Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood

Venlafaxine (VEN) is an antidepressant drug mainly metabolized by the cytochrome P450 (CYP) enzyme CYP2D6 to the active metabolite O-desmethylvenlafaxine (ODV). VEN is also metabolized to N-desmetylvenlafaxine (NDV) via CYP3A4. ODV and NDV are further metabolized to N,O-didesmethylvenlafaxine (DDV). VEN is a racemic mixture of the S- and R-enantiomers and these have in vitro displayed different degrees of serotonin and noradrenaline reuptake inhibition. The aim of the study was to investigate if an enantioselective analysis of VEN and its metabolites, in combination with genotyping for CYP2D6, could assist in the interpretation of forensic toxicological results in cases with different causes of deaths. Concentrations of the enantiomers of VEN and metabolites were determined in femoral blood obtained from 56 autopsy cases with different causes of death. The drug analysis was done by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the CYP2D6 genotyping by PCR and pyrosequencing. The mean (median) enantiomeric S/R ratios of VEN, ODV, NDV and DDV were 0.99 (0.91), 2.17 (0.93), 0.92 (0.86) and 1.08 (1.03), respectively. However, a substantial variation in the relationship between the S- and R-enantiomers of VEN and metabolites was evident (S/R ratios ranging from 0.23 to 17.6). In six cases, a low S/R VEN ratio (mean 0.5) was associated with a high S/R ODV ratio (mean 11.9). Genotyping showed that these individuals carried two inactive CYP2D6 genes indicating a poor metabolizer phenotype. From these data we conclude that enantioselective analysis of VEN and ODV can predict if a person is a poor metabolizer genotype/phenotype for CYP2D6. Knowledge of the relationship between the S- and R-enantiomers of this antidepressant drug and its active metabolite is also important since the enantiomers display different pharmacodynamic profiles.     

Does Separation or Divorce Make any Difference? An Interactional Perspective on Intimate Partner Violence with Focus on Marital Status

This article reports a study of the impact of marital status on interactional aspects of intimate partner violence (IPV) among help-seeking women. Are there differences among marital status groups concerning (a) other sociodemographic variables, (b) IPV categories, (c) interactional IPV variables, and (d) perception and interpretation of IPV? A representative sample of 157 women recruited from family counseling, the police, and shelters were interviewed. There was no significant sociodemographic difference among the marital status groups. There were no significant differences pertaining to IPV categories, neither for IPV severity, injury, duration, frequency, mortal danger, and regularity, nor for physical, psychological, or sexual IPV. However, multivariate logistic regression showed that post-separation women were significantly more likely to have (a) had longer duration since the last psychological and sexual IPV episode, (2) reported the physical IPV to be more predictable, and (3) used more active coping strategies against physical IPV. However, our research was not able to determine if perception and interpretation predict actual leaving behavior, or vice versa, or how the victim’s subjective perception and interpretation of the IPV changes over time.     

Teenagers’ Experiences of Pregnancy and the Parents’ and Partners’ Reactions: A Malaysian Perspective

This study focuses on the experiences of unwed teenage mothers in Malaysia in respect to the reactions of their parents and the fathers of their babies and how the reactions from significant others influence these unwed teenage mothers. The investigation was based on content analysis of interviews with 17 unwed teenage mothers, aged 12 to 18 years, during their probation or placement in shelter houses. The results show that most unwed teenage mothers became pregnant as a result of rape or statutory rape, and thus were at risk of developing mental health problems. Three themes were developed: secrecy, repression, and rejection. Four additional themes—feeling detached, trapped, unworthy, and ambiguous—were developed to describe the teenagers’ experiences of pregnancy.     

First report from the Swedish National Forensic Psychiatric Register (SNFPR)

To the best of our knowledge, the present register is the only nationwide forensic psychiatric patient register in the world. The aim of this article is to describe the content of the Swedish National Forensic Psychiatric Register (SNFPR) for Swedish forensic patients for the year 2010. The subjects are individuals who, in connection with prosecution due to criminal acts, have been sentenced to compulsory forensic psychiatric treatment in Sweden. The results show that in 2010, 1476 Swedish forensic patients were assessed in the SNFPR; 1251 (85%) were males and 225 (15%) were females. Almost 60% of the patients had a diagnosis of schizophrenia, with a significantly higher frequency among males than females. As many as 70% of the patients had a previous history of outpatient psychiatric treatment before becoming a forensic psychiatric patient, with a mean age at first contact with psychiatric care of about 20 years old for both sexes. More than 63% of the patients had a history of addiction, with a higher proportion of males than females. Furthermore, as many as 38% of all patients committed crimes while under the influence of alcohol and/or illicit drugs. This was more often the case for men than for women. Both male and female patients were primarily sentenced for crimes related to life and death (e.g., murder, assault). However, there were more females than males in treatment for general dangerous crimes (e.g., arson), whereas men were more often prosecuted for crimes related to sex. In 2010, as many as 70% of all forensic patients in Sweden had a prior sentence for a criminal act, and males were prosecuted significantly more often than females. The most commonly prescribed pharmaceuticals for both genders were antipsychotics, although more women than men were prescribed other pharmaceuticals, such as antidepressants, antiepileptics, and anxiolytics. The result from the present study might give clinicians an opportunity to reflect upon and challenge their traditional treatment methods.     

Networks and campaigns but not movements: collective action in the disciplining Chinese State

Popular protest, civil society organizing, and non-governmental organizations have become notable features in China’s socio-political development. A mounting body of research has documented both opening opportunity structures and remaining restrictions when it comes to collective action within the authoritarian state. However, given the wide range of definitions and interpretations that are at play in the literature, it can be difficult to distinguish between different forms of collective action and determine which actions represent actual movements. This article argues that a refocus towards the basic components that constitute movement action can provide more clarity and help explain the limitations, as well as the opportunities, that surround collective action within authoritarian states. To illustrate, the article studies the organizational growth, networking, and collective action that have occurred in connection with AIDS in China. It finds that political restrictions and other coordination challenges prevent the mobilization of actual social movements.     

Petechial Hemorrhages and Ethanol in Deaths from Intoxication

Petechiae in conjunctivae and in the palpebrae/skin of the eyelids are of particular interest for the forensic pathologist, because of their association with pressure on the neck. They have been described in the eyelids of intoxicated persons both in case reports and in text books of forensic pathology. We studied 590 deaths caused by intoxication, and 75 had petechiae either in the conjunctivae, the eyelids, or in both locations. We examined the influence of drugs and ethanol on the location of the petechial hemorrhages in these deaths. Deaths with ethanol in blood and in urine/vitreous humor more often had petechiae in both locations than those without. This association was statistically significant, independent of body position and livor mortis. No association between the location of petechiae, medicinal drugs, or narcotics was found. These results suggest that ethanol may contribute to the development of petechial hemorrhages in deaths from intoxication.     

Resilience Factors Among Police Investigators: Hardiness-commitment a Unique Contributor

The aim of this study was to explore the role of individual and contextual buffers against the effects of work stress among police investigators. 156 Norwegian police investigators were assessed on the predictor variables psychological hardiness, work engagement, social support, and meaningfulness, and on the outcome variables of burnout, subjective health complaints, and self-reported sick leave. Hierarchical regression analysis showed that psychological hardiness predicted the variance in burnout beyond that of work engagement, social support, and meaningfulness. When the investigators were divided into two groups based on their field, investigators of assault crime showed higher scores than the group consisting of forensics and investigators of fire, financial, and environmental crime on the variables psychological hardiness, social support, meaningfulness, and subjective health complaints. No differences between the groups were found on burnout, sickness absence, and work engagement. The findings show the importance of resilience factors for coping with work stress, with the commitment dimension of hardiness being particularly important.     

Injustice in School and Students’ Emotions,Well-Being,and Behavior: A Longitudinal study

School can be regarded as an important factor in the development of children’s values and attitudes. Given this great importance of justice experiences for students’ development, this study aimed at examining the influence of perceived injustice in school on students’ emotions, well-being, and behavior with an experimental longitudinal design. In total, 196 students participated in this study and came to the university with their classes to receive extra teaching once a week for six consecutive weeks. To manipulate justice perceptions, a scenario of arbitrary privilege was chosen to lead students of the experimental group to experience injustice from a beneficiary perspective. We found that students in the experimental group reported higher well-being and a higher appreciation of the opportunity to learn than the control group did. Additionally, they showed an increase in justice-related negative emotions over time; that is, they expressed more of a bad conscience and stronger feelings of anger the more they became aware of their privilege. This study shows that even subtle experiences of injustice in school can have an impact on students’ outcomes. These results are discussed with regard to practical implications.