Related Experiment Video
Updated: Jul 13, 2026

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice
Published on: February 26, 2012
Genetic variation in catechol-O-methyltransferase: effects on working memory in schizophrenic patients, their
Catherine M Diaz-Asper1, Terry E Goldberg, Bhaskar S Kolachana
1Clinical Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
Background:
Catechol-O-methyltransferase (COMT) val(108/158)met (rs4680) is thought to affect dopamine regulated prefrontal cortical activity during working memory (WM) tasks, and to weakly increase risk for developing schizophrenia. Recently, other single nucleotide polymorphisms (SNPs) across the gene have emerged as additional risk factors for schizophrenia: namely rs737865, rs165599, and rs2097603. In a large sample, we examined whether these SNPs affect WM.
Methods:
Schizophrenic probands (n = 325), their nonpsychotic siblings (n = 359), and normal control subjects (n = 330) completed tests of WM function. Data were analyzed with a series of mixed model analyses of variance (ANOVAs).
Results:
Val homozygotes performed most poorly on all conditions of the n-back, irrespective of diagnosis. Additionally, there was a trend towards a disease-only val(108/158)met effect on a test of attentional set-shifting; val homozygote probands performed most poorly. Significant or near-significant effects of rs737865 were found on all conditions of the n-back, with G homozygotes performing worst. There also was a disease-only COMT rs737865 effect on the 0-back. None of the other SNPs showed main effects by themselves. A haplotype constructed from promoter and val(108/158)met SNPs showed main effects on WM parameters, consistent with inverted U models of dopamine signaling.
Conclusions:
We extended earlier findings of a val(108/158)met effect on WM function, and suggest that combinations of alleles within COMT may modulate the val(108/158)met effect in a nonlinear manner.
More Related Videos
05:14Standardized Data Acquisition for Neuromelanin-Sensitive Magnetic Resonance Imaging of the Substantia Nigra
Published on: September 8, 2021
14:24An Appetitive Spatial Working Memory Task for Mice in a Semi-Automated 8-Arm Radial Maze, Reducing Fearful Memory Association in the Maze
Published on: July 29, 2025
Related Concept Videos
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Biological Causes of Schizophrenia
Genetic Factors in Schizophrenia
The genetic basis of schizophrenia is strongly supported by family and twin studies.
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings.
Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within the...