The Depression/Schizophrenia Continuum: Does Cytoskeletal Tensegrity Play a Role?

Gardiner, John

doi:10.14704/nq.2017.15.4.1121

Cited by 2 publications

(2 citation statements)

References 70 publications

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“…NMDA receptor signalling influences the reorganisation of cytoskeleton (Forsyth and Lewis, 2017). Microtubule dysfunction has been previously reported in SZ and other psychiatric disorders (Gardiner, 2017;Marchisella et al, 2016). An over representation of de novo mutation encompassing genes from activity-regulated cytoskeleton-associated protein complex in SZ has been previously reported .…”

Section: Discussionmentioning

confidence: 97%

Oligogenic rare variant contributions in schizophrenia and their convergence with genes harbouringde novomutations in schizophrenia, autism and intellectual disability: Evidence from multiplex families

John

Kukshal

Bhatia

et al. 2019

Preprint

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Clinical and genetic heterogeneity has been documented extensively in schizophrenia, a common behavioural disorder with heritability estimates of about 80%. Common and rare de novo variant based studies have provided notable evidence for the likely involvement of a range of pathways including glutamatergic, synaptic signalling and neurodevelopment. To complement these studies, we sequenced exomes of 11 multimember affected schizophrenia families from India. Variant prioritisation performed based on their rarity (MAF <0.01), shared presence among the affected individuals in the respective families and predicted deleterious nature, yielded a total of 785 inherited rare protein sequence altering variants in 743 genes among the 11 families. These showed an enrichment of genes involved in the extracellular matrix and cytoskeleton components, synaptic and neuron related ontologies and neurodevelopmental pathways, consistent with major etiological hypotheses. We also noted an overrepresentation of genes from previously reported gene sets with de novo protein sequence altering variants in schizophrenia, autism, intellectual disability; FMRP target and loss of function intolerant genes. Furthermore, a minimum of five genes known to manifest behavioural/neurological and nervous system abnormalities in rodent models had deleterious variants in them shared among all affected individuals in each of the families. Majority of such variants segregated within and not across families providing strong suggestive evidence for the genetically heterogeneous nature of disease.More importantly, study findings unequivocally support the classical paradigm of cumulative contribution of multiple genes, notably with an apparent threshold effect for disease manifestation and offer a likely explanation for the unclear mode of inheritance in familial schizophrenia.Polyphen2_HDIV, Polyphen2_HVAR, LRT, MutationTaster, MutationAssessor, FATHMM, PROVEAN, MetaSVM, M-CAP and fathmm-MKL_coding and CADD scaled score =>15; or CADD scaled score>=10 and <15 but predicted to be damaging by at least two different software listed above) for further analysis. All these tools were part of Kggseq (Li et al., 2012). All these variants are henceforth referred to as "deleterious shared variants".

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Section: Discussionmentioning

confidence: 97%

Oligogenic rare variant contributions in schizophrenia and their convergence with genes harbouringde novomutations in schizophrenia, autism and intellectual disability: Evidence from multiplex families

John

Kukshal

Bhatia

et al. 2019

Preprint

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“…In a previous paper [42], I suggested that depression, bipolar syndrome, and schizophrenia (and other conditions besides) may be malfunctions of the nervous system cytoskeletal tensegrity framework, particularly in the brain. Indeed, a tensegral understanding is beginning to be developed for treatments in allied health including osteopathy [43] and in oncological diagnosis [44].…”

Section: Microgravity May Promote Mental Illnessmentioning

confidence: 99%

Cytoskeletal Tensegrity in Microgravity

Gardiner¹

2021

Life

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In order for Man to venture further into Space he will have to adapt to its conditions, including microgravity. Life as we know it has evolved on Earth with a substantial gravitational field. If they spend considerable time away from Earth, astronauts experience physiological, mental, and anatomical changes. It is not clear if these are pathological or adaptations. However, it is true that they experience difficulties on their return to stronger gravity. The cytoskeleton is a key site for the detection of gravitational force within the body, due to its tensegrity architecture. In order to understand what happens to living beings in space, we will need to unravel the role cytoskeletal tensegrity architecture plays in the building and function of cells, organs, the body, and mind.

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The Depression/Schizophrenia Continuum: Does Cytoskeletal Tensegrity Play a Role?

Cited by 2 publications

References 70 publications

Oligogenic rare variant contributions in schizophrenia and their convergence with genes harbouringde novomutations in schizophrenia, autism and intellectual disability: Evidence from multiplex families

Oligogenic rare variant contributions in schizophrenia and their convergence with genes harbouringde novomutations in schizophrenia, autism and intellectual disability: Evidence from multiplex families

Cytoskeletal Tensegrity in Microgravity

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