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Depression is a complex and highly heterogeneous disorder with an omnigenic and multifactorial background. This diversity is obvious not only in its symptomatic manifestation but also in its neurobiological underpinnings which is one potential factor contributing to the high observed rate of treatment resistance. Thus, subtyping depressions, understanding their distinct neurobiological and genetic background, and potentially developing biomarkers aiding their differential diagnosis may bring us one step closer to more effective treatment. The present talk will overview the different etiological factors contributing to the emergence of depression along an endogenous-reactive continuum, the contributory roles of different types of stress, different genes involved in distinct processes, and the potential consequences of conceptualising, diagnosing and treating depressions developing in the context or independently of current stress. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: The Mental Health Test serves as the operationalized, comprehensive measurement of Maintainable Positive Mental Theory which defines mental health (for either the non-clinical or psychiatric population) as a high level of global well-being, psychological, social and spiritual functioning, resilience, effective creative and executive functioning, savoring capacities, coping and enjoyment, regardless of the presence or absence of symptoms of psychopathology. Objectives: To assist psychiatrists and clinical psychologists to assess their patients' psychological immune competence–based capacities and resources, depending on the mental health disorder diagnosis and the severity of the symptoms, the present study examined the psychometric properties of the Mental Health Test in a psychiatric sample. Methods: The research was carried out in four Hungarian healthcare facilities using a cross-sectional design. A total of 331 patients (140 male, 188 female, and 3 who preferred not to disclose their gender) completed the Mental Health Test, six well-being and mental health measures, and the Symptom Checklist-90. Clinical psychologists reported the mental disorder status of each participant. Results: Confirmatory factor analysis showed a good fit of the five-factor model to the data for the clinical version of the Mental Health Test (CFI = 0.972, RMSEA = 0.034). High internal consistency coefficients (α: 0.70–0.84; ω: 0.71–0.85) and excellent external and content validity were reported. The Mental Health Test was not sensitive to sociodemographic indicators but was sensitive to correlates of well-being and symptoms of mental disorders in a psychiatric sample. Regression analyses demonstrated that unipolar depression and number of mental disorders were related to a lower overall Mental Health Test score. Personality disorders, unipolar depression, and the greater severity and higher number of mental disorders were associated with a lower global well-being score. Unipolar depression was related to lower savouring capacity. Self-regulation showed a correlation with the self-reported number of mental disorders only. Anxiety and somatization disorders, unipolar depression, and a higher number of self-reported mental disorders were related to a lower psychological resilience score. The regression model for the creative and executive efficiency subscale did not fit our data. The interaction of all combinations of psychotherapy and pharmacotherapy was significantly related to the overall Mental Health Test score and to the subscales. These results can later serve as a basis for designing intervention studies. Conclusions: Our preliminary findings suggest that the Mental Health Test is a suitable measure for assessing mental health capacities and resources in psychiatric samples. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Stressful life events (SLE) may influence the illness course and outcome. Objectives: The present study aimed to characterize sociodemographic and clinical characteristics of euthymic major depressive disorder (MDD) outpatients with SLE relative to those without. Methods: This sample included 628 (mean age=55.1 ± 16.1) currently euthymic MDD outpatients, among them 250 (39.8%) reported SLE and 378 (60.2%) did not. Results: After univariate analyses, outpatients with SLE were most frequently widowed and lived predominantly with friends/others. Furthermore, compared to outpatients without SLE, those with SLE were more likely to have a family history of suicidal behavior, manifested melancholic characteristics and higher Coping Orientation to the Problems Experienced (COPE) positive reinterpretation/growth and less likely to manifest a comorbid panic disorder, residual interepisodic symptoms, have used psychiatric medications, and use current antidepressant medications. After regression analyses, having a family history of suicide (OR=9.697; p=≤.05), history of psychotropic medications use (OR=2.888; p=≤.05), and reduced use of antidepressants (OR=.321; p=.001) were significantly associated with SLE. Mediation analyses demonstrated that the association between current use of antidepressants and SLE was mediated by previous psychiatric medications. Conclusions: Having a family history of suicide, history of psychotropic medications use, and reduced use of antidepressants may confer a specific "at risk" profile related to the enhanced vulnerability to experience SLE. [ABSTRACT FROM AUTHOR]

In the interaction testing, based on the reviewed literature[2],[3], we analyzed the possible interactions between depression and the calculated childhood maltreatment score considering the polymorphisms of CDC45. At the same time, during the interaction analyses, the minor allele (A) of the two polymorphisms yielded significant (p=0.029 for rs13447271 and p=0.040 for rs13447279) protective effects in case of the interaction of childhood maltreatment depression score. [Extracted from the article]

B Background: b A novel candidate for treatment in various psychiatric disorders is the and neuropeptide oxytocin involved in diverging emotional and social behaviours such as anxiety, reward, bonding, stress responsivity and resilience and psychopathologies including autism spectrum and posttraumatic stress disorders. The aim of our present research was to investigate OXTR gene variation in interaction with recent stress influencing the severity of current depressive symptoms in a large European general population sample. [Extracted from the article]

Data from the United States and from several European countries show that patients with major mood disorders, schizophrenia and social phobia smoke at significantly higher rates than the general population. However, there are no published results on this field from Central Europe, including Hungary. In the present study, the rate of current and lifetime smoking of the consecutively screened outpatients with DSM-IV unipolar major depression ( n =92), bipolar disorder ( n =60), schizophrenia ( n =80), schizoaffective disorder ( n =42) and panic disorder without major depression ( n =60) were assessed and the data were compared to the controls ( n =5503), representative for the general population of Hungary. The results showed that, compared to controls, the rates of current and lifetime smoking were significantly higher among patients with unipolar major depression, bipolar disorder, schizophrenia and schizoaffective disorder, but not among patients with panic disorder without major depression. The findings support previous findings from other countries on the strong relationship between cigarette smoking and major mood and schizophrenic spectrum disorders. [ABSTRACT FROM AUTHOR]

In the majority of countries, suicide rates increase progressively with age, the highest suicide rates occurring in men above 75 years. Given the progressive aging of population in industrialized countries, old age suicide is one of the greatest public health problems. Although suicide attempt, and particularly completed suicide are relatively rare events in the community, they are very common among older psychiatric patients who contact different levels of health care system, particularly some weeks or months before the suicide event. More than one-third of suicide victims have at least one prior suicide attempt, which significantly increases the risk of future attempts and completed suicide. However, the rate of attempted to completed suicide decreases with increasing age indicating that the lethality of suicidal behaviour is much higher in older persons. Suicide is a very complex, multifactorial human behaviour with several biological and psychosocial components, associated with a number of 1/ Psychiatric (e.g., major mental disorders), 2/ Psycho-social (e.g., adverse life situations), and 3/ Demographic (e.g., male gender) suicide risk factors. Although depressive disorders and substance-use disorders are the two most common diagnoses among suicide victims, depression is more common and substance abuse is less prevalent in later-life suicide victims. Beside depression and prior suicide attempt, social isolation, loss of relatives/friends and physical illnesses are the most important risk factors for suicide in this age-range. Available studies suggest that appropriate acute and long-term treatment of depression in combination with psychosocial interventions reduces suicide mortality even in this very high-risk population. [ABSTRACT FROM AUTHOR]

Objective: Distinct subtypes of depression presenting with characteristic symptom clusters have different neuroanatomical and neurochemical background, and these subtypes behave differently also pharmacologically. Based on the neurocircuitry theory, several studies investigated the possible neuroanatomical and neurochemical substrates of major depressive symptoms. Our team has developed a new scale, the Depression Profile that incorporates symptoms associated with depression forming symptom clusters that can be mapped to different neurotransmitter systems. Methods: 339 major depressive patients completed the original 90-item structure of Depression Profile. Confirmatory and exploratory factor analysis was used to establish the final structure. The external validity of the new structure was tested against the Zung Self-Rating Depression Scale and Sheehan Patient Rated Anxiety Scale. Results: After exploratory factor analysis the number of items decreased to 67. Reliability of the new structure proved to be very good and its construct validity was supported by confirmatory factor analysis. Convergent validity testing of the new structure showed average correlation with the two other questionnaires. Conclusion: Current depression scales do not provide for the separate in-depth screening of depressive symptom clusters associated with different neurotransmitter systems playing a role in depression. We attempted to develop a new depression scale separately assessing depressive symptom clusters reflecting the activity of different neurotransmitter systems. First psychometric tests indicate that our scale is a promising instrument for decomposing depression to subtypes with different neurochemical backgrounds, which would make it a useful tool in selecting a tailor-made pharmacological treatment for each patient that most effectively treats their depressive symptoms. [Copyright &y& Elsevier]

Background: Affective temperaments as measured by the TEMPS-A are known to be associated with 5-HTTLPR, however, this association is valid in case of all scales within the depressive superfactor (depressive, cyclothymic, irritable, anxious). Less attention was paid to the association of items composing these affective temperament scales with the 5-HTTLPR polymorphism. The aim of our study was to investigate the association of TEMPS-A items with the s allele of the 5-HTTLPR. Method: 138 psychiatrically healthy women completed the TEMPS-A questionnaire and were genotyped for 5-HTTLPR. Scores of subjects on the temperament scales, subscales and items were compared in subjects carrying and not carrying the s allele (dominant model) using ANOVA. We selected items with significantly different mean scores between two groups and performed item analysis. Results: Subjects in the two groups had significantly different scores on the depressive, cyclothymic, irritable and anxious temperament scales. Subjects carrying and not carrying the s allele had significantly different scores on 12 items, 9 of which were retained in a derived 5-HTTLPR phenotype scale after item analysis. Discussion: Our data provide further support for the association of affective temperaments with the s allele. Although the cyclothymic temperament shows the strongest association, all temperaments within the depressive superfactor have a similar share in this association. The newly derived 5-HTTLPR Phenotype Scale shows strong association with 5-HTTLPR genotype and phenotype, therefore this scale should be further investigated in relation to psychiatric disorders, pharmacological response, and suicide, as well as psychological traits and temperaments. [Copyright &y& Elsevier]

Background: Although depressive disorders are common conditions in primary health care service, and many depressed patients consult their general practitioners, GPs have some difficulties in the detection and correct diagnosis of depression. Unrecognized and untreated depression causes great health and economic burden and also contributes to significant suffering, therefore the correct recognition of affective disorder in GP settings is an important healthcare target. The aim of our study was to assess the prevalence of depressive disorders in general practices in Hungary and also to assess the sensitivity and specificity of different depression screening instruments. Method: In the present study the current prevalence of DSM-IV depressive disorders were surveyed among 984 primary care attendees in 6 GP practices in Hungary, using the Beck Depression Inventory and the PRIME-MD screening instrument. Results: The current prevalence rate of any PRIME-MD DSM-IV depressive disorders, including symptomatic major depressive episode, were 18.5% and 7.3% respectively. Beck Depression Inventory identified any current depressive disorders with 95% sensitivity and 56% specificity and the same figures for current symptomatic major depressive episode were 83% and 23%, respectively. Discussion: Our results are similar to those reported previously from Hungary and from other countries. The findings also indicate that the Beck Depression Inventory and PRIME-MD can help in detecting depressive disorders in primary care. [Copyright &y& Elsevier]

B Introduction: b Mental health disorders have a huge impact on the well-being of the population, with affective disorders showing the highest prevalence and depression predicted to become the illness associated with the highest disease burden in the near future. B Aim: b The aim of the present study is to reveal associations between variation of the CLOCK gene, circadian phenotypes ascertained by the Morningness-Eveningness Questionnaire and lifetime depression in a large European general population sample. B Conclusion: b Investigating the genetic background of chronotype and its links to mood disorders contributes to elucidating biological pathways behind MDD and BD as well as alleviates a more precise estimation of the risk of developing depression. [Extracted from the article]

B Background: b Oxytocin is a peptide hormone and neuropeptide involved in various neurobehavioural functions including a variety of emotional and social behaviours including several psychiatric illnesses. In spite of some positive associations between OXTR SNPs and depression also in interaction with recent stress, interaction between childhood maltreatment and the most widely investigated OXTR SNPs could not be confirmed so far. B Results: b In the OXTR gene none of the investigated SNPs had a significant main effect on depression. [Extracted from the article]

Altered serum levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNFalpha) have been implicated in therapy response of depression. We analyzed effects of 4 functional SNPs of VEGF and TNF alpha genes on MDD to test their possible role in pathomechanism of MDD.We recruited 293 inpatients diagnosed for major depressive disorder (MDD) and 443 healthy volunteers. MDD was diagnosed by DSM-IV criteria and measured by Montgomery-Asberg Depression Scale (MADRS). DNA was extracted from buccal mucosa samples given by all participants. Likelihood ratio tests for case-control and mutlivariate linear analysis for quantitative phenotype models were performed in SPSS 17.0 software. We identified a protective allele against MDD as the frequency of G allele of rs1800629 (previously associated with lower TNFa serum level) was 2.7 fold higher in the control group compared to MDD group (LRT=4.197; p=0.040). Higher frequency of the same allele was found among SSRI responders compared to non-responders (LRT=6.281; p=0.012). Significant GxG interactions were shown within MDD group: epistatic effect of allele variants and also genotypes of the four investigated SNPs were significant on MADRS score (for risk alleles: pmodell =0.024; pinteraction =0.005; Adj.R2 =0.259; for genotypes: pmodell =0.035; pinteraction =0.007; Adj.R2 =0.371). These findings suggest that TNFalpha and VEGF genes are associated with MDD and SSRI response. Our results support the molecular crosstalk between VEGF and TNFalpha pathway by a genetic interaction.This study was supported by the Hungarian Scientific Research Fund Grant (OTKA CK 80289/2009). [ABSTRACT FROM AUTHOR]

Background: VEGF exerts diverse effects on the cardiovascular system. VEGF and its receptors are also expressed in the central nervous system. Moreover, accumulating data suggest that VEGF is involved in the etiopathogenesis of depression. To date, the association of the −2578 C/A SNP with depression has been investigated only by two research groups but their results are conflicting. Aims: In the present study we tried to assess the potential association of the −2578 C/A polymorphism with mood disorders (MDD and BD). Methods: 220 patients (MDD: 140; BP: 80) with a current episode of major depression (MDE) were recruited at our department. HADS was used for the assessment of the severity of depressive symptoms. Control subjects without psychiatric history were also enrolled (n=410). VEGF −2578 C/A SNP was analyzed with quantitative PCR. Results: We found no significant differences in allele frequencies between cases and controls (neither in the comparison of whole patient sample vs. controls nor in comparisons of patients with MDD or BP vs. controls). Nevertheless, depression scores of patients with MDD who carry the C allele were significantly higher (p=0.012). Conclusion: Our preliminary results suggest that presence of the C allele might predispose to a more severe MDE in patients with MDD. This is in partial agreement with the results of Viiki et al. who found that the CC genotype was more frequent among patients with MDD than in control subjects and also associated with treatment resistant depression. Acknowledgement: The study was supported by OTKA 80289 national grant. [ABSTRACT FROM AUTHOR]

Introduction: There is a marked overlap between the neuronal pathways involved in sleep/wake regulation and depression. Both the structure and the organization of sleep are altered in depressed patients; they enter the rapid eye movement (REM) sleep earlier, the amount of REM is increased and also the non-REM sleep is reduced in the first sleep cycle. Serotonin reuptake inhibitor antidepressants (SSRIs) exert their therapeutic effect on the serotonergic system, which has a central role in the modulation of mood and vigilance. Aims: The aim of this study was to investigate the acute and long-term effect of the SSRI escitalopram on REM sleep in rats. Methods: The effect of a single (10mg/kg i.p.) and chronically administered (10mg/kg/day, released by an osmotic mini pump for 21-day-long) escitalopram was studied in male Wistar rats. Electroencephalogram, electromyogram and motility were recorded for three hours starting at light onset. Results: The acutely administered escitalopram significantly reduced the time spent in REM sleep in the first three hours, compared to control. However, this REM-reducing effect was abolished after chronic administration. Conclusion: There was a clear difference in the effect of escitalopram on REM sleep following acute and chronic administration, providing evidence for the adaptive changes of serotonin receptors, which take several weeks to evolve, and considered to have a role in the development of therapeutic effect of SSRIs in the treatment of depression. This study was supported by the TAMOP-2.2.1. B-09/1/KMR-2010-0001 and by Richter Gedeon Plc. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study was to assess sociodemographic and clinical differences between BD patients, pure MDD patients, and MDD patients with cyclothymic temperament (MDD-CYC). Methods: Participants were 281 adult inpatients (134 men and 147 women) consecutively admitted to the Department of Psychiatry of the Sant''Andrea University Hospital in Rome, Italy, between January 2008 and June 2010. The patients completed the Hamilton Scale for Depression (HAMD17), the Young Mania Rating Scale, the TEMPS-A (Temperament Evaluation of the Memphis, Pisa, Paris and San Diego - Autoquestionnaire) and the Beck Hopelessness Scale. Results: 38.7% of the MDD patients met criteria to be included in the MDD-CYC group. Above 93% of the MDD-CYC reported suicidal ideation (27.6% suicide attempts) at the item 3 of the HAMD17.Furthermore, MDD-CYC patients reported higher hopelessness compered to other patients. Limitations: Our results are potentially limited by the small number of MDD-CYC patients included in the sample. Conclusions: Our results support the clinical usefulness of the concept of soft bipolar spectrum. Patients with unipolar depression and cyclothymic temperament differ from pure MDD patients and BD patients in terms of temperamental profile and clinical variables. [Copyright &y& Elsevier]

Aims: The aim of the study was to investigate the relationship between the individual pattern of affective temperaments, non-typical symptoms of depression as measured with the Gotland Scale for Male Depression (GSMD), hopelessness and suicidal behavior in major mood disorder patients. Methods: Participants were 346 adult inpatients (151 men and 195 women) with major mood disorders consecutively admitted to the Department of Psychiatry of the Sant''Andrea University Hospital in Rome, Italy. All the patients were administered the TEMPS-A, the GSMD, and the Beck Hopelessness Scale (BHS) and the Mini International Neuropsychiatric Interview (MINI). Results: A Two Step Cluster Analysis procedure, performed to reveal natural groupings within patients'' response set, indicated that there were 2-groups: a cyclothymic-depressive-anxious group and a hyperthymic group. More than 81% of the patients with prevailing cyclothymic-depressive-anxious temperament had mild to severe suicidal risk on the MINI vs. only around 42% of the patients with prevailing hyperthymic temperament., Sixty-four percent of patients with prevailing cyclothymic-depressive-anxious temperament had BHS scores of 9 or higher versus only 13% of patients with prevailing hyperthymic temperament. Also, patients with prevailing cyclothymic-depressive-anxious temperament more likely had higher GSMD than patients with prevailing hyperthymic temperament. Discussion and conclusions: Our results indicate that affective temperament measure along with Gotland Scale for Male Depression could be useful tools in screening and identifying those affective disorder patients who are at higher risk of suicidal behavior. [Copyright &y& Elsevier]

Background: The P2RX7 gene encoding for purinergic receptor P2X has earlier been associated with a susceptibility to anxiety and affective disorders. The aim of our present study was to investigate the association of this polymorphism with different aspects and symptom clusters of major depression. Method: 192 inpatients diagnosed with DSM-IV major depression and bipolar I and bipolar II depression aged 21-69 years (mean=48.2±11.05) participated in our study. All participants were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS). All patients were genotyped for the P2RX7 Gln460Arg SNP (rs2230912) using PCR. Association between genotype and MADRS scores was analysed with ANOVA controlling for age and gender. Results: rs2230912 genotype showed a significant association with depression indicated by the total MADRS score. We also found a significant genotype effect in case of the Affective and Cognitive clusters, but not on the Somatic and Psychomotor clusters of MADRS. Discussion: We managed to confirm earlier results concerning the association of the P2RX7 rs2230912 with major depressive disorder and bipolar depression. Furthermore, we found that this association is carried by the affective and cognitive symptoms associated with depression. Our results bring us closer to decomposing depression to endophenotypes more suitable for research and also for understanding the nature of affective disorders. This work was supported by EU-Hungarian fund, GVOP AKF 311 2004 050324/3.0, the Hungarian National fund, OTKA T048576 and Janos Bolyai Research Fellowship of the Hungarian Academy of Science. [Copyright &y& Elsevier]

Recent studies suggest an evidence for a “male depressive syndrome” in patients with major depressive disorder. Because males are markedly overrepresented among suicide victims and the opposite is true for suicide attempters, we investigated the rate and global severity of Gotland Male Depression as measured by the Gotland Male Depression scale in 86 suicide victims (74 males, 12 females), 86 suicide attempters (21 males, 65 females) with current DSM-IV major depressive episode and in 144 normal controls (116 males, 28 females). The rate of Gotland “Male” Depression (total score of 13 or more) was significantly higher in depressed suicide victims (98%) and in depressed suicide attempters (93%) than in normal controls (2%, p=0.00001). Among depressed suicide victims 100% of males and 83% of females have had Gotland “Male” Depression (p=0.02) while the same figures among the depressed suicide attempters were 91% and 94%, respectively (not significant). The total Gotland Male Depression scores were significantly higher in depressive suicide victims (22.26) and depressive suicide attempters (23.23) than in normal controls (4.01, p=0.00001 and p=0.0001, respectively), with significant gender differences only among depressed suicide victims (males: 22.85, females: 18.58, p=0.009) and normal controls (males: 4.33, females: 2.71, p=0.05). However, since male and female depressed inpatients do not show clinically significant difference in their mean total scores on Gotland scale symptoms (11.99 vs 12.04, Möller-Leimkühler et al, 2004), it would be premature to conclude from our present findings that compared to nonsuicidal female depressives, suicidal female depressives have male-type depression profile. [Copyright &y& Elsevier]