Rs6265, also called Val66Met or G196A, is a gene variation, a

single nucleotide polymorphism In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently larg ...

(SNP) in the BDNF

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

that codes for brain-derived neurotrophic factor. Well over a hundred research studies have examined the polymorphism.

Association with neuropsychiatric disorders

A number of studies have examined the role of this polymorphism in risk of

neuropsychiatric disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...

s , including

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

and depression. It is generally thought that some variants of the polymorphism lead to memory impairment and susceptibility to neuropsychiatric disorders, and a 2007

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

of case-control studies found a relationship between the SNP and

substance-related disorder Substance-related disorders, also known as substance use disorders, can lead to large societal problems. It is found to be greatest in individuals ages 18–25, with a higher likelihood occurring in men compared to women, and urban residents comp ...

eating disorder An eating disorder is a mental disorder defined by abnormal eating behaviors that negatively affect a person's physical or mental health. Only one eating disorder can be diagnosed at a given time. Types of eating disorders include binge eating d ...

s, and

. Another 2007

could, however, find no association between the SNP and

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

. Meta-analyses of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

and

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

also indicate that the SNP has little or no association with these diseases. Also inconsistencies in association studies with depression have been noted. The reason for these inconsistent results have been suggested to stem from several sources, with one recent review arguing that statistical artefact, sampling bias, population stratification and uncontrolled gene-environment interactions are likely to underscore this effect . These same authors recently published a report which found that transgenic mice engineered to express human BDNF as well as carry the Val66Met permutation are selectively sensitive to the glucocorticoid stress hormone corticosterone (rodent equivalent of cortisol), which in turn primes the fear circuitry and hippocampus-dependent memory function of Met/Met homozygous mice . As hippocampal function is a core component of several psychiatric conditions, and stress is a non-specific but substantial risk factor for affective, anxiety, eating and psychotic disorders, Notaras et al. argue that "''there is a long-term effect of glucocorticoids in 66Met carriers that potentiates the fear circuitry into adulthood, which may increase susceptibility to trauma, events with negative emotional valence and related psychopathology''". This interpretation is consistent with a suggested role of BDNF and the Val66Met polymorphism in post-traumatic stress disorder, where it has been shown that 66Met variant perturbs extinction learning in both man and mouse. The Val66Met polymorphism alters vulnerability to stress in mice and humans, which likely contributes to PTSD risk. In treatment response studies val/val homozygotes may respond better than met allele carriers with drug resistant depression treated with

repetitive transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse gener ...

Subject variables in healthy humans

One study has reported that met/met carriers tends to have lower

body mass index Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...

compared to the two other genotypes. Another study showed that subjects with the val/val genotype had higher mean

intelligence Intelligence has been defined in many ways: the capacity for abstraction, logic, understanding, self-awareness, learning, emotional knowledge, reasoning, planning, creativity, critical thinking, and problem-solving. More generally, it can b ...

. The same study found no association with personality traits as measured with the

Tridimensional Personality Questionnaire Tridimensional Personality Questionnaire (TPQ) is a personality test. It was devised by C. Robert Cloninger. A newer version of the questionnaire is called Temperament and Character Inventory. As the name indicates TPQ seeks to measure three dimen ...

. Also a Polish 2007 study observed no significant relationship between the polymorphism and personality in healthy females. A German 2005 study could though find an association with personality traits measured with NEO-Five Factor Inventory, with Val/Val subjects scoring higher on

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

and

neuroticism In the study of psychology, neuroticism has been considered a fundamental personality trait. For example, in the Big Five approach to personality trait theory, individuals with high scores for neuroticism are more likely than average to be moody ...

dimensions. Large studies and a meta-analysis inclusive of over 15,000 subjects, however, found no association between the Val66Met and Neuroticism.

Other studies

A study in

transgenic mice A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse (''Mus musculus'') that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or ...

has found that met/met mice exhibits increased anxiety-related behaviors.

References

{{Reflist SNPs on chromosome 11 Biology of bipolar disorder