Effects of brain-derived neurotrophic factor–catecholamine-O-methyltransferase gene interaction on schizophrenic symptoms

Abstract

The methionine variant of Val66Met brain-derived neurotrophic factor BDNF met and catecholamine-O-methyltransferase (COMT L) is associated with a deficit in attention and aggravation of delusions in schizophrenia. We hypothesized that the BDNF-COMT gene interaction would affect the symptoms and cognition in schizophrenia. Ninety-six schizophrenic patients and 79 control participants were recruited. The patients who were BDNF met/met x COMT L carriers had the highest scores of delusion of Positive Symptoms and the Scale for Assessment of Negative Symptoms, word reading of the color word test, and trail-making test B time, compared with the other three genotype interactions. The current results suggest that patients with the BDNF met/met x COMT L allele had more delusional symptoms and poorer cognitive flexibility, compared with the other three genotype interactions.

BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity

“…Our study provides support for reports that the BDNF 66Met allele may play a role in the pathophysiology of schizophrenia, specifically stress-sensitive clinical aspects such as positive-related symptomology 12,13 neurocognitive function 58,59 and age of onset, [60][61][62][63] and that some of this involvement is likely to occur as a result of differential susceptibility to glucocorticoid signaling during critical periods such as adolescence/young adulthood. Clinical studies assessing a genomic role of BDNF in schizophrenia should therefore consider stratifying their analyses for all 3 Val66Met genotypes, as well as for an effect of adversity, early life stress, trauma or related measures of stress exposure, which may play a role in phenotype determination.…”

“…10,11 Clinical studies have found that the BDNF Met/Met genotype is more frequent in patients reporting more positive than negative symptoms, 12 while another study reported that schizophrenia patients of BDNF Met/Met genotype had significantly more delusional symptoms than patients carrying the BDNF 66Val allele. 13 However, the role of the BDNF Val66Met polymorphism within this disorder remains controversial. 14 Sensorimotor gating refers to the latent ability to inhibit a motor response given a preceding sensory stimulus.…”

Genetic Influence of COMT and BDNF Gene Polymorphisms on Resilience in Healthy College Students

“…This finding suggests a potential modulation effect of the BDNF carrier status on other gene polymorphisms such as the COMT Val158Met polymorphism, although no main effect of the BDNF gene on resilience was shown in the present study. Similarly, according to a recent Korean study, schizophrenic subjects with BDNF Met/Met and COMT Met allele showed lower cognitive flexibility than those with the other genotype interactions [42]. There is additional evidence of interactions between BDNF and dopamine-related genes [43,44,45].…”

Interaction ofCOMTrs4680 andBDNFrs6265 polymorphisms on functional connectivity density of the left frontal eye field in healthy young adults

“…Both COMT rs4680 and BDNF rs6265 polymorphisms act on the dopamine system [Tunbridge et al, ; Pecina et al, ], modulate stress reaction and cognitive functions [Papaleo et al, ; Ren‐Patterson et al, ; Ursini et al, ], and involve in several psychiatric disorders [Nolan et al, ; Ho et al, ; Twamley et al, ]; these findings indicate a possible COMT × BDNF interaction on their external phenotypes. Indeed, significant COMT × BDNF interactions have been reported on boredom susceptibility of sensation seeking traits [Kang et al, ], implicit grammar learning [Witte et al, ], resilience [Kang et al, ], and cognitive performance [Das et al, ] in healthy subjects, and on symptoms and cognition in schizophrenia [Han et al, ], dysfunctional beliefs in obsessive‐compulsive disorder [Alonso et al, ], and anxiety sensitivity in panic disorder [Konishi et al, ]. To investigate the neural mechanisms underlying the COMT × BDNF interaction on these external phenotypes, a COMT × BDNF interaction has been found in paired associative stimulation‐induced plasticity in the motor cortex [Witte et al, ] and resting‐state functional connectivity (rsFC) between the ventral striatum and the anterior cingulate cortex [Wang et al, ].…”