- Email: [email protected]
46.2 THE NEUROIMMUNOLOGY UNDERLYING ANHEDONIA AND DEFICITS IN REWARD PROCESSES IN ADOLESCENTS
SYMPOSIA 46.0 – 46.2
intervention so that parameters for a larger, more adequately powered, RCT could be determined. Methods: Preschool children (N ¼ 53) with ADHD were randomized to 5 weeks of treatment with TEAMS (n ¼ 27) or a closely matched control intervention (n ¼ 26). Clinical and neuropsychological assessments were conducted by separate evaluators who were blind to the treatment group at four time points: pretreatment, posttreatment, 1-month follow-up, and 3month follow-up. Results: Two-way (group time) mixed-model ANOVAs yielded several significant main effects for time, indicating clinical and neuropsychological improvements after treatment. However, there were few significant main effects or interactions involving group. Separate examinations of effect size for TEAMS and the comparison condition relative to pretreatment at all three posttreatment time points indicated consistently larger effect sizes for TEAMS as judged by parents (1.24, 0.72, 0.96 vs. 0.38, 0.65, 0.55, respectively), teachers (0.96, 0.85, 0.57 vs. 0.56, 0.74, 0.30, respectively), and clinicians (0.84, 0.97, 0.57 vs. 0.54, 0.52, 0.43, respectively). Yet, between-group effect sizes were small. Within the active treatment group, time engaged in TEAMS activities was associated with better clinical outcomes. Conclusions: Findings show some promise for TEAMS, but further development is warranted. Ways to modify the intervention to improve efficacy will be discussed.
PSC Supported by NIMH Grant R33 MH085898 http://dx.doi.org/10.1016/j.jaac.2016.07.387
SYMPOSIUM 46 RESEARCH DOMAIN CRITERIA (RDOC) RESEARCH STRATEGIES IN PEDIATRIC MENTAL HEALTH Vilma Gabbay, MD, Nathan Kline Institute, 140 Old Orangeburg Rd., Orangeburg, NY 10962; Marjorie Garvey, MBBCh Objectives: To address the limitations of the current psychiatric classification schema, which is based on clusters of symptoms most likely derived from different etiologies while overlapping, the US NIH NIMH has urged the field to “redefine mental disorders into dimensions or components of observable behaviors.” Toward this goal, the Research Domain Criteria (RDoC) project was launched in which systems based on cognitive, behavioral, and neuronal mechanisms replace DSM diagnoses for research purposes. These systems are examined across multimodal investigative approaches of genetics, neuronal circuitry, biology, and behavior. The purpose of the current panel is to present new data and insights from RDoC research projects focusing on children and adolescents. Methods: The panel will start with a brief introduction of the RDoC initiative and its envisioned goals presented by Marjorie Garvey, the panel’s discussant, from NIMH. The panel will consist of four talks on ongoing RDoC studies using multiple methodologies. Results: Dr. Joan Kaufman will present recent data on negative valence systems and acute threat processing in maltreated children during fMRI, examine epigenetic factors that correlate with the fear circuitry tapped during task performance, and discuss associations of amygdala activation and connectivity with dimensional assessments of lifetime traumatic experiences, social support, and trauma-related symptomatology. Dr. Vilma Gabbay will discuss data on peripheral and central neuroimmunological processes related to anhedonia and the reward circuitry in adolescents with depression and diverse psychiatric conditions. Dr. Brandon Gibb will discuss the role of attentional biases relevant to threat in the processing of emotional cues using behavioral (eye tracking) and physiological (event-related potential, ERP) measures and environmental influences on these biases. Dr. Joel Stoddard will discuss transdiagnostic neural mechanisms associated with irritability in children with disruptive mood dysregulation disorder, ADHD, and AD. Clinical implications of emerging findings will be discussed briefly by each presenter.
J OURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016
Conclusions: Our findings emphasize the importance of RDoC in child psychiatry.
ADOL NIMH RDOC http://dx.doi.org/10.1016/j.jaac.2016.07.389
46.1 UNDERSTANDING INDIVIDUAL DIFFERENCES IN ANXIETY SYMPTOMS AND THREAT PROCESSING IN CHILDREN WHO EXPERIENCE MALTREATMENT Joan Kaufman, PhD, Psychiatry, Johns Hopkins University, 1750 E. Fairmont Street, Room 2050G, Baltimore, MD 21205 Objectives: The goal of this session is to examine associations among anxiety symptoms in children and measures of maltreatment experiences, social supports, methylation in the glutamate receptor (GRIN1) gene, and indices of brain function during threat processing assessed with the emotional go/nogo fMRI task. Methods: The sample group included 49 adolescents ages 9–15 years. The children in the study had a range of trauma experiences, with approximately 25 percent of the children having had a recent out-of-home placement because of indicated reports of child maltreatment. Dimensional assessments of anxiety and maltreatment experiences were obtained, and DNA was derived from saliva specimens to examine methylation in GRIN1. The results from the emotional go/no-go task showed that children completed two blocks, one in which fearful faces were targets and neutral faces were nontargets and the other in which neutral faces served as targets and fearful faces were nontargets. Results: Reaction time discrepancy in response to fearful face targets versus neutral targets was correlated with measures of anxiety (r ¼ 0.53, p < 0.05). Task-related measures of functional connectivity within the fear circuit also correlated significantly with dimensional measures of anxiety symptoms, maltreatment experiences, and methylation in GRIN1. In addition, maltreatment ratings predicted individual differences in activation in the amygdala in response to fearful versus neutral facial stimuli, with the effect of maltreatment on amygdala activation ameliorated in children who rated their biological mothers/primary caregivers as a positive support. The predictors of amygdala activation are as follows: social support (coefficient ¼ 0.36, t ¼ 2.09, R2 ¼ 0.2533), maltreatment ratings (coefficient ¼ 0.18, t ¼ 1.72), and interaction term (coefficient ¼ 0.76, t ¼ 2.62, R2 ¼ 0.2533). Conclusions: The results highlight the importance of examining the dynamic interactions among genetics, adversity, and social context in understanding brain function and clinical symptomatology in maltreated youth.
ANX CAN RDOC http://dx.doi.org/10.1016/j.jaac.2016.07.390
46.2 THE NEUROIMMUNOLOGY UNDERLYING ANHEDONIA AND DEFICITS IN REWARD PROCESSES IN ADOLESCENTS Vilma Gabbay, MD, Mt. Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029 Objectives: Anhedonia, the reduced capacity to experience pleasure, is a core symptom of depression and a salient feature across psychiatric conditions. By use of a dimensional investigative approach, we examined the role of peripheral inflammatory processes and brain chemicals in anhedonia among depressed adolescents, as well in adolescents with diverse psychiatric conditions. Further, to delineate the specific deficits of reward processes associated with peripheral inflammation and neurometabolites abnormalities, we developed the reward flanker task to examine brain function during reward expectancy and attainment. Methods: Participants were adolescents ages 12–18 years (Tanner 4). Participants were diagnosed according to the Kiddie-Sads-Present and
www.jaacap.org
S331
SYMPOSIA 46.3 – 47.0
Lifetime Version, and anhedonia was assessed quantitatively. Kynurenine pathway metabolite, cytokines, and composition of innate and adaptive immune system were examined before and after the Trier Social Stress Test and lipopolysaccharide stimulation. An imaging session consisted of the following: 1) 1H magnetic resonance spectroscopy; and 2) fMRI, including resting-state and the Reward Flanker Task (RFT), a combination of the incentive flanker and monetary incentive tasks, that examines brain function during reward expectancy (motivation) and immediate attainment. Results: Depressed adolescents and those with diverse psychiatric symptoms exhibited a full range of anhedonia severity. We observed positive relationships between inflammatory neurotoxins and anhedonia severity. We also documented that decreased anterior cingulate cortex (ACC) g-aminobutyric acid (GABA) levels in depressed adolescents were driven by the anhedonic subgroup and that there was a negative relationship between anhedonia severity and ACC GABA levels in the whole sample group. Using striatal-based intrinsic functional connectivity, we identified specific network associated with anhedonia severity while controlling for other depressive symptomatology. By use of the RFT, anhedonia severity was associated with specific brain regions during reward anticipation and attainment. Conclusions: Peripheral inflammatory processes and neurochemical alterations implicated across psychiatric conditions may play a role in the neurobiology of anhedonia and be associated with specific deficits of reward processes. Such investigative approaches can facilitate the early identification of alterations within specific neurocircuits.
DDD IMAGS NI http://dx.doi.org/10.1016/j.jaac.2016.07.391
46.3 AVERSIVE CONDITIONING TO FEARFUL FACES INDUCES EMOTION-SPECIFIC ATTENTIONAL BIASES IN CHILDREN Brandon Gibb, PhD, Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY 13902 Objectives: Although attentional biases to emotional stimuli are thought to develop during childhood and contribute to risk for psychopathology across the lifespan, little is known about how these biases develop. The primary aim of this study was to examine environmental influences on attentional biases using laboratory-based conditioning and generalization tasks. Methods: Children (aged 7–11 years) were assigned randomly to one of three conditions: 1) a typical dot-probe task, 2) an active training condition in which white noise (85 dB) was paired with fearful faces, and 3) an active control condition in which the white noise was presented randomly throughout the task. Eye-tracking indices of attention bias were collected throughout the task. After the conditioning task, children completed a passive viewing task during which data from exposure and response prevention were collected, whereas children were presented with a different set of facial expressions of emotion. Results: Children assigned to the active training condition exhibited greater preferential attention (measured via eye-tracking and response times) to fearful faces during the second-half of the conditioning task compared with children in the control conditions. Providing support for the generalization of the conditioning effects, children assigned to the active training condition, compared with children in the control conditions, exhibited a larger late positive potential to fearful faces, an event-related potential component associated with sustained attention, in a subsequent morphed face paradigm. These effects were independent of children’s state affect, suggesting that they simply are not attributed to the impact of the conditioning task on levels of anxiety. Conclusions: The current findings provide promising evidence for attentional plasticity and an experience-dependent model of attentional bias in children.
DEV RDOC http://dx.doi.org/10.1016/j.jaac.2016.07.392
S332
www.jaacap.org
46.4 TRANSDIAGNOSTIC NEURAL MECHANISMS OF IRRITABILITY Joel Stoddard, MD, University of Colorado, 13123 East 16th Avenue, A036\B-130, Gary Pavilion 4th Floor, Aurora, CO 80045 Objectives: We tested whether neural mechanisms mediating irritability are the same across diagnoses, as predicted by research domain criteria. Given longitudinal and mechanistic links between irritability and anxiety, we tested whether interactions between these traits have an impact on brain function. Because irritability is associated with face emotion-processing deficits, we used an implicit emotion-processing task. Methods: We scanned 115 youth (ages 8–17 years) with disruptive mood dysregulation disorder (n ¼ 37), anxiety disorder (n ¼ 32), or ADHD (n ¼ 24) or healthy volunteers (n ¼ 22). The fMRI task involved gender identification of faces showing 50, 100, or 150 percent happy, angry, or fearful emotion. We measured irritability with the affective reactivity index (ARI) and anxiety with the Screen for Child Anxiety Related Disorders (SCARED) using the mean of parent and child report. ANOVA tested the fully interactive effects on behavior and activation of emotion, intensity, ARI, and SCARED (p < 0.05, whole-brain corrected). We used generalized psychophysiological interaction to estimate voxel-wise amygdala functional connectivity during each task condition. Results: Increasing irritability and decreasing accuracy were associated when labeling the gender on 150 percent angry faces (r ¼ 0.31, p < 0.001). Connectivity between left amygdala and left medial prefrontal cortex (mPFC) interacted with all four factors in the omnibus model (p < 0.001; k ¼ 87; x, y, z ¼ 3.7, 55.4, 9.5, respectively). This reflected that the association between ARI score and connectivity when viewing 150 percent angry faces varied with SCARED score (p < 0.001). An ARI by emotion interaction in five regions reflected an increase in activity, with an increase in irritability during processing of happy or angry, relative to fearful, faces (p < 0.023). Diagnosis was not associated with activation or connectivity. Conclusions: During face emotion processing, neural activation varies with irritability but not diagnosis. Relatively low amygdala-mPFC connectivity is present when youth with both high anxiety and high irritability view very angry faces.
IMAGS IMD NEUROA http://dx.doi.org/10.1016/j.jaac.2016.07.393
SYMPOSIUM 47 EMERGING BIOMARKERS FOR AUTISM SPECTRUM DISORDER: USING TECHNOLOGY TO REVOLUTIONIZE CLINICAL TRIALS AND ESTABLISH NOVEL THERAPEUTICS Gahan J. Pandina, PhD, Janssen Research & Development, 1125 Trenton-Harbourton Road, Titusville, NJ 08560-0200; Robert L. Hendren, DO, Psychiatry, University of California San Francisco, 401 Parnassus Ave, Langley Porter, San Francisco, CA 94143-2211 Objectives: In this session, the authors will present and discuss recent advances in imaging and sensor-based biomarkers in ASD and their potential utility in advancing novel treatments for ASD core and associated symptoms. Methods: Four talks will review promising technologies for the development of putative biomarkers for ASD. The first talk by Dr. Geraldine Dawson will provide an overview of biosensor research in identifying novel ASD biomarkers and review noninvasive imaging and biosensors (EEG, MRI, eye tracking). A new trial (Autism Biomarker Consortium—Clinical Trial) will be presented. The next two talks will focus on diverse examples of sensorbased approaches for objective measurement of ASD core symptom biology, presented by Drs. Frederick Shic and Matthew Goodwin. The first
J OURNAL
OF THE
AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016
intervention so that parameters for a larger, more adequately powered, RCT could be determined. Methods: Preschool children (N ¼ 53) with ADHD were randomized to 5 weeks of treatment with TEAMS (n ¼ 27) or a closely matched control intervention (n ¼ 26). Clinical and neuropsychological assessments were conducted by separate evaluators who were blind to the treatment group at four time points: pretreatment, posttreatment, 1-month follow-up, and 3month follow-up. Results: Two-way (group time) mixed-model ANOVAs yielded several significant main effects for time, indicating clinical and neuropsychological improvements after treatment. However, there were few significant main effects or interactions involving group. Separate examinations of effect size for TEAMS and the comparison condition relative to pretreatment at all three posttreatment time points indicated consistently larger effect sizes for TEAMS as judged by parents (1.24, 0.72, 0.96 vs. 0.38, 0.65, 0.55, respectively), teachers (0.96, 0.85, 0.57 vs. 0.56, 0.74, 0.30, respectively), and clinicians (0.84, 0.97, 0.57 vs. 0.54, 0.52, 0.43, respectively). Yet, between-group effect sizes were small. Within the active treatment group, time engaged in TEAMS activities was associated with better clinical outcomes. Conclusions: Findings show some promise for TEAMS, but further development is warranted. Ways to modify the intervention to improve efficacy will be discussed.
PSC Supported by NIMH Grant R33 MH085898 http://dx.doi.org/10.1016/j.jaac.2016.07.387
SYMPOSIUM 46 RESEARCH DOMAIN CRITERIA (RDOC) RESEARCH STRATEGIES IN PEDIATRIC MENTAL HEALTH Vilma Gabbay, MD, Nathan Kline Institute, 140 Old Orangeburg Rd., Orangeburg, NY 10962; Marjorie Garvey, MBBCh Objectives: To address the limitations of the current psychiatric classification schema, which is based on clusters of symptoms most likely derived from different etiologies while overlapping, the US NIH NIMH has urged the field to “redefine mental disorders into dimensions or components of observable behaviors.” Toward this goal, the Research Domain Criteria (RDoC) project was launched in which systems based on cognitive, behavioral, and neuronal mechanisms replace DSM diagnoses for research purposes. These systems are examined across multimodal investigative approaches of genetics, neuronal circuitry, biology, and behavior. The purpose of the current panel is to present new data and insights from RDoC research projects focusing on children and adolescents. Methods: The panel will start with a brief introduction of the RDoC initiative and its envisioned goals presented by Marjorie Garvey, the panel’s discussant, from NIMH. The panel will consist of four talks on ongoing RDoC studies using multiple methodologies. Results: Dr. Joan Kaufman will present recent data on negative valence systems and acute threat processing in maltreated children during fMRI, examine epigenetic factors that correlate with the fear circuitry tapped during task performance, and discuss associations of amygdala activation and connectivity with dimensional assessments of lifetime traumatic experiences, social support, and trauma-related symptomatology. Dr. Vilma Gabbay will discuss data on peripheral and central neuroimmunological processes related to anhedonia and the reward circuitry in adolescents with depression and diverse psychiatric conditions. Dr. Brandon Gibb will discuss the role of attentional biases relevant to threat in the processing of emotional cues using behavioral (eye tracking) and physiological (event-related potential, ERP) measures and environmental influences on these biases. Dr. Joel Stoddard will discuss transdiagnostic neural mechanisms associated with irritability in children with disruptive mood dysregulation disorder, ADHD, and AD. Clinical implications of emerging findings will be discussed briefly by each presenter.
J OURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016
Conclusions: Our findings emphasize the importance of RDoC in child psychiatry.
ADOL NIMH RDOC http://dx.doi.org/10.1016/j.jaac.2016.07.389
46.1 UNDERSTANDING INDIVIDUAL DIFFERENCES IN ANXIETY SYMPTOMS AND THREAT PROCESSING IN CHILDREN WHO EXPERIENCE MALTREATMENT Joan Kaufman, PhD, Psychiatry, Johns Hopkins University, 1750 E. Fairmont Street, Room 2050G, Baltimore, MD 21205 Objectives: The goal of this session is to examine associations among anxiety symptoms in children and measures of maltreatment experiences, social supports, methylation in the glutamate receptor (GRIN1) gene, and indices of brain function during threat processing assessed with the emotional go/nogo fMRI task. Methods: The sample group included 49 adolescents ages 9–15 years. The children in the study had a range of trauma experiences, with approximately 25 percent of the children having had a recent out-of-home placement because of indicated reports of child maltreatment. Dimensional assessments of anxiety and maltreatment experiences were obtained, and DNA was derived from saliva specimens to examine methylation in GRIN1. The results from the emotional go/no-go task showed that children completed two blocks, one in which fearful faces were targets and neutral faces were nontargets and the other in which neutral faces served as targets and fearful faces were nontargets. Results: Reaction time discrepancy in response to fearful face targets versus neutral targets was correlated with measures of anxiety (r ¼ 0.53, p < 0.05). Task-related measures of functional connectivity within the fear circuit also correlated significantly with dimensional measures of anxiety symptoms, maltreatment experiences, and methylation in GRIN1. In addition, maltreatment ratings predicted individual differences in activation in the amygdala in response to fearful versus neutral facial stimuli, with the effect of maltreatment on amygdala activation ameliorated in children who rated their biological mothers/primary caregivers as a positive support. The predictors of amygdala activation are as follows: social support (coefficient ¼ 0.36, t ¼ 2.09, R2 ¼ 0.2533), maltreatment ratings (coefficient ¼ 0.18, t ¼ 1.72), and interaction term (coefficient ¼ 0.76, t ¼ 2.62, R2 ¼ 0.2533). Conclusions: The results highlight the importance of examining the dynamic interactions among genetics, adversity, and social context in understanding brain function and clinical symptomatology in maltreated youth.
ANX CAN RDOC http://dx.doi.org/10.1016/j.jaac.2016.07.390
46.2 THE NEUROIMMUNOLOGY UNDERLYING ANHEDONIA AND DEFICITS IN REWARD PROCESSES IN ADOLESCENTS Vilma Gabbay, MD, Mt. Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029 Objectives: Anhedonia, the reduced capacity to experience pleasure, is a core symptom of depression and a salient feature across psychiatric conditions. By use of a dimensional investigative approach, we examined the role of peripheral inflammatory processes and brain chemicals in anhedonia among depressed adolescents, as well in adolescents with diverse psychiatric conditions. Further, to delineate the specific deficits of reward processes associated with peripheral inflammation and neurometabolites abnormalities, we developed the reward flanker task to examine brain function during reward expectancy and attainment. Methods: Participants were adolescents ages 12–18 years (Tanner 4). Participants were diagnosed according to the Kiddie-Sads-Present and
www.jaacap.org
S331
SYMPOSIA 46.3 – 47.0
Lifetime Version, and anhedonia was assessed quantitatively. Kynurenine pathway metabolite, cytokines, and composition of innate and adaptive immune system were examined before and after the Trier Social Stress Test and lipopolysaccharide stimulation. An imaging session consisted of the following: 1) 1H magnetic resonance spectroscopy; and 2) fMRI, including resting-state and the Reward Flanker Task (RFT), a combination of the incentive flanker and monetary incentive tasks, that examines brain function during reward expectancy (motivation) and immediate attainment. Results: Depressed adolescents and those with diverse psychiatric symptoms exhibited a full range of anhedonia severity. We observed positive relationships between inflammatory neurotoxins and anhedonia severity. We also documented that decreased anterior cingulate cortex (ACC) g-aminobutyric acid (GABA) levels in depressed adolescents were driven by the anhedonic subgroup and that there was a negative relationship between anhedonia severity and ACC GABA levels in the whole sample group. Using striatal-based intrinsic functional connectivity, we identified specific network associated with anhedonia severity while controlling for other depressive symptomatology. By use of the RFT, anhedonia severity was associated with specific brain regions during reward anticipation and attainment. Conclusions: Peripheral inflammatory processes and neurochemical alterations implicated across psychiatric conditions may play a role in the neurobiology of anhedonia and be associated with specific deficits of reward processes. Such investigative approaches can facilitate the early identification of alterations within specific neurocircuits.
DDD IMAGS NI http://dx.doi.org/10.1016/j.jaac.2016.07.391
46.3 AVERSIVE CONDITIONING TO FEARFUL FACES INDUCES EMOTION-SPECIFIC ATTENTIONAL BIASES IN CHILDREN Brandon Gibb, PhD, Psychology, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY 13902 Objectives: Although attentional biases to emotional stimuli are thought to develop during childhood and contribute to risk for psychopathology across the lifespan, little is known about how these biases develop. The primary aim of this study was to examine environmental influences on attentional biases using laboratory-based conditioning and generalization tasks. Methods: Children (aged 7–11 years) were assigned randomly to one of three conditions: 1) a typical dot-probe task, 2) an active training condition in which white noise (85 dB) was paired with fearful faces, and 3) an active control condition in which the white noise was presented randomly throughout the task. Eye-tracking indices of attention bias were collected throughout the task. After the conditioning task, children completed a passive viewing task during which data from exposure and response prevention were collected, whereas children were presented with a different set of facial expressions of emotion. Results: Children assigned to the active training condition exhibited greater preferential attention (measured via eye-tracking and response times) to fearful faces during the second-half of the conditioning task compared with children in the control conditions. Providing support for the generalization of the conditioning effects, children assigned to the active training condition, compared with children in the control conditions, exhibited a larger late positive potential to fearful faces, an event-related potential component associated with sustained attention, in a subsequent morphed face paradigm. These effects were independent of children’s state affect, suggesting that they simply are not attributed to the impact of the conditioning task on levels of anxiety. Conclusions: The current findings provide promising evidence for attentional plasticity and an experience-dependent model of attentional bias in children.
DEV RDOC http://dx.doi.org/10.1016/j.jaac.2016.07.392
S332
www.jaacap.org
46.4 TRANSDIAGNOSTIC NEURAL MECHANISMS OF IRRITABILITY Joel Stoddard, MD, University of Colorado, 13123 East 16th Avenue, A036\B-130, Gary Pavilion 4th Floor, Aurora, CO 80045 Objectives: We tested whether neural mechanisms mediating irritability are the same across diagnoses, as predicted by research domain criteria. Given longitudinal and mechanistic links between irritability and anxiety, we tested whether interactions between these traits have an impact on brain function. Because irritability is associated with face emotion-processing deficits, we used an implicit emotion-processing task. Methods: We scanned 115 youth (ages 8–17 years) with disruptive mood dysregulation disorder (n ¼ 37), anxiety disorder (n ¼ 32), or ADHD (n ¼ 24) or healthy volunteers (n ¼ 22). The fMRI task involved gender identification of faces showing 50, 100, or 150 percent happy, angry, or fearful emotion. We measured irritability with the affective reactivity index (ARI) and anxiety with the Screen for Child Anxiety Related Disorders (SCARED) using the mean of parent and child report. ANOVA tested the fully interactive effects on behavior and activation of emotion, intensity, ARI, and SCARED (p < 0.05, whole-brain corrected). We used generalized psychophysiological interaction to estimate voxel-wise amygdala functional connectivity during each task condition. Results: Increasing irritability and decreasing accuracy were associated when labeling the gender on 150 percent angry faces (r ¼ 0.31, p < 0.001). Connectivity between left amygdala and left medial prefrontal cortex (mPFC) interacted with all four factors in the omnibus model (p < 0.001; k ¼ 87; x, y, z ¼ 3.7, 55.4, 9.5, respectively). This reflected that the association between ARI score and connectivity when viewing 150 percent angry faces varied with SCARED score (p < 0.001). An ARI by emotion interaction in five regions reflected an increase in activity, with an increase in irritability during processing of happy or angry, relative to fearful, faces (p < 0.023). Diagnosis was not associated with activation or connectivity. Conclusions: During face emotion processing, neural activation varies with irritability but not diagnosis. Relatively low amygdala-mPFC connectivity is present when youth with both high anxiety and high irritability view very angry faces.
IMAGS IMD NEUROA http://dx.doi.org/10.1016/j.jaac.2016.07.393
SYMPOSIUM 47 EMERGING BIOMARKERS FOR AUTISM SPECTRUM DISORDER: USING TECHNOLOGY TO REVOLUTIONIZE CLINICAL TRIALS AND ESTABLISH NOVEL THERAPEUTICS Gahan J. Pandina, PhD, Janssen Research & Development, 1125 Trenton-Harbourton Road, Titusville, NJ 08560-0200; Robert L. Hendren, DO, Psychiatry, University of California San Francisco, 401 Parnassus Ave, Langley Porter, San Francisco, CA 94143-2211 Objectives: In this session, the authors will present and discuss recent advances in imaging and sensor-based biomarkers in ASD and their potential utility in advancing novel treatments for ASD core and associated symptoms. Methods: Four talks will review promising technologies for the development of putative biomarkers for ASD. The first talk by Dr. Geraldine Dawson will provide an overview of biosensor research in identifying novel ASD biomarkers and review noninvasive imaging and biosensors (EEG, MRI, eye tracking). A new trial (Autism Biomarker Consortium—Clinical Trial) will be presented. The next two talks will focus on diverse examples of sensorbased approaches for objective measurement of ASD core symptom biology, presented by Drs. Frederick Shic and Matthew Goodwin. The first
J OURNAL
OF THE
AMERICAN ACADEMY OF CHILD & ADOLESCENT P SYCHIATRY VOLUME 55 NUMBER 10S OCTOBER 2016