Cyber bullying victimization and adolescent mental health: The differential moderating effects of intrapersonal and interpersonal emotional competence.

INTRODUCTION: Individuals who experience bullying victimization are at increased risk for future health and social problems. Despite this, studies show that not all bullying victims are in ill health, suggesting the importance of investigating protective factors that could counteract the adverse effects. The present study focused on investigating the moderating effects of emotional competence (EC) in the relationship between cyber-bullying victimization (CV) and mental health among adolescents. METHODS: Responses from 6403 adolescents aged 12 to 18 (1925 male, 4478 female, Mage = 16.35, SD = 1.46) with no missing data were used for analysis. The cross-sectional data analyzed in the present study was a part of a large longitudinal online survey conducted by the University of Tokyo in Japan. Participants were recruited among adolescent users of a social networking service widely used in Japan for communication. RESULTS: Results of regression analysis showed significant direct effects of CV on psychological distress/self-esteem, confirming the adverse effects of victimization. Results also suggested that high intrapersonal EC weakened the relationship between CV and psychological distress, whereas high interpersonal EC strengthened the relationship. There were no significant interactions between CV and EC in predicting self-esteem. CONCLUSIONS: Intrapersonal and interpersonal EC may play differential moderating roles in the relationship between CV and psychological distress, the former by buffering the effect and the latter by exacerbating it. Interventions targeting abilities to handle one's own emotions may help decrease distress among adolescents with CV experiences.

Psychosocial Twin Cohort Studies in Japan: The Keio Twin Research Center (KoTReC).

The Keio Twin Research Center (KoTReC) was established in 2009 at Keio University to combine two longitudinal cohort projects - the Keio Twin Study (KTS) for adolescence and adulthood and the Tokyo Twin Cohort Project (ToTCoP) for infancy and childhood. KoTReC also conducted a two-time panel study of self-control and psychopathology in twin adolescence in 2012 and 2013 and three independent anonymous cross-sectional twin surveys (ToTcross) before 2012 - the ToTCross, the Junior and Senior High School Survey and the High School Survey. This article introduces the recent research designs of KoTReC and its publications.

Application of functional near infrared spectroscopy as supplementary examination for diagnosis of clinical stages of psychosis spectrum.

AIM: Research efforts aiming at neuroimaging-aided differential diagnosis for psychiatric disorders have been progressing rapidly. A previous multisite study has developed a supplementary diagnostic system using functional near-infrared spectroscopy (fNIRS) that can be easily applied to clinical settings. However, few neuroimaging biomarkers have been developed for the psychosis spectrum with various clinical stages. METHODS: We employed the fNIRS as a clinical examination device for 143 participants, comprising 47 ultra-high risk for psychosis (UHR) individuals, 30 patients with first-episode psychosis (FEP), 34 patients with chronic schizophrenia (ChSZ), and 33 healthy controls, who were independent of the previous study. A 12-month follow-up measurement was also carried out on 34 UHR individuals (72%), 21 patients with FEP (70%), and 33 controls. The fNIRS algorithm variables used for classification were the intensity and timing of prefrontal activation following the start of the cognitive task as used in the previous multisite study. RESULTS: The discrimination rate by timing of activation was modest but it became acceptable after adjusting confounding factors. Discrimination by intensity of activation was not improved by similar adjustment. A total of 63.8%, 86.7%, and 81.3% patients were classified as UHR, FEP, and ChSZ, respectively; and 85.1%, 86.7%, and 71.9% of patients in these groups, respectively, were classified as being on the psychosis spectrum. In the follow-up measurement, 88.2% of individuals with UHR and 95.0% of patients with FEP were successfully classified into the psychosis spectrum group. CONCLUSION: The fNIRS for supplementary clinical examination could be validly applied to differentiating people with the psychosis spectrum in various clinical stages. The fNIRS is a candidate biological marker for aiding diagnosis of psychosis spectrum in routine clinical settings.

Detection of resting state functional connectivity using partial correlation analysis: A study using multi-distance and whole-head probe near-infrared spectroscopy.

Multichannel near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that enables easy-to-use and noninvasive measurement of changes in blood oxygenation levels. We developed a clinically-applicable method for estimating resting state functional connectivity (RSFC) with NIRS using a partial correlation analysis to reduce the influence of extraneural components. Using a multi-distance probe arrangement NIRS, we measured resting state brain activity for 8min in 17 healthy participants. Independent component analysis was used to extract shallow and deep signals from the original NIRS data. Pearson's correlation calculated from original signals was significantly higher than that calculated from deep signals, while partial correlation calculated from original signals was comparable to that calculated from deep (cerebral-tissue) signals alone. To further test the validity of our method, we also measured 8min of resting state brain activity using a whole-head NIRS arrangement consisting of 17 cortical regions in 80 healthy participants. Significant RSFC between neighboring, interhemispheric homologous, and some distant ipsilateral brain region pairs was revealed. Additionally, females exhibited higher RSFC between interhemispheric occipital region-pairs, in addition to higher connectivity between some ipsilateral pairs in the left hemisphere, when compared to males. The combined results of the two component experiments indicate that partial correlation analysis is effective in reducing the influence of extracerebral signals, and that NIRS is able to detect well-described resting state networks and sex-related differences in RSFC.

Characterizing prefrontal cortical activity during inhibition task in methamphetamine-associated psychosis versus schizophrenia: a multi-channel near-infrared spectroscopy study.

Methamphetamine abuse and dependence, frequently accompanied by schizophrenia-like psychotic symptoms [methamphetamine-associated psychosis (MAP)], is a serious public health problem worldwide. Few studies, however, have characterized brain dysfunction associated with MAP, nor investigated similarities and differences in brain dysfunction between MAP and schizophrenia. We compared prefrontal cortical activity associated with stop-signal inhibitory task in 21 patients with MAP, 14 patients with schizophrenia and 21 age- and gender-matched healthy controls using a 52-channel near-infrared spectroscopy (NIRS) system. Both the MAP and the schizophrenia groups showed significantly reduced activation in the bilateral ventrolateral prefrontal cortex compared with controls; however, only the MAP group showed reduced activation in the frontopolar prefrontal cortex. The MAP group demonstrated significant positive correlations between task performance and hemodynamic responses in the bilateral ventrolateral, polar and left dorsolateral regions of the prefrontal cortex. The MAP and schizophrenia groups demonstrated a significant difference in the relationship of impulsivity to hemodynamic changes in the bilateral premotor cortex. These findings characterize similarities and differences in prefrontal cortical dysfunction between psychosis associated with methamphetamine and schizophrenia. The reduced hemodynamic changes in the bilateral ventrolateral prefrontal cortex suggest a common underlying pathophysiology of MAP and schizophrenia, whereas those in the frontopolar prefrontal cortex point to an impaired state that is either inherent or caused specifically by methamphetamine use.

Development of a neurofeedback protocol targeting the frontal pole using near-infrared spectroscopy.

AIM: Neurofeedback has been studied with the aim of controlling cerebral activity. Near-infrared spectroscopy is a non-invasive neuroimaging technique used for measuring hemoglobin concentration changes in cortical surface areas with high temporal resolution. Thus, near-infrared spectroscopy may be useful for neurofeedback, which requires real-time feedback of repeated brain activation measurements. However, no study has specifically targeted neurofeedback, using near-infrared spectroscopy, in the frontal pole cortex. METHODS: We developed an original near-infrared spectroscopy neurofeedback system targeting the frontal pole cortex. Over a single day of testing, each healthy participant (n = 24) received either correct or incorrect (Sham) feedback from near-infrared spectroscopy signals, based on a crossover design. RESULTS: Under correct feedback conditions, significant activation was observed in the frontal pole cortex (P = 0.000073). Additionally, self-evaluation of control and metacognitive beliefs were associated with near-infrared spectroscopy signals (P = 0.006). CONCLUSION: The neurofeedback system developed in this study might be useful for developing control of frontal pole cortex activation.

Anxiety and performance: the disparate roles of prefrontal subregions under maintained psychological stress.

Despite increasing interest in anxiety and psychological stress in daily life, little is known about neural correlates that underlie maintained psychological stress and their relationship with anxiety. In particular, the activation characteristics of lateral prefrontal subregions and their relationship with anxiety and cognitive performance under maintained psychological stress remain unknown. This study used near-infrared spectroscopy (NIRS), a noninvasive and "real-world" functional neuroimaging method, to investigate the hemodynamic responses in wide areas of the prefrontal cortex (PFC) and the influence of anxiety under conditions of maintained stress induced by a continuous arithmetic task (2 sets, 15 min each) performed in a natural sitting posture. Although anxiety and performance are not directly correlated, the hemodynamic response in the medial portion of the lateral PFC (dorsolateral and frontopolar PFC) was significantly associated with anxiety, while hemodynamic responses in the ventrolateral PFC were associated with performance. Additionally, in the same medial region of the lateral PFC, trait and state anxieties were related to changes in deoxy- and oxy-hemoglobin concentrations, respectively. This NIRS finding suggests disparate roles for prefrontal subregions in anxiety and performance under psychological stress and may lead to a better understanding of neural correlates for anxiety in everyday life.

Functional abnormalities in the left ventrolateral prefrontal cortex during a semantic fluency task, and their association with thought disorder in patients with schizophrenia.

Thought disorder is one of the primary symptoms in schizophrenia, yet the neural correlates and related semantic processing abnormalities remain unclear. We aimed to investigate the relationship between functional prefrontal abnormalities and thought disorder in schizophrenia using 2 types of verbal fluency tasks: the letter fluency task (LFT) and the category fluency task (CFT). Fifty-six adult patients with schizophrenia and 56 healthy controls matched for age, gender, and IQ participated in the study. During completion of the 2 types of verbal fluency tasks, we measured oxy- and deoxy-hemoglobin concentration ([oxy-Hb] and [deoxy-Hb]) signal changes over a wide area of the bilateral prefrontal cortex, using a 52-channel near-infrared spectroscopy (NIRS) system. Thought disorder scores were evaluated using the positive and negative syndrome scale. CFT performance was significantly higher than LFT performance in both groups, while there was no significant difference in any prefrontal NIRS signal changes between the 2 tasks in either group. In both versions of verbal fluency task, healthy controls exhibited a significantly greater NIRS signal change than did patients with schizophrenia. On the CFT only, left ventrolateral prefrontal NIRS [deoxy-Hb] signals were significantly associated with thought disorder scores in patients with schizophrenia. Our results suggest that left ventrolateral prefrontal abnormalities in category fluency might be related to thought disorder in schizophrenia. This could lead to an improved understanding of the neural mechanisms within the left ventrolateral prefrontal cortex involved in mediating semantic processing, as well as the relationship between semantic processing abnormalities and thought disorder in schizophrenia.

Neuroimaging-aided differential diagnosis of the depressive state.

A serious problem in psychiatric practice is the lack of specific, objective biomarker-based assessments to guide diagnosis and treatment. The use of such biomarkers could assist clinicians in establishing differential diagnosis, which may improve specific individualised treatment. This multi-site study sought to develop a clinically suitable neuroimaging-guided diagnostic support system for differential diagnosis at the single-subject level among multiple psychiatric disorders with depressive symptoms using near-infrared spectroscopy, which is a compact and portable neuroimaging method. We conducted a multi-site, case-control replication study using two cohorts, which included seven hospitals in Japan. The study included 673 patients (women/men: 315/358) with psychiatric disorders (major depressive disorder, bipolar disorder, or schizophrenia) who manifested depressive symptoms, and 1007 healthy volunteers (530/477). We measured the accuracy of the single-subject classification in differential diagnosis among major psychiatric disorders, based on spatiotemporal characteristics of fronto-temporal cortical haemodynamic response patterns induced by a brief (<3 min) verbal fluency task. Data from the initial site were used to determine an optimal threshold, based on receiver-operator characteristics analysis, and to generate the simplest and most significant algorithm, which was validated using data from the remaining six sites. The frontal haemodynamic patterns detected by the near-infrared spectroscopy method accurately distinguished between patients with major depressive disorder (74.6%) and those with the two other disorders (85.5%; bipolar disorder or schizophrenia) that presented with depressive symptoms. These results suggest that neuroimaging-guided differential diagnosis of major psychiatric disorders developed using the near-infrared spectroscopy method can be a promising biomarker that should aid in personalised care in real clinical settings. Potential confounding effects of clinical (e.g., age, sex) and systemic (e.g., autonomic nervous system indices) variables on brain signals will need to be clarified to improve classification accuracy.

Association of decreased prefrontal hemodynamic response during a verbal fluency task with EGR3 gene polymorphism in patients with schizophrenia and in healthy individuals.

The early growth response 3 (EGR3) gene is an immediate early gene that is expressed throughout the brain and has been suggested as a potential susceptibility gene for schizophrenia (SZ). EGR3 impairment is associated with various neurodevelopmental dysfunctions, and some animal studies have reported a role for EGR3 function in the prefrontal cortex. Therefore, EGR3 genotype variation may be reflected in prefrontal function. By using multi-channel near-infrared spectroscopy (NIRS) in an imaging genetics approach, we tested for an association between the EGR3 gene polymorphism and prefrontal hemodynamic response during a cognitive task in patients with SZ. We assessed 73 chronic patients with SZ and 73 age-, gender-, and genotype-matched healthy controls (HC) who provided written informed consent. We used NIRS to measure changes in prefrontal oxygenated hemoglobin concentration (oxyHb) during the letter version of a verbal fluency task (VFT). Statistical comparisons were performed among EGR3 genotype subgroups (rs35201266, GG/GA/AA). The AA genotype group showed significantly smaller oxyHb increases in the left dorsolateral prefrontal cortex (DLPFC) during the VFT than the GG and GA genotype groups; this was true for both patients with SZ and HC. Our findings provide in vivo human evidence of a significant influence of EGR3 polymorphisms on prefrontal hemodynamic activation level in healthy adults and in patients with SZ. Genetic variation in EGR3 may affect prefrontal function through neurodevelopment. This study illustrates the usefulness of NIRS in imaging genetics investigations on psychiatric disorders.

Genetic influences on prefrontal activation during a verbal fluency task in adults: a twin study based on multichannel near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) studies have reported that prefrontal hemodynamic dysfunction during executive function tasks may be a promising biomarker of psychiatric disorders, because its portability and noninvasiveness allow easy measurements in clinical settings. Here, we investigated the degree to which prefrontal NIRS signals are genetically determined. Using a 52-channel NIRS system, we monitored the oxy-hemoglobin (oxy-Hb) signal changes in 38 adult pairs of right-handed monozygotic (MZ) twins and 13 pairs of same-sex right-handed dizygotic (DZ) twins during a letter version of the verbal fluency task. Heritability was estimated based on a classical twin paradigm using structured equation modeling. Significant genetic influences were estimated in the right dorsolateral prefrontal cortex and left frontal pole. The degrees of heritability were 66% and 75% in the variances, respectively. This implies that the prefrontal hemodynamic dysfunction observed during an executive function task measured by NIRS may be an efficient endophenotype for large-scale imaging genetic studies in psychiatric disorders.

A NIRS-fMRI investigation of prefrontal cortex activity during a working memory task.

Near-infrared spectroscopy (NIRS) is commonly used for studying human brain function. However, several studies have shown that superficial hemodynamic changes such as skin blood flow can affect the prefrontal NIRS hemoglobin (Hb) signals. To examine the criterion-related validity of prefrontal NIRS-Hb signals, we focused on the functional signals during a working memory (WM) task and investigated their similarity with blood-oxygen-level-dependent (BOLD) signals simultaneously measured by functional magnetic resonance imaging (fMRI). We also measured the skin blood flow with a laser Doppler flowmeter (LDF) at the same time to examine the effect of superficial hemodynamic changes on the NIRS-Hb signals. Correlation analysis demonstrated that temporal changes in the prefrontal NIRS-Hb signals in the activation area were significantly correlated with the BOLD signals in the gray matter rather than those in the soft tissue or the LDF signals. While care must be taken when comparing the NIRS-Hb signal with the extracranial BOLD or LDF signals, these results suggest that the NIRS-Hb signal mainly reflects hemodynamic changes in the gray matter. Moreover, the amplitudes of the task-related responses of the NIRS-Hb signals were significantly correlated with the BOLD signals in the gray matter across participants, which means participants with a stronger NIRS-Hb response showed a stronger BOLD response. These results thus provide supportive evidence that NIRS can be used to measure hemodynamic signals originating from prefrontal cortex activation.

Comprehensive DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia.

Epidemiological studies have revealed that schizophrenia is highly heritable. However, genetic studies have not fully elucidated its etiology. Accumulating evidence suggests that epigenetic alterations may provide an additional explanation of its pathophysiology. We investigated the methylation profiles of DNA in peripheral blood cells from 18 patients with first-episode schizophrenia (FESZ) and from 15 normal controls. Schizophrenia patients were confined to those at the stage of first-episode psychosis. We analyzed the DNA methylation status of 27,578 CpG sites by means of the Illumina Infinium HumanMethylation27 BeadChip array. Differentially methylated CpG sites, which were particularly abundant within CpG islands, were enriched in genes related to the nuclear lumen, to transcription factor binding, and to nucleotide binding. We also observed differential methylation of the promoters of HTR1E and COMTD1, which are functionally related to genes found to be differentially methylated in schizophrenia patients in previous studies. Our results indicate the site-specific epigenetic alterations in patients with FESZ.

Phonological fluency is uniquely impaired in Japanese-speaking schizophrenia patients: confirmation study.

In alphabet-based language-speaking patients with schizophrenia, category fluency is disproportionately disturbed as compared with phonological fluency. Deficits in category and phonological fluency observed in Japanese patients, however, were similar. The aim of the present study was to replicate these findings by modifying the task to minimize the influence of lack of motivation and concentration in the patients. Similar deficits were found in both types of fluency in Japanese patients. Patients who speak Japanese have deficits in phonological fluency, compared with patients who speak alphabet-based languages, suggesting that the pattern of impairment in verbal fluency in schizophrenia is dependent on the specific language system.

Work-related stressors among hospital physicians: a qualitative interview study in the Tokyo metropolitan area.

OBJECTIVES: We explored Japanese physicians' work-related stressors and identified those unique to this population, as well as clarified the influence of cultural and medical system diversity on these stressors to determine the content of future stress-reducing interventions for hospital physicians in Japan. DESIGN: We conducted a semistructured, face-to-face interview-based qualitative study between August and October 2017. The collected data were analysed using the grounded theory approach. SETTING: Hospitals around the Tokyo metropolitan area, Japan. PARTICIPANTS: Sixteen hospital physicians (mean age (SD)=33.9 (4.2) years; 11 men, 5 women). Seven worked in internal medicine and nine in surgery. RESULTS: We found unique stressors related to the Japanese medical system and culture, such as continuous all-day work after night shifts, and a hierarchical organisational system called Ikyoku. The results also indicated that Japanese physicians shared several stressors with Western physicians, such as sleep deprivation, high pressure and the limits of medicine. CONCLUSIONS: Our study clarifies some sources of work-related stressors among hospital physicians in Japan. While the key components of Western interventions might be useful in a Japanese context, the original evidence obtained from this study highlights the necessity of initiating interventions addressing the unique stressors of Japanese physicians. To reduce physicians' stress and enhance their well-being, psychological interventions for hospital physicians must be introduced in Japan.

Gender difference in right lateral prefrontal hemodynamic response while viewing fearful faces: a multi-channel near-infrared spectroscopy study.

Near-infrared spectroscopy (NIRS) has been widely used to non-invasively assess brain function in various psychiatric disorders. Previous NIRS studies have extensively investigated prefrontal activation associated with cognitive tasks; in contrast, NIRS signals from prefrontal cortex in response to emotional stimuli have received little attention. We investigated spatiotemporal characteristics of hemodynamic response during an emotional activation task using fearful facial expression stimuli. We also evaluated gender difference and the relationship with anxiety-related personality traits. Subjects were 10 women and 10 men, all right-handed and matched for age, education and IQ estimated from the adult reading test. NIRS signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions by 52-channel NIRS. Women showed significantly increased [oxy-Hb] change relative to men in the right ventrolateral prefrontal cortex during the latter half of the task period. Frontopolar [deoxy-Hb] response correlated significantly with trait anxiety scores in the whole sample. These results suggest that gender and trait anxiety have an effect on individual variability of NIRS signals in response to emotional stimuli. This observation may help to establish NIRS as a clinical tool for monitoring prefrontal function on an individual basis.

Association between sigma-1 receptor gene polymorphism and prefrontal hemodynamic response induced by cognitive activation in schizophrenia.

The molecular biological role of the sigma-1 receptor (Sig-1R) has attracted much attention. Evidence suggests that the Sig-1R engaged in modulating NMDA and dopamine receptors is involved in the pathophysiology of schizophrenia and the mechanism of psychotropic drug efficacy. However, whether the Sig-1R genotype affects brain function in schizophrenia in vivo remains unknown. We investigated the association between Sig-1R functional polymorphism (Gln2Pro) and brain function in schizophrenia. The subjects were 40 patients with schizophrenia and 60 healthy controls, all right-handed, who gave written informed consent to participate. Signals, detected from prefrontal regions by 52-channel near-infrared spectroscopy (NIRS) during cognitive activation, were compared between two Sig1-R genotype subgroups (Gln/Gln individuals and Pro carriers) matched for age, gender, premorbid IQ and task performance. The prefrontal hemodynamic response of healthy controls during the verbal fluency task was higher than that of patients with schizophrenia. For the patients with schizophrenia, even after controlling the effect of medication, the [oxy-Hb] increase in the prefrontal cortex of the Gln/Gln genotype group was significantly greater than that of the Pro carriers (false discovery rate corrected p<0.05). Clinical symptoms were not significantly different between the two Sig-1R genotype subgroups. These differences were not significant in the healthy controls. This is the first functional imaging genetics study that implicated the association between Sig-1R genotype and prefrontal cortical function in schizophrenia in vivo. Our findings also suggest that the prefrontal hemodynamic response assessed by noninvasive and less demanding NIRS is a useful intermediate phenotype for translational research in schizophrenia.

Severity-dependent and -independent brain regions of major depressive disorder: A long-term longitudinal near-infrared spectroscopy study.

BACKGROUND: Long-term longitudinal studies are necessary to establish neuroimaging indicators which contribute to the detection of severity changes over time in patients with major depressive disorder (MDD). METHODS: One hundred sixty-five patients with MDD underwent clinical assessments and near-infrared spectroscopy (NIRS) examination at the initial evaluation (T0). After 1.5 years, 45 patients who visited for the follow-up evaluation (T1.5) were included in the analysis. The authors conducted analyses using the 17-item Hamilton Rating Scale for Depression (HAMD) scores and mean oxy-hemoglobin concentration ([oxy-Hb]) changes during a cognitive task in NIRS at T0 (T0_HAMD, T0_[oxy-Hb]) and at T1.5 (T1.5_HAMD, T1.5_[oxy-Hb]), and their intra-individual longitudinal changes (ΔHAMD = T1.5_HAMD - T0_HAMD, Δ[oxy-Hb] = T1.5_[oxy-Hb] - T0_[oxy-Hb]). RESULTS: For severity-dependent regions, the Δ[oxy-Hb] in the right inferior frontal gyrus (IFG) was negatively correlated with the ΔHAMD. For severity-independent regions, the intra-class correlation coefficients between T0_ and T1.5_[oxy-Hb] were moderate in the bilateral middle frontal gyri (MFG). LIMITATIONS: The percentage of patients included in the follow-up examination was relatively small. CONCLUSIONS: Brain activation in the right IFG and the bilateral MFG as measured by NIRS may differentially indicate clinical severity and trait-related abnormalities in MDD.

Adolescent Victimization and Self-Injurious Thoughts and Behaviors: A Genetically Sensitive Cohort Study.

OBJECTIVE: Victimized adolescents have an increased risk of self-injurious thoughts and behaviors. However, poor understanding of causal and non-causal mechanisms underlying this observed risk limits the development of interventions to prevent premature death in adolescents. This study tested whether pre-existing family-wide and individual vulnerabilities account for victimized adolescents' increased risk of self-injurious thoughts and behaviors. METHOD: Participants were 2,232 British children followed from birth to 18 years of age as part of the Environmental Risk Longitudinal Twin Study. Adolescent victimization (maltreatment, neglect, sexual victimization, family violence, peer/sibling victimization, cyber victimization, and crime victimization) was assessed through interviews with participants and co-informant questionnaires at the 18-year assessment. Suicidal ideation, self-harm, and suicide attempt in adolescence were assessed through interviews with participants at 18 years. RESULTS: Victimized adolescents had an increased risk of suicidal ideation (odds ratio [OR] 2.40, 95% CI 2.11-2.74), self-harm (OR 2.38, 95% CI 2.10-2.69), and suicide attempt (OR 3.14, 95% CI 2.54-3.88). Co-twin control and propensity score matching analyses showed that these associations were largely accounted for by pre-existing familial and individual vulnerabilities, respectively. Over and above their prior vulnerabilities, victimized adolescents still showed a modest increase in risk for suicidal ideation (OR 1.45, 95%CI 1.10-1.91) and self-harm (OR 1.50, 95% CI 1.18-1.91) but not for suicide attempt (OR 1.28, 95% CI 0.83-1.98). CONCLUSION: Risk for self-injurious thoughts and behaviors in victimized adolescents is explained only in part by the experience of victimization. Pre-existing vulnerabilities account for a large proportion of the risk. Therefore, effective interventions to prevent premature death in victimized adolescents should not only target the experience of victimization but also address pre-existing vulnerabilities.