[Ideas and work of professor MUDr: Vladimir Vondrácek DrSc. in relation to the development of contemperary psychiatry].
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Czech Republic↗
Biomedical subjects
P Zvolský
Publications and source records attributed to P Zvolský.
Mapping susceptibility genes for bipolar disorder: a pharmacogenetic approach based on excellent response to lithium.
Genetic mapping studies in bipolar disorder (BD) have been hampered by the unclear boundaries of the phenotypic spectrum, and possibly, by the complexity of the underlying genetic mechanisms, and heterogeneity. Among the suggested approaches to circumvent these problems, a pharmacogenetic strategy has been increasingly proposed. Several studies have indicated that patients with BD who respond well to lithium prophylaxis constitute a biologically distinct subgroup. In this study we have conducted a complete genome scan using 378 markers spaced at an average distance of 10 cM in 31 families ascertained through excellent lithium responders. Response to lithium was evaluated prospectively with an average follow-up of 12 years. Evidence for linkage was found with a locus on chromosome 15q14 (ACTC, lod score = 3.46, locus-specific P-value = 0.000014) and suggestive results were observed for another marker on chromosome 7q11.2 (D7S1816, lod score = 2.68, locus-specific P-value = 0.00011). Other interesting findings were obtained with markers on chromosomes 6 and 22, namely D6S1050 (lod score = 2.0, locus-specific P-value = 0.00004) and D22S420 (lod score = 1.91). Nonparametric linkage analysis provided additional support for the role of these loci. Further analyses of these results suggested that the locus on chromosome 15q14 may be implicated in the etiology of BD, whereas the 7q11.2 locus may be relevant for lithium response. In conclusion, our results provide original evidence suggesting that loci on 15q14 and 7q11.2 may be implicated in the pathogenesis of BD responsive to lithium.
Adult↗
The association study of DRD2, ACE and AGT gene polymorphisms and metamphetamine dependence.
We investigated the association between metamphetamine dependence and TaqI A polymorphism of the dopamine receptor D2 gene (DRD2), I/D polymorphism in angiotensin-converting enzyme (ACE) and M235T polymorphism of the angiotensinogen gene (AGT) in 93 unrelated metamphetamine-dependent subjects and 131 controls. Our results did not prove any association of TaqI A polymorphism of the DRD2 gene, I/D polymorphism of ACE gene, and M235T polymorphism of AGT gene with the metamphetamine dependence in Caucasians of Czech origin. However, a significant difference in allele I frequency between male and female control groups for the I/D ACE polymorphism (p<0.03) was found.
Adult↗
Anticipation in bipolar affective disorder: is age at onset a valid criterion?
Anticipation has been suggested among the genetic mechanisms of bipolar disorder (BD), prompting the search for unstable DNA sequences. Past studies of anticipation in BD have generally relied on observed shift in the age at onset between parental and offspring generations. Such a shift, however, may be caused by a number of other factors difficult to correct for. We investigated age at onset distributions in a sample of 161 related subjects and in a sample of "pseudofamilies" consisting of 320 unrelated subjects selected from a large epidemiological cohort using Monte-Carlo simulation to mimic the family sample. Comparison of age at onset distributions in both samples shows a difference between the generations, but of a similar magnitude in each sample. This suggests that age at onset alone may not be a sufficient criterion of anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:804-807, 2000.
Adult↗
Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study.
Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic peptides involved in the stress response and hypothalamic-pituitary axis regulation. Previous research has implicated these peptides in the pathogenesis of affective disorders. In this study we investigated two polymorphisms located in the genes that code for CRH and PENK by means of association and linkage analyses. A total of 138 bipolar patients and 108 controls were included in the association study. In addition, 24 families were available for linkage analysis, including six families of probands with documented periodic positivity of dexamethasone suppression tests (DST) during remission. We found no association of bipolar disorder with either gene. Similarly, we did not find any evidence of linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the subsample of families of DST positive probands. In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:178-181, 2000.
Adult↗
Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci.
BACKGROUND: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. METHODS: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. RESULTS: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t=2.55, df=205, P=0.011), however, this difference disappeared after correction for multiple testing. LIMITATIONS: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. CONCLUSIONS: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.
Adult↗
Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.
OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.
Alleles↗
Polyglutamine tracts: no evidence of a major role in bipolar disorder.
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Base Sequence↗
Evidence for a role of phospholipase C-gamma1 in the pathogenesis of bipolar disorder.
Several studies have indicated that patients with bipolar disorder (BD) who respond well to lithium prophylaxis constitute a biologically distinct subgroup. Lithium is thought to stabilize mood by acting at the phosphoinositide cycle. We have investigated a polymorphism located in the gene (PLCG1) that codes for a gamma-1 isozyme of phospholipase (PLC), an enzyme that plays an important role in the phosphoinositide second messenger system. A population-based association study and a family-based linkage study were carried out on patients who were considered excellent responders to lithium prophylaxis. Response to lithium was evaluated prospectively with an average follow-up of 14.4 +/- 6.8 years. The PLCG1 polymorphism was investigated in 136 excellent lithium responders and 163 controls. In addition, the segregation of this marker was studied in 32 families ascertained through lithium-responsive bipolar probands. The allele distributions between lithium-responsive bipolar patients and controls were different, with a higher frequency of one of the PLCG1 polymorphisms in patients (chi2 = 8.09; empirical P = 0.033). This polymorphism, however, confers only a small risk (OR = 1.88, CI 1.19-3.00). Linkage studies with the same marker yielded modest support for the involvement of this gene in the pathogenesis of BD when unilineal families were considered (Max LOD = 1.45; empirical P = 0.004), but not in the whole sample. Our results provide preliminary evidence that a PLC isozyme may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance. Whether this polymorphism is implicated in the pathogenesis of BD or in the mechanism of lithium response remains to be determined.
Adult↗
"Epileptosis"--a syndrome or useless speculation?
102 patients were divided into 3 groups: epileptics, psychotics and epileptics with psychotic symptoms. All had long been monitored for a number of clinical and laboratory parameters. Though different in many respects, all share states of sudden dysphoria, cacophoria, panic anxiety, horror, and EEG (stereo-EEG, too) signs of epileptic or other gross anomalies, often correlated to those affective disorders. Attacks of dysphoria, epilepsy, and psychosis come spontaneously and in response to biological (hypoglycemia, sleep deprivation, alcohol, menses) or psychosocial stimulation (agitation, quarrels, fear of redundancy, psychic trauma). These states (attacks, dysphoria, "neurotic" or even psychotic episodes) often provoke one another. -Calling this syndrome epileptosis, we believe its mechanism is due to lesions of the limbic and brainstem modulation systems. At the start of the process there is an epileptic focus in the amygdalo-hippocampal complex (AHC) which in itself can trigger simple or complex partial paroxysm but also-by means of electric stimulation of the AHC-states of dysphoria, anxiety, and psychotic hallucinations. Besides, a form of pathological learning develops in premorbid "hypersensitive" personality which can be put down to associative learning and to Overton's phenomenon of "state-dependent retention of learned responses". This may give rise to mutual stimulation where epileptic focal activity in AHC can provoke dysphoria while an external psychosocial situation can trigger epileptic activity there, too (AHC). Since there need not always be mydriasis (though other vegetative signs such as tachycardia, tachypnoea, nausea, blush and others are frequent) or unconsciousness, and some psychomotor manifestations may be out of the ordinary, and scalp EEG may be normal, such patients are often regarded as "hysterics" or malingerers.
Adult↗
[Clozapine--an atypical antipsychotic agents, its advantages and risks].
The authors present a basic review on clozapine (Leponex, Clozaril) which is one of the atypical antipsychotic drugs. It is a derivative of dibenzodiazepine, which contrary to classical neuroleptic drugs, does not exert a marked effect on the extrapyramidal system and its long-term use is not associated with the risk of development of irreversible tardive dyskinesia or dystonia. It is effective also in patients who are resistant to treatment with other neuroleptics and it has a more favourable effect on the negative symptoms of schizophrenia than classical neuroleptics. Its disadvantage is the increased risk of granulocytopenia and agranulocytosis (2%) and therefore its use is justified only in patients where there is evidence that they are resistant to other treatment. The mentioned risk can be controlled effectively by regular checks of the haemogram in patients taking clozapine, along with recording in the central data bank which has a consulting and control function and guaranteeing the method of correct administration of this drug and early therapeutic provisions in case of granulocytopenia. Despite the cost of treatment and checks of the haemogram, clozapine reduces the sum total of expenditure associated with the treatment of chronic schizophrenia by reducing the number of re-admissions to hospital, by shortening the period of hospitalization and by cutting indirect costs, which are influenced by a greater sociability of the patient and a greater probability of successful comprehensive therapeutic procedures.
Clozapine↗
Maintenance of a circadian phase adjustment of the human melatonin rhythm following artificial long days.
In winter, a 5-day exposure of 4 human subjects to a skeleton photoperiod, with 3 h of bright light in the evening and again in the morning, phase advanced the morning serum melatonin offset by 1-3 h as compared with the original winter melatonin rhythm pattern. The phase advance persisted for 3 days even after the bright light withdrawal. The data indicate that the long skeleton photoperiod had a prevailing phase-advancing effect on the melatonin rhythm and its underlying pacemaker. The maintenance of the phase advance might be due to the fixed sleep-wake schedule.
Adult↗
[Observations of participants in a bilateral symposium of the American Psychiatric Association and the Czechoslovak Medical Society].
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Czechoslovakia↗
Human circadian rhythm in serum melatonin in short winter days and in simulated artificial long days.
Serum melatonin rhythm was studied in 6 human subjects experiencing short winter days resembling light/dark (LD) 8:16 h and in 6 subjects exposed at the same time to a long, LD 16:8 h skeleton photoperiod, with 3 h of bright light in the evening and again in the morning; 4 out of the 6 subjects entrained to the simulated summer photoperiod within 3 days. In the synchronized subjects, the nocturnal melatonin signal was 3 h shorter than in those experiencing just winter days. The data indicate that humans are able to respond to environmental day length by forming a proper endogenous photoperiodic signal.
Adult↗
Early morning bright light phase advances the human circadian pacemaker within one day.
One day after a single exposure to bright light from 03.00 to 09.00 h the morning declines in the serum melatonin concentration were phase-advanced in all subjects relative to pre-exposure patterns by 1.2-2.6 h. The evening melatonin rise was phase-advanced in 5 out of 6 subjects by 0.6-2.2 h. The data suggest that an underlying human circadian pacemaker controlling the melatonin rhythm may be phase-advanced within one day; however, the evening melatonin rise and the morning decline do not necessarily phase-shift by the same amount.
Circadian Rhythm↗
[The LDH virus and changes in cellular immunity in schizophrenics and their relatives].
In a long-term investigation the authors investigated in a group of schizophrenics and their grade 1 relatives the immunological response to schizophrenic cortex (from the frontal and temporal lobe) and to LDH viral antigen (lactate dehydrogenase virus). In the group of 261 subjects (84 patients, 60 parents, 37 siblings) a significant increase of a certain type of cytophil antibodies was detected, manifested by positive reactivity to gray matter of the schizophrenic and healthy brain, not only in patients but also in their parents and siblings who were healthy from the clinical and psychiatric aspect. At the same time a highly positive immune response to the LDH viral antigen was found not only in patients but also in their relatives. In some positive subjects, in particular as regards the viral antigen, the number of non-adhered cells in the LAI test (Leucocyte adherence inhibition) exceeded 100% which suggest leucocyte proliferation. Microscopic examination revealed repeatedly that during two-hour leucocyte incubation with antigen at 37 degrees C in these subjects enhanced mitotic leucocyte division occurs. This finding was recorded in 22% of all positive schizophrenics and in 13% of the parents; in healthy siblings (although they had a positive immune response to the viral antigen) direct cell division did no occur in any of the cases. Assessment of circulating immune complexes revealed positive values in a total of 93% of all investigated subjects. As compared with controls (80 mentally and physically healthy blood donors), the mean levels are more than double and the difference is highly significant (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Motor and sensory laterality in the population of Prague].
Laterality is a developmental (not pathological) deviation in shape functional symmetry of paired motor and sensory organs. As it is one of the most specific features of the human being, great attention is paid to it during recent decades. These problems are important also form the point of view of findings of laterality changes in schizophrenics. The authors present results of examination of a normal Prague population sample. The estimated data on stratification of laterality findings in this group may serve as standard control figures for comparison and evaluation of findings in various defects and illnesses. 754 Prague blood donors (367 males and 387 females) aged 18-60 years (mean age 31.1 years) were examined. Probands in whom it could be the case of either pathological or out of necessity laterality or who had a history of mental disease were not included in this population. The motor (hand, foot) and sensory (eye, ear) phenotype of the probands were ascertained using Matĕjcek and Zlab test (8) which was expanded by several important operations. Moreover, the examination was supplemented by aimed questions on some operations. The total numbers found in this population were following: 74% of right-handed, 13.9% of ambidextrous and 12% of left-handed individuals. As for the motor laterality of the lower limbs, an ambiguous laterality of the foot is present more frequently (34.9%), right laterality in 56.9% and left only in 8.2%. The sensory left-sided laterality is generally higher than the motor left-sided laterality--left-sided vision in 26.7% and left-sided hearing in 23.3%.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Incidence of HLA-DR antigens in endogenous psychoses].
The authors examined 29 patients with endogenous psychosis (incl. 25 suffering from paranoid schizophrenia and four suffering from bipolar psychosis diagnosed according to DSM III criteria) with the aim to reveal the relationship of hitherto little studied HLA-DR antigens and the psychotic disease. Moreover, the passesed in the group also the ration of HLA-A, B, C antigens. In patients with paranoid schizophrenia and in all patients they found a higher incidence of HLA-DR2 antigens and a lower incidence of HLA-DRw6 and DR7. A statistically significant result was obtained only for HLA-DR2, and only before correction of p. The corrected p value (for the number of antigens) was no longer significant. This finding may serve as a stimulus to resolve the relationship of HLA-DR antigens and schizophrenia in a larger number of patients and in a greater number of departments.
HLA-DR Antigens↗