We did not find any significant associations between APOE ge
We did not find any significant associations between APOE genotype and BDI-II, BAI, or PAI clinical scale scores. Our results indicate that APOE is not likely to play a major role in psychiatric comorbidities in epilepsy. This is in line with studies in the general population, which have not found a consistent association between the APOE ε4 allele and psychiatric disorders such as depression, bipolar disorder, and schizophrenia .
Introduction The human rilpivirine mg undergoes many alterations as a result of the normal aging process, with notable tissue reduction observed (Kennedy and Raz, 2015). This brain shrinkage is regionally specific, with relative age-related preservation of primary cortices, and pronounced reductions to volume and thickness in heteromodal association cortices (Fjell et al., 2009, Rast et al., 2018, Raz et al., 2010, Salat et al., 2004). This reduction in thickness and volume is highly variable across persons, and this variability likely is driven by individual differences in health, lifestyle/environmental, and genetic factors. Indeed, brain morphometry is highly heritable (Kochunov et al., 2015) and partly under genetic control (Thompson et al., 2001). In complement to heritability estimates, single nucleotide polymorphisms have been identified that exert influence on brain and cognitive aging, and the identification of these candidate genes has allowed for investigation of brain properties not readily available for in vivo study in human cognitive aging. Perhaps the best studied of these is a common polymorphism (COMT ValMet, rs4680) in COMT, a gene that codes for the enzyme catechol-O-methyltransferase (Axelrod and Tomchick, 1958) that breaks down and eliminates dopamine (DA) in the synapse (predominately in D1 receptors: Hirvonen et al., 2010, Slifstein et al., 2008). Widely expressed in the neocortex, COMT regulates dopamine levels in prefrontal D1 receptors through degradation of extracellular dopamine. Individuals with less active enzymatic properties have 3-4 times greater levels of DA in the synapse, thus a progressive reduction in enzymatic activity among the genotypes has been identified to occur in a dose-response manner: Val/Val > Val/Met > Met/Met (Bäckman et al., 2006, Lotta et al., 1995, Weinshilboum et al., 1999). This increased enzymatic activity in the Val variant of COMT results in lower synaptic dopamine relative to COMT Met carriers (Chen et al., 2004, Papenberg et al., 2015). Dopamine is a neurotransmitter highly associated with cognitive function, and its D1 receptors are densely concentrated in neocortical areas, primarily in prefrontal and parietal association cortex (Hall et al., 1994, Lidow et al., 1991, Palomera-Gallahger, Amunts, & Zilles, 2015). Synthesized in the midbrain, dopamine densely innervates the striatum and is distributed throughout the brain via multiple pathways: projections from the substantia nigra to the striatum (the nigrostriatal pathway), and projections from the ventral tegmental area to limbic regions (mesolimbic pathway) and to the neocortex (mesocortical pathway) (Lewis and Sesack, 1997, Li et al., 2010, Stoof and Kebabian, 1984). Neocortical regions receiving these dopaminergic projections are of interest not only because of their high concentrations of D1 receptors (Hall et al., 1994, Lidow et al., 1991) but also because of their vulnerability to age-related reductions in volume and thickness, and their associations with cognition, particularly executive functions (Buchsbaum et al., 2005, Laird et al., 2005, Middleton and Strick, 2000, Yuan and Raz, 2014). Furthermore, the neocortex in particular, unlike the striatum, lacks dopamine transporters and thus depends on COMT locally for regulating dopamine in the synapse (Slifstein et al., 2008, Tunbridge et al., 2004). COMT activity is particularly important in the prefrontal cortex, which is richest in dopaminergic pathways in the brain (Chen et al., 2004, Egan et al., 2001, Lidow et al., 1991, Matsumoto et al., 2003, Slifstein et al., 2008).