The wristwatch - A supplemental tool for determining time of death.

Estimation of the time of death (TOD) is a central task to forensic pathologists. The current gold standard method for TOD-estimation is only applicable in the first 24 h post-mortem and it is advisable to employ multiple methods, if possible. A wristwatch found on the decedent can be a valuable additional tool for TOD-estimation. This technical report provides a brief overview of the two major watch types - mechanical and quartz-based timepieces - and a step-by-step guide to using these for TOD-estimation. The methods are demonstrated using case illustrations.

Impact of the Covid-19 lockdown on sexual assault cases in Eastern Denmark - a retrospective clinical forensic study.

To explore if the shutdown of Danish nightlife during the Covid-19 pandemic caused a decrease in the number of clinical forensic examinations of victims of sexual assault in Eastern Denmark. Secondarily, to investigate, if there was a change in criminological characteristics, e.g. scene and time of crime, relation to the perpetrator and the proportion of possible drug-facilitated sexual assaults. 130 case files from clinical forensic examinations of individuals of alleged sexual assault in the period 1st of April to 30th of June in both 2019 and 2020 were included. 67 and 63 examinations were performed in 2019 and 2020, respectively. 125 cases were female and five were male. Approximately 70% were 15-25 years of age. Pre- and post-lockdown victim profiles were similar regarding assailant relation, location of crime and time of assault. Voluntary intake of alcohol prior to the assault was registered with 46.3% in 2019 and 62% in 2020. The ratio of possible drug-facilitated sexual assault (DFSA) was approximately 50% each year. The lockdown did not seem to change the overall number of examinations or the demographic and criminological characteristics of the sexual assault victims. No decrease in cases of possible DFSA was found despite the lockdown of nightlife venues.

Lethal small bowel obstruction due to pica.

Up to 25% of institutionalized patients with cognitive deficiencies display pica-like behavior, with an estimated annual incidence of small bowel obstruction of 2%. We present a case based on the forensic autopsy of a 41-year-old woman who died as a result of a missed diagnosis of small bowel obstruction after ingesting a foreign body. The case underlines the importance of precaution when treating patients with cognitive deficiency and/or language deficits and gastrointestinal symptoms. In such cases, it is important to employ a liberal threshold for radiological investigations and, if possible, obtain a medical history from a person close to the patient.

Genetic investigations of 100 inherited cardiac disease-related genes in deceased individuals with schizophrenia.

Cardiac diseases and sudden cardiac death (SCD) are more prevalent in individuals diagnosed with schizophrenia compared to the general population, with especially coronary artery disease (CAD) as the major cardiovascular cause of death. Antipsychotic medications, genetics, and lifestyle factors may contribute to the increased SCD in individuals with schizophrenia. The role of antipsychotic medications and lifestyle factors have been widely investigated, while the genetic predisposition to inherited cardiac diseases in schizophrenia is poorly understood. In this study, we examined 100 genes associated with inherited cardiomyopathies and cardiac channelopathies in 97 deceased individuals diagnosed with schizophrenia for the prevalence of genetic variants associated with SCD. The deceased individuals had various causes of death and were included in the SURVIVE project, a prospective, autopsy-based study of mentally ill individuals in Denmark. This is the first study of multiple inherited cardiac disease-related genes in deceased individuals with diagnosed schizophrenia to shed light on the genetic predisposition to SCD in individuals with schizophrenia. We found no evidence for an overrepresentation of rare variants with high penetrance in inherited cardiac diseases, following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG) consensus guidelines. However, we found that the deceased individuals had a statistically significantly increased polygenic burden caused by variants in the investigated heart genes compared to the general population. This indicates that common variants with smaller effects in heart genes may play a role in schizophrenia.

Reliability of police reports when assessing health information at the forensic post-mortem examination-using schizophrenia as a model.

Autopsies continue to be the most reliable source of mortality statistics; however, more and more death certificates are based on the post-mortem external examination (PME) alone. Forensic PMEs differ from clinical PMEs, because the forensic pathologist usually has no preceding knowledge of the health of the decedent and must rely on information from authorities in the form of the police report. It is useful at the forensic PME to know whether the decedent suffered from a mental illness; however, it is unknown how valid such a diagnosis is, when based upon information in the police report alone. This study compared tentative diagnoses of schizophrenia from 500 forensic PMEs with a reference database based on the Danish National Patient Registry. We found that 19.3% of schizophrenia cases were missed, and 9.1 % of identified cases were false positives. Overall, 11.4% of all assessments were incorrect. Subgroup analysis showed that marital status as 'single' and the finding of illegal substances at the scene were predictors for both correctly identified and overlooked schizophrenia cases. The most reliable source of information was the decedent's general practitioner, whereas friends and neighbors were the most unreliable. Future studies should be aware of the risk of assigning a wrong diagnosis and use as many sources of information as possible. Taking the decedent's social history and observations about the scene into account may add to the diagnostic accuracy.

Enlargement of the human adrenal zona fasciculata and chronic psychiatric illness - an autopsy-based study.

Severe mental illness (SMI) is associated with a reduced life expectancy of up to 20 years. One possible contributor to this fact is dysregulation of the hypothalamus-pituitary-adrenal (HPA)-axis. Looking at the morphology of effector organs, such as the adrenal glands themselves, could reveal insights into organ function and response to possible HPA-dysregulation. This forensic autopsy-based study investigated if there were any morphological changes in adrenal glands between decedents who had previously been submitted to a psychiatric hospital with a diagnosis of schizophrenia (n = 34), bipolar (n = 5), or depressive disorder (n = 20), any other psychiatric diagnosis (n = 36) compared with decedents who had no previous psychiatric admission (n = 40). Length of admissions to psychiatric wards and admission in the 180 days preceding death was included in regression as proxy variables for severity of illness. On the macroscopic level, we found no difference in gland weight or volume. On the microscopic level, we found a 25% increase in cross-sectional area of the zona fasciculata (ZF) in decedents who had a diagnosis of schizophrenia compared with controls (p = 0.033). Other diagnosis groups did not differ from controls. Total admission length was positively correlated with area of the ZF.Lay SummaryPeople with a severe mental disorder may be in a constant state of increased stress, which is harmful. This study looked at the adrenal gland, which produces stress hormones, to see if they were different in deceased persons who had suffered from a severe mental illness. We found that the part of the adrenal gland that produces stress hormones is larger in deceased patients who suffered from schizophrenia, but not other types of psychiatric illnesses, compared to deceased persons with no history of psychiatric illness.

Comparison of hippocampal volume measurement by autopsy and post-mortem magnetic resonance imaging.

We present an autopsy-validated, non-invasive, magnetic resonance imaging (MRI) based segmentation algorithm, for determining hippocampal volume. A segmentation algorithm was developed to assess the volume of the hippocampus. Deceased individuals with severe mental illness were used to evaluate the use of MRI imaging to determine hippocampal volume as this group has previously been associated with altered hippocampal volume diagnosed on MRI. The accuracy of the MR- scanning protocol for volume measurement was tested on a water filled phantom control with a known volume of 500 ml, and a difference of 0.08% was found. Thus the scanning protocol was deemed to have produced acceptable results when comparing volume measures of a pair of segmented hippocampi obtained at the 1 T MR scanner and a 3 T MR scanner using the software program Mimics®. The segmentation algorithm was tested by a volume comparison obtained using anterior and posterior landmarks (in situ) and the exact volume of the dissected hippocampus (ex situ). The in situ and ex situ hippocampal volumes were highly correlated; R2 was 96%, with a mean difference of 4-5%. Cases were also examined for intra- and inter-observer agreement. This study presents a validated segmentation algorithm that can be used to determine the hippocampal volume using post-mortem MR and anatomical landmarks.

Targeted exon sequencing in deceased schizophrenia patients in Denmark.

Schizophrenia patients have higher mortality rates and lower life expectancy than the general population. However, forensic investigations of their deaths often fail to determine the cause of death, hindering prevention. As schizophrenia is a highly heritable condition and given recent advances in our understanding of the genetics of schizophrenia, it is now possible to investigate how genetic factors may contribute to mortality. We made use of findings from genome-wide association studies (GWAS) to design a targeted panel (PsychPlex) for sequencing of exons of 451 genes near index single nucleotide polymorphisms (SNPs) identified with GWAS. We sequenced the DNA of 95 deceased schizophrenia patients included in SURVIVE, a prospective, autopsy-based study of mentally ill persons in Denmark. We compared the allele frequencies of 1039 SNPs in these cases with the frequencies of 2000 Danes without psychiatric diseases and calculated their deleteriousness (CADD) scores. For 81 SNPs highly associated with schizophrenia and CADD scores above 15, expression profiles in the Genotype-Tissue Expression (GTEx) Project indicated that these variants were in exons, whose expressions are increased in several types of brain tissues, particularly in the cerebellum. Molecular pathway analysis indicated the involvement of 163 different pathways. As for rare SNP variants, most variants were scored as either benign or likely benign with an average of 17 variants of unknown significance per individual and no pathogenic variant. Our results highlight the potential of DNA sequencing of an exon panel to discover genetic factors that may be involved in the development of schizophrenia.

Hair testing for cortisol by UPLC-MS/MS in a family: External cross-contamination from use of cortisol cream.

In the present study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed, validated, and applied for measuring cortisol in human hair. Baseline levels of cortisol in hair were taken from 12 control subjects, with concentrations for adult controls (n = 8) of 1.7 to 9.1 pg/mg and a median of 4.7 pg/mg and for child controls (n = 4) of 1.1 to 7.2 pg/mg and a median of 3.1 pg/mg. However, the concentrations in the hair of two children whose mother had been applying a cortisol-containing hand cream 2-3 times per week ranged from 30 to 390 pg/mg. No external contamination was observed with the children as judged from wash water concentrations. The mother had hair cortisol concentrations of 80-220 pg/mg. External contamination was observed in her proximal hair segments (0-4 cm) but not in distal ones (8-12 cm). In an experiment, cortisol cream (1%) was applied on the fingers of a subject, who then scratched the head hair once in a while. Hair was collected 1, 5, and 30 days after exposure to the cream. The cortisol level in the hair one day after exposure was 20-186 times higher than the pre-exposure level. High levels in the wash fraction agreed with external contamination. Cortisol concentrations in the hair at 5 and 30 days after exposure were 15-38 and 9-11 times higher, respectively, than the pre-exposure levels. However, no external contamination was suggested from the wash water concentrations in the hair collected 5 and 30 days after exposure. The results showed that the externally applied cortisol had, after some time, been incorporated into the hair matrix and was not removed by a pre-analysis washing. Therefore, the use of a standard decontamination procedure prior to analysis of hair may not be able to prevent the spread of cortisol from applied hand cream within a family.