Association between DβH 5'-insertion/deletion polymorphism and cognition in patients with chronic schizophrenia

Cognitive deficits have been identified as a core feature of patients with schizophrenia. Many genes associated with the dopamine and norepinephrine systems are related to the cognitive deficits of patients with schizophrenia. Dopamine β-hydroxylase (DβH) is a key enzyme that converts dopamine to norepinephrine and for which activity and levels are under strong genetic control.

To examine whether the DβH 5'-insertion/deletion (Ins/Del) polymorphism influences cognitive function in patients with chronic schizophrenia.

The presence of the DβH 5'-Ins/Del polymorphism was determined in 733 patients with chronic schizophrenia (diagnosed according to DSM-IV) and 544 healthy controls using a case-control design. We assessed all of the patients' psychopathology using the Positive and Negative Syndrome Scale (PANSS) and cognition in 540 patients with chronic schizophrenia and 297 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). This study was conducted between 2008 and 2011.

The allelic and genotypic frequencies of the DβH 5'-Ins/Del polymorphism were not significantly different between patients with schizophrenia and healthy controls (both P values > .05). However, the cognitive test scores were significantly lower in patients than in the healthy controls for all scales (all P values < .05), except visuospatial/constructional (P > .05). The attention score significantly differed according to the genotypic group (P < .05) in patients but not in the healthy controls (P > .05). In patients with chronic schizophrenia, the mean ± SD attention score was lower in the DβH 5'-Del/Del genotype (65.7 ± 16.8) than in the DβH 5'-Ins/Del genotype (71.4 ± 18.0; P = .007) and the DβH 5'-Ins/Ins genotype (70.8 ± 17.1; P = .02).

This study found that patients with chronic schizophrenia had poorer cognitive function than the healthy controls in all examined cognitive domains except for visuospatial/constructional. No significant association was found between the DβH 5'-Ins/Del polymorphism and patients with chronic schizophrenia. However, the DβH 5'-Del/Del genotype may be specific to attentional decrements in patients with chronic schizophrenia.