Effect of rs1063843 in theCAMKK2gene on the dorsolateral prefrontal cortex

Abstract

Recently, a single nucleotide polymorphism (SNP) in the CAMKK2 gene (rs1063843) was found to be associated with lower expression of the gene in the dorsolateral prefrontal cortex (DLPFC) and with schizophrenia (SCZ) and deficits in working memory and executive function. However, the brain mechanism underlying this association is poorly understood. A functional magnetic resonance imaging (fMRI) study (N = 84 healthy volunteers) involving multiple cognitive tasks, including a Stroop task (to measure attentional executive control), an N-back task (to measure working memory), and a delay discounting task (to measure decision making) to identify the brain regions affected by rs1063843 was performed. Across all three tasks, it was found that carriers of the risk allele consistently exhibited increased activation of the left DLPFC. In addition, the risk allele carriers also exhibited increased activation of the right DLPFC and the left cerebellum during the Stroop task and of the left caudate nucleus during the N-back task. These findings helped to elucidate the role of CAMKK2 in cognitive functions and in the etiology of SCZ. Hum Brain Mapp 37:2398-2406, 2016. © 2016 Wiley Periodicals, Inc.

Impact of Genetic Variation on Human CaMKK2 Regulation by Ca2+-Calmodulin and Multisite Phosphorylation

“…Consistent with these findings, we reported previously that CaMKK2-null mice display behavioral disturbances similar to those observed in humans with schizophrenia 4 . Strikingly, the decrease in CaMKK2 autonomous activity in the G87R and R139W mutants (>50% decrease) is similar in magnitude to the reduction in CaMKK2 observed in schizophrenic and bipolar patients 11 35 . Since the G87R and R139W mutants exert a dominant-negative effect on CaMKK2 signaling, these mutations could be considered as potential risk markers for these behavioural disorders.…”

From Anti-SARS-CoV-2 Immune Responses to COVID-19 via Molecular Mimicry

“…Neurological disorders: Neuronal PAS domain-containing protein 2 (ASSRSS), which is highly polymorphic in autism spectrum disorder patients [ 60 , 61 ]; Circadian locomotor output cycles protein kaput (ASSRSS) relates to bipolar disorder [ 62 ]; Adenosine receptor A1 (VLPPLL), where sleep is significantly attenuated by the loss of adenosine A1 receptor expression [ 63 ]; BDNF/NT-3 growth factors receptor (SANLAA), alterations may cause temporal lobe epilepsy, memory impairment, anorexia nervosa, bulimia, Alzheimer’s disease [ 64 , 65 , 66 ]; Calcium/calmodulin-dependent protein kinase kinase 2 (PSLATV) is linked to disturbances of higher cognitive functions, such as working memory and executive function. as well as schizophrenia [ 67 ]; Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase (LAFLLF) can cause mental retardation [ 68 ]; Glutaminase kidney isoform, mitochondrial (LQELGK) can associate with epileptic encephalopathy, infantile cataract, skin abnormalities leukocytoclasia at the surface of the dermis, focal vacuolar alterations, hyperkeratosis, parakeratosis, glutamate excess, and impaired intellectual development, global developmental delay, progressive ataxia, and elevated glutamine [ 69 , 70 , 71 ]; Mitochondrial glutamate carrier 1 (RLQSLQ) relates to neonatal myoclonic epilepsy [ 72 ]. …”

“…Calcium/calmodulin-dependent protein kinase kinase 2 (PSLATV) is linked to disturbances of higher cognitive functions, such as working memory and executive function. as well as schizophrenia [ 67 ];…”

Polymorphism in schizophrenia risk gene MIR137 is associated with the posterior cingulate Cortex's activation and functional and structural connectivity in healthy controls

“…The N-back task had been described in our previous studies ( Yu et al, 2016 ; Zhang et al, 2015 ; Zhang et al, 2016 ). Briefly, the stimulus was a white circle presented randomly at one of the four corners of a grey diamond-shaped square.…”