Effectiveness and moderators of individual cognitive behavioral therapy versus treatment as usual in clinically depressed adolescents:A randomized controlled trial

We examined if manualized cognitive behavioral therapy (CBT) was more effective than Treatment As Usual (TAU) for clinically depressed adolescents within routine care. This multisite Randomized controlled trail included 88 clinically depressed adolescents (aged 12-21 years) randomly assigned to CBT or TAU. Multiple assessments (pre-, post treatment and six-month follow-up) were done using semi-structured interviews, questionnaires and ratings and multiple informants. The primary outcome was depressive or dysthymic disorder based on the KSADS. Completers, CBT (n = 19) and TAU (n = 26), showed a significant reduction of affective diagnoses at post treatment (76% versus 76%) and after six months (90% versus 79%). Intention-to-treat analyses on depressive symptoms showed that 41.6% within CBT and 31.8% within the TAU condition was below clinical cut-off at post treatment and after six-months, respectively 61.4% and 47.7%. No significant differences in self-reported depressive symptoms between CBT and TAU were found. No prediction or moderation effects were found for age, gender, child/parent educational level, suicidal criteria, comorbidity, and severity of depression. We conclude that CBT did not outperform TAU in clinical practice in the Netherlands. Both treatments were found to be suitable to treat clinically referred depressed adolescents. CBT needs further improvement to decrease symptom levels below the clinical cut-off at post treatment

Stimulant medication use and apparent cortical thickness development in attention-deficit/hyperactivity disorder: a prospective longitudinal study

BackgroundStimulant medication is commonly prescribed as treatment for attention-deficit/hyperactivity disorder (ADHD). While we previously found that short-term stimulant-treatment influences apparent cortical thickness development in an age-dependent manner, it remains unknown whether these effects persist throughout development into adulthood.PurposeInvestigate the long-term age-dependent effects of stimulant medication use on apparent cortical thickness development in adolescents and adults previously diagnosed with ADHD.MethodsThis prospective study included the baseline and 4-year follow-up assessment of the “effects of Psychotropic drugs On the Developing brain-MPH” (“ePOD-MPH”) project, conducted between June-1-2011 and December-28-2019. The analyses were pre-registered (https://doi.org/10.17605/OSF.IO/32BHF). T1-weighted MR scans were obtained from male adolescents and adults, and cortical thickness was estimated for predefined regions of interest (ROIs) using Freesurfer. We determined medication use and assessed symptoms of ADHD, anxiety, and depression at both time points. Linear mixed models were constructed to assess main effects and interactions of stimulant medication use, time, and age group on regional apparent cortical thickness.ResultsA total of 32 male adolescents (aged mean ± SD, 11.2 ± 0.9 years at baseline) and 24 men (aged mean ± SD, 29.9 ± 5.0 years at baseline) were included that previously participated in the ePOD-MPH project. We found no evidence for long-term effects of stimulant medication use on ROI apparent cortical thickness. As expected, we did find age-by-time interaction effects in all ROIs (left prefrontal ROI: P=.002, right medial and posterior ROIs: P<.001), reflecting reductions in apparent cortical thickness in adolescents. Additionally, ADHD symptom severity (adolescents: P<.001, adults: P=.001) and anxiety symptoms (adolescents: P=0.03) were reduced, and more improvement of ADHD symptoms was associated with higher medication use in adults (P=0.001).ConclusionWe found no evidence for long-term effects of stimulant-treatment for ADHD on apparent cortical thickness development in adolescents and adults. The identified age-dependent differences in apparent cortical thickness development are consistent with existing literature on typical cortical development

Author's Accepted Manuscript Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder Age-dependent effects of acute methylphenidate on amygdala reactivity in

, Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder, Psychiatry Research: Neuroimaging, http://dx.doi.org/10. 1016/j.pscychresns.2017.09.009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Abstract In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N=35 boys; N=46 men) and 23 healthy control subjects (N=11 boys; N=12 men). In ADHD patients, we also measured amygdala reactivity 90 minutes after an acute oral challenge with MPH (0.5 mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = .05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (-31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatment

Do effects of methylphenidate on cognitive performance last beyond treatment? A randomized placebo-controlled trial in boys and men with ADHD

Methylphenidate (MPH) is the first-choice pharmacological treatment for treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) across the lifespan. However, it is unclear whether MPH affects cognitive development, while recent (pre-) clinical studies suggest effects on the developing brain. The present randomized, placebo-controlled trial aims to determine whether MPH has short-term, age-dependent effects on cognitive performance in ADHD after a 1-week washout. Effects of 16 weeks MPH treatment were assessed after a one-week washout on cognitive functioning. Boys (age=10–12) and men (age=23–40) with ADHD were assigned to MPH treatment (boys n=25, men n=24) or placebo (boys n=25, men n=24). Outcome measures were working memory, response inhibition, response speed, episodic memory, and delay aversion. Differences in task performances over time (pre-, mid-, and post-treatment, following a 1-week wash-out) were compared between age and treatment conditions with mixed ANOVAs. MPH improved working memory and response speed, but only during treatment. No lasting age*treatment effects were observed post intervention. Overall, the results from the present randomized, placebo-controlled trial show that the effects of MPH on cognition do not extend past treatment in children or adults. While treatment with MPH improves cognition during treatment, these effects appear transient after 16-weeks of treatment. (Title trial: “Effects of methylphenidate on the developing brain”; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3103

Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder

In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90 min after an acute oral challenge with MPH (0.5 mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = 0.05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (−31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatment

The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design

BACKGROUND: Animal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of different approaches to determine whether there are related findings in humans. METHODS/DESIGN: Animal studies were carried out to investigate age-related effects of psychotropic drugs and to validate new neuroimaging techniques. In addition, we set up two double-blind placebo controlled clinical trials with MPH in 50 boys (10-12 years) and 50 young men (23-40 years) suffering from ADHD (ePOD-MPH) and with FLX in 40 girls (12-14 years) and 40 young women (23-40 years) suffering from depression and anxiety disorders (ePOD-SSRI). Trial registration numbers are: Nederlands Trial Register NTR3103 and NTR2111. A cross-sectional cohort study on age-related effects of these psychotropic medications in patients who have been treated previously with MPH or FLX (ePOD-Pharmo) is also ongoing. The effects of psychotropic drugs on the developing brain are studied using neuroimaging techniques together with neuropsychological and psychiatric assessments of cognition, behavior and emotion. All assessments take place before, during (only in case of MPH) and after chronic treatment. DISCUSSION: The combined results of these approaches will provide new insight into the modulating effect of MPH and FLX on brain development

ADHD and maturation of brain white matter: A DTI study in medication naive children and adults

Several diffusion tensor imaging (DTI) studies in attention deficit hyperactivity disorder (ADHD) have shown a delay in brain white matter (WM) development. Because these studies were mainly conducted in children and adolescents, these WM abnormalities have been assumed, but not proven to progress into adulthood. To provide further insight in the natural history of WM maturation delay in ADHD, we here investigated the modulating effect of age on WM in children and adults. 120 stimulant-treatment naive male ADHD children (10–12 years of age) and adults (23–40 years of age) with ADHD (according to DSM-IV; all subtypes) were included, along with 23 age and gender matched controls. Fractional anisotropy (FA) values were compared throughout the WM by means of tract-based spatial statistics (TBSS) and in specific regions of interest (ROIs). On both TBSS and ROI analyses, we found that stimulant-treatment naive ADHD children did not differ in FA values from control children, whereas adult ADHD subjects had reduced FA values when compared to adult controls in several regions. Significant age × group interactions for whole brain FA (p = 0.015), as well as the anterior thalamic radiation (p = 0.015) suggest that ADHD affects the brain WM age-dependently. In contrast to prior studies conducted in medicated ADHD children, we did not find WM alterations in stimulant treatment naïve children, only treatment-naïve adults. Thus, our findings suggest that the reported developmental delay in WM might appear after childhood, and that previously reported differences between ADHD children and normal developing peers could have been attributed to prior ADHD medications, and/or other factors that affect WM development, such as age and gender

Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder

In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90 min after an acute oral challenge with MPH (0.5 mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = 0.05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (-31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatmen

Effectiveness and moderators of individual cognitive behavioral therapy versus treatment as usual in clinically depressed adolescents: a randomized controlled trial

We examined if manualized cognitive behavioral therapy (CBT) was more effective than Treatment As Usual (TAU) for clinically depressed adolescents within routine care. This multisite Randomized controlled trail included 88 clinically depressed adolescents (aged 12–21 years) randomly assigned to CBT or TAU. Multiple assessments (pre-, post treatment and six-month follow-up) were done using semi-structured interviews, questionnaires and ratings and multiple informants. The primary outcome was depressive or dysthymic disorder based on the KSADS. Completers, CBT (n = 19) and TAU (n = 26), showed a significant reduction of affective diagnoses at post treatment (76% versus 76%) and after six months (90% versus 79%). Intention-to-treat analyses on depressive symptoms showed that 41.6% within CBT and 31.8% within the TAU condition was below clinical cut-off at post treatment and after six-months, respectively 61.4% and 47.7%. No significant differences in self-reported depressive symptoms between CBT and TAU were found. No prediction or moderation effects were found for age, gender, child/parent educational level, suicidal criteria, comorbidity, and severity of depression. We conclude that CBT did not outperform TAU in clinical practice in the Netherlands. Both treatments were found to be suitable to treat clinically referred depressed adolescents. CBT needs further improvement to decrease symptom levels below the clinical cut-off at post treatment