A polymorphism in the dopamine beta-hydroxylase gene is associated with "paranoid ideation" in patients with major depression.

BACKGROUND: Increased dopaminergic activity may play a primary role in psychotic depression. Dopamine beta-hydroxylase (DbetaH) catalyses the key step in biosynthesis of the neurotransmitter noradrenaline from dopamine, and low DbetaH activity is a possible risk factor for developing psychotic depression. An exon 2 polymorphism (DBH*444 g/a) of the DbetaH gene (DBH) is significantly associated with both serum and cerebrospinal fluid levels of DbetaH. METHODS: We determined the genotype of the DBH*444g/a polymorphism in a cohort of 164 patients with major depression and examined the association of this polymorphism with paranoid ideation, interpersonal sensitivity, and psychoticism on the Hopkins Symptom Checklist. RESULTS: Patients who possessed the A allele were significantly more likely to have higher scores for interpersonal sensitivity and paranoia than patients without the A allele (p =.004 and p =.048, respectively), suggesting that this allele may predispose patients to paranoia in major depression. In addition, we found an association between prolactin levels in men and DBH*444 g/a genotype such that homozygous G individuals displayed significantly higher levels than homozygous A or heterozygote individuals. CONCLUSIONS: Depressed patients with the GG genotype of DbetaH have lower scores for interpersonal sensitivity and paranoid ideation. The GG genotype may be protective against the development of psychosis in the presence of a major depressive episode.

A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia.

Low levels of dopamine beta-hydroxylase (DbetaH) protein in the plasma or cerebrospinal fluid (CSF) are associated with greater vulnerability to positive psychotic symptoms in several psychiatric disorders. DbetaH level is a stable, genetically controlled trait. DBH, the locus encoding DbetaH protein, is the major quantitative trait locus controlling plasma and CSF DbetaH levels. We therefore hypothesized that DBH variants or haplotypes, associated with low levels of DbetaH in the plasma, would also associate with greater vulnerability to cocaine-induced paranoia. To test this hypothesis, we first showed that a di-allelic variant, DBH*5'-ins/del, located approximately 3 kb 5' to the DBH transcriptional start site, significantly associates with plasma DbetaH activity in European-Americans (n = 66). Linkage disequilibrium analysis of that polymorphism and DBH*444g/a, another di-allelic variant associated with DbetaH levels, demonstrated that alleles of similar association to DbetaH levels are in positive disequilibrium. We then estimated DBH haplotype frequencies in cocaine-dependent European Americans rated for cocaine-induced paranoia (n = 45). As predicted, the low-DbetaH-associated haplotype, Del-a, was significantly more frequent (P = 0.0003) in subjects endorsing cocaine-induced paranoia (n = 29) than in those denying it (n = 16). Comparison to control haplotype frequencies (n = 145 healthy European-Americans) showed that the association predominantly reflected under-representation of Del-a haplotypes in those denying cocaine-induced paranoia. We conclude that: (a) the two DBH polymorphisms we studied are associated with plasma DBH levels; (b) those two polymorphisms are in significant linkage disequilibrium in European Americans, with alleles of similar association to DbetaH levels in positive disequilibrium; and (c) the haplotype associated with low DBH activity is also associated with cocaine-induced paranoia. Molecular Psychiatry (2000) 5, 56-63.

Arylsulfatase A levels in patients with chronic alcoholism.

BACKGROUND: The goal of this study was to find the association between low arylsulfatase A (ASA) activity and psychiatric disorders in chronic alcoholic patients. METHODS: The study was carried out in 30 chronic alcoholic patients (27 male, 3 female); age range was 25-65 years. There were 20 normal controls (18 males, 2 females), and age range was 24-67 years. ASA and routine aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity laboratory tests were measured in blood serum from all patients and control subjects. RESULTS: Alcoholic patients with psychiatric disorders have ASA average values of 68.25 nmol/mL/4 h. This is less than averages found in the alcoholics without psychiatric disorders group (82.48 nmol/mL/4 h) and the control group (90.8 nmol/mL/4 h). There were no statistically significant differences among the three groups studied. Alcoholic subjects with elevated activity of AST and ALT (n = 10) have ASA activity average values of 134.82 nmol/mL/4 h), which is 48.8% higher than the control group (90.6 nmol/mL/4 h). These means show statistically significant differences (p <0.05). CONCLUSIONS: Results indicate an association between low serum ASA activity and alcoholism. The appearance of psychiatric manifestations could be related to the low activity of this enzyme in chronic alcoholic patients. Alcoholic patients with elevated enzyme activity of AST and ALT in sera also have elevated sera arylsulfatase A (ASA) activity. We consider that these findings may be useful for evaluating the psychiatric state as a prognosis in chronic alcoholic patients, and should be a routine laboratory test in alcoholic patients.

Paranoia and platelet MAO in normals and nonschizophrenic psychiatric groups.

The authors compared the correlation between platelet monoamine oxidase (MAO) activity and the Paranoia (Pa) scale of the Minnesota Multiphasic Personality Inventory in several groups. The data suggest that there is a positive association between high MAO activity and high scores on the Pa scale but only in samples with psychopathology.

Hypocalcaemic myopathy with paranoid psychosis.

A description is given of a patient with idiopathic hypoparathyroidism and a paranoid psychosis. Changes in muscle, electromyograms, and blood enzyme levels were related to hypocalcaemia. Reference is made to the elevations of these enzyme levels found in other cases of psychosis.

Indolethylamine-N-methyltransferase activity in psychiatric patients and controls.

The level of INMT activity was determined in the sera of 29 psychiatric patients and 11 healthy controls from St. Louis; and in 13 psychiatric patients and 15 healthy controls from Chicago. The level of enzyme activity in the serum of paranoid schizophrenics in the St. Louis group was significantly higher than in other types of schizophrenics. The mean level of enzyme activity in the serum in nonschizophrenic psychiatric patients in the Chicago group was significantly higher than that in the same group of patients from St. Louis. The serum level of INMT activity in all psychiatric patients and schizophrenic patients from St. Louis was positively correlated with severity of delusions. The only significant difference in the Chicago patients was that the occurrence of depressive features was greater in the group of patients with a low serum INMT level than in the group with a high enzyme level.