PMC:3839092 / 13542-21308 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3839092","sourcedb":"PMC","sourceid":"3839092","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3839092","text":"Results\n\nParticipants\nDemographic and clinical characteristics are summarized in Table 1. One subject with MDD had been treated with Lexapro and Ambien for 7 months, but was medication-free for approximately 14 months prior to scanning. A second subject with MDD had a brief trial with Prozac which was self-discontinued prior to participation in this study. All other subjects were psychotropic medication-naïve. Fifteen subjects with MDD had experienced only one episode of depression, with length of episode ranging from 4 to 48 months, and two patients reported having two distinct episodes. Two Shapiro–Wilk tests revealed that anhedonia and irritability were both normally distributed within the MDD group, ps = 0.81, 0.48, respectively. Depression severity (excluding the anhedonia- or irritability-related items) was significantly correlated with both severity of anhedonia (r = 0.66, p \u003c 0.005) and irritability (r = 0.66, p \u003c 0.005) within our MDD sample. Anhedonia and irritability were not correlated (r = 0.37, p = 0.15).\nTable 1 Demographic and clinical characteristics of adolescents with major depressive disorder (MDD) and healthy controls. a Respective percentages (may not add up to 100% due to rounding). b Children’s depression rating scale – revised. c Beck depression inventory, 2nd ed. d Beck scale for suicidal ideation. e Multidimensional anxiety scale for children. f Attention deficit hyperactivity disorder. g Generalized anxiety disorder.\n\nWhole-brain group comparison\nNo voxel-wise group comparisons for FA, MD, RD, or AD withstood correction for multiple comparisons. An exploratory analysis using a threshold of p \u003c 0.001, uncorrected with clusters exceeding 10 contiguous voxels, revealed 4 significant clusters (Table 2, Figure 1). Compared with HC, the MDD group had lower FA in the anterior cingulum, and lower AD in the anterior corona radiata (ACR). However, the MDD group also had greater FA and lower RD in the posterior cingulum compared to HC.\nTable 2 Voxel-wise group comparison results. Units for AD and RD = mm2/s. Coordinates in MNI space. Threshold p \u003c 0.001, uncorrected, k \u003e 10. COG, center of gravity; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity; AD, axial diffusivity; WM, white matter; L, left; R, right; ACR, anterior corona radiata.\nFigure 1 (A) Increased WM integrity in the MDD group vs. HC in the posterior cingulum near the hippocampus; (B) decreased WM integrity in the MDD group vs. HC in the anterior cingulum near the precuneus.\n\nWhole-brain correlations with depression severity in MDD\nExploratory analyses revealed a total of 16 uncorrected clusters, with 5 overlapping clusters between the 4 diffusivity measures (Table 3, Figure 2). As depression severity increased, FA decreased in the genu of the corpus callosum, the sagittal stratum, the ATR, and the anterior cingulum. Additionally, a positive correlation between MD and depression severity was found in the same sagittal stratum cluster as the FA analysis, as well as in clusters in the ATR and corticospinal tract. Similarly, illness severity was positively correlated with RD in the same sagittal stratum cluster as the FA and MD analyses, the same genu of the corpus callosum and ATR clusters as the FA analysis, the same ATR cluster as the MD analysis, and a cluster in the superior longitudinal fasciculus (SLF). Finally, increased illness severity was associated with increased AD in the same corticospinal cluster as the MD analysis as well as in clusters in the inferior-fronto-occipital fasciculus (IFOF), the SLF, and fibers projecting to the orbitofrontal cortex (OFC).\nTable 3 Voxel-wise correlations with depression severity (CDRS-R). Coordinates in MNI space. Threshold p \u003c 0.001, uncorrected, k \u003e 10. COG, center of gravity; L, left; R, right; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity; AD, axial diffusivity; WM, white matter; PHG, parahippocampal gyrus; ACC, anterior cingulate cortex; MFG, medial frontal gyrus; OFC, orbitofrontal gyrus; ILF; inferior longitudinal fasciculus; IFOF, inferior-fronto-occipital fasciculus; ATR, anterior thalamic radiation; SLF, superior longitudinal fasciculus.\nFigure 2 Decreased WM integrity as depression severity increased in the (A) sagittal stratum near the PHG; (B) ATR near the pallidum; (C) genu of the corpus callosum and anterior cingulate; (D) anterior cingulate near the precuneus. Key: PHG, parahippocampal gyrus; ATR, anterior thalamic radiation.\n\nWhole-Brain correlations with anhedonia in MDD\nAnalyses revealed a total of 14 uncorrected clusters, with 2 overlapping clusters between FA and RD (Table 4, Figure 3). As anhedonia increased, FA increased in a cluster in the posterior cingulum near the hippocampus – similar to a cluster from the group comparison analysis – and decreased in the anterior limb of the internal capsule, OFC projection fibers, and the posterior cingulum near the precuneus. Furthermore, anhedonia was positively correlated with MD in OFC projection fibers, the external capsule, and the sagittal stratum. Additionally, increased anhedonia severity was associated with greater RD in the same posterior limb of the internal capsule and posterior cingulum clusters as the FA analysis, the same OFC projection fibers as the MD analysis, and clusters in the ATR and corticospinal tract. Finally, there were positive correlations between anhedonia and AD in the corticospinal tract and projection fibers into the occipital cortex.\nTable 4 Voxel-wise correlations with anhedonia. Coordinates in MNI space. Threshold p \u003c 0.001, uncorrected, k \u003e 10. COG, center of gravity; L, left; R, right; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity; AD, axial diffusivity; WM, white matter; OFC, orbitofrontal gyrus; IC, internal capsule; ATR, anterior thalamic radiation; IFOF, inferior-fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus.\nFigure 3 (A) Increased WM integrity as anhedonia increased in the posterior cingulum near the hippocampus; decreased WM integrity as anhedonia increased in the (B) anterior limb of the internal capsule; (C) IFOF near the OFC; (D) posterior cingulum near the precuneus. Key: IFOF, inferior-fronto-occipital fasciculus; OFC, orbitofrontal cortex.\n\nWhole-brain correlations with irritability in MDD\nAnalyses revealed a total of 14 uncorrected clusters, with 2 overlapping clusters (Table 5, Figure 4). As irritability increased, FA decreased in clusters in the sagittal stratum and IFOF, while MD increased in the same sagittal stratum cluster as well as in clusters in the ACR, SLF, and IFOF. For RD, positive correlations with irritability were evident in the same sagittal stratum cluster, the anterior limb of the internal capsule, and the SLF. Positive correlations were also found between AD and irritability in the same ACR cluster as the MD analysis as well as in the IFOF, the corticospinal tract, and the SLF.\nTable 5 Voxel-wise correlations with irritability. Coordinates in MNI space. Threshold p \u003c 0.001, uncorrected, k \u003e 10. COG, center of gravity; L, left; R, right; FA, fractional anisotropy; MD, mean diffusivity; RD, radial diffusivity; AD, axial diffusivity; WM, white matter; IT, inferior temporal gyrus; MFG, medial frontal gyrus; MT, middle temporal gyrus; ILF, inferior longitudinal fasciculus; IFOF, inferior-fronto-occipital fasciculus; ACR, anterior corona radiata; ATR, anterior thalamic radiation; SLF, superior longitudinal fasciculus; IC, internal capsule.\nFigure 4 Decreased WM integrity as irritability increased in the (A) sagittal stratum in the IT; (B) IFOF near the MFG. Key: IT, inferior temporal cortex; IFOF, inferior-fronto-occipital fasciculus; MFG, medial frontal gyrus.\n\nDi","divisions":[{"label":"Title","span":{"begin":0,"end":7}},{"label":"Section","span":{"begin":9,"end":1474}},{"label":"Title","span":{"begin":9,"end":21}},{"label":"Table caption","span":{"begin":1035,"end":1473}},{"label":"Section","span":{"begin":1473,"end":2528}},{"label":"Title","span":{"begin":1473,"end":1501}},{"label":"Table caption","span":{"begin":1990,"end":2321}},{"label":"Figure caption","span":{"begin":2321,"end":2527}},{"label":"Section","span":{"begin":2527,"end":4504}},{"label":"Title","span":{"begin":2527,"end":2583}},{"label":"Table caption","span":{"begin":3638,"end":4201}},{"label":"Figure caption","span":{"begin":4201,"end":4503}},{"label":"Section","span":{"begin":4503,"end":6297}},{"label":"Title","span":{"begin":4503,"end":4549}},{"label":"Table caption","span":{"begin":5509,"end":5949}},{"label":"Figure caption","span":{"begin":5949,"end":6296}},{"label":"Section","span":{"begin":6296,"end":7765}},{"label":"Title","span":{"begin":6296,"end":6345}},{"label":"Table caption","span":{"begin":6967,"end":7536}},{"label":"Figure caption","span":{"begin":7536,"end":7764}}],"tracks":[{"project":"NEUROSES","denotations":[{"id":"T337","span":{"begin":107,"end":110},"obj":"CHEBI_566274"},{"id":"T338","span":{"begin":259,"end":262},"obj":"CHEBI_566274"},{"id":"T339","span":{"begin":436,"end":439},"obj":"CHEBI_566274"},{"id":"T340","span":{"begin":702,"end":705},"obj":"CHEBI_566274"},{"id":"T341","span":{"begin":954,"end":957},"obj":"CHEBI_566274"},{"id":"T342","span":{"begin":185,"end":189},"obj":"PATO_0002316"},{"id":"T343","span":{"begin":286,"end":292},"obj":"CHEBI_5118"},{"id":"T344","span":{"begin":286,"end":292},"obj":"CHEBI_5119"},{"id":"T345","span":{"begin":493,"end":499},"obj":"PATO_0000122"},{"id":"T346","span":{"begin":577,"end":585},"obj":"PATO_0000463"},{"id":"T347","span":{"begin":679,"end":690},"obj":"PATO_0001566"},{"id":"T348","span":{"begin":706,"end":711},"obj":"CHEBI_24433"},{"id":"T349","span":{"begin":476,"end":486},"obj":"PM3425"},{"id":"T350","span":{"begin":744,"end":754},"obj":"PM3425"},{"id":"T351","span":{"begin":476,"end":486},"obj":"PM3425"},{"id":"T352","span":{"begin":744,"end":754},"obj":"PM3425"},{"id":"T711","span":{"begin":1132,"end":1135},"obj":"CHEBI_566274"}],"attributes":[{"subj":"T337","pred":"source","obj":"NEUROSES"},{"subj":"T338","pred":"source","obj":"NEUROSES"},{"subj":"T339","pred":"source","obj":"NEUROSES"},{"subj":"T340","pred":"source","obj":"NEUROSES"},{"subj":"T341","pred":"source","obj":"NEUROSES"},{"subj":"T342","pred":"source","obj":"NEUROSES"},{"subj":"T343","pred":"source","obj":"NEUROSES"},{"subj":"T344","pred":"source","obj":"NEUROSES"},{"subj":"T345","pred":"source","obj":"NEUROSES"},{"subj":"T346","pred":"source","obj":"NEUROSES"},{"subj":"T347","pred":"source","obj":"NEUROSES"},{"subj":"T348","pred":"source","obj":"NEUROSES"},{"subj":"T349","pred":"source","obj":"NEUROSES"},{"subj":"T350","pred":"source","obj":"NEUROSES"},{"subj":"T351","pred":"source","obj":"NEUROSES"},{"subj":"T352","pred":"source","obj":"NEUROSES"},{"subj":"T711","pred":"source","obj":"NEUROSES"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"NEUROSES","color":"#c293ec","default":true}]}]}}