Resting-State Functional Connectivity Bias of Middle Temporal Gyrus and Caudate with Altered Gray Matter Volume in Major Depression

Ma, Chaoqiong; Ding, Jingxin; Li, Jun; Guo, Wenbin; Long, Zhiliang; Liu, Feng; Gao, Qing; Zeng, Lingsen; Zhao, Jingping; Chen, Huafu

doi:10.1371/journal.pone.0045263

Cited by 131 publications

(119 citation statements)

References 60 publications

(82 reference statements)

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“…Caudate connectivity is frequently implicated in major affective disorders (61,62). Major gene candidates represented by multiple SNPs identified in this network included pallidin (PALLD), which encodes for a cytoskeletal protein that controls cell shape, adhesion, and contraction/migration.…”

Section: Ica Derived Dmnsmentioning

confidence: 99%

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Meda

Ruaño

Windemuth

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

213

159

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The brain's default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach. The initial analysis used independent component analysis (ICA) in 324 healthy controls, 296 SZ probands, 300 PBP probands, 179 unaffected first-degree relatives of SZ probands (SZREL), and 206 unaffected first-degree relatives of PBP probands to identify DMNs and to test their biomarker and/ or endophenotype status. A subset of controls and probands (n = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging-genetic relationships. ICA identified three DMNs. Hypoconnectivity was observed in both patient groups in all DMNs. Similar patterns observed in SZREL were restricted to only one network. DMN connectivity also correlated with several symptom measures. Para-ICA identified five sub-DMNs that were significantly associated with five different genetic networks. Several top-ranking SNPs across these networks belonged to previously identified, well-known psychosis/mood disorder genes. Global enrichment analyses revealed processes including NMDA-related long-term potentiation, PKA, immune response signaling, axon guidance, and synaptogenesis that significantly influenced DMN modulation in psychoses. In summary, we observed both unique and shared impairments in functional connectivity across the SZ and PBP cohorts; these impairments were selectively familial only for SZREL. Genes regulating specific neurodevelopment/transmission processes primarily mediated DMN disconnectivity. The study thus identifies biological pathways related to a widely researched quantitative trait that might suggest novel, targeted drug treatments for these diseases.genetics | BSNIP | architecture | molecular S chizophrenia (SZ) and psychotic bipolar disorder (PBP) are common, serious, heritable, genetically complex illnesses, sharing multiple characteristics, including risk genes and abnormalities in cognition, neural function, and brain structure (1-4). However, despite recent advances, their underlying biological mechanisms are largely undetermined and may be shared across the two diagnostic groups. Recent large-scale analyses have used various statistical informatics strategies to dissect these biological underpinnings better (5, 6). A recent study using a pathwayenrichment strategy showed that genes involved in neuronal cell adhesion, synaptic formation, and cell signaling are overrepresented in SZ and bipolar disorder (BP) (6). Another study using an informatics-based approach identified several cohesive genetic networks related to axon guidance, neuronal cell mobility, and synaptic functioning as key players in schizophrenia (5).Although risk for psychotic illnesses is driven in small part by highly penetrant, often private mutations such as copy number variants, substantial...

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Section: Ica Derived Dmnsmentioning

confidence: 99%

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Meda

Ruaño

Windemuth

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

213

159

View full text Add to dashboard Cite

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“…Both the TRD and treatment responsive depression groups showed significant grey matter abnormalities in the right middle temporal cortex and bilateral caudate. In the right middle temporal cortex and bilateral caudate, patterns of restingstate functional connectivity were different between the TRD, treatment responsive depression and healthy controls (Ma, et al, 2012). Alterations in functional connectivity in different brain regions between TRD and treatment responsive patients were found.…”

Section: Neuroendocrine and Immune Systemsmentioning

confidence: 82%

“…Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) neuroimaging techniques have revealed the default-mode network, a system of brain regions (medial prefrontal cortex, posterior cingulate/ retrosplenial cortex and left and right inferior parietal lobules) that show decreased activation during goal-orientated or attention-demanding tasks (Whitfield-Gabrieli & Ford, 2012). The default-mode network is associated with episodic memory, self-reflection and emotional regulation (Drevets, Price, & Furey, 2008;Ma, et al, 2012).…”

Section: Neuroendocrine and Immune Systemsmentioning

confidence: 99%

“…A recent study has used voxel-based morphometry of structural and fMRI data to compare the concentrations of grey matter in the default-mode network regions between TRD (N = 18), treatment responsive depression (N = 17) and healthy controls (N = 17) (Ma, et al, 2012). Restingstate functional connectivity analysis was also conducted to investigate the grey matter abnormalities between the groups (Ma, et al, 2012).…”

Section: Neuroendocrine and Immune Systemsmentioning

confidence: 99%

“…Restingstate functional connectivity analysis was also conducted to investigate the grey matter abnormalities between the groups (Ma, et al, 2012). Both the TRD and treatment responsive depression groups showed significant grey matter abnormalities in the right middle temporal cortex and bilateral caudate.…”

Section: Neuroendocrine and Immune Systemsmentioning

confidence: 99%

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Chronic and treatment-resistant depression

Murphy¹

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Major Depression does not always remit even with appropriate treatment, and unremitting or difficult-to-treat depression is thought to contribute to the large disease burden caused by depression. Difficult-to-treat depression is an overarching term that can be used to describe depression which is chronic, unremitting or treatment-resistant. The concept of difficult-to-treat depression and the terms used to describe it have not been well validated or universally adopted for use in research and clinical practice. Accordingly, the overarching aim of this thesis was to investigate difficult-to-treat depression, including its conceptualisation and its correlates, with a particular focus on chronic and treatment-resistant depression (TRD). Three methodological approaches were employed to examine this complex phenomenon: 1) a systematic review of the literature; 2) analysis of epidemiological data; and 3) analysis of clinical data. found to have a lifetime prevalence of 4.6% (95% CI: 3.9 -5.3%) and was found to be present in 29.4% (95% CI: 25.6 -33.3%) of community-residing individuals with a lifetime depressive disorder. Higher rates of psychiatric co-morbidity (OR = 1.42; 95% CI = 1.26-1.61), older current age (OR = 1.04; 95% CI = 1.02-1.05), a younger age of onset (OR = .97; 95% CI = .95-.98) and more frequent episodes of depression (OR = 1.75; 95% CI = 1.07-2.86) were significant correlates of chronic depression. Differences in health service utilisation associated with chronic depression were assessed to determine whether chronic depression treated in the tertiary care sector was likely to represent TRD. Survey respondents with chronic depression who were treated in tertiary care settings had more complex presentations and many of the clinical features previously associated with TRD, including higher levels of medical and psychiatric co-morbidity, greater traumatic load, higher levels of disability, greater symptom severity and greater risk of attempting suicide. iv The findings from the NSMHWB suggested that those whose chronic depression is treated in tertiary care settings may be less responsive to treatment, thus indicating likely TRD. In order to assess the degree of TRD in patients seen in tertiary care settings a sample of depressed inpatients (N = 70) was recruited. The majority of these depressed inpatients had a chronic illness trajectory (N = 64; 91.4%) and had a moderate to high level of TRD as determined by the five existing staging models of TRD. Each of the five staging models of TRD was highly correlated with the other four models, suggesting a substantial degree of agreement between models on their ratings of TRD. An omnibus measure of TRD (M = 0; SD = 4.5) was created by combining the five TRD models into one composite index. Using this composite index as the outcome variable, the following covariates were found to be associated with higher levels of TRD: higher prevalence of suicide attempts (β = 1.71, t(11) = 3.62, p < .001), older current age (β = 14, t(11) = 2.92, p < .005), earlier a...

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