Attitudes to depression and psychiatric medication amid the enduring financial crisis in Attica: Comparison between 2009 and 2014.

BACKGROUND: Only a handful of studies have explored the effect of the financial crisis on public attitudes to mental illness. AIMS: This study examines changes in lay attitudes to depression and psychiatric medication between 2009 and 2014 in Attica region. Furthermore, it explored a potential interaction with employment status. METHODS: Data were drawn from two surveys conducted in 2009 and 2014 using the same sampling procedure, interview mode, and survey instrument. Specifically, a random and representative sample of 586 people was recruited in 2009 and of 604 in 2014. Attitudes to depression were measured by the Personal Stigma subscale of the Depression Stigma Scale and attitudes to psychiatric medication by a self-constructed scale with good psychometric properties. Data collection occurred via telephone. RESULTS: There has been no overall change in lay attitudes to depression. Nonetheless, a positive change was recorded with regard to the belief that depression is a sign of personal weakness and a negative change with respect to people with depression being dangerous. Attitudes to psychiatric medication have worsened during the study period. Employment status was not found to interact with the survey year. CONCLUSION: Anti-stigma efforts should be tailored on counteracting the dangerousness stereotype, while they should prioritize targeting attitudes to psychiatric medication.

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood.

Neurocognitive abilities constitute complex traits with considerable heritability. Impaired neurocognition is typically observed in schizophrenia (SZ), whereas convergent evidence has shown shared genetic determinants between neurocognition and SZ. Here, we report a genome-wide association study (GWAS) on neuropsychological and oculomotor traits, linked to SZ, in a general population sample of healthy young males (n = 1079). Follow-up genotyping was performed in an identically phenotyped internal sample (n = 738) and an independent cohort of young males with comparable neuropsychological measures (n = 825). Heritability estimates were determined based on genome-wide single-nucleotide polymorphisms (SNPs) and potential regulatory effects on gene expression were assessed in human brain. Correlations with general cognitive ability and SZ risk polygenic scores were tested utilizing meta-analysis GWAS results by the Cognitive Genomics Consortium (COGENT) and the Psychiatric Genomics Consortium (PGC-SZ). The GWAS results implicated biologically relevant genetic loci encoding protein targets involved in synaptic neurotransmission, although no robust individual replication was detected and thus additional validation is required. Secondary permutation-based analysis revealed an excess of strongly associated loci among GWAS top-ranked signals for verbal working memory (WM) and antisaccade intra-subject reaction time variability (empirical P < 0.001), suggesting multiple true-positive single-SNP associations. Substantial heritability was observed for WM performance. Further, sustained attention/vigilance and WM were suggestively correlated with both COGENT and PGC-SZ derived polygenic scores. Overall, these results imply that common genetic variation explains some of the variability in neurocognitive functioning among young adults, particularly WM, and provide supportive evidence that increased SZ genetic risk predicts neurocognitive fluctuations in the general population.

Neuroticism, social network, stressful life events: association with mood disorders, depressive symptoms and suicidal ideation in a community sample of women.

According to the stress-diathesis hypothesis, depression and suicidal behavior may be precipitated by psychosocial stressors in vulnerable individuals. However, risk factors for mental health are often gender-specific. In the present study, we evaluated common risk factors for female depression in association with depressive symptoms and suicidal ideation in a community sample of women. The sample was composed by 415 women evaluated for mood disorders (MDs), depressive symptoms and suicidal ideation by structured interviews and the Beck depression inventory II (BDI II). All women also filled in the Eysenck personality questionnaire to evaluate neuroticism and were interviewed for social contact frequency and stressful life events (SLEs). In the whole sample, 19% of the women satisfied criteria for MD and suicidal ideation was reported by 12% of the women. Though stressful life events, especially personal and interpersonal problems, and poor social network were associated with all the outcome variables (mood disorder, depressive symptomatology and suicidal ideation), neuroticism survived to all multivariate analyses. Social network, together with neuroticism, also showed strong association with depressive severity, independently from current depressive state. Though we were unable to compare women and men, data obtained from the present study suggest that in women neurotic traits are strongly related to depression and suicidal ideation, and potentially mediate reporting of stressful life events and impaired social network. Independently from a current diagnosis of depression, impaired social network increases depressive symptoms in the women.

The influence of an anti-stigma intervention on adolescents' attitudes to schizophrenia: a mixed methodology approach.

BACKGROUND: This study aimed at exploring adolescents' attitudes to schizophrenia and the impact of an educational intervention on improving them, by employing a mixed methodology. METHOD: A total of 1081 secondary-school students were randomly allocated to a control and intervention condition. Stigma endorsement was assessed by a free association card and a questionnaire, before and 2 weeks after the intervention. RESULTS: The intervention yielded substantial changes in students' beliefs, attitudes and social distance levels as well as in their associations with the term 'severe mental illness'. CONCLUSIONS: Educational interventions can contribute substantially to preventing consolidation of unfavourable attitudes towards mental illness.

Potential role of membrane-bound COMT gene polymorphisms in female depression vulnerability.

BACKGROUND: Several polymorphic variants within the catechol-O-methyltransferase (COMT) gene locus have been associated with a number of diverse psychiatric phenotypes including affective disorders. COMT enzyme participates in metabolic pathways involving brain catecholamines, as well as steroid hormones such as estrogens. Given the suggested mood enhancing role of estrogens and the higher prevalence of depression in women, we set out to investigate the potential impact of functional COMT genetic variants on depression and anxiety symptoms in a homogeneous female community sample. METHODS: We genotyped three common polymorphisms within the COMT gene in a rural female population isolate (n=391) interviewed for the presence of lifetime major depression episodes and generalized anxiety disorder. Furthermore, well validated self-rated questionnaires were administered evaluating state depressive symptoms and neuroticism personality trait. Single-marker and haplotype association analyses were performed. RESULTS: Two highly correlated markers located in the membrane-bound (MB) COMT promoter region (rs2020917, rs737865) were significantly associated with both self-rated and clinician-rated depressive symptomatology. We did not detect any robust association with generalized anxiety disorder or neuroticism. Exploratory haplotype analysis examining the two promoter markers in combination with the extensively studied val 158met polymorphism (rs4680) did not provide any further support for the contribution of this variant in depressive mood. LIMITATIONS: The relative small sample size should be considered a limitation of this study. CONCLUSIONS: Our results provide promising evidence that MB-COMT specific genetic variation may represent an as yet unrecognized genetic factor that influences predisposition to depression amongst females.

Major depression in the era of economic crisis: a replication of a cross-sectional study across Greece.

BACKGROUND: The study endeavoured to gauge the impact of the current economic crisis on the mental health of the Greek population. Particularly, it explored changes in the prevalence rates of major depression between 2008 and 2011, and its link to financial hardship. Furthermore, the study also identified potential predictors of major depression in 2011. METHODS: Two nationwide cross-sectional teleophone surveys were conducted in 2008 and 2011 following the same methodology. A random and representative sample of 2.197 and 2.256 people, respectively, participated in the studies. Major depression was assessed with the Structural Clinical Interview, whereas financial strain with the Index of Personal Economic Distress (IPED), an original scale with good psychometric properties. RESULTS: In 2011, one-month prevalence rate of major depression was found to be 8.2%, as compared to the corresponding rate in 2008, which was 3.3%. Significant increases in prevalence rates were observed for the majority of the population subgroups. A significant association was recorded between major depression and economic hardship. Young people, married persons, individuals with financial distress and people who use medication displayed increased odds of suffering from major depression in 2011. LIMITATIONS: Participants' responses concerning financial difficulties were not confirmed from collateral accounts. Moreover, the direction of causality between financial hardship and major depression is unclear. CONCLUSIONS: The impact of the economic crisis on the mental health of the population is pervasive. Services and clinicians should focus on the primary prevention of major depression as well as on its timely recognition and treatment.

Schizophrenia candidate gene ERBB4: covert routes of vulnerability to psychosis detected at the population level.

Prior genetic and functional evidence established ERBB4 as a probable schizophrenia susceptibility gene that may confer risk via modulating brain information processing dependent on the integrity of frontotemporal brain circuitry. Utilizing retrospective data drawn from the cross-sectional population-based Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS) (n = 1127), we attempted to independently replicate and further extend previous findings by examining the effects of ERBB4 gene variants on 3 broad population-based psychosis-related phenotypes: verbal working memory (VWM), trait schizotypy, and stress-induced subclinical psychotic experiences (PE). Three common ERBB4 single nucleotide polymorphisms that were previously associated with schizophrenia and impaired frontotemporal-related information processing (rs7598440, rs839523, and rs707284), their haplotypes, and corresponding diplotypes were tested. VWM performance was significantly associated with rs839523 and rs707284 markers even after correction for multiple testing, thus validating reported findings that have implicated ERBB4 gene variation on working memory. No associations were detected between these ERBB4 variants and trait schizotypy. However, we were able to detect a significant effect of rs7598440 marker on PE expressed under stressful environmental conditions. Combined haplotype analysis of the above 3 markers, identified a "yin-yang" pattern of association, confirmed at the diplotype level. While GGG haplotype homozygotes were associated with "protective" effects on VWM performance and PE, AAA "risk" haplotype carriers were associated with worse VWM performance and simultaneously exhibited significantly elevated PE. This dual, possibly pleiotropic, impact on frontotemporal circuitry and increased sensitivity to psychosocial stress may represent subtle manifestations of ERBB4-related vulnerability to psychosis, expressed at the population level.

Variation in psychosis gene ZNF804A is associated with a refined schizotypy phenotype but not neurocognitive performance in a large young male population.

Genetic variability within the ZNF804A gene has been recently found to be associated with schizophrenia and bipolar disorder, although the pathways by which this gene may confer risk remain largely unknown. We set out to investigate whether common ZNF804A variants affect psychosis-related intermediate phenotypes such as cognitive performance dependent on prefrontal and frontotemporal brain function, schizotypal traits, and attenuated psychotic experiences in a large young male population. Association analyses were performed using all 4 available self-rated schizotypy questionnaires and cognitive data retrospectively drawn from the Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS). DNA samples from 1507 healthy young men undergoing induction to military training were genotyped for 4 previously studied polymorphic markers in the ZNF804A gene locus. Single-marker analysis revealed significant associations between 2 recently identified candidate schizophrenia susceptibility variants (rs1344706 and rs7597593) and a refined positive schizotypy phenotype characterized primarily by self-rated paranoia/ideas of reference. Nominal associations were noted with all positive, but not negative, schizotypy related factors. ZNF804A genotype effect on paranoia was confirmed at the haplotype level. No significant associations were noted with central indexes of sustained attention or working memory performance. In this study, ZNF804A variation was associated with a population-based self-rated schizotypy phenotype previously suggested to preferentially reflect genetic liability to psychosis and defined by a tendency to misinterpret otherwise neutral social cues and perceptual experiences in one's immediate environment, as personally relevant and significant information. This suggests a novel route by which schizophrenia-implicated ZNF804A genetic variation may confer risk to clinical psychosis at the general population level.

The role of serotonergic genes and environmental stress on the development of depressive symptoms and neuroticism.

BACKGROUND: Depression is considered to be the result of a complicated synergy between genetic and environmental factors. Several genes of the serotonergic neurotransmission have been related to depression phenotypes, however results are inconsistent, possibly due to the oversight of the role of environmental stress. METHODS: We examined gene-environment (GxE) interactions with serotonergic genes on depressive symptoms and neuroticism in a homogeneous population-based sample of 415 females. We chose several genetic variants within candidate genes (SLC6A4, TPH2, HTR1A) that have been previously found to provide some evidence of association with depression outcomes. RESULTS: Single marker analyses showed a significant GxE interaction with several TPH2 variants, including rs4570625, on depressive symptoms. Significant GxE interactions were also observed with TPH2 haplotypes. No reliable associations were observed with SLC6A4 and HTR1A genes. We did not find any robust evidence of a direct impact of serotonergic genes on depressive symptoms or neuroticism. LIMITATIONS: Due to the high number of analyses conducted, results must be interpreted with caution. CONCLUSIONS: The present study indicates an association between TPH2 and depressive symptoms that is conditional on prior experience of stressful life events. Further evidence is provided about the role of the environment in genetic vulnerability to depression.

The 3111T/C polymorphism interacts with stressful life events to influence patterns of sleep in females.

Genetic variations in clock-relevant genes have been investigated in relation to sleep abnormalities, both in healthy populations and in mood-disorder patients with inconsistent results. Environmental influences may moderate associations between genes and phenotype. The authors examined the CLOCK 3111T/C polymorphism and several variants within the PER3 gene and their possible interaction with stressful life events in a group of female volunteers (n = 415). Gene-environment (G × E) interactions and gene main effects were investigated on depressive symptoms using the Beck Depression Inventory and on change of sleep patterns (Item 16). Results showed a G × E interaction on alteration of sleeping pattern: the 3111C homozygous genotype reported greater disruption in sleep pattern after the experience of stressful life events. Within the PER3 gene, one G × E interaction was observed with rs228642 on sleep change. These findings show that the 3111T/C polymorphism is not associated with depressive symptoms, but only with symptoms of sleep change in the case of prior stressful life experiences. The combination of a sensitive genotype (3111C/C) and environmental stress increases vulnerability to circadian rhythm disruption in females.

Bipolar disorder ANK3 risk variant effect on sustained attention is replicated in a large healthy population.

Independent genome-wide association studies have implicated a common single nucleotide polymorphism within the ANK3 gene (rs10994336) in bipolar disorder (BD) susceptibility, thus establishing rs10994336 marker as a strong candidate predisposing genetic factor for BD. Furthermore, recent findings demonstrate that this variant impacts on cognitive functioning in BD patients, their unaffected relatives, and healthy controls by influencing sustained attention. Here, we aimed to replicate this finding in a large population-based sample of healthy young adults (n=1808). Sustained attention was evaluated using the Continuous Performance Test as in the original study and working memory was assessed with the n-back task. Individuals carrying the BD risk T-allele showed significantly reduced sensitivity in target detection, increased errors of commission, and atypical response latency variability. In addition, we confirmed the lack of an association between the rs10994336 variant and working memory, as well as general intellectual ability, suggesting a specific effect on the Continuous Performance Test performance.

Medical students' beliefs and attitudes towards schizophrenia before and after undergraduate psychiatric training in Greece.

AIMS: The aim of the present study was to explore medical students' beliefs and attitudes towards people with schizophrenia (PwS) prior to receiving any training in psychiatry and to assess the impact of the psychiatric placement on changing them. METHODS: A questionnaire addressing beliefs, attitudes and desired social distance from PwS was distributed to all final year medical students before the beginning of their 4-week undergraduate psychiatric placement and upon its completion. RESULTS: Students did not endorse stereotypes commonly attached to PwS, such as being dangerous, lazy or of lower intelligence, but they held the view that PwS are unpredictable and suffer from split personality. Furthermore, the baseline level of desired social distance was found to increase as the intimacy of the interaction increased, and the only variable associated with it was personal experience of serious mental illness. Moreover, the placement was found to have either no influence at all or in a negative direction. Upon its completion more students were found to believe that PwS cannot recover, have no insight into their condition, cannot make reasonable decisions, cannot work in regular jobs and are dangerous to the public. No difference was recorded in social distance scores. CONCLUSIONS: A close and critical examination of the various elements of the undergraduate placement in psychiatry is needed in order to develop an evidence-based, fully rounded education with an anti-stigma orientation.

The interference of introversion-extraversion and depressive symptomatology with reasoning performance: a behavioural study.

The objective of this study was to investigate the link between the Eysenck Personality Questionnaire (EPQ) scores and depressive symptomatology with reasoning performance induced by a task including valid and invalid Aristotelian syllogisms. The EPQ and the Zung Depressive Scale (ZDS) were completed by 48 healthy subjects (27 male, 21 female) aged 33.5 ± 9.0 years. Additionally, the subjects engaged into two reasoning tasks (valid vs. invalid syllogisms). Analysis showed that the judgment of invalid syllogisms is a more difficult task than of valid judgments (65.1% vs. 74.6% of correct judgments respectively, p < 0.01). In both conditions, the subjects' degree of confidence is significantly higher when they make a correct judgment than when they make an incorrect judgment (83.8 ± 11.2 vs. 75.3 ± 17.3, p < 0.01). Subjects with extraversion as measured by EPQ and high sexual desire as rated by the relative ZDS subscale are more prone to make incorrect judgments in the valid syllogisms, while, at the same time, they are more confident in their responses. The effects of extraversion/introversion and sexual desire on the outcome measures of the valid condition are not commutative but additive. These findings indicate that extraversion/introversion and sexual desire variations may have a detrimental effect in the reasoning performance.

Predictive smooth eye pursuit in a population of young men: I. Effects of age, IQ, oculomotor and cognitive tasks.

Smooth eye pursuit is believed to involve the integration of an extraretinal signal formed by an internal representation of the moving target and a retinal signal using the visual feedback to evaluate performance. A variation of the smooth eye pursuit paradigm (in which the moving target is occluded for a short period of time and subjects are asked to continue tracking) designed to isolate the predictive processes that drive the extraretinal signal was performed by 1,187 young men. The latency to the onset of change in pursuit speed, the time of decelerating eye-movement speed and the steady state residual gain were measured for each subject and correlated with measures of other oculomotor (closed-loop smooth eye pursuit, saccade, antisaccade, active fixation) and cognitive tasks (measuring sustained attention and working memory). Deceleration time increased with increasing age, while education, general IQ and cognitive variables had no effect on predictive pursuit performance. Predictive pursuit indices were correlated to those of closed-loop pursuit and antisaccade performance, but these correlations were very weak except for a positive correlation of residual gain to saccade frequency in the fixation task with distracters. This correlation suggested that the maintenance of active fixation is negatively correlated with the ability to maintain predictive pursuit speed. In conclusion, this study presents predictive pursuit performance in a large sample of apparently healthy individuals. Surprisingly, predictive pursuit was weakly if at all related to closed-loop pursuit or other oculomotor and cognitive tasks, supporting the usefulness of this phenotype in the study of frontal lobe integrity in normal and patient populations.

Predictive smooth eye pursuit in a population of young men: II. Effects of schizotypy, anxiety and depression.

Smooth pursuit eye movement dysfunction is considered to be a valid schizophrenia endophenotype. Recent studies have tried to refine the phenotype in order to identify the specific neurophysiological deficits associated with schizophrenia. We used a variation of the smooth eye pursuit paradigm, during which the moving target is occluded for a short period of time and subjects are asked to continue tracking. This is designed to isolate the predictive processes that drive the extraretinal signal, a process previously reported to be defective in schizophrenia patients as well as their healthy relatives. In the current study, we investigated the relationship between predictive pursuit performance indices and age, education, non-verbal IQ, schizotypy and state anxiety, depression in 795 young Greek military conscripts. State anxiety was related to better predictive pursuit performance (increase in residual pursuit gain), while disorganized schizotypy was related to deficient predictive pursuit performance (decreased residual gain). This effect was independent of the effect of disorganized schizotypy on other oculomotor functions supporting the hypothesis that predictive pursuit might be specifically affected in schizophrenia spectrum disorders and could be considered as a distinct oculomotor endophenotype.

Schizophrenia-related neuregulin-1 single-nucleotide polymorphisms lead to deficient smooth eye pursuit in a large sample of young men.

Neuregulin-1 (NRG1) variations have been shown to modulate schizophrenia candidate endophenotypes related to brain structure and function. The aim of this study was to determine the effect of NRG1 on several oculomotor schizophrenia endophenotypes. The effects of 5 core single-nucleotide polymorphisms (SNPs) within the NRG1 gene to oculomotor parameters in a battery of oculomotor tasks (saccade, antisaccade, smooth eye pursuit, fixation) were investigated in a sample of 2243 young male military conscripts. Additive regression models, bootstrap and permutation techniques, were used as well as structural equation modeling and haplotype analysis. A deficit in global smooth eye pursuit performance measured using the root-mean-square error (RMSE) was related to the risk allele of SNP8NRG243177, and a deficit in global smooth eye pursuit performance measured using the saccade frequency was related with the risk allele of SNP8NRG433E1006. Structural equation modeling confirmed a global effect of NRG1 genotype on smooth eye pursuit performance using the RMSE, while the effect on saccade frequency was not confirmed. Haplotype analysis further confirmed the prediction from the structural equation modeling that a combination of alleles corresponding to the Icelandic high-risk haplotype was related to a deficit in global pursuit performance. NRG1 genotype variations were related to smooth eye pursuit variations both at the SNP level and at the haplotype level adding to the validation of this gene as a candidate gene for the disorder.

Monitoring antisaccades: inter-individual differences in cognitive control and the influence of COMT and DRD4 genotype variations.

Conscious monitoring of behavior is an essential control function for adaptation and learning. Antisaccade performance was investigated in a large sample of young healthy men in two tasks, one that required conscious error monitoring and one that did not. Conscious error monitoring did not lead to changes in error rate between the two tasks, while other antisaccade parameters were significantly modulated. Application of signal detection theory showed a large inter-individual variability in error detection sensitivity: the majority of individuals were unable to monitor antisaccade errors (chance error detection group), while a minority that successfully monitored their errors (non-chance error detection group) were worse in antisaccade performance in both tasks. These results were explained by the hypothesis of two modes of antisaccade processing favored by each one of the two groups: a mode of conscious cortical cognitive control leading to error monitoring, worse performance and no post-error adaptation and a mode of non-conscious subcortical control leading to chance error monitoring, post-error slowing and better performance of the antisaccade task. This hypothesis was corroborated by the results of the genotype analysis. Error-monitoring sensitivity in the non-chance error detection group was modulated by COMT genotype variations that in turn did not have an effect on error rate. On the other hand, DRD4 genotype variations were related to differences in antisaccade error rate while not affecting error-monitoring sensitivity.

Perceived social stigma, self-concept, and self-stigmatization of patient with schizophrenia.

The advent of community-based mental health care in Greece emphasized clinicians' need to understand patients' attitudes and their experience of their illness. A 42-item self-administered questionnaire (Self-Stigmatization Questionnaire) with flexible format was designed and administered to 150 outpatients with schizophrenia who fulfilled the criteria for inclusion in the vocational rehabilitation program where the study took place. The patients participated voluntarily. Multivariate regression models were applied to each item to assess the degree of patients' self-stigmatization experience as well as the effect of potential factors such as age, sex, psychopathologic condition, hospitalization, and duration of illness. The options selected by the patients revealed stigmatized attitudes in most items. The odds of selecting these options were mainly influenced by the severity of the patients' psychopathologic condition and the duration of illness and less by sex, age, and hospitalization.