The proposed study aims to discover the neural circuit abnormalities contributing to amotivation in schizophrenia, and identify quantitative behavioral and imaging measures of amotivation that can accelerate future translational and therapeutic research. A pathological loss of motivation is one of the """"""""negative symptoms"""""""" of schizophrenia, which involve deficits in emotional and social capacities. Together with other negative symptoms such as anhedonia (reduced pleasure), asociality (reduced social drive), and reduced expressivity, amotivation contributes strongly to the disability caused by schizophrenia. Unlike positive symptoms (hallucinations, delusions) which are generally responsive to antipsychotic medications, negative symptoms including amotivation respond poorly to current treatments, and therefore constitute a major unmet therapeutic need in psychiatry. Despite this importance, amotivation in schizophrenia has been understudied and the brain abnormalities causing this deficit remain largely unknown. Validation and application of laboratory motivation paradigms in schizophrenia has lagged behind research in hedonic and emotion- processing deficits, and narrowing this gap is a major aim of this proposal. Over four years, the proposed study will evaluate motivation in 80 adults with schizophrenia with a wide range of negative symptoms, as well as 40 healthy control subjects.
The specific aims are: 1) To quantify motivational deficits in schizophrenia using translational laboratory tasks, 2) To identif neural circuit dysfunction associated with motivation deficits in schizophrenia, and 3) To define a complex whole-brain phenotype predicting amotivation severity. To achieve these aims we will apply novel behavioral and functional imaging tasks together with advanced multivariate pattern analysis techniques. This study will provide a detailed brain-behavior pattern predicting amotivation severity which will help advance the understanding, treatment, and prevention of schizophrenia.
Schizophrenia is a complex brain disorder that imposes heavy costs on individuals suffering with this illness, as well as their families and society. The disorder causes abnormalities in emotional systems including brain motivation circuits, which strongly contribute to disability and which have no known treatments. The proposed study focuses on understanding the biology of these motivational deficits and accurately measuring their severity, in order to accelerate the development and testing of new and more effective treatments.
|Sharma, Anup; Satterthwaite, Theodore D; Vandekar, Lillie et al. (2016) Divergent relationship of depression severity to social reward responses among patients with bipolar versus unipolar depression. Psychiatry Res 254:18-25|
|Kaczkurkin, Antonia N; Moore, Tyler M; Ruparel, Kosha et al. (2016) Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety. Biol Psychiatry 80:775-785|
|Hershenberg, Rachel; Satterthwaite, Theodore D; Daldal, Aylin et al. (2016) Diminished effort on a progressive ratio task in both unipolar and bipolar depression. J Affect Disord 196:97-100|
|Eavani, Harini; Hsieh, Meng Kang; An, Yang et al. (2016) Capturing heterogeneous group differences using mixture-of-experts: Application to a study of aging. Neuroimage 125:498-514|
|Lin, Hsiang-Yu; Chuang, Chih-Kuang; Huang, Yu-Hsiu et al. (2016) Causes of death and clinical characteristics of 34 patients with Mucopolysaccharidosis II in Taiwan from 1995-2012. Orphanet J Rare Dis 11:85|
|Lin, Hsiang-Yu; Chuang, Chih-Kuang; Wang, Chung-Hsing et al. (2016) Long-term galsulfase enzyme replacement therapy in Taiwanese mucopolysaccharidosis VI patients: A case series. Mol Genet Metab Rep 7:63-9|
|Shanmugan, Sheila; Wolf, Daniel H; Calkins, Monica E et al. (2016) Common and Dissociable Mechanisms of Executive System Dysfunction Across Psychiatric Disorders in Youth. Am J Psychiatry 173:517-26|
|Satterthwaite, Theodore D; Wolf, Daniel H; Calkins, Monica E et al. (2016) Structural Brain Abnormalities in Youth With Psychosis Spectrum Symptoms. JAMA Psychiatry 73:515-24|
|van Erp, T G M; Hibar, D P; Rasmussen, J M et al. (2016) Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol Psychiatry 21:547-53|
|Satterthwaite, Theodore D; Kable, Joseph W; Vandekar, Lillie et al. (2015) Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression. Neuropsychopharmacology 40:2258-68|
Showing the most recent 10 out of 21 publications