Dataset Information

Reduced olfactory bulb volume in depression-A structural moderator analysis.

ABSTRACT:

Background

Removal of the olfactory bulb (OB) leads to depression like behavior in rodents. A link between depression and olfactory function is also established in humans. We hypothesized that the human OB volume relates to depressive state and tested whether such a potential coherence is moderated by structural alterations in other brain regions.

Methods

Eighty-three participants (32 patients with major depression and 51 matched healthy controls) underwent structural MR scanning. Individual OB volumes were compared between patients and controls and the impact of depression and comorbidity was analyzed with multiple regression analysis. Whole-brain voxel-based morphometry revealed structures co-varying with both depressive state and OB volume.

Results

The OB volume of patients was significantly reduced and this reduction averaged out at 17% compared to the controls. The OB volume was correlated to the volume of the insula, superior temporal cortex, and amygdala. The independent variables of depression (??=?-.37), age (??=?-.25), and gender (??=?-.40) explained the individual OB volume variation (R² ?=?.37). The correlation between OB volume and depression was moderated by volumetric reductions in a cluster including the insula and superior temporal gyrus (STG).

Conclusions

The OB volume relates to depression in humans and to the volume of structures which are critical for salience detection. We assume that a reduced OB volume causes diminished neural olfactory input which facilitates volume reduction in the insula and STG. The OB volume may hence constitute a factor of vulnerability to depression. Olfactory-based deep brain stimulation is discussed as a future therapeutic approach.

SUBMITTER: Rottstadt F

PROVIDER: S-EPMC6866619 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Publications

Reduced olfactory bulb volume in depression-A structural moderator analysis.

Rottstädt Fabian F Han Pengfei P Weidner Kerstin K Schellong Julia J Wolff-Stephan Sylvia S Strauß Timmy T Kitzler Hagen H Hummel Thomas T Croy Ilona I

Human brain mapping 20180228 6

<h4>Background</h4>Removal of the olfactory bulb (OB) leads to depression like behavior in rodents. A link between depression and olfactory function is also established in humans. We hypothesized that the human OB volume relates to depressive state and tested whether such a potential coherence is moderated by structural alterations in other brain regions.<h4>Methods</h4>Eighty-three participants (32 patients with major depression and 51 matched healthy controls) underwent structural MR scanning. ...[more]

PMID: 29493048

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Project description:Neurogenesis in the adult brain is largely restricted to the subependymal zone (SVZ) of the lateral ventricle, olfactory bulb (OB) and the dentate subgranular zone, and survival of adult-born cells in the OB is influenced by factors including sensory experience. We examined, in mice, whether survival of adult-born cells is also regulated by the rate of precursor proliferation in the SVZ. Precursor proliferation was decreased by depleting the SVZ of dopamine after lesioning dopamine neurons in the substantia nigra compacta with 6-hydroxydopamine. Subsequently, we examined the effect of reduced SVZ proliferation on the generation, migration and survival of neuroblasts and mature adult-born cells in the SVZ, rostral migratory stream (RMS) and OB. Proliferating cells in the SVZ, measured by 5-bromo-2-deoxyuridine (BrdU) injected 2 hours prior to death or by immunoreactivity against Ki67, were reduced by 47% or 36%, respectively, 7 days after dopamine depletion, and by 29% or 31% 42 days after dopamine depletion, compared to sham-treated animals. Neuroblast generation in the SVZ and their migration along the RMS were not affected, neither 7 nor 42 days after the 6-hydroxydopamine injection, since the number of doublecortin-immunoreactive neuroblasts in the SVZ and RMS, as well as the number of neuronal nuclei-immunoreactive cells in the OB, were stable compared to control. However, survival analysis 15 days after 6-hydroxydopamine and 6 days after BrdU injections showed that the number of BrdU+ cells in the SVZ was 70% higher. Also, 42 days after 6-hydroxydopamine and 30 days after BrdU injections, we found an 82% increase in co-labeled BrdU+/?-aminobutyric acid-immunoreactive cell bodies in the granular cell layer, while double-labeled BrdU+/tyrosine hydroxylase-immunoreactive cell bodies in the glomerular layer increased by 148%. We conclude that the number of OB interneurons following reduced SVZ proliferation is maintained through an increased survival of adult-born precursor cells, neuroblasts and interneurons.

Project description:Olfactory sensory neurons distinguish a large variety of odor molecules and direct the information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. Olfaction is very important for most mammals for the maintenance of a good quality of life. Accumulating evidences endorse that olfactory sensory decline is connected with neurodegenerative disorders including schizophrenia, depression, multiple sclerosis, Huntington's, Alzheimer's and Parkinson's diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques employed to characterize the olfactory bulb functionality. Diagnosis and treatment of olfactory dysfunction remain significant health care challenges to society. Novel strategies and clues that assist in the identification of biomarker and drug development for aid in the prevention and cure of neurological diseases are necessary. However, little attention has been focused specifically on the molecular composition of the olfactory bulb from the perspective of proteomics. To this end, an in-depth mapping of the olfactory bulb proteome was carried out using high resolution tandem mass spectrometry, revealing a repertoire of 7,754 proteins. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including signal transduction, metabolism, transport, olfaction and protein synthesis. Pathway analysis of the identified proteins shows that, these proteins are predominantly involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission. In total, our study offers valuable understandings into the molecular composition of the human olfactory bulb proteome that could possibly help neuroscience community to understand the olfactory bulb better and open avenues for intervention strategies for olfactory dysfunction in the future.

Project description:Recent studies suggest that accelerated aging of the brain is a neuroanatomical signature of the state of mental diseases. In major depression, this pre-aging effect is negatively associated with the duration since the first onset of the disease. The olfactory bulb (OB) shrinks with age in healthy subjects and patients with mental diseases show reduced OB volumes, especially those with major depression. It is unclear whether this OB reduction in mental diseases resembles a pre-aging process and whether it is associated to the duration since the onset of the mental disease. To this aim, we investigated OB volume in 73 patients (mean-age 40.4 years, SD = 12.1 years, 57 women) with major depression and mixed comorbid mental diseases (diagnoses ranged from 1 to 6, median: 3) and 51 healthy controls (mean-age 39.2 years, SD = 13.0 years, 26 women) matched for age and sex. Patient's first onset of disease ranged from 15 to 53 years (mean 24.2 years). All participants underwent structural MR imaging with a spin-echo T2-wheighted sequence covering the anterior and middle segments of the skull base. All results were corrected for total intracranial volume (TIV) and sex. Individual OB volume was calculated by planimetric manual contouring and the pronounced diameter change in transition from bulb to tract was used as the distal demarcation of the OB. Inter-rater correlation between two independent persons analyzing the data was high (IRC = 0.81, p < 0.005). An age-dependent decline of the OB volume was confirmed in healthy controls (r = -0.34, p < 0.05). However, this pattern was altered in patients where the OB volume was not related to age, but to the duration since the onset of the mental disease (r = -0.25, p < 0.05). This association remained stable when controlling for age. Additionally, analyses of age sub-groups revealed that the association between duration since the onset of the mental disease and OB volume was mainly driven by the group aged 50 years and above (r = -0.68; p < 0.01). We conclude that there are time windows where the OB volume is susceptible for the effects of a mental disease, e.g., depression. These effects result in cumulative pre-aging in the OB in older patients with mental diseases.

Dataset Information

Reduced olfactory bulb volume in depression-A structural moderator analysis.

Background

Methods

Results

Conclusions

Publications

Reduced olfactory bulb volume in depression-A structural moderator analysis.

Similar Datasets

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