[Artistic creativity in the light of Jungian analytical psychology]. / A muvészi alkotás a Jungi analitikus pszichológia megközelítésében.

C.G. Jung's analytical psychology points at important issues in the psychological understanding of creativity. The theories of the Collective Unconscious and the Archetypes contributed to important discoveries in the interpretation of artistic creativity. Jung was concerned to show the relevance of Analytical Psychology to the understanding of European Modernism. Our paper deals with a short Jungian interpretation of Csontvary's art, too.

Minor physical anomalies in affective disorders. A review of the literature.

BACKGROUND: The increased frequency of MPAs may be external markers of abnormal brain development in affective disorders. METHODS: A MEDLINE, psychInfo and Web of Science search was evaluated to collect all publications on the prevalence of minor physical anomalies in bipolar affective disorder and unipolar major depression. AIMS: As reports on the prevalence of MPAs in affective disorders were controversial, were based on highly different number of patients and were evaluated by the use of scales with different sensitivities, we considered as important to review the current state of knowledge and to recommend directions to further research. RESULTS: 14 publications on 12 studies were found after a careful literature search. 5 studies have dealt with the prevalence of MPAs in bipolar affective disorder, 3 have reported on examinations among patients with unipolar major depression, while 5 publications on 3 studies combined patients with bipolar affective disorder, schizoaffective disorder and unipolar major depression. 1 study was published on the prevalence of MPAs among mood disorders, without the differentiation of the data of patients with bipolar affective disorder and unipolar major depression. LIMITATIONS: Few studies with relatively small size were published, there is no data on the distinction between bipolar I and bipolar II disorders. CONCLUSION: The reviewed data suggest a higher probability of the role of an aberrant neurodevelopment in bipolar affective disorder and a smaller in unipolar major depression.

DNA sequence variants in the metabotropic glutamate receptor 3 and risk to schizophrenia: an association study.

OBJECTIVES: Recent studies investigating the association of DNA variants in the metabotropic glutamate receptor gene (GRM3) with schizophrenia susceptibility revealed conflicting results. In this study, we focused on DNA sequence variants, for which association was reported and attempted to replicate association with schizophrenia or with cognitive deficits known to be present in patients with schizophrenia. METHODS: A sample of 242 families with affected offspring and five single nucleotide markers located in the genomic region of GRM3 has been used to replicate association with schizophrenia. In addition, results of neuropsychological tests, trail making test B and the Stroop color-naming task were available for a subgroup of these families (N=88) and an independent sample of 148 patients with schizophrenia. Correlation of these measurements with genotypic data was performed using analysis of variance. RESULTS: No statistical evidence for association with schizophrenia or correlation with cognitive deficits as measured by the trail making test B or the Stroop color-naming task and the five DNA sequence variants could be detected. A trend towards association with schizophrenia was revealed for a single marker (rs2237562, P=0.056) and for 2-marker and 3-marker haplotypes containing this variant. CONCLUSIONS: Our study of DNA sequence variants in the GRM3 gene did not provide further support for genetic association with schizophrenia or for correlation with cognitive deficits.

[Switching patients with schizophrenia to ziprasidone from conventional or other atypical antipsychotics]. / Váltás ziprasidonra hagyományos vagy más atípusos antipszichotikumokról szkizofréniában szenvedö betegekben.

OBJECTIVES: The aim of the study was to assess the efficacy, tolerability and safety of ziprasidone in patients with schizophrenia who were already treated with conventional or other atypical antipsychotics that had to be switched due the lack of efficacy or bad tolerance. METHODS: The study was a 12-week, open label, multicenter, non comparative trial on oral ziprasidone. 106 patients with DSM-IV schizophrenia were switched to ziprasidone from their previous antipsychotic without a washout phase. The study required fixed dosing with ziprasidone. For the first week the patient received 80 mg of study drug daily, followed for 3 weeks 120 mg/day. Subsequently for 8 weeks either 80 mg, or 120 mg, or 160 mg total daily dose could be given at the discretion of the investigator. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Calgary Depression Scale (CAD), Hamilton Depression Scale (HAMD), Drug Attitude Inventory (DAI), Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) and Barnes Akathisia Rating Scale (BARS). Changes in overall body weight were also evaluated. RESULTS: After 12 weeks on ziprasidone therapy, significant improvements were observed on all major symptoms measures and subscales. 34 (51,5%) patients (ITT) were rated much or very much improved on CGI-I at week 12. The mean SAS score significantly reduced during the ziprasidone treatment period (p<0.001). In the DAI ziprasidone treatment was also favorable rated. During treatment with ziprasidone for 12 weeks the body weight of the patients was significantly reduced (mean: 1,2 kg, SD=3,79, p=0.002). 58 adverse events occurred in 41 subjects (38.7%), of whom 7 patients (6.6%) encountered 9 severe adverse events. The adverse events were mainly mild and moderate. 15 patients (14.2%) were discontinued from the study due to adverse events. The reason for discontinuation in 4 cases was mainly insufficient clinical response. CONCLUSION: Switching patients from their previous antipsychotic to ziprasidone without a washout phase was generally well tolerated and was associated with symptoms improvements 12 weeks later. At least 50% of patients who needed to be switched because of unsatisfactory efficacy or poor tolerance were significantly improved on ziprasidone therapy. The favorable safety profile of ziprasidone treatment was consistent with that seen in other clinical trials. KEYWORDS: switching, ziprasidone, schizophrenia.

Further evidence for association of variants in the AKT1 gene with schizophrenia in a sample of European sib-pair families.

BACKGROUND: Involvement of AKT signaling pathways in schizophrenia has been recently suggested, on the basis of several lines of evidence. In addition to impairment of protein-levels and phosphorylation levels in the pathway, association of DNA sequence variants in the AKT1 gene with schizophrenia has been detected in a family sample. METHODS: We investigated the reported association of DNA sequence variants in the AKT1 gene in a sample of 79 sib-pair families with schizophrenia using the five single nucleotide polymorphisms (SNPs) of the original study and two additional SNPs in the neighborhood of the SNP for which association had been reported. RESULTS: We obtained statistical significance for single markers (p = .002) and multilocus haplotypes (p = .0013) located in the same region as has been reported in the previous study. CONCLUSIONS: The replication of association of variants in the AKT1 gene in a family sample with similar ethnical background as in the original study adds further evidence for involvement of AKT1 in development of schizophrenic disorders.

Association of DNA polymorphisms in the synaptic vesicular amine transporter gene (SLC18A2) with alcohol and nicotine dependence.

The brain synaptic vesicular amine transporter SLCA18A2 is a key component for the uptake of monoamines like dopamine or serotonin into vesicles. We have analyzed seven DNA polymorphisms located in the genomic region of SLC18A2 for association with alcohol- and nicotine dependence, using a family-based design. Our sample comprised 131 families with alcohol-dependent offspring and 96 families with at least one nicotine-dependent offspring. For the alcohol-dependent sample, we found statistical significant association for two single markers (rs363387, P=0.03; rs363333, P=0.0066) as well as for several haplotypes (minimal P=0.0038). When the sample with alcohol dependence was stratified according to gender, we observed increased association for the male subgroup (rs363387, P=0.0011). None of the markers showed association in the sample of families with nicotine dependence. However, analysis of a combined sample of alcohol and nicotine-dependent families resulted in single markers as well as several haplotypes showing statistical significant association with substance dependence (minimal P=0.0044). We conclude that DNA polymorphisms located in SLC18A2 might contribute to the development of substance dependence.

Use of antipsychotics in the management of schizophrenia during pregnancy.

The rapid development of pharmacotherapy has resulted in a growing clinical importance for the treatment of the increasing number of women with schizophrenia during pregnancy. An evolving database on reproductive health safety factors for women with schizophrenia has begun to be of assistance in optimising clinical benefits for women with childbearing potential. Given the prevalence of antipsychotic use during pregnancy in women with schizophrenia, it is important for the clinician to have a prepared approach to the administration of these agents. In general, the use of psychotropic medication during pregnancy is indicated when risk to the fetus from exposure to this medication is outweighed by the risks of untreated psychiatric illness in the mother. The preponderance of evidence from registries to large health surveys indicate that treatment with antipsychotic medication confers either no or a small nonspecific risk for organ malformations. According to the relevant literature published on the safety of antipsychotic medication during pregnancy, the findings are encouraging; however, the currently available data are very limited. Until there are more controlled prospective data on the impact of drugs on fetal and later development, the clinician will continue to work in a state of potential uncertainty, weighing partially estimated risks against managing individual clinical problems. The aim for the clinician should be to provide the best information available regarding the scope of possible risks associated with the treatment of schizophrenia during pregnancy. On the basis of the available data, generalisation is impossible and recommendations should be made on a drug-by-drug basis. The risks and benefits must always be carefully weighed for each patient on an individual basis. Only a woman who is well enough to acknowledge her pregnancy and her mental illness can effectively weigh the relative and partially unknown risks of treatment with antipsychotic medication against the highly probable risks of illness exacerbation if untreated.

Investigation of linkage and association/linkage disequilibrium of HLA A-, DQA1-, DQB1-, and DRB1-alleles in 69 sib-pair- and 89 trio-families with schizophrenia.

The hypothesis that HLA antigens confer susceptibility to schizophrenic disorders has been tested by studying linkage and association in a family sample with 69 sib-pair families. Suggestive evidence for linkage was obtained by nonparametric multipoint LOD score analysis with a maximum around DQB CAR (P = 0.0004), a microsatellite marker that is in linkage disequilibrium with the HLA antigen DQB1. Spurious evidence for negative association as calculated by the transmission disequilibrium test was found for HLA- DRB1*11 (chi-square = 11.72, corrected P value = 0.03) and for the haplotype DQB1*301-DQA1*501-DRB1*11 (chi-square = 11.3, corrected P value = 0.043). No evidence of association with these alleles was obtained in a sample of 89 trios with schizophrenic offspring and parents. Our results are not in favor of a direct involvement of the HLA system in development of schizophrenia, but are compatible with the possible existence of a susceptibility gene in the MHC region at chromosome 6p 21.31.

Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia.

BACKGROUND: Tumor necrosis factor alpha (TNFalpha), a cytokine involved in inflammatory processes, has been implicated in the pathophysiology of schizophrenia. The chromosomal location in the major histocompatibility complex (MHC) region on 6p21.1-21.3, a region with evidence for linkage, suggests a role in susceptibility to schizophrenia. Association of the minor (A) allele of the -G308A TNFalpha gene polymorphism with schizophrenia has been reported [Mol. Psychiatry 6 (2001) 79]. METHODS: Association of the -G308A TNFalpha gene and the lymphotoxin alpha (LTalpha)+A252G gene polymorphisms with schizophrenia was studied in 79 sib pair families with linkage in the MHC region and in 128 trio families using the transmission disequilibrium test (TDT). RESULTS: Weak association of the common G allele was detected for TNFalpha -G308A in both samples independently with borderline significance in the sib pair families (0.064) and with a nominally significant value of P=0.022 in the trio families. Combining both samples produced P=0.003, while LTalpha+A252G, located approximately 2-3 kb distally, revealed P=0.03 and the two locus haplotype yielded a P value of 0.001. CONCLUSION: Our data suggests association of the common G allele of the -G308A TNFalpha gene polymorphism with schizophrenia in a sample of 207 families. However, linkage disequilibrium with a different allele of the TNFalpha gene or another gene in the MHC region cannot be excluded.

Minor physical anomalies in non-familial unipolar recurrent major depression.

BACKGROUND: The prevalence of minor physical anomalies (MPAs) was evaluated in patients with unipolar recurrent major depression to get indirect data on the possible role of aberrant neurodevelopment in the aetiology of major depression. One published study [Lohr et al., Am. J. Geriatr. Psychiatry 5 (1997) 318] on the MPA prevalence in unipolar depression, evaluated by the recently widely criticized Waldrop-scale, reports on a significantly higher MPA rate among patients. METHODS: A scale developed by Méhes [Prog. Clin. Biol. Res. 163 (1985) 45] was used to detect the presence or absence of 57 MPAs in 30 patients with major depression and in 30 matched controls. RESULTS: The depressive sample did not differ significantly from the control group (P=0.200). By comparing each MPA individually we could not find any significant differences between the depressive and the control sample. LIMITATIONS: Patients and control subjects had a negative family history in connection with affective disorders; a high-risk population should give significant positive results. CONCLUSIONS: The results do not support the role of an 'early neurodevelopmental origin' in unipolar depression.

[The connection between mentalization deficit and pragmatic language skills and neurocognition in schizophrenia]. / A mentalizációs zavar nyelvpragmatikai és neurokognitív összefüggései szkizofréniában.

OBJECTIVE: There is an increasing interest in the background of mentalization deficit in schizophrenia. On the one hand, according to developmental psychological studies, mentalization development is connected with the development of pragmatic language skills. On the other hand, studies suggest that mentalization is dependent on the maturation of neurocognitive skills such as executive functions. Our study investigated the role of these domains in the mentalization deficit of schizophrenia. METHOD: 28 patients with schizophrenia and 20 control patients with depression took part in the first part of the study. Participants were presented first-order and second-order mentalization tasks, metaphor and irony tasks for the assessment of mentalizing skills. The pragmatic language skills were examined by "question and answer" vignettes. 20 patients with schizophrenia took part in the second part of the study. The test battery was completed with a picture recognition task and neurocognitive tests were made by all patients. RESULTS: Patients with schizophrenia performed significantly worse in the irony and pragmatic tasks, but there was no correlation between their performances in the irony and in the pragmatic tasks. Selective attention and verbal working memory showed correlation with the cumulative verbal mentalization index. Selective attention correlated with the recognition of complex mental states from pictures as well, but the successful decoding of complex mental states was dependent on the recognition of basic expressions. Attention correlated with mental state recognition as well. CONCLUSIONS: Our results suggest that the mentalization deficits of people with schizophrenia cannot be explained by pragmatic language deficits alone, and the manifest impairment is the consequence of disturbances in multiple cognitive processes. Basic neurocognitive factors such as attention, selective attention and verbal working memory can influence the mentalization skills.

No support for an association with TAAR6 and schizophrenia in a linked population of European ancestry.

Single nucleotide polymorphisms (SNPs) in the trace amine associated receptor trace amine associated receptor 6 gene and 3' flanking region have been shown to be associated with schizophrenia. To replicate these findings, we conducted a family-based association study with the five most significant SNPs in our sample of 79 sib-pair families (56/79 sib-pair families showed linkage to 6q23) and 125 triads. No evidence for association was obtained between these SNPs and schizophrenia in our sample, even when limited to the 56 linked families (P>0.2). We conclude that trace amine associated receptor 6 is not important for the development of schizophrenia in our family samples.

Coexistence of folie communiquée and folie simultanée.

Objective. The authors report a case during which they observed serious subtypes of induced delusional psychosis (folie communiquée and folie simultanée) without any common genetic background or premorbid psychosis in the case of the secondary patient. Method. The clinical phenomenology of the case is described. Results. Mild intellectual disability and environmental-psychological factors (social isolation and the symbiotic-like interpersonal relatedness) play an essential aetiological role in the case of the secondary recipient patient. Conclusion. The authors emphasize the importance of subclassification of induced delusional psychosis for further aetiological and clinical research.

'Clonal pluralization of the self': a new form of delusional misidentification syndrome.

The authors present a patient with paranoid schizophrenia, who has the delusion that he exists in plural numbers. The patient declares these doubles to be both psychologically and physically completely identical to him, and he believes 'them' to be in fact women. In connection with the case, the authors discuss the phenomena of reduplicative paramnesia and clonal pluralization, and they suggest introducing the psychopathological term 'clonal pluralization of the self' for the reported phenomenon.

Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families.

Genetic variants in a gene on 6p22.3, dysbindin, have been shown recently to be associated with schizophrenia (Straub et al. 2002a). There is no doubt that replication in other independent samples would enhance the significance of this finding considerably. Since the gene is located in the center of the linkage peak on chromosome 6p that we reported earlier, we decided to test six of the most positive DNA polymorphisms in a sib-pair sample and in an independently ascertained sample of triads comprising 203 families, including the families for which we detected linkage on chromosome 6p. Evidence for association was observed in the two samples separately as well as in the combined sample (P=.00068 for SNP rs760761). Multilocus haplotype analysis increased the significance further to .00002 for a two-locus haplotype and to .00001 for a three-locus haplotype. Estimation of frequencies for six-locus haplotypes revealed one common haplotype with a frequency of 73.4% in transmitted, and only 57.6% in nontransmitted, parental haplotypes. All other six-locus haplotypes occurring at a frequency of >1% were less often transmitted than nontransmitted. Our results represent a first successful replication of linkage disequilibrium in psychiatric genetics detected in a region with previous evidence of linkage and will encourage the search for causes of schizophrenia by the genetic approach.