Serotonin transporters in depression
<p>Major depression is a common, recurrent and severe mental illness and is a leading cause of medical disability worldwide. The pathophysiology of depression is not well understood but evidence strongly suggests that dysfunction in brain serotonin (5-HT) neurons may play a significant role. T...
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| Format: | Thesis |
| Language: | English |
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2010
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| _version_ | 1797109174276980736 |
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| author | Selvaraj, S |
| author2 | Cowen, P |
| author_facet | Cowen, P Selvaraj, S |
| author_sort | Selvaraj, S |
| collection | OXFORD |
| description | <p>Major depression is a common, recurrent and severe mental illness and is a leading cause of medical disability worldwide. The pathophysiology of depression is not well understood but evidence strongly suggests that dysfunction in brain serotonin (5-HT) neurons may play a significant role. The serotonin transporter (5-HTT) recycles released 5-HT back into neurons and is a key regulator of 5-HT neurotransmission. Abnormality in the 5-HTT has been proposed as an important mechanism in the etiopathophysiology and the treatment of depression. Using positron emission tomography (PET) in conjunction with [11C] DASB, a selective 5-HTT radiotracer, it is now possible to measure the 5-HTT in the living human brain. The aim of this thesis was to study 5-HTT binding in major depression and also to identify the effect of a 5-HTT genetic polymorphism on 5-HTT binding and brain morphology.</p>
<p>Unmedicated, acutely depressed patients had diminished availability of the 5-HTT in several brain regions including the brain stem, thalamus, caudate, putamen, anterior cingulate cortex and frontal cortex. However, there was no significant difference in 5-HTT availability between unmedicated recovered depressed patients and healthy comparison subjects in any of the brain regions studied. There was no significant difference in brain 5-HTT availability in healthy controls with different 5-HTT polymorphic variations. However, brain morphological analysis revealed reduced brain gray matter volume in S’ allele carriers vs L’L’ homozygotes in several brain regions including anterior cingulate cortex.</p>
<p>The results suggest at least in a subgroup of patients, acute depression is associated with decreased availability of the 5-HTT as measured by ligand PET. The results indicate that this abnormality is a state marker of depression but this needs to be confirmed by future studies following the same group of patients through depression, treatment and its resolution. The findings also suggest that if the 5-HTT promoter polymorphism exerts a reliable effect on the risk of depression it is not mediated through changes in the 5-HTT but more probably through modifications in brain morphology perhaps of neurodevelopmental origin.</p> |
| first_indexed | 2024-03-07T07:38:12Z |
| format | Thesis |
| id | oxford-uuid:93616e61-2165-4665-a557-c14368f9593c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:38:12Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:93616e61-2165-4665-a557-c14368f9593c2023-03-23T14:34:13ZSerotonin transporters in depressionThesishttp://purl.org/coar/resource_type/c_db06uuid:93616e61-2165-4665-a557-c14368f9593cClinical pharmacologyNeurobiologyMedical sciencesNeuropsychopharmacologyneuroimagingMajor depressive disorderAffective neuroscienceEnglishHyrax Deposit2010Selvaraj, SCowen, P<p>Major depression is a common, recurrent and severe mental illness and is a leading cause of medical disability worldwide. The pathophysiology of depression is not well understood but evidence strongly suggests that dysfunction in brain serotonin (5-HT) neurons may play a significant role. The serotonin transporter (5-HTT) recycles released 5-HT back into neurons and is a key regulator of 5-HT neurotransmission. Abnormality in the 5-HTT has been proposed as an important mechanism in the etiopathophysiology and the treatment of depression. Using positron emission tomography (PET) in conjunction with [11C] DASB, a selective 5-HTT radiotracer, it is now possible to measure the 5-HTT in the living human brain. The aim of this thesis was to study 5-HTT binding in major depression and also to identify the effect of a 5-HTT genetic polymorphism on 5-HTT binding and brain morphology.</p> <p>Unmedicated, acutely depressed patients had diminished availability of the 5-HTT in several brain regions including the brain stem, thalamus, caudate, putamen, anterior cingulate cortex and frontal cortex. However, there was no significant difference in 5-HTT availability between unmedicated recovered depressed patients and healthy comparison subjects in any of the brain regions studied. There was no significant difference in brain 5-HTT availability in healthy controls with different 5-HTT polymorphic variations. However, brain morphological analysis revealed reduced brain gray matter volume in S’ allele carriers vs L’L’ homozygotes in several brain regions including anterior cingulate cortex.</p> <p>The results suggest at least in a subgroup of patients, acute depression is associated with decreased availability of the 5-HTT as measured by ligand PET. The results indicate that this abnormality is a state marker of depression but this needs to be confirmed by future studies following the same group of patients through depression, treatment and its resolution. The findings also suggest that if the 5-HTT promoter polymorphism exerts a reliable effect on the risk of depression it is not mediated through changes in the 5-HTT but more probably through modifications in brain morphology perhaps of neurodevelopmental origin.</p> |
| spellingShingle | Clinical pharmacology Neurobiology Medical sciences Neuropsychopharmacology neuroimaging Major depressive disorder Affective neuroscience Selvaraj, S Serotonin transporters in depression |
| title | Serotonin transporters in depression |
| title_full | Serotonin transporters in depression |
| title_fullStr | Serotonin transporters in depression |
| title_full_unstemmed | Serotonin transporters in depression |
| title_short | Serotonin transporters in depression |
| title_sort | serotonin transporters in depression |
| topic | Clinical pharmacology Neurobiology Medical sciences Neuropsychopharmacology neuroimaging Major depressive disorder Affective neuroscience |
| work_keys_str_mv | AT selvarajs serotonintransportersindepression |