Different gene sets contribute to different symptom dimensions of depression and anxiety

Goeman, Jelle J.; Monajemi, Ramin; Wardenaar, Klaas J.; Hartman, Catharina A.; Snieder, Harold; Nolte, Ilja M.; Penninx, Brenda W. J. H.; Zitman, Frans G.

doi:10.1002/ajmg.b.32058

Cited by 16 publications

(9 citation statements)

References 89 publications

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“…The pathway analyses of gene ontology groups commonly identify structural plasticity- and cytoskeleton-related signaling pathways as being highly modulated by stress and depression-like behavioral paradigms (Piubelli et al, 2011; Andrus et al, 2012). Furthermore, genetic association studies among individuals with lifetime depression have shown that a pathway consisting of genes that regulate cytoskeletal dynamics significantly associates with anhedonic depression (van Veen et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

Altered expression of neuroplasticity-related genes in the brain of depressed suicides

et al. 2015

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Background Expression of the neuronal membrane glycoprotein M6a (GPM6A), the proteolipid protein (PLP/DM20) family member, is downregulated in the hippocampus of chronically stressed animals. Its neuroplastic function involves a role in neurite formation, filopodium outgrowth and synaptogenesis through an unknown mechanism. Disruptions in neuroplasticity mechanisms have been shown to play a significant part in the etiology of depression. Thus, the current investigation examined whether GPM6A expression is also altered in human depressed brain. Methods Expression levels and coexpression patterns of GPM6A, GPM6B, and PLP1 (two other members of PLP/DM20 family) as well as of the neuroplasticity-related genes identified to associate with GPM6A were determined using quantitative polymerase chain reaction (qPCR) in postmortem samples from the hippocampus (n =18) and the prefrontal cortex (PFC) (n= 25) of depressed suicide victims and compared with control subjects (hippocampus n= 18; PFC n =25). Neuroplasticity-related proteins that form complexes with GPM6A were identified by coimmunoprecipitation technique followed by mass spectrometry. Results Results indicated transcriptional downregulation of GPM6A and GPM6B in the hippocampus of depressed suicides. The expression level of calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) and coronin1A (CORO1A) was also significantly decreased. Subsequent analysis of coexpression patterns demonstrated coordinated gene expression in the hippocampus and in the PFC indicating that the function of these genes might be coregulated in the human brain. However, in the brain of depressed suicides this coordinated response was disrupted. Conclusions Disruption of coordinated gene expression as well as abnormalities in GPM6A and GPM6B expression and expression of the components of GPM6A complexes were detected in the brain of depressed suicides.

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Section: Discussionmentioning

confidence: 99%

Altered expression of neuroplasticity-related genes in the brain of depressed suicides

et al. 2015

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“…The PTSD phenotype is comprised of different types of symptom clusters that may be associated with different psychopathological and biological processes (Asmundson et al, 2004;O'Donnell et al, 2004;Strigo et al, 2010). To reduce the heterogeneity of a complex mental disorder such as PTSD and to increase the chances of identifying distinct contributions by the specific genes, an alternative approach is using more homogeneous symptom clusters as alternative phenotypes in further genetic research (Rietkerk et al, 2008), which demonstrated to be promising (Rietkerk et al, 2008;Labbe et al, 2012;van Veen et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

TPH2 genotype is associated with PTSD’s avoidance symptoms in Chinese female earthquake survivors

Cao

Wang

et al. 2014

Psychiatric Genetics

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Genetic factors are important in the development of post-traumatic stress disorder (PTSD) following exposure to traumatic events. However, the molecular genetic underpinnings of this disorder have not been definitive. This study examined the association between tryptophan hydroxylase 2 (TPH2) rs11178997 genotype, a single-nucleotide polymorphism (SNP) located in the transcriptional control region, and PTSD symptoms. A total of 326 Chinese adults who suffered from the deadly 2008 Wenchuan earthquake and lost their children during the disaster participated in this study. PTSD symptoms were measured with PTSD checklist, and the SNP was successfully genotyped by the MassARRAY system. The results indicated that, although the rs11178997 genotype was not associated with total PTSD symptoms, it could significantly predict severity of PTSD's avoidance symptoms in women. These findings support that TPH2 may play an important functional role in the development of PTSD and contribute to the limited literature regarding the genetic basis and the sex-specific expression of PTSD's symptoms.

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“…For example, patient samples grouped according to general distress, anhedonic depression and anxious arousal (the tripartite model of depression) [Clark and Watson, 1991], show an association with genes encoding cytoskeletal regulators. Thus, MAP4 (a glial enriched MAP), is significantly altered in patients with general distress, while MAPT and MAP2 are altered in the anhedonic dimension of MDD [van Veen et al, 2012]. Also, changes in tubulin PTMs are observed in MDD and schizophrenia samples and are reported to disrupt physiological connections within the brain by imposing abnormal cytoskeletal organization [Wong et al, 2013].…”

Section: Introductionmentioning

confidence: 99%

Microtubule and microtubule associated protein anomalies in psychiatric disease

2016

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Anomalies in neuronal cell architecture, in particular dendritic complexity and synaptic density changes, are widely observed in the brains of subjects with schizophrenia or mood disorders. The concept that a disturbed microtubule cytoskeleton underlies these abnormalities and disrupts synaptic connectivity is supported by evidence from clinical studies and animal models. Prominent changes in tubulin expression levels are commonly found in disease specific regions such as the hippocampus and prefrontal cortex of psychiatric patients. Genetic linkage studies associate tubulinbinding proteins such as the dihydropyrimidinase family with an increased risk to develop schizophrenia and bipolar disorder. For many years, altered immunoreactivity of microtubule associated protein-2 has been a hallmark found in the brains of individuals with schizophrenia. In this review, we present a growing body of evidence that connects a dysfunctional microtubule cytoskeleton with neuropsychiatric illnesses. Findings from animal models are discussed together with clinical data with a particular focus on tubulin posttranslational modifications and on microtubule-binding proteins. V C 2016 Wiley Periodicals, Inc.Key Words: microtubule; depression; schizophrenia; MAP2; JNK Introduction I t is almost 50 years since tubulin was identified as the globular protein that makes up microtubules [Mohri, 1968]. Tubulin polymers, or microtubules, along with actin microfilaments and intermediate filaments, make up the cytoskeletal framework, which provides structure and dynamics to cells [Wells, 2005]. Neuronal cells are exceptional in their usage of microtubules to generate a highly polarized morphology consisting of long axons and dendritic arbors that form the receptive field for electrochemical input. Axonal microtubules are polarized and confer the rigidity that is necessary for long distance transport, whereas dendritic microtubules show mixed polarity and influence processes such as arborization and signaling to dendritic spines .In cells, a and b tubulin exist as heterodimers. They are structurally homologous, comprising two b-strands surrounded by a-helices. Each subunit is divided into three functional domains: the N-terminal domain that incorporates a nucleotide-binding region (i.e., GTP), an intermediate domain comprising the taxol-binding site, and a Cterminal domain which provides the binding surface for motor proteins [Nogales et al., 1998]. a/b heterodimers interact in a head-to-tail conformation giving rise to linear polymers with inherent polarity known as protofilaments [Black and Baas, 1989]. Typically, a microtubule consists of a cylindrical assembly of 13 protofilaments with a diameter of 25 nm, and highly variable length. Microtubules actively modify their structure through dynamic cycles of assembly and disassembly. The plus end where b-tubulin is exposed elongates more rapidly than the a-tubulin exposed, minus end [Horio et al., 2014]. The process of rapid growth and collapse of microtubules is known as dynamic instability a...

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Different gene sets contribute to different symptom dimensions of depression and anxiety

Cited by 16 publications

References 89 publications

Altered expression of neuroplasticity-related genes in the brain of depressed suicides

Altered expression of neuroplasticity-related genes in the brain of depressed suicides

TPH2 genotype is associated with PTSD’s avoidance symptoms in Chinese female earthquake survivors

Microtubule and microtubule associated protein anomalies in psychiatric disease

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