Mima Simic

Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controls

BACKGROUND There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naïve adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. METHODS Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naïve adolescents with a first-episode of MDD aged 14-17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). RESULTS In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. CONCLUSIONS This study shows first evidence that medication-naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.

Fronto-Striato-Cerebellar Dysregulation in Adolescents with Depression During Motivated Attention

BACKGROUND Pediatric major depressive disorder (MDD) is associated with deficits in sustained attention, thought to be related to underlying motivation deficits. This hypothesis, however, has never directly been tested using functional magnetic resonance imaging. In this study, we investigated the neurofunctional correlates of the interplay between attention and motivation in medication-naive pediatric MDD using a rewarded sustained attention task. METHODS Functional magnetic resonance imaging was used to compare brain activation between 20 medication-naïve, noncomorbid, first-episode adolescents with MDD aged 13 to 18 years and 21 gender-, age-, and IQ-matched healthy adolescents. Participants performed a sustained attention task with and without a monetary reward to assess the impact of reward on sustained attention networks. RESULTS During nonrewarded sustained attention, adolescents with MDD showed reduced activation compared with healthy control subjects in occipital cortex. When sustained attention was rewarded, however, the underactivation in adolescents with MDD was in an extensive right hemispheric network of inferior fronto-striato-thalamic attention and limbic hippocampus-anterior cingulate reward processing areas. Major depressive disorder patients showed increased activation in cerebellum, which correlated with reduced frontal activation and depressive symptoms, suggesting compensatory response. Further analysis showed that reward upregulated fronto-striatal and hippocampal/temporal activation in control subjects but deactivated these regions in MDD, with opposite effects in the cerebellum. CONCLUSIONS Medication-naïve MDD adolescents show abnormalities in the regulation in fronto-striato-cerebellar brain regions involved in attention and reward during motivated but not unmotivated attention. This suggests a dysfunctional interplay between motivation and cognition in pediatric MDD, where motivation appears less capable of upregulating attention networks relative to healthy youths.

Comparison of specialist and nonspecialist care pathways for adolescents with anorexia nervosa and related eating disorders

OBJECTIVE To explore the role of specialist outpatient eating disorders services and investigate how direct access to these affects rates of referral, admissions for inpatient treatment, and continuity of care. METHOD Services beyond primary care in Greater London retrospectively identified adolescents who presented with an eating disorder over a 2-year period. Data concerning service use were collected from clinical casenotes. RESULTS In areas where specialist outpatient services were available, 2-3 times more cases were identified than in areas without such services. Where initial outpatient treatment was in specialist rather than nonspecialist services, there was a significantly lower rate of admission for inpatient treatment and considerably higher consistency of care. DISCUSSION Developing specialist outpatient services with direct access from primary care is likely to lead to improvements in treatment and reduce overall costs.

Depressive conduct disorder: symptom patterns and correlates in referred children and adolescents

BACKGROUND In order to examine the validity of the ICD-10 diagnostic category of depressive conduct disorder (DCD), a sample of 58 patients (mean age 11.6) with this diagnosis consecutively referred to a teaching hospital was compared with 151 patients with conduct disorder (CD) (mean age 12.3) and with 128 patients with depressive disorder (DD) (mean age 14.2). METHOD Data on symptom profile, sociodemographic characteristics, duration of disorder, family history and psychosocial background were collected using the Maudsley item sheet. Comparison of the three groups was performed using SPSS. RESULTS Controlling for age and gender differences, the DCD group had fewer biological depressive symptoms, fewer anxiety symptoms, less guilt and lower severity of overall depression compared to the DD group. They also displayed more self-injurious behaviour and had more adverse psychosocial circumstances than the DD subjects. Compared to the CD group, the DCD patients were less overtly aggressive and violent than the CD subjects, in addition to having significant depressive symptoms and a more frequent history of abuse. LIMITATIONS The study was based on case-control and diagnosis had been reached after the discussion of clinicians involved in assessment. CONCLUSIONS Overall, the results tentatively support the validity of this diagnostic subgrouping.

Diagnosing eating disorders in adolescents: A comparison of the eating disorder examination and the development and well‐being assessment

OBJECTIVE To compare the diagnostic properties of the Eating Disorder Examination (EDE) and the online version of the Development and Well-Being Assessment (DAWBA). METHOD Fifty-Seven adolescents (mean age 15.7 years) who attended consecutive assessments at a specialist eating disorders clinic completed the DAWBA, the EDE, and a standard clinical assessment with a multidisciplinary team. Cohens Kappas were used to make pairwise comparisons between the diagnoses generated by the three assessments. RESULTS Participants had anorexia nervosa (n = 30), eating disorders NOS (n = 21) or no eating disorder (n = 6) according to the clinical diagnosis. Agreement between the clinical and DAWBA diagnoses was moderate (kappa = 0.59), agreement between the DAWBA and EDE diagnoses was fair (kappa = 0.21), and agreement between the clinical and EDE diagnoses was poor (kappa = 0.10). The EDE did not identify an eating disorder in 20 participants (35% of the sample) who were clinically assessed as cases. CONCLUSION Computerized measures using multiple informants may be more suitable for assessing clinical samples of adolescents with anorexia nervosa or eating disorders NOS than individual interviews with young people.

Do Children and Adolescents with Anorexia Nervosa Display an Inefficient Cognitive Processing Style

Objective This study aimed to examine neuropsychological processing in children and adolescents with Anorexia Nervosa (AN). The relationship of clinical and demographic variables to neuropsychological functioning within the AN group was also explored. Method The performance of 41 children and adolescents with a diagnosis of AN were compared to 43 healthy control (HC) participants on a number of neuropsychological measures. Results There were no differences in IQ between AN and HC groups. However, children and adolescents with AN displayed significantly more perseverative errors on the Wisconsin Card Sorting Test, and lower Style and Central Coherence scores on the Rey Osterrieth Complex Figure Test relative to HCs. Conclusion Inefficient cognitive processing in the AN group was independent of clinical and demographic variables, suggesting it might represent an underlying trait for AN. The implications of these findings are discussed.

Attachment and mentalization and their association with child and adolescent eating pathology: A systematic review.

OBJECTIVE Insecure attachment and mentalizing difficulties have been associated with eating pathology in adulthood. However, it is unclear whether eating pathology is associated with attachment or mentalization in children. The aim of this study is to systematically review the literature in this emerging field. METHOD Electronic databases were used to search for articles. RESULTS Twenty-two studies were identified. In the 15 studies investigating attachment, an association with eating pathology was found in all studies. Mentalizing difficulties and eating pathology were found to be correlated in the seven studies which examined their association. DISCUSSION In keeping with the adult literature, cross-sectional studies of children and adolescents consistently report associations with eating pathology. There is some evidence from prospective studies that insecure attachment may be a risk factor for the development of eating pathology in adolescence. The literature on mentalization and eating pathology suggests that adolescents with anorexia nervosa may have difficulties in recognizing emotions. Further research using clinical samples and well-validated measures of attachment and mentalization are required to shed further light on this area.

Family Therapy for Child and Adolescent Eating Disorders: A Critical Review

Eating disorder-focused family therapy has emerged as the strongest evidence-based treatment for adolescent anorexia nervosa, supported by evidence from nine RCTs, and there is increasing evidence of its efficacy in treating adolescent bulimia nervosa (three RCTs). There is also emerging evidence for the efficacy of multifamily therapy formats of this treatment, with a recent RCT demonstrating the benefits of this approach in the treatment of adolescent anorexia nervosa. In this article, we critically review the evidence for eating disorder-focused family therapy through the lens of a moderate common factors paradigm. From this perspective, this treatment is likely to be effective as it provides a supportive and nonblaming context that: one, creates a safe, predictable environment that helps to contain anxiety generated by the eating disorder; two, promotes specific change early on in treatment in eating disorder-related behaviors; and three, provides a vehicle for the mobilization of common factors such as hope and expectancy reinforced by the eating disorder expertise of the multidisciplinary team. In order to improve outcomes for young people, there is a need to develop an improved understanding of the moderators and mediators involved in this treatment approach. Such an understanding could lead to the refining of the therapy, and inform adaptations for those families who do not currently benefit from treatment.

Intensive multi-family therapy for adolescent anorexia nervosa: adolescents’ and parents’ day-to-day experiences

The experiences of six families involved in a 4-day multi-family therapy (MFT) group for adolescent anorexia nervosa were examined day by day. Participants completed daily records (journals and rating scales) of their experiences. Parents completed the parents versus anorexia scale pretreatment and post-treatment. The researcher kept an observation journal of the MFT process. A week post-treatment, adolescents and parents took part in separate focus groups. The participants’ insights into the illness increased rapidly from Day 1 to 3, while participants’ emotions fluctuated throughout the 4 days. Motivation for recovery was enhanced for four of the five adolescents and self-efficacy improved for seven of 10 parents. In addition, some improvement in intra-family communication was reported in five of six families. Change was facilitated by the sharing of experiences with other families in a similar situation, role play activities, the increased ability to express emotions and the perceived mutual learning and support. Practitioner points Sharing of experiences in intensive MFT for AN can help improve insight into the disorder and instill hope Parents becoming ‘firm’ as well as supportive with eating may be the most useful practical strategy Role plays can help increase empathy, motivation and mobilize families for action Open expression of feelings works positively, promotes cohesiveness in the group even when this includes difficult emotions MFT treatment context can be experienced as challenging but nevertheless supportive

Testing a cognitive model of generalized anxiety disorder in the eating disorders

Generalized anxiety disorder (GAD) is one of the most common comorbid disorders found in individuals with eating disorders. Despite this, little is known of shared vulnerability factors between the two disorders. The aim of the present study was to examine the four main components of a cognitive model for GAD in the eating disorders. One hundred and sixty-two females took part. Three groups were formed comprising of 19 participants with an eating disorder and GAD, 70 with an eating disorder without GAD and 73 healthy controls. All completed self-report questionnaires that measured eating attitudes, levels of GAD, intolerance of uncertainty, positive beliefs about worry, negative problem orientation, and cognitive avoidance. Participants with an eating disorder and GAD scored the highest on all four components when compared to healthy individuals and on most components when compared to those with an eating disorder. Participants with an eating disorder without GAD scored higher on all components compared to healthy controls. Findings extend our understanding of shared vulnerability factors between the eating disorders and GAD.