Nenad Jakšić

Association between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia.

Abstract Vuksan-Cusa B, Sagud M, Jakovljevic M, Mihaljevic Peles A, Jaksic N, Mihaljevic S, Zivkovic M, Kudlek Mikulic S, Jevtovic S. Association between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia. Nord J Psychiatry 2012;Early Online:1–6. Background: Previous studies revealed high prevalence of metabolic syndrome (MetS) in patients with bipolar disorder and schizophrenia. C-Reactive protein (CRP) and homocysteine have also both emerged as independent risk factors for the development of cardiovascular disease (CVD) but are less investigated in psychiatric disorders. Aims: The aim of this study was to ascertain which specific subcomponents of MetS are associated with levels of CRP and homocysteine in patients with bipolar disorder and schizophrenia. Methods: Our sample consisted of patient group (n = 122) (60 bipolar and 62 schizophrenic patients) treated with second-generation antipsychotics (SGA) and healthy controls (n = 59). MetS was defined according to NCEP ATP-III criteria; the cut-off point for elevated CRP was set up at 5 mg/l and for hyperhomocysteinemia at 15 μmol/l. Results: In the patient group, homocysteine was correlated with waist circumference, systolic and diastolic blood pressure, triglycerides and blood glucose, while CRP was correlated with waist circumference and diastolic blood pressure. Patients with hyperhomocysteinemia had an 8.442 times higher chance to have met the criteria for MetS while elevated CRP was not a significant predictor of MetS. Conclusions: There is a complex association between CRP and homocysteine with specific subcomponents of MetS in patients with bipolar disorder and schizophrenia. Given the high risk of cardiovascular disorders in psychiatric patients, these relationships deserve further investigation. Clinically, it could be useful to include the measurement of homocysteine and CRP levels in routine psychiatric diagnostic procedures.

Pathological Narcissism and Depressive Symptoms in Psychiatric Outpatients: Mediating Role of Dysfunctional Attitudes

OBJECTIVE The aim of this study was to examine the relationships between pathological narcissism (narcissistic grandiosity and narcissistic vulnerability), dysfunctional attitudes (perfectionism and dependency on other people), and depressive symptoms in psychiatric outpatients. METHOD A sample of 234 adult psychiatric outpatients (57.3% male; mean age 44.39 years) completed the Pathological Narcissism Inventory, the Dysfunctional Attitudes Scale-Form A, and the Depression, Anxiety, Stress Scales-21. RESULTS Narcissistic vulnerability exhibited unique positive correlations with depressive symptoms, whereas narcissistic grandiosity showed substantially weaker correlations with depressive symptoms. Perfectionism partially mediated the relationship between narcissistic vulnerability and depressive symptoms. The mediating role of dependency was not confirmed. CONCLUSIONS Among adult psychiatric outpatients, narcissistic vulnerability is more strongly related to depressive symptoms than narcissistic grandiosity, and dysfunctional perfectionism represents one of the underlying mechanisms of this relationship. The implications of these findings are discussed in relation to the Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria and the treatment of pathological narcissism.

Psychometric properties and factor structure of the Temperament and Character Inventory-Revised (TCI-R) in a Croatian psychiatric outpatient sample

OBJECTIVE The goal of this study was to investigate psychometric properties and factorial structure of the Croatian adaptation of the Temperament and Character Inventory-Revised (TCI-R) in a sample of psychiatric outpatients (n=328). METHOD The participants filled out the TCI-R, as well as self-report measures of the Big-Five personality traits (IPIP-50), trait impulsivity (BIS-11), depression (BDI-II), suicidality (SBQ-R), and life satisfaction (SWLS). We explored the internal consistency of 7 domains and 29 subscales and compared it with the Croatian version of the original TCI used in prior studies. Principal component analysis with promax rotation was conducted on temperament and character subscales separately, while concurrent validity was examined through the TCI-Rs relations with the abovementioned psychological measures. RESULTS The TCI-R scales showed adequate internal consistencies, with Cronbachs alpha values ranging from 0.77 to 0.93. The internal consistency showed to be higher in comparison with the Croatian version of the original TCI. The postulated four-factor structure of temperament and the three-factor structure of character were confirmed. The meaningful associations with other measures supported the concurrent validity of the TCI-R. CONCLUSION The Croatian adaptation of the TCI-R exhibited satisfactory reliability and validity in a sample of psychiatric outpatients. These findings support the use of the TCI-R in Croatian clinical settings over its predecessor (TCI).

Monoamine Oxidase A Gene Methylation and Its Role in Posttraumatic Stress Disorder: First Evidence from the South Eastern Europe (SEE)- PTSD Study

Abstract Background Posttraumatic stress disorder is characterized by an overactive noradrenergic system conferring core posttraumatic stress disorder symptoms such as hyperarousal and reexperiencing. Monoamine oxidase A is one of the key enzymes mediating the turnover of noradrenaline. Here, DNA methylation of the monoamine oxidase A gene exonI/intronI region was investigated for the first time regarding its role in posttraumatic stress disorder risk and severity. Methods Monoamine oxidase A methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells in a total sample of N=652 (441 male) patients with current posttraumatic stress disorder, patients with remitted posttraumatic stress disorder, and healthy probands (comparison group) recruited at 5 centers in Bosnia-Herzegovina, Croatia, and the Republic of Kosovo. Posttraumatic stress disorder severity was measured by means of the Clinician-Administered Posttraumatic Stress Disorder Scale and its respective subscores representing distinct symptom clusters. Results In the male, but not the female sample, patients with current posttraumatic stress disorder displayed hypermethylation of 3 CpGs (CpG3=43656362; CpG12=43656514; CpG13=43656553, GRCh38.p2 Assembly) as compared with remitted Posttraumatic Stress Disorder patients and healthy probands. Symptom severity (Clinician-Administered Posttraumatic Stress Disorder Scale scores) in male patients with current posttraumatic stress disorder significantly correlated with monoamine oxidase A methylation. This applied particularly to symptom clusters related to reexperiencing of trauma (cluster B) and hyperarousal (cluster D). Conclusions The present findings suggest monoamine oxidase A gene hypermethylation, potentially resulting in enhanced noradrenergic signalling, as a disease status and severity marker of current posttraumatic stress disorder in males. If replicated, monoamine oxidase A hypermethylation might serve as a surrogate marker of a hyperadrenergic subtype of posttraumatic stress disorder guiding personalized treatment decisions on the use of antiadrenergic agents.

The Effects of Electroconvulsive Therapy Augmentation of Antipsychotic Treatment on Cognitive Functions in Patients With Treatment-Resistant Schizophrenia

Objectives Treatment-resistant schizophrenia (TRS) continues to be a challenge in modern psychiatry. Most of these patients have severe neurocognitive deficits. Electroconvulsive therapy (ECT) has proved effective and safe in the treatment of TRS, but because of potential neurocognitive adverse effects, it is associated with many controversies. The aim of this prospective, open study was to evaluate the effects of ECT augmentation of antipsychotics on cognitive functions in patients with TRS. Methods Overall, 31 inpatients with TRS were included, 16 men, with an average (SD) age of 34.1 (11.187) years. The evaluation of clinical symptoms and global impression, as well as verbal memory, visual memory, working memory, psychomotor speed, verbal fluency, and executive functioning, was conducted before and after the completion of ECT treatment. Results We ran a series of paired-samples t tests, and the Bonferroni adjustment for multiple comparisons reduced the significance level to P = 0.004. The neurocognitive domains that demonstrated statistically significant improvement were immediate and delayed verbal memory, and executive functioning, whereas statistical trend was observed for visual memory and psychomotor speed. None of the neurocognitive functions exhibited significant deterioration after the ECT treatment. Electroconvulsive therapy was effective in reducing general symptoms of schizophrenia, resulting in more than 30% decrease in the overall symptom severity measured by the Positive and Negative Syndrome Scale. Conclusions Notwithstanding some limitations of this study, the combination of ECT and antipsychotics has improved several neurocognitive domains, without evidence of worsening of any cognitive functions.

Harm avoidance moderates the relationship between internalized stigma and depressive symptoms in patients with schizophrenia

This study investigated the associations between internalized stigma, depressive symptoms, and temperament dimension Harm avoidance. One hundred and seventeen stable outpatients with schizophrenia completed a battery of self-report instruments. Internalized stigma was significantly positively related to depressive symptoms, while Harm avoidance moderated the internalized stigma-depressive symptoms relationship.

CARDIOVASCULAR DISEASE RISK FACTORS IN PATIENTS WITH POSTTRAUMATIC STRESS DISORDER (PTSD): A NARRATIVE REVIEW

Posttraumatic stress disorder (PTSD) is a chronic condition related to severe stress and trauma. There is a mounting evidence about increased prevalence and mortality from cardiovascular diseases (CVD) in patients with PTSD. This review summarizes the current data on possible relations between PTSD and increased risks of CVD, including biological, psychological and behavioral factors. Biological factors refer to increased prevalence of metabolic syndrome (MetS), hypertension, elevation of pro-inflammatory cytokines and homocysteine levels. Peripheral Brain-derived neurotropic factor (BDNF), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and quantitative electroencephalogram (qEEG) are promising surrogate markers of increased cardiovascular risk. Among psychological factors, some personality traits, such as neuroticism and trait impulsivity/hostility, contribute to the development of PTSD, and are associated with general cardiovascular distress. Recently, type-D (distressed) personality is usually investigated in relation to cardiovascular morbidity, but in populations other than PTSD patients. Behavioral factors refer to unhealthy life-styles, encompassing high smoking rate, drug substances abuse and addiction, physical inactivity and unhealthy diet. The relationships among all these factors are complex and yet incompletely taken into consideration. Because of a high prevalence of CVD in patients with PTSD, there is a strong need for a more intensive focus on this vulnerable population in both primary and secondary cardiovascular prevention as well as in effective treatment possibilities.

F97. CHRONIC PHYSICAL MULTIMORBIDITIES, GENDER DISPARITIES AND TREATMENT OUTCOME IN SCHIZOPHRENIA

Abstract Background Increased physical morbidity in patients with schizophrenia (SCH) is well established. However, our knowledge on the role of gender in chronic physical multimorbidities (CPM) remains limited, and the evidence about the effect of CPM on SCH treatment outcome is sparse. The present study explored the gender-dependent differences in the prevalence, and age of onset of CPM between SCH and the general population (GEP), as well as the effect of CPM on hospital readmission in patients with SCH. Methods This cross-sectional study was nested within the larger frame of a prospective cohort study conducted at Psychiatric Hospital ‘‘Sveti Ivan’’, Croatia. Data were collected for a consecutive sample of 136 (49 female and 87 male) patients diagnosed with SCH (ICD-10) and 861 (467 female and 394 male) participants from the general population. The primary outcome was the prevalence of CPM. A secondary outcome was the number of psychiatric readmissions since diagnosis. Results In the total sample we observed the significant difference in CPM prevalence between SCH and GEP in the youngest age group, <35 years old (p=0.006). Among the male participants <35 years old, there were no significant differences in the prevalence of CPM between SCH (25%) and GEP (15%) (p=0.216). However, among the female participants <35 years old, the difference was significant and clinically relevant (p=0.002). Prevalence of CPM was 50% in SCH patients, and 14% in GEP. After the adjustment for age, sex, a number of psychiatric comorbidities and duration of SCH, the number of physical illness comorbidities was significantly associated with the number of previous psychiatric hospital readmission. (multivariate, robust regression; B=0.98; β=0.24; p=0.022). Approximately, the number of rehospitalizations increases for one with each chronic physical illness. Discussion This study identified gender differences in the prevalence of CPM in SCH patients, and the significant association of CPM with psychiatric hospital readmission. Higher physical morbidity points to a substantial disadvantage of female patients early in the course of illness. Understanding the nature and biological basis of gender-determined differences in risk and outcome of CPM might help to identify new therapeutic targets, allow more individualized treatment, and facilitate better risk prediction and application of healthcare resources.

Hypermethylation of the monoamine oxidase A gene – a new epigenetic marker for posttraumatic stress disorder?

Posttraumatic Stress Disorder (PTSD) can develop after experiencing or witnessing any severe traumatic event such as combat. Point prevalence rates in war-affected regions, e.g. Bosnia-Herzegovina and Kosovo, range from 18% to 35%. Noradrenergic dysfunction as represented by e.g. elevated noradrenaline concentrations in the cerebrospinal fluid of PTSD patients is known to play a substantial role in the pathogenesis of PTSD symptoms [1]. Epigenetic regulation (i.e. DNA methylation) is strongly suggested to moderate the interaction between environmental influences and a genetic predisposition. Therefore, differential methylation of genes involved in the noradrenergic system such as the monoamine oxidase A (MAOA) gene might be part of the complex biological underpinnings of a dysregulated noradrenergic system and thereby contribute to PTSD risk. The present study aimed at investigating MAOA gene methylation as a possible epigenetic marker of PTSD status and severity in a sample comprising patients with PTSD and healthy controls recruited from war-affected regions in Bosnia-Herzegovina, Croatia and Kosovo. DNA methylation levels of MAOA (exonI/intronI region) were analyzed in PTSD patients [N=216; m=157, age (mean±s.d.): 50.08±6.74 years], remitted PTSD patients [N=151; m=98, age (mean±s.d.): 49.48±8.20 years] and healthy controls [N=349, m=232, age (mean±s.d.): 48.81±8.50 years] by direct sequencing of sodium bisulfite-treated DNA followed by semi-quantitative analysis of the sequencing results via the Epigenetic Sequencing Methylation software. Severity of PTSD symptoms was assessed by the Clinician-Administered PTSD Scale (CAPS). All participants were assessed for potential confounders of methylation (sex, age, or smoking status). Possible categorical differences were analyzed by (M)ANCOVAs with age and smoking status as covariates. Post-hoc tests (Bonferroni) were performed to test individual differences in methylation across groups. Associations between dimensional measures were analyzed performing partial correlation analyses controlled for age and smoking status. In the male subsample, analyses revealed significant methylation differences at three out of 13 CpG sites between patients with current PTSD, remitted PTSD patients, and healthy controls. Post-hoc tests showed trend-wise significant (padjusted In the female subsample, we failed to observe association of MAOA methylation with either current or remitted PTSD, while there was a positive correlation between MAOA methylation and symptom severity (r=0.294, p=0.033). The results of the present study for the first time suggest MAOA hypermethylation – possibly resulting in an increased noradrenergic tonus – as a disease status and severity marker of PTSD particularly in male patients. Given robust replication, MAOA hypermethylation might thus serve as an epigenetic marker within the complex risk factor constellation of PTSD. Furthermore, applying a personalized pharmaco-therapeutic approach, anti-adrenergic agents might prove to be beneficial in counterbalancing increased noradrenergic signalling specifically in male PTSD patients displaying MAOA hypermethylation.

Experience of Shame Mediates the Relationship Between Pathological Narcissism and Suicidal Ideation in Psychiatric Outpatients

OBJECTIVE Pathological narcissism, described by 2 dysfunctional phenotypic forms-grandiosity and vulnerability-has often been connected to suicidal tendencies in theoretical and clinical literatures. Furthermore, shame proneness has been implicated as a key mechanism that links these 2 constructs. However, empirical evidence for the presumed relationship between pathological narcissism and suicidal tendencies is sparse, and no prior research has investigated the role of shame proneness in this relationship. The objective of the present research was to investigate the complex relations among pathological narcissism, experience of shame, and suicidal ideation in psychiatric outpatients. METHOD A sample of 250 adult psychiatric outpatients (61% female; mean age 39.15 years) were assessed between January and May 2014. The participants filled out the Pathological Narcissism Inventory, the Experience of Shame Scale, and the Suicide Assessment Scale-self-rating. RESULTS Narcissistic vulnerability was found to have unique positive associations with acute suicidal ideation, whereas narcissistic grandiosity exhibited substantially weaker relations with the same construct. Two dimensions of shame-characterological and bodily shame-mediated the relationship between narcissistic vulnerability and suicidal ideation. The mediating role of behavioral shame was not demonstrated. CONCLUSIONS Narcissistic vulnerability seems to be more strongly related to suicidal tendencies than narcissistic grandiosity, while experience of shame represents one of the underlying mechanisms of this relationship among psychiatric outpatients. The implications of these findings are discussed in relation to the role of pathological narcissism in the psychotherapeutic management of suicidality.