Aysen Esen-Danaci

Serum BDNF Levels in Suicide Attempters Related to Psychosocial Stressors: A Comparative Study with Depression

Although many studies have examined the neurobiological aspects of suicide, the molecular mechanisms and pathophysiologic mechanisms associated with suicide remain unclear. In this study, it is aimed to investigate whether there is a difference in serum brain-derived neurotrophic factor (BDNF) levels among suicide attempters without a major psychiatric disorder, compared to major depressive disorder patients and healthy subjects. It was undertaken with the hypothesis that suicide per se lowers serum BDNF levels, since it is a source of stress. The study was carried out in Celal Bayar University Hospital, Manisa, Turkey. Ten suicide attempters, 24 patients with major depressive disorder and 26 subjects without any psychiatric diagnosis and any psychiatric treatment were included in the study. All subjects were asked to give their written consent. Blood samples were collected at the baseline. Serum BDNF was kept at –70°C before testing, and assayed with an ELISA kit (Promega; Madison, Wisc., USA) after dilution with the block and sample solution provided with the kit. The data were subjected to the Kruskal-Wallis test for nonparametric analysis of variance. Mean serum BDNF levels were significantly lower in the suicide group (21.2 ± 12.4 ng/ml) and the major depressive disorder group (21.2 ± 11.3 ng/ml) than the control group (31.4 ± 8.8 ng/ml; p = 0.004). These results suggest that BDNF may play an important role in the neurobiology of suicidal behavior. BDNF levels may be a biological marker for suicidal behavior. To investigate the role of BDNF in suicide, further studies with a wider sample size and a variety of psychiatric diagnoses accompanying suicide attempt are needed.

Effects of second generation antipsychotics on leptin and ghrelin.

BACKGROUND Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin. METHOD 112 patients who were treated either with clozapine (n=20), olanzapine (n=28), risperidone (n=22), quetiapine (n=20) or amisulpride (n=22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group (n=23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay. RESULTS When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2+/-6.7) and amisulpride group had the lowest mean value (3.7+/-2.1) but still there was no statistically significant difference between six groups (F=1993, p=0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups (F=11,473, p=0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5+/-86.8). Quetiapine treated group (378.1+/-260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0+/-150.0). CONCLUSION The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.

Oxidative stress in schizophrenia: a case-control study on the effects on social cognition and neurocognition.

BackgroundSchizophrenia is a debilitating mental disorder that presents impairments in neurocognition and social cognition. Several studies have suggested that the etiology of schizophrenia can be partly explained by oxidative stress. However, our knowledge about the implications of oxidative stress on illness-related cognitive deficits is still far from being clear. The aim of this work was to study the role of oxidative stress molecules on social cognition and neurocognition in patients with schizophrenia.MethodsWe assessed the peripheral levels of several molecules associated with oxidative stress, namely nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), homocysteine, superoxide dismutase (SOD) and neurotrophin 4/5 (NT4/5), in forty-one patients with schizophrenia and forty-three healthy participants. A battery of tests to measure neurocognition and social cognition was also administered to the schizophrenia group.ResultsWe found that the schizophrenia group presented substantially higher levels of oxidative stress than the control group, as revealed by elevated quantities of the pro-oxidants NO and MDA, and decreased levels of the antioxidants GSH, SOD and NT4/5. Interestingly, the levels of NT4/5, which have been shown to have antioxidant effects, correlated with executive functioning, as measured by two distinct tests (WCST and TMT). However, social cognition and symptom severity were not found to be associated with oxidative stress.ConclusionsWe propose a protective role of NT4/5 against oxidative stress, which appears to have a potentially beneficial impact on neurocognition in schizophrenia.

Serum brain-derived neurotrophic factor levels in conversion disorder: Comparative study with depression.

Abstract  The aim of the present study was to compare serum brain‐derived neurotrophic factor (BDNF) levels of patients with major depressive disorder (MDD) and conversion disorder (CD). Serum BDNF levels were measured in the following three groups: 15 CD patients without any comorbid diagnosis of psychiatric disorder, 24 patients with MDD, and 26 healthy subjects without any psychiatric diagnosis or psychiatric treatment. The serum BDNF level of the healthy control group (31.4 ± 8.8 ng/mL) was statistically higher than the level of the MDD group (21.2 ± 11.3 ng/mL) and the CD group (24.3 ± 9.0 ng/mL; P = 0.008). This suggests that BDNF level may play a similar role in the pathophysiology of MDD and CD.

A closer look at the relationship between the subdomains of social functioning, social cognition and symptomatology in clinically stable patients with schizophrenia

Impairments in social functioning commonly seen in schizophrenia are thought to be mediated by deficits in the domains of social cognition. Some previous research has explored how social cognitive skills and psychotic symptoms are associated with social functioning, however these associations are still under debate. The main aim of this study was to investigate the relationship between different domains of social cognition and psychotic symptomatology, and also to look at the relationships with individual subdomains of social functioning within a clinically stable schizophrenia population. 45 outpatients were recruited and symptoms were assessed with the PANSS, and measures of emotion processing, affective and cognitive theory of mind (ToM), mental state reasoning attributional biases, and social functioning were taken. A correlational analysis was performed with the data. Following this, a regression analysis was used to reveal which domains of social cognition best predicted psychotic symptoms. In this stable group of patients, our results support the suggestion of a likely distinction between affective and cognitive components of ToM. The study also demonstrated that ToM and mental state reasoning were the best predictors of psychotic symptoms. Here we reveal that cognitive ToM had the most widespread relationship with social functioning, across multiple subdomains, while only some specific subdomains of social functioning correlated with other domains of social cognition and symptomatology. Further to this, positive symptoms were associated with much fewer subdomains of social functioning than negative and general symptoms. These findings imply that different aspects of social functioning may be served by different domains of social cognition and symptomatology.

Social approach and avoidance behaviour for negative emotions is modulated by endogenous oxytocin and paranoia in schizophrenia

Patients with schizophrenia suffer from dysfunctional social behaviour. Social approach and avoidance (AA) has been associated with motor responses, as the affective valence and gaze direction of facial stimuli can bias push and pull motor tendencies. The aim of this study was to investigate the role of endogenous oxytocin in social AA behaviour in schizophrenia. Basal plasma oxytocin levels were collected from 28 patients who were then given a joystick-based Approach-Avoidance Task (AAT). Reaction times were recorded and AAT effect scores calculated for responses to happy and angry faces, which either had direct or averted gaze. Individual differences in basal oxytocin had a significant relationship with AAT responses, and patients with higher levels of oxytocin tended to avoid angry faces more. Furthermore, greater avoidance of angry faces was correlated with more severe psychotic (positive and general) symptoms and greater paranoia. This suggests that the endogenous effects of oxytocin may be specific to the interpretation of negative threatening emotions in schizophrenia patients, and also provides evidence that psychotic symptoms and paranoia can impact on social AA behaviour by heightening threat avoidance.

Associations of oxytocin and vasopressin plasma levels with neurocognitive, social cognitive and meta cognitive function in schizophrenia

Many with schizophrenia experiences deficits in social cognition, neurocognition and metacognition. Yet the biological mechanisms which may underpin these cognitive deficits are poorly understood. Two candidate causes of these deficits are disturbances in oxytocin (OT) and vasopressin (VP). To explore this we assessed plasma OT and VP in 34 schizophrenia patients and 31 healthy controls. We also concurrently assessed social cognition using the Reading the Mind from the Eyes test, neurocognition using the Wisconsin Card Sorting Test and metacognition using the Metacognitive Assessment Scale-Abbreviated. Group comparisons revealed lower plasma OT levels in the schizophrenia group. Plasma VP levels did not differ between groups. Correlations revealed that lower levels of OT were associated with poorer levels of metacognitive functioning in the schizophrenia group but not poorer social cognition or neurocognition. In a stepwise multiple regression, plasma OT level, neurocognition and social cognition contributed uniquely to the prediction of metacognition in the schizophrenia group. Results may suggest that disturbance in OT is linked with deficits in metacognition and may interact with other forms of cognitive deficits, interfering with the persons abilities to form a complex and integrated sense of self and others.

Cortisol response to stress in schizophrenia: Associations with oxytocin, social support and social functioning

Previous studies reported attenuated cortisol reactivity as one explanation for poor social functioning in schizophrenia. Recent research has demonstrated that both glucocorticoid and oxytocin systems are central to stress regulation. Here, we studied the associations between basal oxytocin, stress-induced cortisol levels, and social functioning and social support in schizophrenia. A mock job interview was used as an ecologically-valid social stressor in 32 schizophrenia patients. Blood samples were taken before and after stress induction to assess basal oxytocin and cortisol levels. In addition social functioning and social support scales were collected. Patients were divided into cortisol responders and non-responders according to percentage change following stress induction. Our findings revealed a possible subgroup of patients who did not exhibit attenuated cortisol responses. Importantly, cortisol responders had generally better social functioning, but perceived social support was not different between groups. There was also no evidence of a relationship between cortisol and oxytocin. This study highlights the heterogeneity of cortisol responses to stress in a schizophrenia population, and the importance of the relationship between social functioning and cortisol reactivity. These findings could be relevant when considering therapeutic interventions that manipulate endocrinology in order to improve real-world functioning.