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DMN connectivity is strongly heritable, making it a promising endophenotype candidate (23).A challenge in imaging–genetic analyses is correcting for multiple univariate statistical tests, making it difficult to observe weak effects across multiple variables, as presumed in the CDCV model (10).
To overcome this problem and to identify aggregate effects, there has been a recent shift toward using multivariate techniques (12, 24–26) such as parallel-independent component analysis (para-ICA), an approach previously validated in psychiatric disorders including SZ and Alzheimer’s disease, yielding robust results with practical sample sizes (12, 24, 25, 27).
Given the substantial overlap in the clinical, neurophysiologic, genetic, and molecular characteristics of SZ and BP, we first sought to clarify similarities and differences between SZ and PBP using DMN connectivity as a quantitative disease marker.
A recent study using a pathway-enrichment 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).
We next wanted to test whether trait measures found to be abnormal in probands were transmitted to their unaffected relatives and to quantify heritability.
Our third goal was to identify the genes and the underlying molecular/biological mechanisms associated with such SZ and PBP intermediate phenotypes to illuminate the etiology of these disease processes.
A core component within the resting state is the default mode network (DMN), comprising posterior cingulate cortex (PCC), retrosplenial cortex/precuneus, medial prefrontal cortex (MPFC), medial and lateral parietal cortex, inferior/middle temporal gyri, and parts of cerebellum and basal ganglia that is thought to characterize basal neural activity (14).
Connectivity within the DMN is compromised in multiple mental disorders including SZ and PBP (4, 15–21) within this circuit is related to risk of psychosis. (17) reported reduced MPFC resting-state DMN connectivity in both SZ and BP.
A subset of controls and probands ( = 549) then was subjected to a parallel ICA (para-ICA) to identify imaging–genetic relationships. Hypo-connectivity was observed in both patient groups in all DMNs.
Similar patterns observed in SZREL were restricted to only one network.
Although risk for psychotic illnesses is driven in small part by highly penetrant, often private mutations such as copy number variants, substantial risk also is likely conferred by multiple genes of small effect sizes interacting together (7).Tags: Adult Dating, affair dating, sex dating