Frits Boer

The genetic background to PTSD

Although extensive research has already been done on the genetic bases of psychiatric disorders, little is known about polygenetic influences in posttraumatic stress disorder (PTSD). This article reviews molecular genetic studies relating to PTSD that were found in a literature search in Medline, Embase and Web of Science. Association studies have investigated 8 major genotypes in connection with PTSD. They have tested hypotheses involving key candidate genes in the serotonin (5-HTT), dopamine (DRD2, DAT), glucocorticoid (GR), GABA (GABRB), apolipoprotein systems (APOE2), brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). The studies have produced inconsistent results, many of which may be attributable to methodological shortcomings and insufficient statistical power. The complex aetiology of PTSD, for which experiencing a traumatic event forms a necessary condition, makes it difficult to identify specific genes that substantially contribute to the disorder. Gene-finding strategies are difficult to apply. Interactions between different genes and between them and the environment probably make certain people vulnerable to developing PTSD. Gene-environmental studies are needed that focus more narrowly on specific, distinct endophenotypes and on influences from environmental factors.

Factors of perceived parental rearing styles: the EMBU-C examined in a sample of Dutch primary school children

The aim of the present study was to explore the dimensional framework underlying the original item pool of 81 items of the Dutch EMBU-C in a large sample of primary school aged children (n = 824). It was demonstrated that the full range of 81 items of the Dutch EMBU-C, could be reduced to four reliable factors, Emotional Warmth, Rejection, Overprotection and Favouring Subject. It was shown that the EMBU-C Scales for children have conceptually much in common with their adult and adolescent counterparts. Thus, the EMBU-C can be considered to be a suitable measure examining whether relations between psychological disorders and the perception of parenting style, as found in older subjects., can be confirmed in childhood. Preliminary results showed that the associations between perceived parenting, as measured by the EMBU-C, and trait anxiety in children, as measured with the STAIC, are consistent with findings yielded in studies with adults where anxious individuals expressed that they had been reared in a more rejective and protected way than their non-anxious equivalents

Paediatric obsessive-compulsive disorder, a neurodevelopmental disorder? Evidence from neuroimaging.

OBJECTIVE To present an overview of neuroimaging data on paediatric obsessive-compulsive disorder (OCD) and discuss implications for further research. METHOD Medline PsycINFO databases and reference lists were searched for relevant articles. All neuroimaging studies up to October 1, 2008 involving children and adolescents with obsessive-compulsive disorder were included. RESULTS Twenty-eight neuroimaging studies using various neuroimaging techniques (CT (2) MRI (15) MRS (8) and SPECT (2) fMRI (2) but no PET or DTI) including a total of 462 paediatric patients were identified. A number of findings indicate a dysfunction of the prefrontal-striatal-thalamic circuit with the involvement of other basal ganglia structures (putamen globus pallidus) and the thalamus in contrast to adult studies which report mainly involvement of the caudate nucleus and orbitofrontal cortex. Several findings point at an aberrant development of the brain in paediatric OCD, patients when compared with healthy controls. CONCLUSION Neuroimaging studies have contributed to our understanding of the neurobiological basis of paediatric OCD. This review provides an agenda for further theory driven research in particular aimed at identifying a critical window of abnormal maturation of prefrontal-striatal-thalamic and limbic circuitry in paediatric OCD patients.

Developmental aspects of error and high-conflict-related brain activity in pediatric obsessive-compulsive disorder: a fMRI study with a Flanker task before and after CBT

BACKGROUND Heightened error and conflict monitoring are considered central mechanisms in obsessive-compulsive disorder (OCD) and are associated with anterior cingulate cortex (ACC) function. Pediatric obsessive-compulsive patients provide an opportunity to investigate the development of this area and its associations with psychopathology. METHODS Repeated measures were carried out using functional magnetic resonance imaging (fMRI) during the performance of an interference task, the arrow version of the Flanker paradigm, before and after cognitive-behavioral treatment of 25 medication-free pediatric obsessive-compulsive patients compared with age- and gender-matched healthy controls. RESULTS During error trials compared to correct trials, pediatric OCD patients and controls showed an interaction effect of Group × Time × Age in the ACC and insula. This effect was mainly driven by an increased activation in older OCD subjects, which was also present after treatment. During high-conflict trials compared with low-conflict trials, a Group × Time × Age interaction effect was found in bilateral insula. This effect was driven by an increase of BOLD (blood oxygen level dependent) signal in older OCD patients before but not after treatment. In addition, a Group × Time interaction effect in dorsomedial prefrontal cortex, premotor region and ACC was found. This effect was driven by an increase of BOLD signal in OCD subjects relative to controls over time. CONCLUSIONS Compared to healthy controls, children and adolescents with OCD show increased activation of the ACC during error responses and in bilateral insular cortex during high-conflict tasks, which is age dependent and which is only partially affected by cognitive-behavioral therapy (CBT). Therefore, we suggest that ACC functioning is a vulnerability marker in pediatric OCD, whereas insular dysfunction may be state dependent.

Cognitive Behavior Therapy for Pediatric Functional Abdominal Pain: A Randomized Controlled Trial

OBJECTIVE: This randomized controlled trial investigated the effectiveness of a 6-session protocolized cognitive behavior therapy (CBT) compared with 6 visits to a pediatrician (intensive medical care; IMC) for the treatment of pediatric functional abdominal pain (FAP). METHODS: One hundred four children aged 7 to 18 were randomized to CBT or IMC. CBT was delivered primarily by trained master’s degree students in psychology; IMC was delivered by pediatricians or pediatric gastroenterologists. Assessments were performed pretreatment, posttreatment, and at 6- and 12-month follow-up. Primary outcomes were level of abdominal pain (AP) as reported on questionnaires and diaries. Secondary outcomes were other gastrointestinal complaints, functional disability, other somatic complaints, anxiety, depression, and quality of life. RESULTS: Both CBT and IMC resulted in a significant decrease in AP (P < .001), but no significant difference was found between the treatments in their effectiveness (P > .05 for all end points). According to the questionnaire-derived data, 1 year after treatment, 60% of children that received CBT had significantly improved or recovered, versus 56.4% of children receiving IMC, which did not significantly differ (P = .47). These percentages were 65.8% versus 62.8% according to the diary-derived data, which also did not significantly differ (P = .14). Additionally, nearly all secondary outcomes improved after treatment. CONCLUSIONS: CBT was equally effective as IMC in reducing AP in children with FAP. More research into the specific working mechanisms of CBT for pediatric FAP is needed.

Mediators of cognitive behavioral therapy for anxiety-disordered children and adolescents : cognition, perceived control, and coping

The purpose is to investigate whether a change in putative mediators (negative and positive thoughts, coping strategies, and perceived control over anxious situations) precedes a change in anxiety symptoms in anxiety-disordered children and adolescents receiving cognitive behavioral therapy (CBT). Participants were 145 Dutch children (8–18 years old, M = 12.5 years, 57% girls) with a primary anxiety disorder. Assessments were completed pretreatment, in-treatment, posttreatment, and at 3-month follow-up. Sequential temporal dependencies between putative mediators and parent- and child-reported anxiety symptoms were investigated in AMOS using longitudinal Latent Difference Score Modeling. During treatment an increase of positive thoughts preceded a decrease in child-reported anxiety symptoms. An increase in three coping strategies (direct problem solving, positive cognitive restructuring, and seeking distraction) preceded a decrease in parent-reported anxiety symptoms. A reciprocal effect was found for perceived control: A decrease in parent-reported anxiety symptoms both preceded and followed an increase in perceived control. Using a longitudinal design, a temporal relationship between several putative mediators and CBT-outcome for anxious children was explored. The results suggest that a change in positive thoughts, but not negative thoughts, and several coping strategies precedes a change in symptom reduction and, therefore, at least partly support theoretical models of anxiety upon which the anxiety intervention is based.

Traumatic Stress Symptomatology After Child Maltreatment and Single Traumatic Events: Different Profiles

The sequelae of child maltreatment tend to extend current posttraumatic stress disorder (PTSD) symptoms. This study examined this assumption, hypothesizing that (a) PTSD and trauma-related symptoms are more severe after single trauma than after child maltreatment; (b) symptoms unrelated to trauma are more severe after child maltreatment than after single trauma; and (c) a comorbid association of clinical PTSD with trauma-related symptoms is more prevalent after single trauma, whereas a comorbid association of clinical PTSD with trauma unrelated symptoms is more prevalent after child maltreatment. The Trauma Symptom Checklist for Children (TSCC) assessed PTSD and trauma-related symptoms in 256 children (83 children exposed to single trauma, 173 to child maltreatment). The Strengths and Difficulties Questionnaire (SDQ) assessed trauma-unrelated symptoms. Single-trauma children reported significantly more severe PTSD and trauma-related symptoms. Significantly more severe trauma unrelated symptoms were reported after child maltreatment. A significant relation was found between clinical PTSD and more severe trauma-related symptoms in both samples. Likelihood of children meeting PTSD symptoms after trauma seems to decrease when traumatization becomes more complex. Findings support our assumption that symptomatology of maltreated children extends current PTSD symptoms.

Abdominal pain in Dutch schoolchildren: relations with physical and psychological comorbid complaints in children and their parents.

Objectives: Children with functional abdominal pain (FAP) frequently report comorbid complaints such as anxiety and activity limitations. Their parents often experience heightened levels of anxiety, depression, and somatization. The aim of the present study was to investigate whether these comorbid complaints in children and their parents are specific for FAP or can also be found in a community sample. Patients and Methods: Six hundred sixty-five schoolchildren (ages 7–18 years) filled out questionnaires concerning AP, activity limitations, somatic complaints, quality of life, and symptoms of anxiety and depression. A total of 391 of their parents filled out questionnaires concerning parental anxiety, depression, and somatization. Pearson correlations and multiple regression analyses were performed. Results: A total of 56.5% of the children reported AP at least once in a 2-week period. Univariate relations with AP were found for activity limitations (r = 0.392), somatic complaints (r = 0.408), 3 of 5 domains of quality of life (r ranging from −0.120 to −0.209), and symptoms of anxiety and depression (r, respectively, 0.329 and 0.361). Multivariate analyses showed only significant relations for female sex (β = 0.230), younger age (β = −0.077), activity limitations (β = 0.247), somatic complaints (β = 0.170), and depressive symptoms (β = 0.093). Conclusions: Activity limitations, somatic complaints, and depressive symptoms are related to AP in the general population, whereas a reduced quality of life, anxiety, and parental internalizing problems seem specific comorbid complaints for FAP. Future research on parental internalizing problems, quality of life, and anxiety as risk factors for FAP is warranted.

Temperament and parental child-rearing style: unique contributions to clinical anxiety disorders in childhood

Both temperament and parental child-rearing style are found to be associated with childhood anxiety disorders in population studies. This study investigates the contribution of not only temperament but also parental child-rearing to clinical childhood anxiety disorders. It also investigates whether the contribution of temperament is moderated by child-rearing style, as is suggested by some studies in the general population. Fifty children were included (25 with anxiety disorders and 25 non-clinical controls). Child-rearing and the child’s temperament were assessed by means of parental questionnaire (Child Rearing Practices Report (CRPR) (Block in The Child-Rearing Practices Report. Institute of Human Development. University of California, Berkely, 1965; The Child-Rearing Practices Report (CRPR): a set of Q items for the description of parental socialisation attitudes and values. Unpublished manuscript. Institute of Human Development. University of California, Berkely, 1981), EAS Temperament Survey for Children (Boer and Westenberg in J Pers Assess 62:537–551, 1994; Buss and Plomin in Temperament: early developing personality traits. Lawrence Erlbaum Associates, Inc, Hillsdale, 1984s). Analysis of variance showed that anxiety-disordered children scored significantly higher on the temperamental characteristics emotionality and shyness than non-clinical control children. Hierarchical logistic regression analyses showed that temperament (emotionality and shyness) and child-rearing style (more parental negative affect, and less encouraging independence of the child) both accounted for a unique proportion of the variance of anxiety disorders. Preliminary results suggest that child-rearing style did not moderate the association between children’s temperament and childhood anxiety disorders. The limited sample size might have been underpowered to assess this interaction.

Increased Auditory Startle Reflex in Children with Functional Abdominal Pain

OBJECTIVE To test the hypothesis that children with abdominal pain-related functional gastrointestinal disorders have a general hypersensitivity for sensory stimuli. STUDY DESIGN Auditory startle reflexes were assessed in 20 children classified according to Rome III classifications of abdominal pain-related functional gastrointestinal disorders (13 irritable bowel syndrome [IBS], 7 functional abdominal pain syndrome; mean age, 12.4 years; 15 girls) and 23 control subjects (14 girls; mean age, 12.3 years) using a case-control design. The activity of 6 left-sided muscles and the sympathetic skin response were obtained by an electromyogram. We presented sudden loud noises to the subjects through headphones. RESULTS Both the combined response of 6 muscles and the blink response proved to be significantly increased in patients with abdominal pain compared with control subjects. A significant increase of the sympathetic skin response was not found. Comorbid anxiety disorders (8 patients with abdominal pain) or Rome III subclassification did not significantly affect these results. CONCLUSIONS This study demonstrates an objective hyperresponsivity to nongastrointestinal stimuli. Children with abdominal pain-related functional gastrointestinal disorders may have a generalized hypersensitivity of the central nervous system.