TY - JOUR
T1 - Striatum-based circuitry of adolescent depression and anhedonia
AU - Gabbay, Vilma
AU - Ely, Benjamin A.
AU - Li, Qingyang
AU - Bangaru, Saroja D.
AU - Panzer, Aviva M.
AU - Alonso, Carmen M.
AU - Castellanos, F. Xavier
AU - Milham, Michael P.
N1 - Funding Information:
Disclosure: Dr. Gabbay has served as a sub-investigator on studies sponsored by Otsuka, Biovail, Shire Pharmaceuticals, Bristol-Myers Squibb, and Boehringer Ingestion, but has received no compensation for this work. She has received funding from the Tourette Syndrome Association, NIH, and Hope for Depression Research Foundation. She has received honoraria from the National Center for Complementary and Alternative Medicine (NCCAM)/NIH Mechanistic Research on CAM Natural Products, NIH Mechanisms Explaining Differences in Depressive and Anxiety Disorders Across Racial/Ethnic Groups, and the Centers of Excellence for Research on CAM. Dr. Castellanos has received funding from the National Institute of Child Health and Human Development (NICHD), the Children’s Tumor Foundation, the National Institute of Mental Health (NIMH), the National Center for Research Resources, the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the Brain Research Foundation, and Autism Speaks. He has served as the Vice-Chair for the Workgroup on Attention-Deficit/Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorders, DSM-5 Task Force, American Psychiatric Association, and has served as a member of the National Advisory Council on Drug Abuse, NIH, the National Advisory Council on Drug Abuse Steering Committee, and the NIH Council of Councils. He holds U.S. patent no. 8,003,406 awarded to the National Human Genome Research Institute on behalf of inventors Maximilian Muenke, Mauricio Arcos-Burgos, and F. Xavier Castellanos for “Method of Detecting and Treating Attention-Deficit/Hyperactivity Disorder;” Provisional application filed 9/9/2008 through New York University on the “Use of Carbon Monoxide as a Therapeutic Agent” on behalf of inventors Donald F. Klein and F. Xavier Castellanos. Dr. Milham has received funding from NIMH, the Child Mind Institute, Autism Speaks, and NICHD. Dr. Alonso, Mr. Ely, Mr. Li, Ms. Bangaru, and Ms. Panzer report no biomedical financial interests or potential conflicts of interest.
Funding Information:
This study was supported by grants from the National Institutes of Health (NIH) (AT002395, AT004576, MH077072, MH077072-03S1, MH075895, and MH095807), the Chrissy Rossi National Alliance for Research on Schizophrenia and Depression Award, and generous gifts from the Leon Levy and Anita Saltz Foundations. These sources of funding had no further role in study design and conduct; in the collection, management, analysis, and interpretation of data; and in preparation, review and approval of this manuscript. Dr. Gabbay had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
PY - 2013/6
Y1 - 2013/6
N2 - Objective: Striatum-based circuits have been implicated in both major depressive disorder (MDD) and anhedonia, a symptom that reflects deficits of reward processing. Yet adolescents with MDD often exhibit a wide range of anhedonia severity. Addressing this clinical phenomenon, we aimed to use intrinsic functional connectivity (iFC) to study striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity. Method: A total of 21 psychotropic medication-free adolescents with MDD and 21 healthy controls (HC), group-matched for age and sex, underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxelwise maps indicating correlation strengths of spontaneous blood-oxygenation-level-dependent (BOLD) signals among 6 bilateral striatal seeds (dorsal caudate, ventral caudate, nucleus accumbens, dorsal-rostral putamen, dorsal-caudal putamen, ventral-rostral putamen) and the remaining brain regions were compared between groups. Relationships between striatal iFC and severity of MDD and anhedonia were examined in the MDD group. Analyses were corrected for multiple comparisons. Results: Adolescents with MDD manifested increased iFC between all striatal regions bilaterally and the dorsomedial prefrontal cortex (dmPFC), as well as between the right ventral caudate and the anterior cingulate cortex (ACC). MDD severity was associated with iFC between the striatum and midline structures including the precuneus, posterior cingulate cortex, and dmPFC. However, distinct striatal iFC patterns involving the pregenual ACC, subgenual ACC, supplementary motor area, and supramarginal gyrus were associated with anhedonia severity. Conclusions: Although MDD diagnosis and severity were related to striatal networks involving midline cortical structures, distinct circuits within the reward system were associated with anhedonia. Findings support the incorporation of both categorical and dimensional approaches in neuropsychiatric research.
AB - Objective: Striatum-based circuits have been implicated in both major depressive disorder (MDD) and anhedonia, a symptom that reflects deficits of reward processing. Yet adolescents with MDD often exhibit a wide range of anhedonia severity. Addressing this clinical phenomenon, we aimed to use intrinsic functional connectivity (iFC) to study striatum-based circuitry in relation to categorical diagnosis of MDD and anhedonia severity. Method: A total of 21 psychotropic medication-free adolescents with MDD and 21 healthy controls (HC), group-matched for age and sex, underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxelwise maps indicating correlation strengths of spontaneous blood-oxygenation-level-dependent (BOLD) signals among 6 bilateral striatal seeds (dorsal caudate, ventral caudate, nucleus accumbens, dorsal-rostral putamen, dorsal-caudal putamen, ventral-rostral putamen) and the remaining brain regions were compared between groups. Relationships between striatal iFC and severity of MDD and anhedonia were examined in the MDD group. Analyses were corrected for multiple comparisons. Results: Adolescents with MDD manifested increased iFC between all striatal regions bilaterally and the dorsomedial prefrontal cortex (dmPFC), as well as between the right ventral caudate and the anterior cingulate cortex (ACC). MDD severity was associated with iFC between the striatum and midline structures including the precuneus, posterior cingulate cortex, and dmPFC. However, distinct striatal iFC patterns involving the pregenual ACC, subgenual ACC, supplementary motor area, and supramarginal gyrus were associated with anhedonia severity. Conclusions: Although MDD diagnosis and severity were related to striatal networks involving midline cortical structures, distinct circuits within the reward system were associated with anhedonia. Findings support the incorporation of both categorical and dimensional approaches in neuropsychiatric research.
KW - depression
KW - functional connectivity
KW - functional magnetic resonance imagining (fMRI)
KW - intrinsic functional connectivity (iFC)
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U2 - 10.1016/j.jaac.2013.04.003
DO - 10.1016/j.jaac.2013.04.003
M3 - Article
C2 - 23702452
AN - SCOPUS:84878248754
SN - 0890-8567
VL - 52
SP - 628-641.e13
JO - Journal of the American Academy of Child Psychiatry
JF - Journal of the American Academy of Child Psychiatry
IS - 6
ER -
