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The association between substance P and white matter integrity in medication-naive patients with major depressive disorder.

ABSTRACT: Substance P (SP) has been implicated in major depressive disorder (MDD), with SP antagonists being studied as potential antidepressants. Although impaired neural plasticity is considered a key mechanism in MDD pathophysiology, the association between SP and brain structural changes in depression has not been investigated. We investigated the correlations between SP levels and white matter (WM) integrity in 42 medication-naive patients with MDD and 57 healthy controls (HCs). Plasma levels of SP were determined, and diffusion tensor imaging (DTI) was performed to investigate microstructural changes in WM tracts. In patients, negative correlations between SP levels and fractional anisotropy (FA) values of the forceps minor of the corpus callosum, and positive correlations between SP levels and radial diffusivity (RD) and mean diffusivity (MD) values of the right corticospinal tract (CST) were observed, with no significant correlations in HCs. Linear regression analyses showed SP levels to significantly predict FA values of the forceps minor, and RD and MD values of the right CST in patients, but not in HCs. We consider our findings to contribute to the neurobiological evidence on the association between SP and brain structural changes in depression, which may be related with the pathophysiology and treatment of MDD.

SUBMITTER: Won E

PROVIDER: S-EPMC5575350 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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The association between substance P and white matter integrity in medication-naive patients with major depressive disorder.

Won Eunsoo E Kang June J Choi Sunyoung S Kim Aram A Han Kyu-Man KM Yoon Ho-Kyoung HK Cho Su-Hee SH Tae Woo-Suk WS Lee Min-Soo MS Joe Sook-Haeng SH Kim Yong-Ku YK Ham Byung-Joo BJ

Scientific reports 20170829 1

Substance P (SP) has been implicated in major depressive disorder (MDD), with SP antagonists being studied as potential antidepressants. Although impaired neural plasticity is considered a key mechanism in MDD pathophysiology, the association between SP and brain structural changes in depression has not been investigated. We investigated the correlations between SP levels and white matter (WM) integrity in 42 medication-naive patients with MDD and 57 healthy controls (HCs). Plasma levels of SP w ...[more]

PMID: 28852030

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Project description:BackgroundAn overlap of clinical symptoms between major depressive disorder (MDD) and social anxiety disorder (SAD) suggests that the two disorders exhibit similar brain mechanisms. However, few studies have directly compared the brain structures of the two disorders. The aim of this study was to assess the gray matter volume (GMV) and cortical thickness alterations between non-comorbid medication-naive MDD patients and SAD patients.MethodsHigh-resolution T1-weighted images were acquired from 37 non-comorbid MDD patients, 24 non-comorbid SAD patients and 41 healthy controls (HCs). Voxel-based morphometry analysis of the GMV (corrected with a false discovery rate of p<0.001) and vertex-based analysis of cortical thickness (corrected with a clusterwise probability of p<0.001) were performed, and group differences were compared by ANOVA followed by post hoc tests.OutcomesRelative to the HCs, both the MDD patients and SAD patients showed the following results: GMV reductions in the bilateral orbital frontal cortex (OFC), putamen, and thalamus; cortical thickening in the bilateral medial prefrontal cortex, posterior dorsolateral prefrontal cortex, insular cortex, left temporal pole, and right superior parietal cortex; and cortical thinning in the left lateral OFC and bilateral rostral middle frontal cortex. In addition, MDD patients specifically showed a greater thickness in the left fusiform gyrus and right lateral occipital cortex and a thinner thickness in the bilateral lingual and left cuneus. SAD patients specifically showed a thinner cortical thickness in the right precentral cortex.InterpretationOur results indicate that MDD and SAD share common patterns of gray matter abnormalities in the orbitofrontal-striatal-thalamic circuit, salience network and dorsal attention network. These consistent structural differences in the two patient groups may contribute to the broad spectrum of emotional, cognitive and behavioral disturbances observed in MDD patients and SAD patients. In addition, we found disorder-specific involvement of the visual processing regions in MDD and the precentral cortex in SAD. These findings provide new evidence regarding the shared and specific neuropathological mechanisms that underlie MDD and SAD.

Project description:It is unknown if young medication-naïve bipolar II (BPII) depressed patients have increased white matter (WM) disruptions. 27 each of young (average 23 years) and treatment-naïve BPII depressed, unipolar depressed (UD) patients and age-sex-education matched healthy controls (HC) underwent 3 T MRIs with diffusion tensor imaging. Diagnostic ratings included Structured Clinical Interview for DSM Disorders (SCID), Montgomery-Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Hamilton Anxiety Rating Scale (HAM-A). Patients were clinically depressed (MADRS-BPII: 26.15 [SD9.25], UD: 25.56 [5.24], p = 0.86). Compared to UD, BPII had increased family bipolarity (BPII 13.6% vs UD 2.5%, p = 0.01, φc = 0.28), hypomanic symptoms (YMRS-BPII: 4.22 [4.24], UD: 1.33 [2], p = 0.02, d = 0.87), lifetime number of depressive episodes (BPII: 2.37 [1.23], UD: 1.44 [0.75], p = 0.02, d = 0.91), lifetime and current-year number of episodes (lifetime BPII: 50.85 [95.47], UD: 1.7 [1.03]; current-year BPII: 9.93 [16.29], UD: 1.11 [0.32], ps = 0.04, ds = 0.73-0.77) and longer illness duration (BPII: 4.96 years [3.96], UD: 2.99 [3.33], p = 0.15, d = 0.54). BPII showed no increased WM disruptions vs UD or HC in any of the 15 a priori WM tracts. UD had lower right superior longitudinal fasciculus (SLF) (temporal) axial diffusivity (AD) (1.14 vs 1.17 (BPII), 1.16 (HC); F = 6.93, 95% CI of [Formula: see text]: 0.00073, 5.22, ηp2 = 0.15). Principal component analysis followed by exploratory linear discriminant analysis showed that increased R-SLF (temporal) AD, YMRS and family bipolarity distinguished BPII from UD (81.5% sensitivity, 85.2% specificity) independent of episode number and frequency. Young, medication-naïve adults with BPII depression did not show the WM disruptions distinguishing more chronically ill BP patients from UD. These WM disruptions may therefore be partly attributable to illness chronicity. Longitudinal studies should examine the trajectory of WM changes in BPII and UD and predictive validity of these baseline clinical and imaging parameters.

Project description:Background:Almost half of patients with major depressive disorder (MDD) also have clinically meaningful levels of anxiety. Anxious depression is a distinct clinical subtype of MDD, which has poor response to pharmacotherapy; however, the neural mechanisms behind are largely unknown. In the present study, we explored the white matter (WM) integrity traits of anxious depression in first-episode and medication-free (medication-naïve and medication washout) Chinese young adult patients by detecting differences in diffusion tensor imaging (DTI) with the tract-based spatial statistics (TBSS) method. Subjects and methods:DTI was obtained from 39 first-episode, medication-free anxious depressive patients, 45 nonanxious depressive patients, and 50 demographically similar healthy controls. All subjects underwent clinical assessments. TBSS was carried out to investigate the difference in WM integrity among three groups within DTI parameter maps. WM integrity was measured using fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD). The correlations between WM integrity and clinical features were also computed. Results:When compared with nonanxious patients, lower FA values in anxious depressive patients were found in multiple regions of the brain, mainly involving left uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), and forceps major and minor. Higher RD in forceps major and minor and SLF were also detected. The decreased FA values and increased RD values correlated with both anxiety level and depression level in the pooled depressive group. Conclusion:The anxious depressive patients had more abnormalities in WM integrity at the early phase than the nonanxious group. Alternations in WM integrity in fiber pathways, including SLF, UF, and forceps major and minor, may play a critical role in the neuropathology of anxious depression and might help to identify anxious MDD from nonanxious MDD. Further study with larger sample size, larger age range, and longitudinal design is needed to confer a robust inference to better understand the dynamic neurological change and neuropathology of WM integrity in anxious MDD.

Project description:Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients.

Dataset Information

The association between substance P and white matter integrity in medication-naive patients with major depressive disorder.

Publications

The association between substance P and white matter integrity in medication-naive patients with major depressive disorder.

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