Authors: Ahanaf Shakil.
The amygdala, a major constituent of limbic region, is recognized for playing a pivotal role in emotion, behavior, memory, autonomic integration, and motivation. Genome instability and multifactorial inheritance are plausible agents to cause dysfunctional amygdala. Some examples of genetic amygdaloid disorders: Williams syndrome (WS), Urbach-Wiethe disease, anxiety disorders, major depressive disorder (MDD), intermittent explosive disorder, Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Although prenatal maternal depression and hypochondriasis are correlated with larger amygdala volume, distinctively, schizophrenia, posttraumatic stress disorder, and inhibitory control deficits have low volumetric abnormalities of amygdala. Subtle disruption of amygdala is an ordinary integrant of pediatric neurodevelopmental diseases (e.g., autism spectrum disorder (ASD), pediatric bipolar disorder, etc.). A significant percentage, i.e., 4.5%-9% of progressive amygdala enlargement has been shown in very young children with ASD. Regardless of the individuals with more common genetic amygdaloid disorders, WS has historically been estimated to affect 1 per 7,500-20,000 births. Importantly, recent genome-wide association studies (GWAS) have identified few SNPs within UCN, BDNF, 5-HT, Tacr3, and NPSR1 loci that induced hyperresponsive amygdala. It is noteworthy that increased MAOA-uVNTR expression in prefrontal cortex but not in amygdala of peripubertally stressed animals may lead to aggressive behavior and orbito-frontal reactivity. Interestingly, anxiety candidate genes, including 5-HTTLPR, TMEM132D, and MAD1L1 influence the susceptibility to dependent risk factors for loneliness and incident depression across the lifespan in intact depression-psychological vulnerability spectrum. Mutated genes of shift work sleep disorder (i.e., CLOCK, Rev-erbβ, and BMAL1) confer robust players for MDD morbidity and mortality. NR3C1 and FKBP5 expression were markedly decreased in amygdala of completed suicide male victims without manifestations of diagnosable psychiatric disorders like suicidality, paranoid personality disorder, substance abuse, manic depression, etc. The presented paper is the first, to the best of my knowledge, in its approach to scrutinize the genetics of amygdaloid disorders. Moreover, it is novel in exhibiting that neurological disorders-associated genetic variants can potentially trigger multisystem diseases. Lastly, many rare but important amygdaloid disorders and monogenic mutations implicated in the phylogenetic etiology of several neuropsychiatric diseases are intensively analyzed in this review article.
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