Autonomic nervous system function before and after trauma-focused psychotherapy in youth with (partial) posttraumatic stress disorder.

While trauma-focused psychotherapies have been shown effective in youth with PTSD, the relationship between treatment response and alterations in the autonomic nervous system (ANS) associated with PTSD, remains incompletely understood. During neutral and personalized trauma script imagery heart rate (HR), pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) were recorded in youth aged 8-18 with PTSD or partial PTSD (n = 76) and trauma-exposed controls (TEC) (n = 27) to determine ANS activity and stress reactivity. Within the patient group, 77.6% met the full DSM-IV diagnostic criteria for PTSD, the remaining 22.4% met the criteria for partial PTSD. Youth with (partial) PTSD were subsequently treated with eight sessions of either trauma-focused cognitive behavioral therapy or eye movement desensitization and reprocessing. PTSD severity was assessed using the Clinician-Administered PTSD scale for Children and Adolescents to divide patients into responders and non-responders. Youth with (partial) PTSD relative to TEC had higher overall HR during both neutral and trauma imagery (p = .05). Youth with (partial) PTSD showed RSA decrease during trauma imagery relative to neutral imagery, the reverse of TEC (p = .01). Relative to non-responders, responders demonstrated a significant baseline to posttreatment increase of RSA response to stress only when employing a ≥ 50% response criterion (p = .05) and not with the primary ≥ 30% criterion (p = .12). Our results suggest overall higher HR and sympathetic nervous system activity as well as vagal withdrawal in response to stress in youth with (partial) PTSD and only provide partial support for normalization of the latter with successful trauma-focused psychotherapy.

Individual prediction of trauma-focused psychotherapy response in youth with posttraumatic stress disorder using resting-state functional connectivity.

Randomized controlled trials have shown efficacy of trauma-focused psychotherapies in youth with posttraumatic stress disorder (PTSD). However, response varies considerably among individuals. Currently, no biomarkers are available to assist clinicians in identifying youth who are most likely to benefit from treatment. In this study, we investigated whether resting-state functional magnetic resonance imaging (rs-fMRI) could distinguish between responders and non-responders on the group- and individual patient level. Pre-treatment rs-fMRI was recorded in 40 youth (ages 8-17 years) with (partial) PTSD before trauma-focused psychotherapy. Change in symptom severity from pre- to post-treatment was assessed using the Clinician-Administered PTSD scale for Children and Adolescents to divide participants into responders (≥30% symptom reduction) and non-responders. Functional networks were identified using meta-independent component analysis. Group-differences within- and between-network connectivity between responders and non-responders were tested using permutation testing. Individual predictions were made using multivariate, cross-validated support vector machine classification. A network centered on the bilateral superior temporal gyrus predicted treatment response for individual patients with 76% accuracy (pFWE = 0.02, 87% sensitivity, 65% specificity, area-under-receiver-operator-curve of 0.82). Functional connectivity between the frontoparietal and sensorimotor network was significantly stronger in non-responders (t = 5.35, pFWE = 0.01) on the group-level. Within-network connectivity was not significantly different between groups. This study provides proof-of-concept evidence for the feasibility to predict trauma-focused psychotherapy response in youth with PTSD at an individual-level. Future studies are required to test if larger cohorts could increase accuracy and to test further generalizability of the prediction models.

Trauma-focused psychotherapy response in youth with posttraumatic stress disorder is associated with changes in insula volume.

Randomized controlled trials have shown efficacy of trauma-focused psychotherapies in youth with posttraumatic stress disorder (PTSD), but little is known about the relationship between treatment response and alternations in brain structures associated with PTSD. In this study, we longitudinally examined the association between treatment response and pre-to posttreatment changes in structural magnetic resonance imaging (MRI) scans using a voxel-based morphometry approach. We analyzed MRI scans of 35 patients (ages 8-18 years, 21 female) with PTSD (80%) or partial PTSD (20%) before and after eight weekly sessions of trauma-focused psychotherapy. PTSD severity was assessed longitudinally using the Clinician-Administered PTSD scale for Children and Adolescents to divide participants into responders and non-responders. Group by time interaction analysis showed significant differences in grey-matter volume in the bilateral insula due to volume reductions over time in non-responders compared to responders. Despite the significant group by time interaction, there were no significant group differences at baseline or follow-up. As typical development is associated with insula volume increase, these longitudinal MRI findings suggest that treatment non-response is associated with atypical neurodevelopment of the insula, which may underlie persistence of PTSD in youth. The absence of structural MRI changes in treatment responders, while in need of replication, suggest that successful trauma-focused psychotherapy may not directly normalize brain abnormalities associated with PTSD.

Pretreatment cortisol predicts trauma-focused psychotherapy response in youth with (partial) posttraumatic stress disorder.

BACKGROUND: Despite availability of effective trauma-focused psychotherapies, treatment non-response in youth with (partial) posttraumatic stress disorder remains substantial. Studies in adult PTSD have suggested that cortisol is associated with treatment outcome. Furthermore, cortisol prior to treatment could be used to predict treatment success. However, there is a lack of comparable studies in youth with (partial) PTSD. The objective of the current study was therefore to test whether cortisol prior to treatment would differ between treatment responders and non-responders and would positively predict the extent of clinical improvement in youth with (partial) PTSD. METHODS: Youth aged 8-18 with PTSD (79.2%) or partial PTSD (20.8%) were treated with 8 sessions of either trauma-focused cognitive behavioral therapy (TF-CBT) or eye movement desensitization and reprocessing (EMDR). Prior to treatment initiation, salivary cortisol was measured in treatment responders (n = 23) and treatment non-responders (n = 30) at 10 and 1 min before and 10, 20 and 30 min after personalized trauma script driven imagery (SDI). The cortisol stress response (>1.5 nmol/L increase from baseline) and basal cortisol secretion was assessed during the SDI procedure. We hypothesized that treatment responders would display higher cortisol levels caused by increased cortisol reactivity prior to trauma-focused psychotherapy relative to psychotherapy non-responders and higher cortisol levels would positively predict the extent of clinical improvement. RESULTS: Script driven imagery did not induce a cortisol stress response in all but two participants. Prior to treatment responders showed significantly higher basal cortisol secretion during SDI compared to treatment non-responders. This effect remained significant after controlling for gender. Higher pre-treatment basal cortisol secretion further positively predicted the extent of clinical improvement during trauma-focused psychotherapy. CONCLUSION: Because SDI failed to provoke a cortisol stress response in our sample, the question if cortisol reactivity differs between treatment responders and non-responders remains inconclusive. However, our results do suggest that higher pretreatment basal cortisol secretion forms a potential indicator of prospective trauma-focused psychotherapy response in youth with (partial) PTSD. Although, the amount of uniquely explained variance in clinical improvement by pre-treatment cortisol secretion is limited and still renders insufficient basis for clinical applicability, these findings do suggest directions for future studies to delineate the mechanisms of treatment success in youth with (partial) PTSD.

Executive functions in trauma-exposed youth: a meta-analysis.

An earlier meta-analysis and review indicated that trauma exposure may be related to lower levels of executive functioning in youth. Since different developmental trajectories were found for three core executive functions, the present study focused on working memory, inhibition, and cognitive flexibility specifically. We conducted a multi-level meta-analysis on 55 studies and 322 effect sizes published between 2001 and 2017 that were retrieved from MEDLINE, Embase, and PsycINFO. The 8070 participants in selected studies were aged 2-25 years. We investigated whether the association between constructs would be moderated by trauma-specific moderators (onset, duration, and type), and study (age, gender, ethnicity, and socio-economic status) and measurement (quality) characteristics. We found small to medium effect sizes for working memory (d = -0.49), inhibition (d = -0.46), and cognitive flexibility (d = -0.44). Moderator analyses showed that, for working memory, when studies used low-quality measurements the effect size was significantly stronger than when studies used high-quality measurements.Compared to single trauma-exposed youth, violence-exposed/abused and foster care/adopted youth showed more problems in inhibition, and foster care/adopted youth showed more problems in cognitive flexibility. Our findings imply that trauma-exposed youth have lower levels of executive functions. Clinical practice should incorporate problems in executive functioning, especially working memory, inhibition, and cognitive flexibility, in assessment and treatment guidelines.

Planteamiento: Un metanálisis y una revisión previos indicaron que la exposición al trauma podría estar relacionada con niveles más bajos de funcionamiento ejecutivo en los jóvenes.Objetivo: A medida que se encontraron diferentes trayectorias de desarrollo para tres funciones ejecutivas centrales, nos enfocamos específicamente en la memoria de trabajo, la inhibición y la flexibilidad cognitiva.Método: Realizamos un metanálisis multinivel con 55 estudios y 322 tamaños de efectos publicados entre 2001 y 2017, obtenidos de MEDLINE, Embase y PsycINFO. Los 8070 participantes en los estudios seleccionados tenían entre 2 y 25 años. Investigamos si la asociación entre los constructos sería moderada por los moderadores específicos del trauma (inicio, duración y tipo), y las características del estudio (edad, género, etnia, estatus socioeconómico) y características de medición (calidad).Resultados: Encontramos tamaños de efecto de pequeño a mediano para la memoria de trabajo (d = −0.49), la inhibición (d = −0.46) y la flexibilidad cognitiva (d = −0.44). Los análisis del moderador mostraron que, para la memoria de trabajo, cuando los estudios utilizaron mediciones de baja calidad, el tamaño del efecto fue significativamente más fuerte que cuando los estudios utilizaron mediciones de alta calidad. En comparación con los jóvenes expuestos a un solo trauma, los jóvenes expuestos a violencia /abuso y los jóvenes que viven en condiciones de acogida o han sido adoptados mostraron más problemas en la inhibición y los jóvenes que viven en condi- ciones de acogida o han sido adoptados mostraron más problemas de flexibilidad cognitiva.Conclusión: Nuestros hallazgos implican que los jóvenes expuestos a trauma tienen niveles más bajos de funciones ejecutivas. En sus guías de evaluación y tratamiento, la práctica clínica debe incorporar problemas en el funcionamiento ejecutivo, especialmente la memoria de trabajo, la inhibición y la flexibilidad cognitiva.

Executive function as a mediator in the link between single or complex trauma and posttraumatic stress in children and adolescents.

PURPOSE: In this study, we examined whether there is a mediating role of executive function (EF) in the relationship between trauma exposure and posttraumatic stress in youth. METHODS: Children and adolescents exposed to trauma were recruited at an academic center for child psychiatry in The Netherlands. The total sample consisted of 119 children from 9 to 17 years old (M = 13.65, SD = 2.45). Based on retrospective life event information, the sample was divided into three groups: a single trauma group (n = 41), a complex trauma group (n = 38), and a control group that was not exposed to traumatic events (n = 40). RESULTS: Our findings revealed that youth exposed to complex trauma had more deficits in EF compared to youth in the single trauma and control groups. EF was found to partly mediate posttraumatic stress symptoms for youth exposed to complex trauma, but not for youth exposed to single trauma. Youth exposed to complex trauma showed more deficits in EF, which was in turn associated with higher levels of posttraumatic stress symptoms. CONCLUSIONS: Our findings provide partial support for the role of EF in mediating posttraumatic stress outcomes for youth exposed to complex trauma. This points to the important role of EF in the etiology and treatment of complexly traumatized youth.