Rudineia Toazza

The multidimensional evaluation and treatment of anxiety in children and adolescents: rationale, design, methods and preliminary findings

OBJECTIVE This study aims to describe the design, methods and sample characteristics of the Multidimensional Evaluation and Treatment of Anxiety in Children and Adolescents - the PROTAIA Project. METHOD Students between 10 and 17 years old from all six schools belonging to the catchment area of the Primary Care Unit of Hospital de Clínicas de Porto Alegre were included in the project. It comprises five phases: (1) a community screening phase; (2) a psychiatric diagnostic phase; (3) a multidimensional assessment phase evaluating environmental, neuropsychological, nutritional, and biological factors; (4) a treatment phase, and (5) a translational phase. RESULTS A total of 2,457 subjects from the community were screened for anxiety disorders. From those who attended the diagnostic interview, we identified 138 individuals with at least one anxiety disorder (apart from specific phobia) and 102 individuals without any anxiety disorder. Among the anxiety cases, generalized anxiety disorder (n = 95; 68.8%), social anxiety disorder (n = 57; 41.3%) and separation anxiety disorder (n = 49; 35.5%) were the most frequent disorders. CONCLUSION The PROTAIA Project is a promising research project that can contribute to the knowledge of the relationship between anxiety disorders and anxiety-related phenotypes with several genetic and environmental risk factors.

Anxiety disorders in adolescence are associated with impaired facial expression recognition to negative valence

OBJECTIVE The aim of the present study was to test the ability of adolescents with a current anxiety diagnosis to recognize facial affective expressions, compared to those without an anxiety disorder. METHODS Forty cases and 27 controls were selected from a larger cross sectional community sample of adolescents, aged from 10 to 17 years old. Adolescents facial recognition of six human emotions (sadness, anger, disgust, happy, surprise and fear) and neutral faces was assessed through a facial labeling test using Ekmans Pictures of Facial Affect (POFA). RESULTS Adolescents with anxiety disorders had a higher mean number of errors in angry faces as compared to controls: 3.1 (SD=1.13) vs. 2.5 (SD=2.5), OR=1.72 (CI95% 1.02 to 2.89; p=0.040). However, they named neutral faces more accurately than adolescents without anxiety diagnosis: 15% of cases vs. 37.1% of controls presented at least one error in neutral faces, OR=3.46 (CI95% 1.02 to 11.7; p=0.047). No differences were found considering other human emotions or on the distribution of errors in each emotional face between the groups. CONCLUSION Our findings support an anxiety-mediated influence on the recognition of facial expressions in adolescence. These difficulty in recognizing angry faces and more accuracy in naming neutral faces may lead to misinterpretation of social clues and can explain some aspects of the impairment in social interactions in adolescents with anxiety disorders.

Impulsivity-based thrifty eating phenotype and the protective role of n-3 PUFAs intake in adolescents.

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults.

Amygdala-based intrinsic functional connectivity and anxiety disorders in adolescents and young adults.

Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in adolescents and young adults. Nevertheless, the pathophysiology of anxiety disorders is still poorly understood. This study investigated differences in the functional connectivity of intrinsic amygdala-based networks of participants with and without AD. Resting state fMRI data were obtained from 18 participants with an AD and 19 healthy comparison individuals. Psychiatric diagnosis was assessed using standardized structured interviews. The comparison between groups was carried out using functional connectivity maps from six seed regions defined using probabilistic maps bilaterally within the amygdala (basolateral, superficial and centromedial amygdala). We found significant between-group differences in five clusters, which showed aberrant functional connectivity with the left basolateral amygdala: right precentral gyrus, right cingulate gyrus, bilateral precuneus, and right superior frontal gyrus in subjects with AD as compared with the comparison subjects. For the comparison subjects, the correlations between the amygdala and the five clusters were either non-significant, or negative. The present study suggests there is an intrinsic disruption in the communication between left basolateral amygdala and a network of brain regions involved with emotion regulation, and with the default mode network in adolescents and young adults with anxiety disorders.

Decreased comfort food intake and allostatic load in adolescents carrying the A3669G variant of the glucocorticoid receptor gene

BACKGROUND The A3669G single nucleotide polymorphism (SNP) of the glucocorticoid receptor (GR) gene NR3C1 is associated with altered tissue sensitivity to glucocorticoids (GCs). GCs modulate the food reward circuitry and are implicated in increased intake of palatable foods, which can lead to the metabolic syndrome and obesity. We hypothesized that presence of the G variant of the A3669G SNP would affect preferences for palatable foods and alter metabolic, behavioural, and neural outcomes. METHODS One hundred thirty-one adolescents were genotyped for the A3669G polymorphism, underwent anthropometric assessment and nutritional evaluations, and completed behavioural measures. A subsample of 74 subjects was followed for 5 years and performed a brain functional magnetic resonance imaging (fMRI) paradigm to verify brain activity in response to food cues. RESULTS Sugar and total energy consumption were lower in A3669G G allele variant carriers. On follow-up, this group also had reduced serum insulin concentrations, increased insulin sensitivity, and lower anxiety scores. Because of our unbalanced sample sizes (31/37 participants non-G allele carriers/total), our imaging data analysis failed to find whole brain-corrected significant results in between-group t-tests. CONCLUSION These results highlight that a genetic variation in the GR gene is associated, at the cellular level, with significant reduction in GC sensitivity, which, at cognitive and behavioural levels, translates to altered food intake and emotional stress response. This genetic variant might play a major role in decreasing risk for metabolic and psychiatric diseases.

Interaction between perceived maternal care, anxiety symptoms, and the neurobehavioral response to palatable foods in adolescents.

Abstract Studies in rodents have shown that early life trauma leads to anxiety, increased stress responses to threatening situations, and modifies food intake in a new environment. However, these associations are still to be tested in humans. This study aimed to verify complex interactions among anxiety diagnosis, maternal care, and baseline cortisol on food intake in a new environment in humans. A community sample of 32 adolescents and young adults was evaluated for: psychiatric diagnosis using standardized interviews, maternal care using the Parental Bonding Inventory (PBI), caloric consumption in a new environment (meal choice at a snack bar), and salivary cortisol. They also performed a brain fMRI task including the visualization of palatable foods vs. neutral items. The study found a three-way interaction between anxiety diagnosis, maternal care, and baseline cortisol levels on the total calories consumed (snacks) in a new environment. This interaction means that for those with high maternal care, there were no significant associations between cortisol levels and food intake in a new environment. However, for those with low maternal care and who have an anxiety disorder (affected), cortisol was associated with higher food intake; whereas for those with low maternal care and who did not have an anxiety disorder (resilient), cortisol was negatively associated with lower food intake. In addition, higher anxiety symptoms were associated with decreased activation in the superior and middle frontal gyrus when visualizing palatable vs. neutral items in those reporting high maternal care. These results in humans mimic experimental research findings and demonstrate that a combination of anxiety diagnosis and maternal care moderate the relationship between the HPA axis functioning, anxiety, and feeding behavior in adolescents and young adults.

Decoupling of the Occipitotemporal Cortex and the Brain’s Default-Mode Network in Dyslexia and a Role for the Cingulate Cortex in Good Readers: A Brain Imaging Study of Brazilian Children

ABSTRACT The goal of the present study was to investigate intrinsic and reading-related brain function associated with dyslexia and typical readers in monolingual Brazilian children. Two fMRI studies were carried out: a resting-state and a word-reading study. The results show (a) underconnectivity between the occipitotemporal region (visual word form area) and the brain’s default-mode network in dyslexic readers and (b) more activation of the anterior cingulate cortex for typical readers relative to dyslexic readers. The findings provide evidence for brain connectivity and function differences in an underrepresented population in fMRI studies of dyslexia; the results suggest atypical intrinsic function, and differences in directed attention processes in dyslexia.

Attention, memory, visuoconstructive, and executive task performance in adolescents with anxiety disorders: a case-control community study

Objective: The aim of the present study was to assess children and adolescents with mild and severe anxiety disorders for their performance in attention, verbal episodic memory, working memory, visuoconstructive skills, executive functions, and cognitive global functioning and conduct comparative analyses with the performance of children free from anxiety disorders. Methods: Our sample comprised 68 children and adolescents aged 10 to 17 years (41 with current diagnoses of anxiety disorders and 27 controls) selected from a larger cross-sectional community sample of adolescents. Children and adolescents with anxiety disorders were categorized into two groups on the basis of anxiety severity (mild or severe). All participants underwent a neuropsychological assessment battery to evaluate attention, verbal episodic memory, working memory, visuoconstructive skills, and executive and cognitive functions. Results: No differences were found in any neuropsychological tests, with the single exception that the group with mild anxiety had better performance on the Digit Span backward test compared to subjects with severe anxiety and to controls (p = 0.041; η2 = 0.11). Conclusions: Not only might anxiety disorders spare main cognitive functions during adolescence, they may even enhance certain working memory processes.

Phonemic verbal fluency and severity of anxiety disorders in young children

INTRODUCTION Previous studies have implicated impaired verbal fluency as being associated with anxiety disorders in adolescents. OBJECTIVES To replicate and extend previously reported evidence by investigating whether performance in phonemic verbal fluency tasks is related to severity of anxiety symptoms in young children with anxiety disorders. We also aim to investigate whether putative associations are independent from co-occurring attention deficit hyperactivity disorder (ADHD) symptoms. METHODS Sixty children (6-12 years old) with primary diagnoses of anxiety disorders participated in this study. Severity of symptoms was measured using clinician-based, parent-rated and self-rated validated scales. Verbal fluency was assessed using a simple task that measures the number of words evoked in 1-minute with the letter F, from which we quantified the number of isolated words, number of clusters (groups of similar words) and number of switches (transitions between clusters and/or between isolated words). RESULTS There was a significant association between the number of clusters and anxiety scores. Further analysis revealed associations were independent from co-occurring ADHD symptoms. CONCLUSION We replicate and extend previous findings showing that verbal fluency is consistently associated with severity in anxiety disorders in children. Further studies should explore the potential effect of cognitive training on symptoms of anxiety disorders.