The purpose of this study is to understand the effects of anxiety on reward responsiveness in adolescents with anorexia nervosa (AN), and how this interaction predicts clinical outcome subsequent to intensive treatment. AN is notorious for its resistance to interventions and for the highest mortality rate of all psychiatric disorders. Variou forms of intensive treatment may succeed in restoring weight, yet overall benefits of treatment remain limited and early relapse is unusually high. While evidence suggests that genetic factors play a role in susceptibility, remarkably little is known about AN's mechanistic neural circuitry. Individuals with AN typically exhibit prodromal anxiety early in life prior to disordered eating. This phenotypic expression may manifest as exaggerated threat perception, and hypersensitivity to and avoidance of signals of weight and shape change. In parallel, individuals with restricting-type AN, beginning in early childhood, are reticent to exposure to novel and high reward environments. This is in line with most psychometric and neuroimaging studies that suggest low responsiveness to natural rewards, as well as aberrant reward system activity and dopaminergic function. However, the interaction between anxiety and reward circuits has never been interrogated in AN. There is substantial evidence of distinct yet overlapping neural systems mediating approach (related to reward) and avoidance (related to anxiety), which are integrated in balancing and switching between behaviors related to the predominant valence state. Thus, we posit that high degrees of reactivity of cortico-limbic circuits underlying anxiety may contribute to diminished capacity to respond to reward stimuli. This may translate clinically to lower motivation to engage in treatment; in effect, a lower drive to change behaviors and thought patterns necessary for improvement based on expectancy of benefits of future outcome, resulting in a course trajectory of weight loss and worsening of symptoms. Accordingly, this study investigates this anxiety and reward interaction in individuals with AN who have recently completed intensive treatment, and whom will be followed for degree of symptom relapse over 6 months. Forty two adolescents with restricting-type AN and 42 matched controls will engage in reward tasks in which individually- tailored anxiety provoking word stimuli are interleaved, while undergoing functional magnetic resonance imaging (fMRI). Reward and anxiety neural circuit activity, and their interaction, will be analyzed in relationship to their ability to predict trajetory of BMI and symptom severity changes over the subsequent 6 months. Using novel designs for interrogating the functionality of positive and negative valence circuits may thus lead to identification of dimensional phenotypes associated with disease persistence, a critical step towards developing individualized and targeted treatment strategies (such as reduction of stimuli-specific anxiety and/or enhancement of positive affect) for high-risk subgroups.
The proposed study will test the interactions between brain circuits involved in reward and anxiety, and how activity in these circuits predicts clinical relape in adolescents with anorexia nervosa after intensive treatment. This study would be the first to use functional neuroimaging markers as predictors of behavioral outcomes in eating disorders. In addition, it sets the foundation for development of much-needed, individually tailored treatment approaches for adolescents at greater risk for relapse, such as targeting engagement of reward motivation timed with anxiety reduction strategies during early treatment.
| Motivala, Sarosh J; Arellano, Maria; Greco, Rebecca L et al. (2018) Relationships between obsessive-compulsive disorder, depression and functioning before and after exposure and response prevention therapy. Int J Psychiatry Clin Pract 22:40-46 |
| Burke, Sarah M; Manzouri, Amir H; Dhejne, Cecilia et al. (2018) Testosterone Effects on the Brain in Transgender Men. Cereb Cortex 28:1582-1596 |
| Khalsa, Sahib S; Adolphs, Ralph; Cameron, Oliver G et al. (2018) Interoception and Mental Health: A Roadmap. Biol Psychiatry Cogn Neurosci Neuroimaging 3:501-513 |
| Tadayonnejad, Reza; Deshpande, Rangaprakash; Ajilore, Olusola et al. (2018) Pregenual Anterior Cingulate Dysfunction Associated with Depression in OCD: An Integrated Multimodal fMRI/1H MRS Study. Neuropsychopharmacology 43:1146-1155 |
| Khalsa, Sahib S; Portnoff, Larissa C; McCurdy-McKinnon, Danyale et al. (2017) What happens after treatment? A systematic review of relapse, remission, and recovery in anorexia nervosa. J Eat Disord 5:20 |
| Moody, Teena D; Shen, Vivian W; Hutcheson, Nathan L et al. (2017) Appearance evaluation of others' faces and bodies in anorexia nervosa and body dysmorphic disorder. Int J Eat Disord 50:127-138 |
| Feusner, Jamie D; Lidström, Andreas; Moody, Teena D et al. (2017) Intrinsic network connectivity and own body perception in gender dysphoria. Brain Imaging Behav 11:964-976 |
| Feusner, Jamie; Deshpande, Rangaprakash; Strober, Michael (2017) A translational neuroscience approach to body image disturbance and its remediation in anorexia nervosa. Int J Eat Disord 50:1014-1017 |
| Moody, T D; Morfini, F; Cheng, G et al. (2017) Mechanisms of cognitive-behavioral therapy for obsessive-compulsive disorder involve robust and extensive increases in brain network connectivity. Transl Psychiatry 7:e1230 |
| Khalsa, Sahib S; Kumar, Rajesh; Patel, Vandan et al. (2016) Mammillary body volume abnormalities in anorexia nervosa. Int J Eat Disord 49:920-929 |
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