Enuresis as a premorbid developmental marker of schizophrenia

Abstract

SUMMARY There is comparatively little information about premorbid maturational brain abnormalities in schizophrenia. We investigated whether a history of childhood enuresis, a well-established marker of neurodevelopmental delay, is associated with schizophrenia and with measures of brain abnormalities also associated with schizophrenia. A DSM-IV based history of enuresis, volumetric brain MRI scans, and neuropsychological testing were obtained in patients with schizophrenia, their non-psychotic siblings, and non-psychiatric controls. The subjects were 211 patients (79.6% male), 234 of their siblings (43.2% male), and 355 controls (39.2% male). Frequency of enuresis was compared across groups and correlated with cognitive measures. Total and regional brain volumes were determined using VBM on matched subsets of probands (n=82) with or without enuresis (n=16, n=66, respectively) and controls (n=102) with or without enuresis (n=11, n=91, respectively). Patients with schizophrenia had higher rates of childhood enuresis (21%) compared with siblings (11%; χ2=6.42, p=0.01) or controls (7%; χ2=23.65, p<0.0001) and relative risk for enuresis was increased in siblings (λS=2.62). Patients with enuresis performed worse on two frontal lobe cognitive tests [Letter Fluency (t=1.97, p=0.05, df=200) and Category Fluency (t=2.15, p=0.03, df=200)] as compared with non-enuretic patients. VBM analysis revealed gray matter volume reductions in several frontal regions (right BA 9, right BA 10, and bilateral BA 45), and right superior parietal cortex (BA 7) in patients with a history of enuresis as compared with non-enuretic patients (all t>3.57, all p<0.001). The high frequency of childhood enuresis associated with schizophrenia, and abnormalities in prefrontal function and structure in patients with a childhood history of enuresis suggest that childhood enuresis may be a premorbid marker for neurodevelopmental abnormalities related to schizophrenia. These findings add to the evidence implicating prefrontal dysmaturation in this disorder, potentially related to genetic risk factors.

The Central Nervous System and its Role in Bowel and Bladder Control

“…Hyde et al [16] found that adult patients with schizophrenia (SCZ) have an increased rate of childhood enuresis (21%) compared with their healthy siblings (11%) or with normal control patients (7%). This is the first, and thus far largest, study of childhood enuresis in adult patients with SCZ to date, and is the only study of adults with a history of enuresis examined with both neuropsychological testing and structural brain imaging.…”

“…Hyde et al [16] found that enuresis potentially is heritable: the familial risk of enuresis was 2.6 times greater in siblings of enuretic probands than in siblings of nonenuretic probands. Moreover, they found that at least healthy female siblings of patients with SCZ have a significantly increased frequency of enuresis, suggesting that enuresis may be related to genetic risk factors for SCZ.…”

Mental disorders in children and adolescents with lower urinary tract dysfunction

“…Areas of the brain such as the insula, the anterior cingulate cortex, and the prefrontal cortex are responsible for bladder control and monitoring 9 and have been implicated in ADHD and LUTD. 8 Hyde et al 10 considered enuresis during childhood a premorbid developmental marker of schizophrenia. In a group of patients with schizophrenia, 21% had enuresis during childhood versus 11% of their siblings and 7% of healthy controls.…”

Nocturnal Enuresis in Children and Adolescent with Sickle cell Anemia

“…These abnormalities were located in the thalamus, frontal lobe, anterior cingulate cortex and insula [101]. Adults patients with schizophrenia who had NE in their childhood were found to have significant reduction in the brain gray matter involving the frontal and parietal lobes [102]. Further evidences were derived from neurophysiological studies [103][104][105].…”