Correction: Mobile Insight in Risk, Resilience, and Online Referral (MIRROR): Psychometric Evaluation of an Online Self-Help Test.

[This corrects the article DOI: 10.2196/19716.].

Mobile Insight in Risk, Resilience, and Online Referral (MIRROR): Psychometric Evaluation of an Online Self-Help Test.

BACKGROUND: Most people who experience a potentially traumatic event (PTE) recover on their own. A small group of individuals develops psychological complaints, but this is often not detected in time or guidance to care is suboptimal. To identify these individuals and encourage them to seek help, a web-based self-help test called Mobile Insight in Risk, Resilience, and Online Referral (MIRROR) was developed. MIRROR takes an innovative approach since it integrates both negative and positive outcomes of PTEs and time since the event and provides direct feedback to the user. OBJECTIVE: The goal of this study was to assess MIRROR's use, examine its psychometric properties (factor structure, internal consistency, and convergent and divergent validity), and evaluate how well it classifies respondents into different outcome categories compared with reference measures. METHODS: MIRROR was embedded in the website of Victim Support Netherlands so visitors could use it. We compared MIRROR's outcomes to reference measures of PTSD symptoms (PTSD Checklist for DSM-5), depression, anxiety, stress (Depression Anxiety Stress Scale-21), psychological resilience (Resilience Evaluation Scale), and positive mental health (Mental Health Continuum Short Form). RESULTS: In 6 months, 1112 respondents completed MIRROR, of whom 663 also completed the reference measures. Results showed good internal consistency (interitem correlations range .24 to .55, corrected item-total correlations range .30 to .54, and Cronbach alpha coefficient range .62 to .68), and convergent and divergent validity (Pearson correlations range -.259 to .665). Exploratory and confirmatory factor analyses (EFA+CFA) yielded a 2-factor model with good model fit (CFA model fit indices: χ219=107.8, P<.001, CFI=.965, TLI=.948, RMSEA=.065), conceptual meaning, and parsimony. MIRROR correctly classified respondents into different outcome categories compared with the reference measures. CONCLUSIONS: MIRROR is a valid and reliable self-help test to identify negative (PTSD complaints) and positive outcomes (psychosocial functioning and resilience) of PTEs. MIRROR is an easily accessible online tool that can help people who have experienced a PTE to timely identify psychological complaints and find appropriate support, a tool that might be highly needed in times like the coronavirus pandemic.

The Dissociative Subtype of PTSD Interview (DSP-I): Development and Psychometric Properties.

The inclusion of the dissociative subtype of post-traumatic stress disorder (PTSD-DS) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reflects the importance of assessing PTSD-DS. We developed the Dissociative Subtype of PTSD Interview (DSP-I). This clinician-administered instrument assesses the presence and severity of PTSD-DS (i.e., symptoms of depersonalization or derealization) and contains a supplementary checklist that enables assessment and differentiation of other trauma-related dissociative symptoms (i.e., blanking out, emotional numbing, alterations in sensory perception, amnesia, and identity confusion). The psychometric properties were tested in 131 treatment-seeking individuals with PTSD and histories of multiple trauma, 17.6 % of whom met criteria for PTSD-DS in accordance with the DSP-I. The checklist was tested in 275 treatment-seeking individuals. Results showed the DSP-I to have high internal consistency, good convergent validity with PTSD-DS items of the CAPS-5, and good divergent validity with scales of somatization, anxiety and depression. The depersonalization and derealization scales were highly associated. Moreover, the DSP-I accounted for an additional variance in PTSD severity scores of 8% over and above the CAPS-5 and number of traumatic experiences. The dissociative experiences of the checklist were more strongly associated with scales of overall distress, somatization, depression, and anxiety than scales of depersonalization and derealization. In conclusion, the DSP-I appears to be a clinically relevant and psychometrically sound instrument that is valuable for use in clinical and research settings.

Concurrent whole-genome haplotyping and copy-number profiling of single cells.

Methods for haplotyping and DNA copy-number typing of single cells are paramount for studying genomic heterogeneity and enabling genetic diagnosis. Before analyzing the DNA of a single cell by microarray or next-generation sequencing, a whole-genome amplification (WGA) process is required, but it substantially distorts the frequency and composition of the cell's alleles. As a consequence, haplotyping methods suffer from error-prone discrete SNP genotypes (AA, AB, BB) and DNA copy-number profiling remains difficult because true DNA copy-number aberrations have to be discriminated from WGA artifacts. Here, we developed a single-cell genome analysis method that reconstructs genome-wide haplotype architectures as well as the copy-number and segregational origin of those haplotypes by employing phased parental genotypes and deciphering WGA-distorted SNP B-allele fractions via a process we coin haplarithmisis. We demonstrate that the method can be applied as a generic method for preimplantation genetic diagnosis on single cells biopsied from human embryos, enabling diagnosis of disease alleles genome wide as well as numerical and structural chromosomal anomalies. Moreover, meiotic segregation errors can be distinguished from mitotic ones.

G&T-seq: parallel sequencing of single-cell genomes and transcriptomes.

The simultaneous sequencing of a single cell's genome and transcriptome offers a powerful means to dissect genetic variation and its effect on gene expression. Here we describe G&T-seq, a method for separating and sequencing genomic DNA and full-length mRNA from single cells. By applying G&T-seq to over 220 single cells from mice and humans, we discovered cellular properties that could not be inferred from DNA or RNA sequencing alone.

Structural Validity of the World Assumption Scale.

The World Assumption Scale (WAS) is a frequently used measure in trauma research. The 32 items of the WAS are intended to represent eight assumptions about the benevolence of the world, the meaningfulness of events, and the worthiness of the self. Debate about the validity of the WAS is ongoing, particularly in terms of its empirical factor structure; some studies have confirmed a model of eight correlated factors whereas several other studies have not. The WAS items were administered to a clinical sample of patients who sought professional help because of posttraumatic complaints (n = 1,791) as well as a sample of healthcare professionals (n = 236). We split the clinical sample into three subsamples, then performed exploratory factor analysis using data from one subsample and tested the factor structure with confirmatory factor analysis using the other two subsamples. A consistent model of eight correlated factors was demonstrated, with almost all factors showing acceptable reliability, Cronbach's αs = .68-.84. We tested this factor model against data from the sample of healthcare professionals with increasingly stringent levels of invariance and found it to be scalar invariant (same structure, loadings, and thresholds). In a regression analysis, five factors showed significant associations with posttraumatic stress disorder (PTSD) symptoms, and two factors had unique associations with PTSD symptoms after we controlled for traumatic events: Self-Worth, ß = -.31; and Luck, ß = -.15. Future research should aim to distinguish between different assumptions and their individual influences on posttraumatic complaints.

The dissociative post-traumatic stress disorder (PTSD) subtype: A treatment outcome cohort study in veterans with PTSD.

OBJECTIVES: Dissociation is a prevalent phenomenon among veterans with post-traumatic stress disorder (PTSD) that may interfere with the effectiveness of treatment. This study aimed to replicate findings of a dissociative PTSD subtype, to identify corresponding patterns in coping style, symptom type, and symptom severity, and to investigate its impact on post-traumatic symptom improvement. METHODS: Latent profile analysis (LPA) was applied to baseline data from 330 predominantly (97%) male treatment-seeking veterans (mean age 39.5 years) with a probable PTSD. Multinomial logistic models were used to identify predictors of dissociative PTSD. Eighty veterans with PTSD that commenced with psychotherapy were invited for a follow-up measure after 6 months. The majority (n = 64, 80% response rate) completed the follow-up measure. Changes in post-traumatic stress between baseline and follow-up were explored as a continuous distal outcome. RESULTS: Latent profile analysis revealed four distinct patient profiles: 'low' (12.9%), 'moderate' (33.2%), 'severe' (45.1%), and 'dissociative' (8.8%) PTSD. The dissociative PTSD profile was characterized by more severe pathology levels, though not post-traumatic reactions symptom severity. Veterans with dissociative PTSD benefitted equally from PTSD treatment as veterans with non-dissociative PTSD with similar symptom severity. CONCLUSIONS: Within a sample of veterans with PTSD, a subsample of severely dissociative veterans was identified, characterized by elevated severity levels on pathology dimensions. The dissociative PTSD subtype did not negatively impact PTSD treatment. PRACTITIONER POINTS: The present findings confirmed the existence of a distinct subgroup veterans that fit the description of dissociative PTSD. Patients with dissociative PTSD subtype symptoms uniquely differed from patients with non-dissociative PTSD in the severity of several psychopathology dimensions. Dissociative and non-dissociative PTSD patients with similar post-traumatic severity levels showed similar levels of improvement after PTSD treatment. The observational design and small sample size caution interpretation of the treatment outcome data. The IES-R questionnaire does not assess all PTSD DSM-IV diagnostic criteria (14 of 17), although it is considered a valid measure for an indication of PTSD.

Attachment Representation and Sensitivity: The Moderating Role of Posttraumatic Stress Disorder in a Refugee Sample.

It has been hypothesized that adult attachment representations guide caregiving behavior and influence parental sensitivity, and thus affect the child's socio-emotional development. Several studies have shown a link between posttraumatic stress disorder (PTSD) and reduced parental sensitivity, so it is possible that PTSD moderates the relationship between insecure attachment representations and insensitivity. In this study symptoms of PTSD (Harvard Trauma Questionnaire), parental sensitivity (Emotional Availability Scales), and attachment representations (Attachment Script Assessment) were assessed in 53 parents who were asylum seekers or refugees. Results showed that when parents were less able to draw on secure attachment representations, symptoms of PTSD increased the risk of insensitive parenting. These findings suggest that parental sensitivity is affected not just by attachment representations, but by a conjunction of risk factors including symptoms of PTSD and insecure attachment representations. These parents should therefore be supported to establish or confirm secure models of attachment experiences, to facilitate their ability interact sensitively and form a secure relationship with their children.

Genome-wide copy number profiling of single cells in S-phase reveals DNA-replication domains.

Single-cell genomics is revolutionizing basic genome research and clinical genetic diagnosis. However, none of the current research or clinical methods for single-cell analysis distinguishes between the analysis of a cell in G1-, S- or G2/M-phase of the cell cycle. Here, we demonstrate by means of array comparative genomic hybridization that charting the DNA copy number landscape of a cell in S-phase requires conceptually different approaches to that of a cell in G1- or G2/M-phase. Remarkably, despite single-cell whole-genome amplification artifacts, the log2 intensity ratios of single S-phase cells oscillate according to early and late replication domains, which in turn leads to the detection of significantly more DNA imbalances when compared with a cell in G1- or G2/M-phase. Although these DNA imbalances may, on the one hand, be falsely interpreted as genuine structural aberrations in the S-phase cell's copy number profile and hence lead to misdiagnosis, on the other hand, the ability to detect replication domains genome wide in one cell has important applications in DNA-replication research. Genome-wide cell-type-specific early and late replicating domains have been identified by analyses of DNA from populations of cells, but cell-to-cell differences in DNA replication may be important in genome stability, disease aetiology and various other cellular processes.

Single-cell paired-end genome sequencing reveals structural variation per cell cycle.

The nature and pace of genome mutation is largely unknown. Because standard methods sequence DNA from populations of cells, the genetic composition of individual cells is lost, de novo mutations in cells are concealed within the bulk signal and per cell cycle mutation rates and mechanisms remain elusive. Although single-cell genome analyses could resolve these problems, such analyses are error-prone because of whole-genome amplification (WGA) artefacts and are limited in the types of DNA mutation that can be discerned. We developed methods for paired-end sequence analysis of single-cell WGA products that enable (i) detecting multiple classes of DNA mutation, (ii) distinguishing DNA copy number changes from allelic WGA-amplification artefacts by the discovery of matching aberrantly mapping read pairs among the surfeit of paired-end WGA and mapping artefacts and (iii) delineating the break points and architecture of structural variants. By applying the methods, we capture DNA copy number changes acquired over one cell cycle in breast cancer cells and in blastomeres derived from a human zygote after in vitro fertilization. Furthermore, we were able to discover and fine-map a heritable inter-chromosomal rearrangement t(1;16)(p36;p12) by sequencing a single blastomere. The methods will expedite applications in basic genome research and provide a stepping stone to novel approaches for clinical genetic diagnosis.

Profiles of posttraumatic stress disorder and negative world assumptions in treatment-seeking refugees.

Background: Refugees often suffer from trauma-related psychopathology, specifically posttraumatic stress disorder (PTSD). Negative world assumptions are strongly correlated with the development, course, and severity of PTSD.Objective: This study aimed to investigate whether there are distinct profiles of PTSD and negative world assumptions (NWA) and examine whether trauma load, torture, and gender differentially predict such symptom profiles.Method: In a sample of 225 treatment-seeking refugees who had resettled in the Netherlands, latent profile analysis was used to identify subgroups of patients sharing the same profile of PTSD and NWA symptoms. Predictors of profile membership were analyzed via multinomial logistic regression.Results: A three-profile solution yielded the best model fit: a low PTSD/low NWA profile (23.6%), a high PTSD/high NWA profile (41.8%), and a high PTSD/low NWA profile (34.7%). Participants who reported a higher trauma load, were more likely to be part of the high PTSD/high NWA profile or the high PTSD/low NWA profile in comparison to low PTSD/low NWA profile. Participants who reported having experienced torture were more likely to be part of the high PTSD/high NWA profile in comparison to low PTSD/low NWA profile. Gender did not differentiate between the profiles.Conclusions: This study reveals that among treatment-seeking refugees resettled in the Netherlands, there are distinct profiles of PTSD and NWA. These profiles indicate that PTSD and NWA are not uniformly experienced among refugees, emphasizing the diversity in their psychological responses to trauma. Among individuals experiencing severe PTSD symptoms, a subgroup was identified of individuals who additionally exhibited negative assumptions about themselves, others, and the world. Recognizing this heterogeneity is crucial in both research and clinical practice, particularly in the context of refugee mental health. Directions for future research are discussed.

Three profiles of PTSD and negative world assumptions were identified in a group of treatment-seeking refugees.Directions for future research and the importance of recognizing heterogeneity in psychological responses to traumatic experiences in refugees are discussed.

Potentially morally injurious experiences and associated factors among Dutch UN peacekeepers: a latent class analysis.

Background: During peacekeeping missions, military personnel may be involved in or exposed to potentially morally injurious experiences (PMIEs), such as an inability to intervene due to a limited mandate. While exposure to such morally transgressive events has been shown to lead to moral injury in combat veterans, research on moral injury in peacekeepers is limited.Objective: We aimed to determine patterns of exposure to PMIEs and associated outcome- and exposure-related factors among Dutch peacekeepers stationed in the former Yugoslavia during the Srebrenica genocide.Method: Self-report data were collected among Dutchbat III veterans (N = 431). We used Latent Class Analysis to identify subgroups of PMIE exposure as assessed by the Moral Injury Scale-Military version. We investigated whether deployment location, posttraumatic stress disorder (PTSD), posttraumatic growth, resilience, and quality of life differentiated between latent classes.Results: The analysis identified a three-class solution: a high exposure class (n = 79), a moderate exposure class (n = 261), and a betrayal and powerlessness-only class (n = 135). More PMIE exposure was associated with deployment location and higher odds of having probable PTSD. PMIE exposure was not associated with posttraumatic growth. Resilience and quality of life were excluded from analyses due to high correlations with PTSD.Conclusions: Peacekeepers may experience varying levels of PMIE exposure, with more exposure being associated with worse outcomes 25 years later. Although no causal relationship may be assumed, the results emphasize the importance of better understanding PMIEs within peacekeeping.

Peacekeeping veterans reported different patterns of exposure to potentially morally injurious experiences: high exposure, moderate exposure, or experiences of betrayal and powerlessness only.Deployment location predicted the pattern of exposure.More exposure was associated with worse psychological outcomes 25 years later.

Genetic and environmental influences on individual differences in sleep duration during adolescence.

This study assessed to what extent genetic and environmental factors contributed to individual differences in adolescent sleep duration, and whether genetic and environmental contributions to sleep duration changed throughout adolescence. A twin-family design was used to gain insight into the genetic and environmental contributions to variation in sleep duration. The study sample consisted of 6,319 adolescent twins (44% males) and 1,359 non-twin siblings (44% males) in the age range of 12 to 20 years (mean age = 16.85, SD = 1.40). The participants self-reported usual sleep duration, which was categorized as less than 8 hours per night, 8-9 hours per night, and more than 9 hours per night. Results showed that the prevalence of shorter than optimum sleep duration, that is, less than 8 hours per night, was high, with the highest prevalence rates in later adolescence. The contribution of genetic and environmental factors to individual differences in sleep duration was dependent on age. Variation in sleep duration at the age of 12 years was accounted for by genetic (boys: 34%, girls: 36%), shared environmental (boys: 28%, girls: 45%), and non-shared environmental factors (boys: 38%, girls: 19%). At the age of 20 years, the role of genetic (boys: 47%, girls: 33%) and non-shared environmental factors (boys: 53%, girls: 67%) was more pronounced. It can be concluded from the results that individual differences in sleep duration were accounted for by genetic and non-shared environmental factors throughout adolescence, whereas shared environmental factors account for a substantial part of variation during early adolescence only.

Treatment response and treatment response predictors of a multidisciplinary day clinic for police officers with PTSD.

OBJECTIVE: Police officers typically face multiple potentially traumatic events and consequently have a higher conditional probability of developing PTSD. Although most police officers with PTSD benefit from first-line treatment, it is unknown whether recommended intensification of treatment for low responders is effective and which factors contribute to response. This study aimed to examine the treatment response of a day clinic for police officers with PTSD and identify predictors of treatment response. METHOD: Between 2009 and 2019, routine outcome monitoring measurements consisting of PTSD symptom severity and general psychological distress were administered at two timepoints among 102 patients undergoing a day clinic treatment consisting of trauma-focused therapy, sociotherapy, and psychomotor therapy. Hierarchical regression was used to assess whether change in PTSD symptom severity was associated with baseline PTSD and depression severity, gender, age, and eligibility for a recognition procedure. RESULTS: Significant improvements in PTSD symptom severity were found over the course of the treatment (d = .59), with 47% of patients showing statistically reliable improvement in their symptoms. The only significant predictor of treatment response was eligibility for a recognition procedure, with the total model explaining approximately 10% of the variation in treatment response. CONCLUSIONS: Intensifying treatment for police officers with PTSD who do not respond to previous trauma-focused treatment appears beneficial for a substantial number of patients. However, eligibility for a recognition procedure may negatively impact treatment response. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Trauma-focused treatment for traumatic stress symptoms in unaccompanied refugee minors: a multiple baseline case series.

Introduction: Unaccompanied refugee minors (URMs) are at increased risk of developing mental health problems, such as symptoms of posttraumatic stress disorder (PTSD) and depression. In addition, URMs face several barriers to mental health care. Few studies have evaluated trauma-focused interventions for URMs that target these issues. The current study evaluated a multimodal trauma-focused treatment approach for URMs. It aimed to provide an initial indication of the effectiveness of this treatment approach and to provide a qualitative evaluation assessing treatment satisfaction of the participating URMs. Methods: A mixed-methods study was conducted among ten URMs, combining quantitative data with qualitative data through triangulation. Quantitative data were collected using a non-concurrent multiple baseline design in which repeated, weekly assessments were carried out during a randomized baseline period, during treatment, and during a 4-week follow-up period. Questionnaires assessing PTSD (Children's Revised Impact of Event Scale) and symptoms of depression (The Patient Health Questionnaire-9, modified for adolescents) were used. In addition, treatment satisfaction was measured post-treatment using a semi-structured interview. Results: During the qualitative evaluation, all but one URM noted they found the trauma-focused treatment approach useful and felt the treatment had positively impacted their wellbeing. However, the results of the quantitative evaluation did not show clinically reliable symptom reductions at posttest or follow-up. Implications for clinical practice and research are discussed. Discussion: The current study presents our search in developing a treatment approach for URMs. It adds to the current knowledge about methodological considerations in evaluating treatments for URMs, the potential effects of trauma-focused treatments on URMs, and the implementation of treatments for URMs.Clinical trial registration: The study was registered in the Netherlands Trial Register (NL8519), 10 April 2020.

Psychometric evaluation of the Dutch International Trauma Questionnaire for the 11th revision of the International Classification of Diseases posttraumatic stress disorder and complex posttraumatic stress disorder.

BACKGROUND: The International Trauma Questionnaire (ITQ) is a recent self-report measure to assess the severity and probable posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) as defined by the 11th revision of the International Classification of Diseases. Few studies have examined the psychometric properties of full and short ITQ versions in depth. Therefore, we aimed to evaluate the psychometric properties of the Dutch-translated 28-item ITQ and the 12-item version. METHOD: Data were used from existing clinical studies and routine clinical assessments for the 28-item (n = 956) and 12-item (N = 4,944) ITQ versions in trauma-exposed treatment-seeking individuals in the Netherlands. Internal consistency and factor validity were assessed, and rates of probable PTSD and CPTSD were estimated. In addition, convergent and discriminant validity were examined by correlations with similar and dissimilar measures. RESULTS: Both versions of the ITQ showed good internal consistency and convergent validity. Confirmatory factor analysis showed that both a first-order correlated six-factor model and a two-factor second-order model were a good representation of the latent structure for the ITQ-12. The ITQ-12 resulted in higher CPTSD rates compared to the ITQ-28 (47% vs. 36.3%), while a similar number of patients met the criteria for either PTSD or CPTSD (70.6% vs. 76.4%). CONCLUSION: Internal consistency and convergent validity for the ITQ-12 and ITQ-28 were supported. The factorial validity was good for the ITQ-12 and acceptable for the ITQ-28. The discrepancy in CPTSD rates between the ITQ-12 and ITQ-28 calls for further testing of scoring methods against diagnostic clinical interviews for CPTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Moral Injury in Trauma-Exposed, Treatment-Seeking Police Officers and Military Veterans: Latent Class Analysis.

Exposure to morally injurious events may have a severe, prolonged negative impact on psychosocial functioning, known as moral injury (MI). Research into the prevalence of MI has mostly focused on event exposure rather than on psychosocial impact. Also, the relationship between MI and post-traumatic stress disorder (PTSD) remains a matter of interest. The aim of this study was to identify MI and PTSD symptom profiles among trauma-exposed, treatment-seeking police officers and military veterans, and to explore demographic and clinical differences between symptom profiles. Latent class and multinomial regression analyses were conducted in a sample of 1,703 participants, using the Clinician-Administered PTSD Scale for DSM-5 and the Brief Symptom Inventory. Four classes of participants were identified, labeled as a MI class (n = 192; 11.27%), a MI-PTSD class (n = 565; 33.18%), a PTSD class (n = 644; 37.82%), and a Neither MI-nor PTSD class (n = 302; 17.73%), resulting in 44.45% (n = 757) of participants who met an MI symptom profile with or without PTSD. There were significant differences between the classes in terms of gender as well as PTSD and comorbid psychopathology symptom severity, the latter of which was highest in the MI-PTSD class. In conclusion, a substantial subgroup of trauma-exposed, treatment-seeking police officers and military veterans could be classified as suffering from MI. Routinely screening for MI in treatment-seeking police officers and military veterans is recommended, and interventions aimed at relieving MI in these populations may be indicated.

The relevance of social capital and sense of coherence for mental health of refugees.

Introduction: Migration puts refugees in a completely new social context when simultaneously some have to deal with previously experienced traumatic events and post-migration stressors. Social capital and sense of coherence could be key resources to improve mental health of refugees. This study aims to examine the interplay between social capital (structural and cognitive), sense of coherence and mental health of refugees in the Netherlands. Objective: The present study was conducted to i) examine if social capital (structural and cognitive) and mental health are related in a population of Dutch refugees, and ii) test if sense of coherence has a moderating and/or a mediating effect on this relation. Method: Data were collected through questionnaires (n = 154) in a cross-sectional survey at different locations throughout the Netherlands. The data were analysed with multiple regression analyses and nonparametric bootstrapping using SPSS. Results: Social capital (structural and cognitive) was positively related to mental health. In addition a positive relation between sense of coherence and mental health of refugees was found. The relationship between cognitive social capital and mental health was completely mediated by sense of coherence. No moderation effect of sense of coherence on the relation between social capital and mental health was found. Conclusions: The current study contributed to understanding the social mechanism that determines refugee mental health: participating in social groups (structural social capital) and having supportive and trusting relationships (cognitive social capital), whilst experiencing life as comprehensible, manageable, and meaningful (sense of coherence) are positively related to better mental health of refugees. Findings indicate that preventive interventions aiming to enhance refugees' mental health may be more effective when targeting and promoting both social capital and sense of coherence, from a relatively early stage after arrival in the Netherlands.

Breakage-fusion-bridge cycles leading to inv dup del occur in human cleavage stage embryos.

Recently, a high incidence of chromosome instability (CIN) was reported in human cleavage stage embryos. Based on the copy number changes that were observed in the blastomeres it was hypothesized that chromosome breakages and fusions occur frequently in cleavage stage human embryos and instigate subsequent breakage-fusion-bridge cycles. In addition, it was hypothesized that the DNA breaks present in spermatozoa could trigger this CIN. To test these hypotheses, we genotyped both parents as well as 93 blastomeres from 24 IVF embryos and developed a novel single nucleotide polymorphism (SNP) array-based algorithm to determine the parental origin of (aberrant) loci in single cells. Paternal as well as maternal alleles were commonly rearranged in the blastomeres indicating that sperm-specific DNA breaks do not explain the majority of these structural variants. The parent-of-origin analyses together with microarray-guided FISH analyses demonstrate the presence of inv dup del chromosomes as well as more complex rearrangements. These data provide unequivocal evidence for breakage-fusion-bridge cycles in those embryos and suggest that the human cleavage stage embryo is a major source of chromosomal disorders.

Moderation of genetic factors by parental divorce in adolescents' evaluations of family functioning and subjective wellbeing.

Adolescents' evaluations of family functioning may have a significant impact on their subjective well-being and adjustment. The aim of the study was to investigate the degree to which genetic and environmental influences affect variation in evaluations of general family functioning, family conflict, and quality of life and the overlap between them. We assessed whether genetic and environmental influences are moderated by parental divorce by analyzing self-report data from 6,773 adolescent twins and their non-twin siblings. Genetic, shared, and nonshared environmental influences accounted for variation in general family functioning and family conflict, with genetic influences being relatively more important in girls than boys in general family functioning. Genetic and nonshared environmental influences accounted for variation in quality of life, with genetic influences being relatively more important in girls. Evidence was found for interaction between genetic factors and parental divorce: genetic influence on general family functioning was larger in participants from divorced families. The overlap between general family functioning and quality of life, and family conflict and quality of life was accounted for the largest part by genetic effects, with nonshared environmental effects accounting for the remaining part. By examining the data from monozygotic twins, we found evidence for interaction between genotype and nonshared, non-measured, environmental influences on evaluations of general family functioning, family conflict, and quality of life.