Viola Kappel

The Brain's Response to Reward Anticipation and Depression in Adolescence: Dimensionality, Specificity, and Longitudinal Predictions in a Community-Based Sample.

OBJECTIVE The authors examined whether alterations in the brains reward network operate as a mechanism across the spectrum of risk for depression. They then tested whether these alterations are specific to anhedonia as compared with low mood and whether they are predictive of depressive outcomes. METHOD Functional MRI was used to collect blood-oxygen-level-dependent (BOLD) responses to anticipation of reward in the monetary incentive task in 1,576 adolescents in a community-based sample. Adolescents with current subthreshold depression and clinical depression were compared with matched healthy subjects. In addition, BOLD responses were compared across adolescents with anhedonia, low mood, or both symptoms, cross-sectionally and longitudinally. RESULTS Activity in the ventral striatum was reduced in participants with subthreshold and clinical depression relative to healthy comparison subjects. Low ventral striatum activation predicted transition to subthreshold or clinical depression in previously healthy adolescents at 2-year follow-up. Brain responses during reward anticipation decreased in a graded manner between healthy adolescents, adolescents with current or future subthreshold depression, and adolescents with current or future clinical depression. Low ventral striatum activity was associated with anhedonia but not low mood; however, the combined presence of both symptoms showed the strongest reductions in the ventral striatum in all analyses. CONCLUSIONS The findings suggest that reduced striatal activation operates as a mechanism across the risk spectrum for depression. It is associated with anhedonia in healthy adolescents and is a behavioral indicator of positive valence systems, consistent with predictions based on the Research Domain Criteria.

White-matter microstructure and gray-matter volumes in adolescents with subthreshold bipolar symptoms

Abnormalities in white-matter (WM) microstructure, as lower fractional anisotropy (FA), have been reported in adolescent-onset bipolar disorder and in youth at familial risk for bipolarity. We sought to determine whether healthy adolescents with subthreshold bipolar symptoms (SBP) would have early WM microstructural alterations and whether those alterations would be associated with differences in gray-matter (GM) volumes. Forty-two adolescents with three core manic symptoms and no psychiatric diagnosis, and 126 adolescents matched by age and sex, with no psychiatric diagnosis or symptoms, were identified after screening the IMAGEN database of 2223 young adolescents recruited from the general population. After image quality control, voxel-wise statistics were performed on the diffusion parameters using tract-based spatial statistics in 25 SBP adolescents and 77 controls, and on GM and WM images using voxel-based morphometry in 30 SBP adolescents and 106 controls. As compared with healthy controls, adolescents with SBP displayed lower FA values in a number of WM tracts, particularly in the corpus callosum, cingulum, bilateral superior and inferior longitudinal fasciculi, uncinate fasciculi and corticospinal tracts. Radial diffusivity was mainly higher in posterior parts of bilateral superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi and right cingulum. As compared with controls, SBP adolescents had lower GM volume in the left anterior cingulate region. This is the first study to investigate WM microstructure and GM morphometric variations in adolescents with SBP. The widespread FA alterations in association and projection tracts, associated with GM changes in regions involved in mood disorders, suggest altered structural connectivity in those adolescents.

Neuropsychological and Behavioural Short‐Term Effects of Cognitive Remediation Therapy in Adolescent Anorexia Nervosa: A Pilot Study

OBJECTIVE Cognitive remediation therapy (CRT) aims to strengthen weak cognitive flexibility and central coherence in adult and adolescent anorexia nervosa (AN). Currently, there are no studies in adolescents with AN that control for learning effects because of re-testing while evaluating CRT. METHOD Twenty in- and outpatients with AN aged 12 to 18 years received CRT. Assessment took place directly before and after the intervention. Performance was compared to 20 age-, gender-, IQ-, and test-retest interval matched healthy controls, which did not receive CRT. RESULTS AN patients showed an improvement in flexibility on neuropsychological assessment directly after CRT, whereas HC did not improve over time. Self-report assessment of flexibility, as well as central coherence, did not show significant improvement after CRT. DISCUSSION Results suggest that CRT may be beneficial for enhancing flexibility in adolescents with AN. However, randomized controlled studies are essential to determine the actual efficacy of this intervention.

Sleep habits, academic performance, and the adolescent brain structure

Here we report the first and most robust evidence about how sleep habits are associated with regional brain grey matter volumes and school grade average in early adolescence. Shorter time in bed during weekdays, and later weekend sleeping hours correlate with smaller brain grey matter volumes in frontal, anterior cingulate, and precuneus cortex regions. Poor school grade average associates with later weekend bedtime and smaller grey matter volumes in medial brain regions. The medial prefrontal - anterior cingulate cortex appears most tightly related to the adolescents’ variations in sleep habits, as its volume correlates inversely with both weekend bedtime and wake up time, and also with poor school performance. These findings suggest that sleep habits, notably during the weekends, have an alarming link with both the structure of the adolescent brain and school performance, and thus highlight the need for informed interventions.

Effect of brain structure and function on reward anticipation in children and adults with attention deficit hyperactivity disorder combined subtype

Attention deficit hyperactivity disorder (ADHD) is associated with decreased ventral-striatal responsiveness during reward anticipation. However, previous research mostly focused on adults with heterogeneous ADHD subtype and divers drug treatment status while studies in children with ADHD are sparse. Moreover, it remains unclear to what degree ADHD is characterized by a delay of normal brain structure or function maturation. We therefore attempt to determine whether results from structural and functional magnetic resonance imaging (fMRI) are associated with childhood and adult ADHD combined subtype (ADHD-CT). This study used fMRI to compare VS structure and function of 30 participants with ADHD-CT (16 adults, 14 children) and 30 controls (20 adults, 10 children), using a monetary incentive delay task. Joint analyses of structural and functional imaging data were conducted with Biological Parametric Mapping. Reward anticipation elicited decreased ventral-striatal responsiveness in adults but not in children with ADHD-CT. Children and adults with ADHD showed reduced ventral-striatal volume. Taking these gray matter differences into account, the results remained the same. These results suggest that decreased ventral-striatal responsiveness during reward anticipation is present in adults but not in children with ADHD-CT, irrespective of structural characteristics. The question arises whether ventral-striatal hypoactivity is an ADHD correlate that develops during the course of illness.

Inattention and Reaction Time Variability Are Linked to Ventromedial Prefrontal Volume in Adolescents

BACKGROUND Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have most commonly reported volumetric abnormalities in the basal ganglia, cerebellum, and prefrontal cortices. Few studies have examined the relationship between ADHD symptomatology and brain structure in population-based samples. We investigated the relationship between dimensional measures of ADHD symptomatology, brain structure, and reaction time variability-an index of lapses in attention. We also tested for associations between brain structural correlates of ADHD symptomatology and maps of dopaminergic gene expression. METHODS Psychopathology and imaging data were available for 1538 youths. Parent ratings of ADHD symptoms were obtained using the Development and Well-Being Assessment and the Strengths and Difficulties Questionnaire (SDQ). Self-reports of ADHD symptoms were assessed using the youth version of the SDQ. Reaction time variability was available in a subset of participants. For each measure, whole-brain voxelwise regressions with gray matter volume were calculated. RESULTS Parent ratings of ADHD symptoms (Development and Well-Being Assessment and SDQ), adolescent self-reports of ADHD symptoms on the SDQ, and reaction time variability were each negatively associated with gray matter volume in an overlapping region of the ventromedial prefrontal cortex. Maps of DRD1 and DRD2 gene expression were associated with brain structural correlates of ADHD symptomatology. CONCLUSIONS This is the first study to reveal relationships between ventromedial prefrontal cortex structure and multi-informant measures of ADHD symptoms in a large population-based sample of adolescents. Our results indicate that ventromedial prefrontal cortex structure is a biomarker for ADHD symptomatology. These findings extend previous research implicating the default mode network and dopaminergic dysfunction in ADHD.

Cognitive Remediation Therapy for Children with Anorexia Nervosa

OBJECTIVE Evidence-based treatment programs for children with anorexia nervosa (AN) are scarce, while their prognosis is negative and the incidence rate rises. A new therapeutic approach recently received positive attention: cognitive remediation therapy (CRT). This intervention targets inflexibility and the inability to perceive the bigger picture in persons with AN. So far, studies and case reports have focused on either adolescent or adult patients and less on young children with AN. This case report therefore describes and evaluates the implementation of CRT with a child with AN. METHOD A 12-year-old girl with severe chronic AN was treated with 10 sessions of CRT. Her clinical and neuropsychological evaluations before, directly after and 7 months after CRT are reported. Additionally, the patients written and verbal feedbacks are reviewed. RESULTS At the 7-month follow-up the patient showed a stable healthy weight and reported a reduced presence of psychopathology. Her neuropsychological performance directly after CRT and after 7 months did not improve. CONCLUSIONS The clinical evaluation of our case report suggests that CRT may be a promising add-on therapy in the clinical treatment of young girls with AN.

CID: a valid incentive delay paradigm for children.

Despite several modifications and the wide use of the monetary incentive delay paradigm (MID; Knutson et al. in J Neurosci 21(16):RC159, 2001a) for assessing reward processing, evidence concerning its application in children is scarce. A first child-friendly MID modification has been introduced by Gotlib et al. (Arch Gen Psychiatry 67(4): 380–387, 2010); however, comparability in the results of different tasks and validity across different age groups remains unclear. We investigated the validity of a newly modified MID task for children (CID) using functional magnetic resonance imaging. The CID comprises the integration of a more age appropriate feedback phase. We focused on reward anticipation and their neural correlates. Twenty healthy young adults completed the MID and the CID. Additionally, 10 healthy children completed the CID. As expected, both paradigms elicited significant ventral and dorsal striatal activity in young adults during reward anticipation. No differential effects of the tasks on reaction times, accuracy rates or on the total amount of gain were observed. Furthermore, the CID elicited significant ventral striatal activity in healthy children. In conclusion, these findings demonstrate evidence for the validity of the CID paradigm. The CID can be recommended for the application in future studies on reward processing in children, adolescents, and in adults.

Outcome of childhood anorexia nervosa—The results of a five‐ to ten‐year follow‐up study

OBJECTIVE Although admissions of children with anorexia nervosa (AN) are increasing, there remains a dearth of up-to-date knowledge of the course and outcome of early-onset AN. The aim of the present study was to investigate the outcomes of patients with AN onset before the age of 14. METHOD Sixty-eight consecutive former patients who met the DSM-IV criteria for AN and who had been treated at one of three German university hospitals were asked to participate in a follow-up study. Body mass index, body height, outcome of the eating disorder (ED), psychiatric morbidity, and health related quality of life (HRQoL) were assessed through a personal examination after an average time span of 7.5 years (range: 4.5-11.5 years) after admission. RESULTS One patient had died. Fifty-two subjects with a mean age of 12.5 (SD 1.0) years at admission and of 20.2 (SD 2.0) years at follow-up agreed to participate in the follow-up assessment, aggregating to 77.9% of the original sample. Approximately 41% of the participants had a good outcome, while 35% and 24% had intermediate and poor outcomes, respectively. Twenty-eight percent of the sample met the DSM-IV criteria for a current non-ED psychiatric disorder, and 64% met the criteria for a past non-ED psychiatric disorder. Mental HRQoL and ED-specific psychopathology was strongly associated with the outcome of AN. Average body height was below the normal range. A higher weight at admission was the only significant positive indicator of outcome. DISCUSSION Childhood AN is a serious disorder with an unfavorable course in many patients and high rates of chronicity and psychiatric comorbidity in young adulthood. Early detection and intervention are urgently needed.

Ventromedial prefrontal volume in adolescence predicts hyperactive/inattentive symptoms in adulthood

Youths with attention-deficit/hyperactivity disorder symptomatology often exhibit residual inattention and/or hyperactivity in adulthood; however, this is not true for all individuals. We recently reported that dimensional, multi-informant ratings of hyperactive/inattentive symptoms are associated with ventromedial prefrontal cortex (vmPFC) structure. Herein, we investigate the degree to which vmPFC structure during adolescence predicts hyperactive/inattentive symptomatology at 5-year follow-up. Structural equation modeling was used to test the extent to which adolescent vmPFC volume predicts hyperactive/inattentive symptomatology 5 years later in early adulthood. 1104 participants (M = 14.52 years, standard deviation = 0.42; 583 females) possessed hyperactive/inattentive symptom data at 5-year follow-up, as well as quality controlled neuroimaging data and complete psychometric data at baseline. Self-reports of hyperactive/inattentive symptomatology were obtained during adolescence and at 5-year follow-up using the Strengths and Difficulties Questionnaire (SDQ). At baseline and 5-year follow-up, a hyperactive/inattentive latent variable was derived from items on the SDQ. Baseline vmPFC volume predicted adult hyperactive/inattentive symptomatology (standardized coefficient = -0.274, P < 0.001) while controlling for baseline hyperactive/inattentive symptomatology. These results are the first to reveal relations between adolescent brain structure and adult hyperactive/inattentive symptomatology, and suggest that early structural development of the vmPFC may be consequential for the subsequent expression of hyperactive/inattentive symptoms.