranged glucose metabolism may reflect biological events antecedent to, or concomitant with, completed suicide, with the following clinical implications: recurring hyperglycemia due to defective glucose transport, which may give rise to depression and suicidal ideation, and elevated HbA1c levels, which may represent an assayable correlate to neurobiological conditions predisposing to suicide.

Intra- and extra-familial child homicide in Sweden 1992-2012: A population-based study.

Previous studies have shown decreasing child homicide rates in many countries - in Sweden mainly due to a drop in filicide-suicides. This study examines the rate of child homicides during 21 years, with the hypothesis that a decline might be attributable to a decrease in the number of depressive filicide offenders (as defined by a proxy measure). In addition, numerous characteristics of child homicide are presented. All homicide incidents involving 0-14-year-old victims in Sweden during 1992-2012 (n = 90) were identified in an autopsy database. Data from multiple registries, forensic psychiatric evaluations, police reports, verdicts and other sources were collected. Utilizing Poisson regression, we found a 4% annual decrease in child homicides, in accordance with prior studies, but no marked decrease regarding the depressive-offender proxy. Diagnoses from forensic psychiatric evaluations (n = 50) included substance misuse (8%), affective disorders (10%), autism-spectrum disorders (18%), psychotic disorders (28%) and personality disorders (30%). Prior violent offences were more common among offenders in filicides than filicide-suicides (17.8% vs. 6.9%); and about 20% of offenders in each group had previously received psychiatric inpatient care. Aggressive methods of filicide predominated among fathers. Highly lethal methods of filicide (firearms, fire) were more commonly followed by same-method suicide than less lethal methods. Interestingly, a third of the extra-familial offenders had an autism-spectrum disorder. Based on several findings, e.g., the low rate of substance misuse, the study concludes that non-traditional risk factors for violence must be highlighted by healthcare providers. Also, the occurrence of autism-spectrum disorders in the present study is a novel finding that warrants further investigation.

Lipid-specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab.

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a serious side effect associated with natalizumab treatment in multiple sclerosis (MS). PML risk increases in individuals seropositive for anti-John Cunningham virus (JC) antibodies, with prolonged duration of natalizumab treatment, and with prior exposure to immunosuppressants. We explored whether the presence of lipid-specific immunoglobulin M oligoclonal bands in cerebrospinal fluid (CSF; IgM bands), a recognized marker of highly inflammatory MS, may identify individuals better able to counteract the potential immunosuppressive effect of natalizumab and hence be associated with a reduced risk of developing PML. METHODS: We studied 24 MS patients who developed PML and another 343 who did not suffer this opportunistic infection during natalizumab treatment. Patients were recruited at 25 university hospitals. IgM bands were studied by isoelectric focusing and immunodetection. CSF lymphocyte counts were explored in 151 MS patients recruited at Ramon y Cajal Hospital in Madrid, Spain. RESULTS: IgM bands were independently associated with decreased PML risk (odds ratio [OR] = 45.9, 95% confidence interval [CI] = 5.9-339.3, p < 0.0001) in patients treated with natalizumab. They were also associated with significantly higher CSF CD4, CD8, and B-cell numbers. Patients positive for IgM bands and anti-JC antibodies had similar levels of reduced PML risk to those who were anti-JC negative (OR = 1.55, 95% CI = 0.09-25.2, p = 1.0). Higher risk was observed in patients positive for anti-JC antibodies and negative for IgM bands (19% of the total cohort, OR = 59.71, 95% CI = 13.6-262.2). INTERPRETATION: The presence of IgM bands reflects a process that may diminish the risk of PML by counteracting the excess of immunosuppression that may occur during natalizumab therapy.

Functional and structural alterations in the cingulate motor area relate to decreased fronto-striatal coupling in major depressive disorder with psychomotor disturbances.

Psychomotor disturbances are a classic feature of major depressive disorders. These can manifest as lack of facial expressions and decreased speech production, reduced body posture and mobility, and slowed voluntary movement. The neural correlates of psychomotor disturbances in depression are poorly understood but it has been suggested that outputs from the cingulate motor area (CMA) to striatal motor regions, including the putamen, could be involved. We used functional and structural magnetic resonance imaging to conduct a region-of-interest analysis to test the hypotheses that neural activation patterns related to motor production and gray matter volumes in the CMA would be different between depressed subjects displaying psychomotor disturbances (n = 13) and matched healthy controls (n = 13). In addition, we conducted a psychophysiological interaction analysis to assess the functional coupling related to self-paced finger-tapping between the caudal CMA and the posterior putamen in patients compared to controls. We found a cluster of increased neural activation, adjacent to a cluster of decreased gray matter volume in the caudal CMA in patients compared to controls. The functional coupling between the left caudal CMA and the left putamen during finger-tapping task performance was additionally decreased in patients compared to controls. In addition, the strength of the functional coupling between the left caudal CMA and the left putamen was negatively correlated with the severity of psychomotor disturbances in the patient group. In conclusion, we found converging evidence for involvement of the caudal CMA and putamen in the generation of psychomotor disturbances in depression.

Multiple sclerosis and psychiatric disorders: comorbidity and sibling risk in a nationwide Swedish cohort.

BACKGROUND: Psychiatric disorders are known to be prevalent in multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nationwide cohort and to determine whether shared genetic liability underlies the putative association. METHODS: We identified ICD-diagnosed patients with MS (n = 16,467), bipolar disorder (n = 30,761), schizophrenia (n = 22,781) and depression (n = 172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison. RESULTS: The risk of MS was increased in patients with bipolar disorder (hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.6-2.2, p < 0.0001) and depression (HR 1.9, 95% CI 1.7-2.0, p < 0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4-0.9, p = 0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant. CONCLUSION: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.

Methodological aspects of ELISA analysis of thioredoxin 1 in human plasma and cerebrospinal fluid.

Thioredoxin-1 (Trx1) is a protein antioxidant involved in major cellular processes. Increased plasma levels of Trx1 have been associated with human diseases suggesting that Trx1 is a marker for oxidative stress with putative clinical use. However, the reported mean levels of Trx1 in the control cohorts vary a hundred-fold between studies (0.8-87 ng/ml), possibly due to methodological differences between the capture ELISA used in the different studies. The aim of this study was to investigate methodological aspects related to the ELISA measurement of Trx1. ELISAs utilizing different capture and detection combinations of antibodies to Trx1 and as well as recombinant human (rh) Trx1 standards from two sources were characterized. The different ELISAs were subsequently used to measure Trx1 in human plasma and cerebrospinal fluid samples (CSF) from healthy donors and from patients with various neurological diagnoses. The Trx1 standards differed in their content of monomeric and oligomeric Trx1, which affected the ELISAs composed of different antibody combinations. Thus, the levels of Trx1 determined in human plasma and CSF samples varied depending on the antibody used in the ELISAs and on the rhTrx1 standard. Furthermore, the relevance of preventing interference by heterophilic antibodies (HA) in human plasma and CSF was investigated. The addition of a HA blocking buffer to human samples drastically reduced the ELISA signals in many samples showing that HA are likely to cause false positive results unless they are blocked. In conclusion, the study shows that the design of a Trx1 ELISA in regards to antibodies and standards used has an impact on the measured Trx1 levels. Importantly, analyses of human plasma and CSF without preventing HA interference may obscure the obtained data. Overall, the results of this study are crucial for the improvement of future studies on the association of Trx1 levels with various diseases.

Impact of cerebrospinal-fluid oligoclonal immunoglobulin bands and HLA-DRB1 risk alleles on brain magnetic-resonance-imaging lesion load in Swedish multiple sclerosis patients.

Approximately 95% of Nordic multiple sclerosis (MS) patients display oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid. From a cohort of 2094 MS patients we retrieved well-characterized data from 40 OCB-negative and 60 OCB-positive patients, in an effort to determine whether lesion load on brain magnetic resonance imaging is affected by OCB status and carriage of HLA-DRB1*15 or HLA-DRB1*04. Positivity for OCB did not increase the risk of belonging to higher-lesion-load groups; nor did carrying HLA-DRB1*15 or HLA-DRB1*04. A trend was seen, however, whereby OCB positivity conferred a two-fold risk of displaying higher lesion loads infratentorially.

No influence on disease progression of non-HLA susceptibility genes in MS.

Recently, several non-HLA loci have been shown to be convincingly associated with Multiple Sclerosis (MS) susceptibility, assumingly indicating important pathways in the pathogenesis. A genotype influence on disease outcome measures by these genes would support a role of these pathways in ongoing tissue damage. Here, however, we report a consistent dissociation between causation and progression for five non-HLA genotypes (IL7R, IL2RA, CLEC16A, CD226 and SH2B3) in 1776 Scandinavian MS patients.

A rare variant of the TYK2 gene is confirmed to be associated with multiple sclerosis.

A rare functional variant within the TYK2 gene (rs34536443) has been reported as protective in multiple sclerosis (MS) in recent studies. However, because of the low frequency of the minor allele (minor allele frequency=0.04), genome-wide significant association has been hard to establish. We genotyped 5429 Nordic MS cases and 6167 healthy controls for this TYK2 non-synonymous single-nucleotide polymorphism (ns-SNP), and combined the Nordic genotype data with raw genotypes from previous studies. The combined Nordic analysis showed significant association with MS (P=5 x 10(-4), odds ratio (OR) 0.78), and by mega-analysis of 10 642 MS patients, 10 620 controls and 2110 MS trios, the association at genome-wide significance level (P=5.08 x 10(-9), OR 0.77) was shown.