Costas N. Stefanis

A meta-analysis and transmission disequilibrium study of association between the dopamine D3 receptor gene and schizophrenia

We performed a meta-analysis of over 30 case-control studies of association between schizophrenia and a bi-allelic, BalI polymorphism in exon 1 of the dopamine D3 receptor gene. We observed a significant excess of both forms of homozygote in patients (P = 0.0009, odds ratio (OR) = 1.21, 95% Confidence Interval (CI) = 1.07–1.35) in the combined sample of 5351 individuals. No significant heterogeneity was detected between samples and the effects did not appear to be the product of publishing bias. In addition we undertook an independent, family-based association study of this polymorphism in 57 parent/proband trios, taken from unrelated European multiplex families segregating schizophrenia. A transmission disequilibrium test (TDT) showed a significant excess of homozygotes in schizophrenic patients (P = 0.004, odds ratio (OR) = 2.7, 95% CI = 1.35–5.86). Although no significant allelic association was observed, a significant association was detected with the 1–1 genotype alone (P = 0.02, OR = 2.32, 95% CI = 1.13–4.99). In addition when the results of the family-based association study were included in the meta-analysis, the homozygosity effect increased in significance (P = 0.0002, OR = 1.23, 95% CI = 1.09–1.38). The results of the meta-analysis and family-based association study provide independent support for a relationship between schizophrenia and homozygosity at the BalI polymorphism of the D3 receptor gene, or between a locus in linkage disequilibrium with it.

Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients.

A number of immunological parameters were studied in 82 DSM-III-R diagnosed schizophrenic patients (53 first drug-naive and 29 medicated chronic patients) as well as 62 healthy blood donors. The serum levels of interleukin-2 (IL-2), interleukin-1 beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) were measured and correlated with cellular immunity, as assessed by the autologous mixed lymphocyte reaction (AMLR). T lymphocyte subsets were also examined. The above immune parameters were reassessed in a subgroup of 11 first-episode, drug-naive patients 1month after neuroleptic medication. IL-2 serum levels were significantly lower, and IL-1beta and TNF-alpha were significantly higher in schizophrenic patients compared with healthy donors (P<0.001); no significant difference was observed between the two patient groups (medicated and not medicated). Abnormal cytokine serum levels were associated with decreased AMLR responses in vitro. Increased percentages of activated CD4+ and CD16+ natural killer cells, as well as cells expressing ICAM-1 adhesion molecules and IL-2 specific receptors, were detected in the patients. Immunophenotype studies revealed a higher percentage of cells expressing IL-2 receptors in medicated chronic schizophrenic patients compared with drug-naive patients. The abnormal cytokine production in vivo, along with the low AMLR responses in vitro, and the high percentage of activated CD4+ lymphocytes presented in this study suggest alterations in the immune system of schizophrenic patients (medicated or not medicated) consistent with immune activation.

Variation in catechol-o-methyltransferase val158 met genotype associated with schizotypy but not cognition: A population study in 543 young men

BACKGROUND Increased catechol-O-methyltransferase activity associated with variation in catechol-O-methyltransferase valine158 methionine genotypes may result in reduced dopamine neurotransmission in the prefrontal cortex and thus contribute to the poor performance of frontally mediated cognitive tasks and the occurrence of associated negative symptoms observed in patients with schizophrenia; however, reported associations between catechol-O-methyltransferase valine158 methionine genotypes and measures of cognition have not been consistent. METHODS Catechol-O-methyltransferase genotyping, measures of schizotypy, cognitive measures of memory and attention, as well as the antisaccade eye movement task, a measure sensitive to prefrontal cortical function, were obtained in a sample of 543 young men representative for that age group (mean age 21 years). RESULTS None of the cognitive measures was associated with catechol-O-methyltransferase valine158 methionine genotypes; however, there was an effect of high-activity allele loading on schizotypy, in particular the negative and disorganization dimensions. CONCLUSIONS Previously reported inconsistencies in the relationship between catechol-O-methyltransferase valine158 methionine genotypes and cognition were not resolved; however, catechol-O-methyltransferase genotype may affect expression of negative schizotypy by direct or indirect effects on central dopamine neurotransmitter signaling.

Duration of flooding sessions in the treatment of obsessive-compulsive patients

Abstract This study investigated the duration effect of flooding ‘ in vivo ’ and ‘in fantasy’ in twelve obsessive-compulsive patients treated in a balanced Latin square design. Clinical assessments regarding twenty one clinical variables were carried out before and after each treatment condition. Long practice sessions proved significantly superior to other treatment conditions. Short and long sessions ‘in fantasy’ did not diner significantly. Long fantasy sessions appear to have potentiating effects on in vivo practice sessions. The order effect and the intercorrelation of the variables prior to treatment and to the outcome, are also presented. Some prognostic factors and the follow-up findings are discussed.

Increased suicidality amid economic crisis in Greece

Greece has entered a long period of economic crisis with adverse eff ects on various aspects of daily life, including the mental health of its citizens. Within this context, the Greek Ministry of Health reported that the annual suicide rate has increased by 40%; nonetheless, a systematic investigation to address the eff ect of the Greek economic crisis on suicidality is still lacking. In an endeavour to fi ll this gap, the University Mental Health Research Institute (UMHRI) imple mented a nationwide cross-sectional telephone survey, completed on May 1, 2011. The study adopted the same methods as an earlier one done during February–April, 2009, which explored the links between major depressive symptoms and socioeconomic variables. A representative sample of 2256 respondents was drawn from the national telephone-number databank, with telephone numbers belonging to businesses or services being excluded. Informed consent was obtained from all participants and the study was approved by the UMHRI Ethics Committee. Recent suicidality was assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and fi nancial strain was measured by the Index of Personal Economic Distress (IPED), an eight-item scale with good psychometric properties. Of the study fi ndings, the most alarming one pertained to suicidal attempts. There was a 36% increase in the number who reported having attempted suicide in the month before the survey from 24 (1·1%) in 2009 to 34 (1·5%) in 2011. We also found that a signifi cantly higher proportion of respondents with an IPED score of 15 or more (ie, high economic distress) had attempted suicide in the month before the survey than had respondents with an IPED lower than 15 (27 [10%] vs 7 [0·6%], p<0·001). Similarly, a IMF and European co-workers attack public health in Greece

Impact of Schizophrenia Candidate Genes on Schizotypy and Cognitive Endophenotypes at the Population Level

BACKGROUND Aspects of cognitive function and schizotypy have been proposed as potential endophenotypes for schizophrenia. It is unknown whether the expression of these endophenotypes at the population level is modulated by the genetic variability of candidate susceptibility genes for schizophrenia. METHODS We examined the potential impact of 18 single nucleotide polymorphisms (SNPs) within the DTNBP1, NRG1, DAOA/G32, and DAAO genes, on cognition and self-rated schizotypy, in a representative population of 2243 young male military conscripts. Single SNP and haplotype associations were evaluated. RESULTS The DTNBP1 SNPs rs2619522 and rs760761 exhibited several single marker associations, the minor alleles being associated with lower attention capacity but also a decrease in positive and paranoid schizotypy scores. The DTNBP1 haplotype load had borderline associations with nonverbal IQ, paranoid schizotypy, and sustained attention. For individual NRG1 polymorphisms, isolated but weak signals of association were noted with sustained attention and working memory but not schizotypy. The risk allele of functional SNP8NRG243177 was associated with reduced spatial working memory capacity. An isolated effect of DAAO haplotype variability was noted on negative and disorganization schizotypy. No convincing association of DAOA/G32 variability was detected. CONCLUSIONS The DTNBP1 and, less so, NRG1 and DAAO variants might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level.

Five-factor model of schizophrenic psychopathology: how valid is it?

Abstract Aim of the study was to examine the consistency of the five-factor model of schizophrenic symptoms, assess its validity and evaluate its dimensional factor structure using confirmatory factor (CFA) analysis. ¶A sample of 258 randomly assigned DSM-III R patients with schizophrenic disorders were studied by means of the structured clinical interview for the Greek validated Positive and Negative Syndrome Scale (PANSS) and were rated on its 30 items. Patients’ scores were subjected to principal component analysis (PCA) with varimax rotation. Internal consistency for each of the components was determined by the use of Cronbach’s alpha. External validity of the model derived was investigated by searching for possible relationships between the components and sociodemographic characteristics with the aid of canonical correlation analysis. Confirmatory factor analysis (CFA) was also performed. Using the scree plot criterion PCA revealed a five-factor model. These factors were interpreted as representing – in a decreasing order of relative importance – the following dimensions of schizophrenic psychopathology: negative, excitement, depression, positive and cognitive impairment. The model was comparable with six previous factor analytic studies. Internal consistency was quite satisfactory whereas external validity was found to be not so powerful. CFA did not show that the proposed model yields an adequate factor structure.

Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele.

The gene for COMT is located on chromosome 22q11, an area that has been implicated in the pathogenesis of schizophrenia through linkage studies and through the detection of deletions in schizophrenics and velocardiofacial syndrome patients that often present psychotic symptomatology. Additionally catechol-O-methyl transferase activity has been found increased in schizophrenia and a functional polymorphism in the COMT gene itself has been associated with the disease, as well as with aggression in patients. We tested the hypothesis that COMT genotype for the functional Val158Met might contribute to the variance of self reported schizotypy and aggression scores in the normal population. We genotyped 379 healthy 18- to 24-year-old male individuals who had completed the PAS, SPQ and AQ questionnaires. Our results showed that self-reported schizotypy scores in both questionnaires were significantly related to COMT genotype (P = 0.028 for the PAS and P = 0.015 for the SPQ) with individuals homozygous for the high activity allele showing the highest scores. No significant differences were detected for AQ scores. We conclude that the COMT genotype for the functional Val158Met polymorphism is correlated to self-reported schizotypy in healthy males. This finding is in the same direction as reported findings on schizophrenia and it adds to the list of evidence that COMT or a nearby gene in linkage disequilibrium is involved in the pathogenesis of the disease.

Suicidal ideation and reported suicide attempts in Greece during the economic crisis.

The financial crisis in Greece is largely impinging on the health and mental health of the population, raising concerns about a potential rise in suicide rates. The aim of this study was to explore changes in suicidal ideation and reported suicide attempts between 2009 and 2011 in a representative sample of the population and in several population subgroups. The socio‐economic predictors of suicidal ideation and suicide attempts in 2011 were also investigated. Two nationwide cross‐sectional telephone surveys were conducted in 2009 and 2011 using the same methodology. A random and representative sample of 2192 and 2256 people, respectively, took part in the surveys. Between 2009 and 2011, there was a substantial increase in the prevalence of suicidal ideation and reported suicide attempts. People suffering from depression, men, married individuals, people experiencing financial strain, people with low interpersonal trust, and individuals with a history of suicide attempts were particularly vulnerable.

Depression and economic hardship across Greece in 2008 and 2009: two cross-sectional surveys nationwide

PurposeIn many western countries during the recent years, people have witnessed the deterioration of their economies and the emergence of related phenomena such as loss of property, unemployment and social disruption. These phenomena have also been associated with increasing levels of demoralization and the developing of major depressive episodes (MDE). Greece in the years 2008 and mainly in 2009 started facing a sharp economic decline. The purpose of this study was to explore the consequences of this condition and the ways are reflected in the prevalence of MDE during these two critical years.MethodTwo nationwide cross-sectional telephone surveys were carried out in 2008 and 2009 with representative samples of 2,197 and 2,192 respondents, respectively. The interview comprised the SCID I module of MDE and an Index of Personal Economic Distress (IPED).ResultsThe 1-month prevalence of MDE in 2009 was found to be 6.8%, compared to corresponding rates of 3.3% in 2008. Respondents facing serious economic hardship (with higher scores in IPED) were mostly at risk for developing an MDE.ConclusionsThe findings of both studies underline the significance of the risk involved in developing MDE when individuals have been exposed in extreme and stressful economic situations.