Psychopathology and personality traits in patients with treated Wilson disease grouped according to gene mutations

Abstract

Wilson disease (WD) is a recessively inherited copper storage disorder mainly affecting liver and brain. Genotype/phenotype correlations have been report ed but as yet not regarding psychic symptoms. Our aim was to investigate if a correlation might exist between genotype and phenotype concerning psy cho pathology and/or personality traits in patients with treated WD. Nine homozygous and three compound heterozygous Swedish patients were retrospectively investigated, representing four different mutation set tings. Psychopathological symptoms were studied using the Comprehensive Psychopathological Rating Scale (CPRS), personality traits using the Karo lin ska Scales of Personality (KSP) and mutations were analyzed by manifold sequencing. Psychopathological symptoms: Patients with the Trp779Stop mutation had the lowest scores on the total CPRS, due to less pronounced reported CPRS items, as compared to the other three groups of patients. Compound heterozygotes for the His1069Gln/ Arg1319Stop mutation show ed the highest total CPRS scores. Personality traits: Patients homozygous for the Trp779Stop and the Thr977Met mutations had high scores on Psycho pathy related scales whereas patients with His1069Gln/Arg1319Stop mutations had the lowest scores on these scales. Serum ceruloplasmin levels were undetectable in all patients with the Trp779Stop and Thr977Met mutations. The results show a trend towards a genotype/phenotype correlation regarding psychopathological symptoms and personality traits in treated patients with WD. If replicable, these results might contribute to the elucidation of the possible clinical importance of functionally deleterious gene mutations in WD psychopathology and personality traits.

Quality of life in patients with treated and clinically stable Wilson's disease

“…The study comprised 60 consecutive patients with WD recruited from the WD Clinical Research Program at the University of Belgrade who were clinically stable (no significant clinical change in the preceding 6 months) and had been on standardized therapy for WD for at least 2 years (ie, at the time of investigation, all patients were in a copper‐depleted state, as previously defined). 12 The diagnosis of WD was established by the following criteria: (1) history, (2) physical examination, (3) serum ceruloplasmin and copper levels, (4) 24‐hour urinary copper excretion, (5) liver biopsy, and (6) slit‐lamp ophthalmologic examination. 4 In 47 patients the diagnosis was confirmed by DNA analysis.…”

The Role of Copper Overload in Modulating Neuropsychiatric Symptoms

“…Finally, there is wide heterogeneity in the prevalence of psychiatric disorders in patients having WD, ranging from 4 to 47% for major depressive disorder and 1.4 to 11.3% for psychosis [ 88 ]. Interestingly, it has also been shown that some mutations in the ATP7B gene could be associated with specific psychopathological symptoms and personality traits [ 107 ]. For instance, patients who are homozygous for the Trp779Stop and the Thr977Met mutations had high scores on Psychopathy-related scales, whereas patients having His1069Gln/Arg1319Stop mutations had the lowest scores on these scales [ 107 ].…”

“…Interestingly, it has also been shown that some mutations in the ATP7B gene could be associated with specific psychopathological symptoms and personality traits [ 107 ]. For instance, patients who are homozygous for the Trp779Stop and the Thr977Met mutations had high scores on Psychopathy-related scales, whereas patients having His1069Gln/Arg1319Stop mutations had the lowest scores on these scales [ 107 ]. However, the evidence for the association of specific ATP7B gene variations with a specific pattern of psychopathology is, at best, preliminary.…”