Developmental Risk Factors Research Articles

30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed Into the Developmental Risk Factor Model of Psychosis

At its re-birth 30 years ago, the neurodevelopment hypothesis of schizophrenia focussed on aberrant genes and early neural hazards, but then it grew to include ideas concerning aberrant synaptic pruning in adolescence. The hypothesis had its own stormy development and it endured some difficult teenage years when a resurgence of interest in neurodegeneration threatened its survival. In early adult life, it over-reached itself with some reductionists claiming that schizophrenia was simply a neurodevelopmental disease. However, by age 30, the hypothesis has matured sufficiently to incorporated childhood and adult adversity, urban living and migration, as well as heavy cannabis use, as important risk factors. Thus, it morphed into the developmental risk factor model of psychosis and integrated new evidence concerning dysregulated striatal dopamine as the final step on the pathway linking risk factors to psychotic symptoms.

Pathophysiological trajectories and biological consequences of early life trauma

ABSTRACTExperience of early life stress (ELS) (childhood trauma, maltreatment, neglect, separation, physical and sexual abuse, parental loss and other severe anxiety/stress symptoms) is highly prevalent in the general population and constitutes a major public health problem (Gilbert et al., 2009). The objective of this paper is to review evidence on epidemiological risk factors, pathophysiological trajectories and neurobiological pathways exerting the enduring adverse effects of ELS and leading to compromised overall health in adulthood.Prolonged neuropsychobiological alterations as sequelae of early trauma could mediate the risk of disease in adulthood, and lead to cumulative disadvantages and increased physical and mental morbidity in later life. In particular, a higher risk of psychiatric disorders (e.g. depression, post-traumatic stress disorder and other anxiety disorders) and their unfavourable outcomes (e.g. treatment resistance, suicide) has been associated with a history of ELS in several retrospective but also prospective studies, while the moderating interaction of ELS and pre-existing genetic vulnerability in these disorders has been extensively discussed in recent literature. Nevertheless, the chronic physical health consequences of childhood adversities may be as substantial as mental health consequences. Prior research suggests an association of ELS with cardiovascular, pulmonary and metabolic diseases, chronic inflammatory and pain syndromes, frequency of medical consultations and number of medical diagnoses. In addition, risk behaviour patterns such as substance use, and especially tobacco and alcohol consumption, are considered significantly increased in individuals with experience of ELS. Consequently, many studies have reported a negative impact of ELS on adult general mental and physical health-related quality of life, while recognizing the additive effect of the number or different types of childhood adversities is important for understanding their cumulative effect on later life adjustment (Agorastos, Pittman et al., 2014).The distinct impact of ELS may lie in enhanced plasticity mechanisms during this period that lead to persistent functional and epigenetic alterations and to higher allostatic load over time. Experience of ELS has been shown to lead to an increased neuroendocrine stress response and vulnerability to stress, hypothalamic–pituitary–adrenal axis dysregulation, long-lasting alterations in emotional and psychophysiological reactivity, impaired adaptive functioning, malfunction of fear response circuits and structural changes in the central nervous system. ELS can also lead to epigenetic modifications in response to environmental influences through stress-related gene expression and, thus, play a central role in the long-term biological trajectories leading to stress-related disease, and may explain interindividual variation. In addition, ELS represents an independent risk factor for neuroendocrine–immunological abnormalities with the development, to some level, of a proinflammatory phenotype in adulthood. Finally, recent literature has focused on the potentially fundamental role of sleep and circadian rhythms in the development of ELS-related disorders. Central and peripheral circadian disruption after severe stress in childhood could engrave pathophysiological trajectories of ELS through impaired homeostatic balance, with overall neuroendocrine, immune, metabolic and autonomic dysregulation (Agorastos, Kellner et al., 2014).Taken together, persistent structural, functional and epigenetic changes in neural circuits after ELS could foster chronic chronodisruption and thus mediate the risk of disease and resilience in adults, following a distinct dose–response relationship. The long-term effects of ELS may be conceptualized as a common developmental risk factor triggering a health-related risk cascade with high public health impact. Future studies should focus on prospective investigation of potential predictors and mediators, their temporal sequence and combined effects at epidemiological, biological and epigenetic levels, while taking into account the potentially delayed time-frame for the expression of their effects. Screening strategies for ELS need to be improved, as they would help to identify an individual’s risk level for disease development and predict the response to treatment, towards a better understanding of the relationship between gene and environmental exposures that impacts resilience.

Review: Prevention of anxiety among at-risk children and adolescents - a systematic review and meta-analysis.

Anxiety disorders are common, often start in childhood and run a chronic course. As such there is a need for effective prevention. We conducted a systematic review and meta-analyses of randomized, controlled trials to prevent the onset of anxiety disorders in 'at risk' young people. Diagnostic and symptom outcomes were examined. Putative moderators were tested as was publication bias. We included 16 trials (2545 young people). Two trials reported diagnostic outcomes, and significant effects were found for these at end-of-programme (RR=.09, 95%CI=.02 to .16), 6- (RR=.17, 95%CI=.06 to .27) and 12-month (RR=.31, 95%CI .17 to .45) follow-ups. Based on 16 trials, improved anxiety symptoms were significant compared to nonattention controls only, with small effect sizes reported by young people at the end-of-programmes, 6- and 12-month follow-ups; and by parents at the end of the programmes and 12-, but not 6-, month follow-ups. There was no evidence of significant moderation or publication bias. Fourteen studies included children and young people who presented with elevated anxiety symptoms, but anxiety disorder was not ruled out in the participants in these studies. Hence, these studies might be reporting results of mixed prevention/early intervention programmes. Prevention programmes that target developmental risk factors, not only disorder maintaining factors, appear most promising. The clinically meaningful impact of anxiety disorder prevention programmes remains unknown.

Feasibility of a school-based parenting intervention for adolescent parents

AbstractAssociated with complex developmental, personal, and environmental risk factors, adolescent parents have been found to display higher rates of unfavorable parenting practices than adult parents, placing their children at high risk for social, emotional and behavioral concerns. Nevertheless, interventions targeting this group often focus solely on adolescents’ personal outcomes. This study evaluated the acceptability and fidelity of a relationship-focused intervention to increase positive parenting among adolescents with young children, adapted from the Parents Interacting with Infants model. The intervention was delivered via groups in high schools that housed daycare centers for children born to adolescents. Multiple-case study data were evaluated for adolescent parents from each group to describe potential effects of the intervention on parenting behaviors. Delivery of the intervention was feasible and acceptable in a high school group context, suggesting this program can be implemented in a hig...

Maternal Prenatal Stress and Other Developmental Risk Factors for Adolescent Depression: Spotlight on Sex Differences.

Maternal stress during pregnancy has been linked to premorbid abnormalities associated with depression (e.g., difficult temperament, cognitive deficits) in offspring. However, few studies have looked across developmental periods to examine maternal stress during pregnancy and offspring depression during adolescence and whether these associations differ by sex. The current study used data from 1711 mother-offspring dyads (offspring sex: 49.8% male) in a longitudinal birth cohort study. Maternal narratives collected during pregnancy were qualitatively coded for stress-related themes by independent raters. Latent class analysis (LCA) identified distinct subgroups of offspring based on exposure to maternal prenatal stress and other developmental factors from the prenatal, childhood, and adolescent periods that have been associated with depression and/or maternal prenatal stress. LCA identified subgroups that were compared to determine whether and to what extent they differed on adolescent depressive symptoms. LCA revealed a subgroup of "high-risk" individuals, characterized by maternal factors during pregnancy (higher ambivalence/negativity and lower positivity towards the pregnancy, higher levels of hassles, lower maternal education and higher maternal age at birth, higher pre-pregnancy BMI) and offspring developmental factors (decreased cognitive functioning during childhood and adolescence, lower perceived parental support during adolescence, and higher levels of maternal depression during adolescence). High-risk females exhibited elevated conduct symptoms and higher birth order, while high-risk males exhibited decreased internalizing symptoms and lower birth order. Both high-risk males and females reported elevated depressive symptoms during adolescence relative to their "low-risk" counterparts.

Supporting the developmental health of refugee children and youth.

The Canadian Government has announced that over 50,000 refugees from the Middle East will be resettled in Canada by 2018. More than one-third of these refugees are expected to be children. The Canadian Paediatric Society has called for the Canadian government to prepare for the influx of these children. This should include addressing developmental, behavioural, and mental health needs. The focus of this paper is the role of paediatricians and family physicians in caring for the developmental health of refugee children, as a means of supporting their developmental and learning potential. The authors suggest the use of EMPOWER (Education, Migration, Parents and Family, Outlook, Words, Experience of Trauma and Resources), a mnemonic checklist they developed for assessing developmental risk factors in refugee children. EMPOWER can be used along with online web resources such as Caring For Kids New to Canada in providing evidence-informed care to these children.

Friends' Alcohol-Related Social Networking Site Activity Predicts Escalations in Adolescent Drinking: Mediation by Peer Norms

PurposeAdolescents' increased use of social networking sites (SNS) coincides with a developmental period of heightened risk for alcohol use initiation. However, little is known regarding associations between adolescents' SNS use and drinking initiation nor the mechanisms of this association. This study examined longitudinal associations among adolescents' exposure to friends' alcohol-related SNS postings, alcohol-favorable peer injunctive norms, and initiation of drinking behaviors. MethodsParticipants were 658 high-school students who reported on posting of alcohol-related SNS content by self and friends, alcohol-related injunctive norms, and other developmental risk factors for alcohol use at two time points, 1 year apart. Participants also reported on initiation of three drinking behaviors: consuming a full drink, becoming drunk, and heavy episodic drinking (three or more drinks per occasion). Probit regression analyses were used to predict initiation of drinking behaviors from exposure to alcohol-related SNS content. Path analyses examined mediation of this association by peer injunctive norms. ResultsExposure to friends' alcohol-related SNS content predicted adolescents' initiation of drinking and heavy episodic drinking 1 year later, controlling for demographic and known developmental risk factors for alcohol use (i.e., parental monitoring and peer orientation). In addition, alcohol-favorable peer injunctive norms statistically mediated the relationship between alcohol-related SNS exposure and each drinking milestone. ConclusionsResults suggest that social media plays a unique role in contributing to peer influence processes surrounding alcohol use and highlight the need for future investigative and preventive efforts to account for adolescents' changing social environments.

Propranolol treatment of infantile hemangioma is not associated with psychological problems at 7 years of age

Concern has been raised about the potential long-term effects of propranolol treatment for infantile hemangioma (IH). We sought to assess psychologic (social, emotional, behavioral, and executive) functioning in children treated with propranolol for IH. Twenty-seven patients with IH (6.1-7.6years of age) treated with propranolol for ≥6months during infancy, and without other developmental risk factors, were recruited. Parents completed the Behavior Rating Inventory of Executive Function, Social Emotional Questionnaire, Child Behavior Checklist, and Strengths and Difficulties Questionnaire. For each questionnaire, the number of patients with abnormal scores, based on established cutoff points, was calculated. Only 1 child (3.7%) scored outside the normal range. The Hemangioma Severity Scale did not correlate with psychologic problems in these patients. Longer treatment duration was found to correlate with less attention-deficit hyperactivity disorder (ADHD) characteristics (ρ=-0.476; P=.012) and better executive functioning (ρ=-0.466; P=.014). Exclusion of children born at gestational age <36weeks or small for gestational age, no reference group and relatively small study size. We found no increased risk for psychologic problems at age 7 in IH patients treated with propranolol.

Domestic violence offending behaviors: A review of the literature examining childhood exposure, implicit theories, trait aggression and anger rumination as predictive factors

The prevalence of domestic violence (DV) is an increasing public health concern globally. This paper outlines the current literature on what is known about DV proclivity, with particular attention to predictors for DV perpetration from childhood. We begin by reviewing key methodological issues that are inherent within DV literature and hinder the development of interventions and treatments for DV offenders. The main body of this article provides an overview of four main predictive components for DV perpetration: (1) developmental risk factors for DV offending (e.g. childhood exposure to DV); (2) specific implicit theories related to sexual, violent and DV offenders; (3) the role of anger rumination as a psychological process of DV offending; and (4) an exploration of the role of trait aggression in increasing DV Proclivity. Finally, it was concluded that there is a need for the development of a psychometric measure to encompass these four key predictors of DV Proclivity and future offending.

A Sociobiological Model of Early Childhood Caries: The Role of Allostatic Load

Objective: Even though many factors have been linked to increased ECC risk, few studies have specifically presented this information as a single comprehensive model. The purpose of this paper is to review the scope and usefulness of the proposed conceptual model in guiding future research of ECC risk as it relates to allostatic load. Methods: The various social, behavioural, and biological risk factors that emerge from the cumulative effects of chronic stress, defined as allostatic load, are discussed separately before being incorporated into a single sociobiological model of ECC. Results: In addition to biological realities, children experience profound impacts from their environments and family circumstances. The risk of developing ECC is especially pronounced in socially disadvantaged contexts. This information, as it is presented in the proposed conceptual model, reveals unique allostatic factors that work to increase risk at the level of the individual child, family, community, and society. Giving clinicians an idea of these realities has the capacity to more effectively screen and risk stratify children on the basis of dental health in the hopes of ultimately increasing their overall health as well. Conclusion: The proposed model provides a conceptual framework that relates factors of allostatic load to increased ECC risk. It demonstrates that a population-based, interprofessional collaboration strategy is essential to delivering effective prevention and treatment modalities to at-risk children. Future research regarding translational strategies has the capacity to reduce the prevalence of the biological, developmental, and psychosocial risk factors and thus ECC as a whole.

Adenosine A2A receptor regulation of microglia morphological remodeling-gender bias in physiology and in a model of chronic anxiety.

Developmental risk factors, such as the exposure to stress or high levels of glucocorticoids (GCs), may contribute to the pathogenesis of anxiety disorders. The immunomodulatory role of GCs and the immunological fingerprint found in animals prenatally exposed to GCs point towards an interplay between the immune and the nervous systems in the etiology of these disorders. Microglia are immune cells of the brain, responsive to GCs and morphologically altered in stress-related disorders. These cells are regulated by adenosine A2A receptors, which are also involved in the pathophysiology of anxiety. We now compare animal behavior and microglia morphology in males and females prenatally exposed to the GC dexamethasone. We report that prenatal exposure to dexamethasone is associated with a gender-specific remodeling of microglial cell processes in the prefrontal cortex: males show a hyper-ramification and increased length whereas females exhibit a decrease in the number and in the length of microglia processes. Microglial cells re-organization responded in a gender-specific manner to the chronic treatment with a selective adenosine A2A receptor antagonist, which was able to ameliorate microglial processes alterations and anxiety behavior in males, but not in females.

Validation of a culturally adapted developmental screening tool for Australian Aboriginal children: Early findings and next steps

BackgroundEarly detection of developmental problems is important for facilitating access to targeted intervention and maximising its positive effects. The later problems are identified, the more likely that they will become increasingly difficult to ameliorate. Standardised developmental screening tools are known to improve detection rates of developmental problems compared to clinical judgement alone and are widely recommended for use with all children. The Ages and Stages Questionnaire (ASQ-3) is a tool that is widely used in Australia. However, mainstream screening tools may not be appropriate for remote-dwelling Australian Aboriginal children. While Australian Aboriginal children face multiple developmental risk factors, there are no developmental screening tools that have been validated for use in this population. AimsTo determine the concurrent validity of the culturally adapted ASQ-3 – the ASQ-TRAK – for Australian Aboriginal children compared to the Bayley Scales of Infant and Toddler Development (Bayley-III), a standardised, professionally administered developmental assessment. SubjectsThe ASQ-TRAK and Bayley-III were administered cross-sectionally to 67 Central Australian Aboriginal children between 2 and 36months of age. ResultsThe ASQ-TRAK communication, gross motor, fine motor and problem-solving domains and the corresponding domains on the Bayley-III were moderately correlated. Overall sensitivity for the ASQ-TRAK was 71% (95% CI 29–96) and specificity was 92% (95% CI 88–99). Percentage agreement between the ASQ-TRAK and the Bayley-III was 90%. ConclusionsThe ASQ-TRAK shows promise as a tool that can be used to improve developmental monitoring for remote dwelling Australian Aboriginal children. Further research is necessary to build on the current findings.

Examining the Historical Developments and Contemporary Relevance of the Longitudinal–Experimental Design of the Cambridge-Somerville Youth Study: Utility for Research on Intergenerational Transmission of Offending

Founded in 1939, the Cambridge-Somerville Youth Study represents the earliest longitudinal–experimental study in developmental crime prevention, combining the aims of understanding how the developmental process is related to future offending (i.e., longitudinal focus) as well as attempting to prevent offending through an experimental intervention during early adolescence. This article examines the historical context in which this novel design arose and provides a review of studies performed by Joan McCord based on her age-45 follow up of the study. The study made possible decades of research on developmental risk factors for delinquency and criminal offending. A central question that arises from McCord’s body of research is how these risk factors are transmitted from parents to children. This article reviews extant research on the transmission of intergenerational offending, and discusses the potential of the Cambridge-Somerville Youth Study to contribute to this literature. Specifically, the prospective longitudinal design makes it possible to include the children of the study participants and investigate the intergenerational transmission of offending, while the longitudinal–experimental design allows for the investigation of the transmission of treatment effects. This potential research stands as a testament to the study’s design and vision.

Contributions of the Nurses' Health Studies to Reproductive Health Research.

To review the Nurses' Health Study's (NHS's) contribution to identifying risk factors and long-term health consequences of reproductive events. We performed a narrative review of the NHS I, NHS II, NHS3, and Growing Up Today Study (GUTS) publications between 1976 and 2016. Collection of detailed reproductive history to identify breast cancer risk factors allowed the NHS to document an association between menstrual irregularities, a proxy for polycystic ovary syndrome (PCOS), and increased risk of diabetes and cardiovascular disease. The NHS II found that infertility associated with ovulation problems and gestational diabetes are largely preventable through diet and lifestyle modification. It also identified developmental and nutritional risk factors for pregnancy loss, endometriosis, and uterine leiomyomata. As women in NHS II age, it has become possible to address questions regarding long-term health consequences of pregnancy complications and benign gynecologic conditions on chronic disease risk. Furthermore, the NHS3 and GUTS are allowing new lines of research into human fertility, PCOS, and transgenerational effects of environmental exposures. The multigenerational resources of the NHSs and GUTS, including linkages of related individuals across cohorts, can improve women's health from preconception through late adulthood and onto the next generation.

Motor Problems as a Risk Factor for Poorer Mental Health in Children and Adolescents: What Do We Know and Should We Be Screening for Psychological Difficulties in Those with Poor Motor Skills?

The individual and societal costs of mental health problems in children and adolescents and the associated potential negative outcomes for adulthood have been highlighted. While the importance of increasing knowledge and awareness of developmental risk factors for mental health issues has been noted, the significant relationship between motor skill and mental health difficulties continues to be under-recognized and lacks public awareness, including in health professionals. This paper discusses the evidence demonstrating that motor skill difficulties may increase risk for poorer mental health outcomes, such as anxiety and depression. It is argued that increased awareness of this relationship, with screening of associated mental health problems as a first step, is imperative in order to target assessment and intervention efforts and improve outcomes for individuals with movement problems.

Developmental risk factors in generalized anxiety disorder and panic disorder

BackgroundThere is a lack of clarity regarding specific risk factors discriminating generalized anxiety disorder (GAD) from panic disorder (PD). GoalThis study investigated whether GAD and PD could be discriminated through differences in developmental etiological factors including childhood parental loss/separation, psychological disorders, and maternal and paternal attachment. MethodTwenty people with adult generalized anxiety disorder (GAD), 20 with adult panic disorder (PD), 11 with adult comorbid GAD and PD, and 21 adult non-anxious controls completed diagnostic interviews to assess symptoms of mental disorders in adulthood and childhood. Participants also reported on parental attachment, loss and separation. ResultsChildhood diagnoses of GAD and PD differentiated clinical groups from controls as well as from each other, suggesting greater likelihood for homotypic over heterotypic continuity. Compared to controls, specific phobia was associated with all three clinical groups, and childhood depression, social phobia, and PTSD were uniquely associated with adult GAD. Both maternal and paternal attachment also differentiated clinical groups from controls. However, higher levels of subscales reflecting maternal insecure avoidant attachment (e.g., no memory of early childhood experiences and balancing/forgiving current state of mind) emerged as more predictive of GAD relative to PD. There were no group differences in parental loss or separation. ConclusionsThese results support differentiation of GAD and PD based on developmental risk factors. Recommendations for future research and implications of the findings for understanding the etiology and symptomatology of GAD and PD are discussed.

Alcohol and Cigarette Use Among Warsaw Adolescents: Factors Associated With Risk and Resilience

ABSTRACTBackground: Youth in Poland are at notable risk for substance use. Guided by resiliency theory, we examine if developmental risk and promotive factors are associated with substance abuse risk. Objectives: We examined the association between adolescent cigarette and alcohol use and related risk and promotive factors including maternal support, neighbors' informal social control, friends' acceptance of substance use, and alcohol and cigarette use by nonparental adults. Method: Data were collected from a random sample of 13- to 14-year-old students attending Warsaw middle schools (N = 3029). We used hierarchical regression models and examined compensatory and protective models of resilience, controlling for sociodemograhic factors. Results: Our results indicated that friends' acceptance of substance use and perceived drug use among nonparental adults was associated with increased risk cigarette and alcohol use among youth. We found that maternal support moderated the relationship between friends' acceptance of substance use and cigarette use (protective model of resilience). Thus, mother support buffered the negative effects of friends' acceptance of substance use on youths' cigarette use. Neighbor's informal social control and maternal support were associated with reduced risk of alcohol use (compensatory model of resilience). Conclusion: Collectively, results of the study support compensatory and protective models of resilience in a large representative sample of Warsaw adolescents.

A Longitudinal Study of IPV Victimization Among Sexual Minority Youth.

Although intimate partner violence (IPV) is highly prevalent among lesbian, gay, bisexual, and transgender (LGBT) youth, little is known regarding its developmental patterns, risk factors, or health-related consequences. We examined IPV victimization in an ethnically diverse community-based convenience sample of 248 LGBT youth (aged 16-20 at study outset) who provided six waves of data across a 5-year period. Results from multilevel models indicated high, stable rates of IPV victimization across this developmental period (ages 16-25 years) that differed between demographic groups. Overall, 45.2% of LGBT youth were physically abused and 16.9% were sexually victimized by a dating partner during the study. Odds of physical victimization were 76% higher for female than for male LGBT youth, 2.46 times higher for transgender than for cisgender youth, and 2 to 4 times higher for racial-ethnic minorities than for White youth. The prevalence of physical IPV declined with age for White youth but remained stable for racial-ethnic minorities. Odds of sexual victimization were 3.42 times higher for transgender than for cisgender youth, 75% higher for bisexual or questioning than for gay or lesbian youth, and increased more with age for male than female participants. Within-person analyses indicated that odds of physical IPV were higher at times when youth reported more sexual partners, more marijuana use, and lower social support; odds of sexual IPV were higher at times when youth reported more sexual partners and more LGBT-related victimization. In prospective analyses, sexual IPV predicted increased psychological distress; both IPV types marginally predicted increased marijuana use.

Neurocognitive Characteristics of Early Marijuana Use Initiation in Adolescents: A Signature Mapping Analysis.

Prior studies of the association between neurocognitive functions and marijuana use among adolescents are mostly cross-sectional and conducted in adolescents who have already initiated marijuana use. The current study used a longitudinal design on a preadolescent, substance-naive sample. We sought to identify demographic factors associated with neurocognitive functions and the complement of neurocognitive function characteristics that predict marijuana initiation in adolescents. Substance-naive adolescents (n = 465) ages 10-12 years (51% male) were recruited from a community with high levels of adolescent marijuana use and prospectively followed to ages 12-15. Tasks measuring neurocognitive functions were administered and audio-assisted interviews were conducted. Two types of models were estimated for each outcome: forced-entry models and another using stepwise selection via bidirectional elimination with varying tolerance levels to account for selection misspecification. About 10% (n = 49) initiated marijuana use over the study period. Child's age, academic achievement, and parental education were associated with baseline neurocognitive functions; namely, positive emotion attributions and lower impulsivity. Facial recognition-particularly misattribution of sad faces-was the strongest predictor of marijuana initiation, including in the stepwise model (partial OR = 1.3, 95% CI [1.03, 1.63], p < .05) that resulted in the best-fitting model. Prediction of marijuana initiation was improved in stepwise models compared with forced-entry models. Emotion perception appears to be an early developmental risk factor that is prospectively associated with marijuana initiation; as expected, other neurocognitive functions did not play an interactive role. Future studies of the interrelationships between emotion perception and the myriad other factors implicated in marijuana initiation, including neurocognitive functions not measured here, will provide a more comprehensive understanding of risk for marijuana initiation.

Childhood trauma predicts onset and recurrence of depression, and comorbid anxiety and depressive disorders

ABSTRACT FROM: Hovens JG, Giltay EJ, Spinhoven P, et al . Impact of childhood life-events and childhood trauma on the onset and recurrence of depressive and anxiety disorders. J Clin...