| dc.identifier.uri | http://hdl.handle.net/11401/78282 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.type | Dissertation | |
| dcterms.abstract | Major Depressive Disorder (MDD) is a heterogeneous and debilitating disorder. As of now, there is no reliable biomarker for this disorder, either for diagnosis or prediction of treatment response. The serotonin 1A (5-HT1A) receptor has been shown through animal, post-mortem, and in vivo human studies to be elevated in mood disorders such as MDD, and thus may be a promising biomarker. In my dissertation, I aim to explore this receptor and the serotonin system in order to better understand MDD pathophysiology and to establish tools for future research and clinical use. The raphe nucleus (RN) is the major source of serotonin in the brain, and the amygdala is known to be hyperactive in MDD. Therefore, I first aimed to replicate a study from my lab showing that white matter integrity from the RN to the amygdala, measured through diffusion tensor imaging (DTI) could predict response to selective serotonin reuptake inhibitor (SSRI) treatment in MDD. While there were significant associations between white matter integrity and treatment response, the effect size was too small to be of clinical utility. A series of experiments using positron emission tomography (PET) were undertaken to understand the role of the 5-HT1A receptor specifically. First, to understand 5-HT1A effects on brain structure, 5-HT1A binding, I correlated binding in the RN to cortical thickness across the brain. While there was positive correlation throughout, only the posterior cingulate survived multiple comparisons correction. As this region is known to be part of the default mode network, this may point to a link between serotonin and negative self-directed processing and rumination. Another set of PET experiments sought to refine and understand 5-HT1A as a biomarker for MDD. This involved correlating binding in the RN to binding in other regions of the brain with high 5-HT1A expression. In healthy controls, binding in these regions correlated strongly—however, in MDD the correlation was much weaker, which suggests dysregulation of homeostatic mechanisms. In addition, the PET-defined RN was separated into individual component nuclei—by only using the rostral RN and not the caudal RN, MDD patients could be differentiated from controls with 94% sensitivity and 84% specificity. Finally, in an effort to make 5-HT1A imaging more accessible to vulnerable populations, I correlated 5-HT1A binding to an electroencephalography paradigm known as loudness dependence of auditory evoked potentials (LDAEP). LDAEP significantly correlated with 5-HT1A binding in the RN and in the temporal lobe, indicating that this could serve as a noninvasive surrogate for serotonin PET imaging. | |
| dcterms.available | 2018-06-21T13:38:53Z | |
| dcterms.contributor | Evinger, Craig | en_US |
| dcterms.contributor | Parsey, Ramin V | en_US |
| dcterms.contributor | DeLorenzo, Christine | en_US |
| dcterms.contributor | Yang, Jie | en_US |
| dcterms.contributor | Whitaker-Azmitia, Patricia | en_US |
| dcterms.creator | Pillai, Rajapillai Laban Isaac | |
| dcterms.dateAccepted | 2018-06-21T13:38:53Z | |
| dcterms.dateSubmitted | 2018-06-21T13:38:53Z | |
| dcterms.description | Department of Neuroscience | en_US |
| dcterms.extent | 214 pg. | en_US |
| dcterms.format | Application/PDF | en_US |
| dcterms.format | Monograph | |
| dcterms.identifier | http://hdl.handle.net/11401/78282 | |
| dcterms.issued | 2017-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2018-06-21T13:38:53Z (GMT). No. of bitstreams: 1
Pillai_grad.sunysb_0771E_13558.pdf: 17501212 bytes, checksum: 71c9bf4a7f8c1456ae96fd746915980b (MD5)
Previous issue date: 12 | en |
| dcterms.subject | electroencephalography | |
| dcterms.subject | Neurosciences | |
| dcterms.subject | magnetic resonance imaging | |
| dcterms.subject | Psychobiology | |
| dcterms.subject | major depressive disorder | |
| dcterms.subject | Medicine | |
| dcterms.subject | positron emission tomography | |
| dcterms.subject | raphe nuclei | |
| dcterms.subject | serotonin 1A | |
| dcterms.title | The Role of the Serotonin 1A Receptor in Mood Disorders | |
| dcterms.type | Dissertation | |
