Distinct association of plasma BDNF concentration and cognitive function in depressed patients treated with vortioxetine or escitalopram.

RATIONALE: Cognitive dysfunction is frequent in major depressive disorder (MDD), and brain-derived neurotrophic factor (BDNF) is involved both in regulation of cognition and in therapeutic response in MDD. OBJECTIVES: The aim of this study was to determine if baseline plasma BDNF might predict change in cognitive function in MDD patients treated with vortioxetine or escitalopram, and whether the alterations in BDNF levels correlate with changes in cognitive performance during treatment. METHODS: Drug-naive or drug-free patients with MDD (N=121) were sampled and evaluated at baseline and 4 weeks after treatment initiation with vortioxetine or escitalopram. Cognitive function was evaluated using the F-A-S test, Digit Span test, and Digit Symbol Coding test. Plasma BDNF was determined using ELISA. RESULTS: The results of the study indicate that both vortioxetine (V) and escitalopram (E) improved cognitive functions evaluated with F-A-S test (V: p<0.001; r=-0.427, E: p<0.001; r=-0.370), Digit Symbol Coding test (V: p<0.001; r=-0.706, E: p<0.001; r=-0.435), and Digit Span test-backward span (V: p=0.001; r=-0.311, E: p=0.042; r=-0.185), while only vortioxetine (p<0.001; r=-0.325) improved cognition evaluated with the Digit Span test-forward span. A moderate positive correlation between pretreatment plasma BDNF levels and improvement in cognitive performance was only detected in patients treated with vortioxetine (delta F-A-S test: p=0.011; r=0.325, delta Digit Span test-forward span: p=0.010, r=0.326). CONCLUSIONS: These results suggest that higher baseline plasma BDNF levels might be associated with improvements in verbal fluency and working memory in vortioxetine, but not escitalopram treated patients. Vortioxetine treatment was superior in simple attention efficiency.

Physical and social anhedonia are associated with suicidality in major depression, but not in schizophrenia.

OBJECTIVE: This cross-sectional study investigated the association of physical and social anhedonia with suicidality in patients with major depressive disorder (MDD), schizophrenia, and in non-psychiatric controls. METHOD: All participants completed the revised Physical Anhedonia Scale (RPAS) and the revised Social Anhedonia Scale (RSAS) and were subdivided according to positive life-time suicide attempt history. MDD patients were evaluated with the Montgomery-Ãsberg Depression Rating Scale (MADRS), healthy respondents with the Patient Health Questionnaire-9 (PHQ-9), and schizophrenia patients with the Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: In 683 study participants, the prevalence of each anhedonia was the highest in MDD, followed by schizophrenia, and lowest in the control group. Among MDD patients, those with physical and social anhedonia had greater rates of recent suicidal ideation, while a higher frequency of individuals with life-time suicide attempts was detected in those with only social anhedonia. In contrast, no association between either anhedonia and life-time suicide attempts or recent suicidal ideation was found in patients with schizophrenia. CONCLUSIONS: Assessing social and physical anhedonia might be important in MDD patients, given its association with both life-time suicide attempts and recent suicidal ideation. Suicidality in schizophrenia, while unrelated to anhedonia, might include other risk factors.

Effect of vortioxetine vs. escitalopram on plasma BDNF and platelet serotonin in depressed patients.

Escitalopram and vortioxetine are efficacious antidepressants. They directly target serotonin (5-HT) system, but vortioxetine mechanism of action is distinct from the one of selective serotonin reuptake inhibitors (SSRIs). Treatment with SSRIs decrease platelet 5-HT concentration and increase peripheral brain-derived neurotrophic factor (BDNF) levels. Since vortioxetine has a multimodal mechanism of action, it is expected to have a greater effect on circulatory BDNF concentration, compared to conventional antidepressants. This longitudinal study aimed to explore and compare the effects of 4-weeks of treatment with vortioxetine and escitalopram on plasma BDNF and platelet 5-HT concentration in patients with major depressive disorder (MDD). The results revealed that vortioxetine significantly increased plasma BDNF concentration (p = .018) and significantly decreased platelet 5-HT concentration (p < .001). Treatment with escitalopram significantly decreased platelet 5-HT concentration (p < .001), but it did not affect plasma BDNF concentration (p = .379). Response to vortioxetine was not predicted by baseline plasma BDNF or platelet 5-HT concentration, but response to escitalopram was predicted by baseline platelet 5-HT concentration. These effects might be due to vortioxetine unique mechanism of action, but the clinical implications are unclear. It remains to be determined whether this finding extends during long-term vortioxetine treatment, and which, if any, clinical effects emerge from BDNF increase.

The Role of Religiosity in Coping with Infertility Treatment.

BACKGROUND: To analyze relationship between religiosity and psychological distress in woman undergoing in vitro fertilization. SUBJECTS AND METHODS: The study was based on 103 woman engaged in a fertility treatment with in vitro fertilization. The questionnaires (Religiosity Questionnaire, Clinical Outcomes in Routine Evaluation - Outcome Measure, and socio-demographic questionnaire) were administered by investigators. RESULTS: The results suggest that the level of religiosity significantly differs participants in terms of problems (F=1.92, p=0.01), functioning (F=1.79, p=0.03), risk behaviors (F=3.02, p=0.00), anxiety (F=1.72, p=0.03) and physical problems (F=1.82, p=0.02). There were no significant differences in subjective wellbeing, depression and traumatization according to religiosity. CONCLUSION: Results of a present study point out that religiosity could be considered as a protective factor for psychological distress.

Anhedonia in Schizophrenia: Mini-Review.

The perception of reward exerts a powerful influence on human behavior. While anhedonia might occur in healthy individuals, its prevalence and severity are much higher in psychiatric patients, particularly those with depression and schizophrenia. Anhedonia is a negative symptom, and presumably a trait marker in schizophrenia. Recent research confirmed that anhedonia is a complex construct, consisting of anticipatory, consummatory, and reward learning components. In general, schizophrenia patients show anticipation deficits, and a substantial portion of them have physical (PA) and social anhedonia (SA). The relationship between anhedonia and psychopathology appears bidirectional. While gene-environment interactions affect reward circuity, anhedonia modulates clinical features, such as suicidality and nicotine consumption. Future clinical research employing longitudinal designs may shed more light on the dynamics and treatment of anhedonia in schizophrenia.

The relationship among psychopathology, religiosity, and nicotine dependence in Croatian war veterans with posttraumatic stress disorder.

AIM: To examine relationships among combat exposure, posttraumatic stress disorder (PTSD) symptoms, depression, suicidality, nicotine dependence, and religiosity in Croatian veterans. METHODS: This cross-sectional study used Combat Exposure Scale (CES) to quantify the stressor severity, PTSD Checklist 5 (PCL) to quantify PTSD severity, Duke University Religion Index to quantify religiosity, Montgomery Asberg (MADRS) and Hamilton Depression (HAM-D) rating scales to measure depression/suicidality, and Fagerstrom Test for Nicotine Dependence to assess nicotine dependence. Zero-order correlations, cluster analysis, multivariate regression, and mediation models were used for data analysis. RESULTS: Of 69 patients included, 71% met "high religiosity" criteria and 29% had moderate/high nicotine dependence. PTSD was severe (median PCL 71), depression was mild/moderate (median MADRS 19, HAM-D 14), while suicidality was mild. A subset of patients was identified with more severe PTSD/depression/suicidality and nicotine dependence (all P<0.001). Two "chains" of direct and indirect independent associations were detected. Higher CES was associated with higher level of re-experiencing and, through re-experiencing, with higher negativity and hyperarousal. It also showed "downstream" division into two arms, one including a direct and indirect association with higher depression and lower probability of high religiosity, and the other including associations with higher suicidality and lower probability of high nicotine dependence. CONCLUSIONS: Psychopathology, religiosity, and nicotine dependence are intertwined in a complex way not detectable by simple direct associations. Heavy smoking might be a marker of severe PTSD psychopathology, while spirituality might be targeted in attempts of its alleviation. Oxford Centre for Evidence-based Medicine level of evidence: 3.

Haplotypic and Genotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia.

Treatment-resistant schizophrenia (TRS) continues to be a challenge. It was related to different factors, including alterations in the activity of brain dopaminergic system, which could be influenced by the dopamine-degrading enzyme, catechol-O-methyltransferase (COMT). Variants of the COMT gene have been extensively studied as risk factors for schizophrenia; however, their association with TRS has been poorly investigated. The aim of the present study was to determine the haplotypic and genotypic association of COMT rs4680 and rs4818 polymorphisms with the presence of TRS. Overall, 931 Caucasian patients diagnosed with schizophrenia (386 females and 545 males) were included, while 270 participants met the criteria for TRS. In males, no significant haplotypic and genotypic associations between COMT rs4680 and rs4818 polymorphisms and TRS were detected. However, genotypic analyses demonstrated higher frequency of COMT rs4680 AA genotype carriers compared to G-allele carriers (p = 0.033) and higher frequency of COMT rs4818 CC genotype carriers than G-allele carriers (p = 0.014) in females with TRS. Haplotype analyses confirmed that the presence of the G allele in females was associated with lower risk of TRS. In women with TRS, the high activity G-G/G-G haplotype was rare, while carriers of other haplotypes were overrepresented (p = 0.009). Such associations of COMT rs4680 and rs4818 high-activity (G variants), as well as G-G/G-G haplotype, with the lower risk of TRS in females, but not in males, suggest significant, but sex-specific influence of COMT variants on the development of treatment-resistance in patients with schizophrenia. However, due to relatively low number of females, those findings require replication in a larger sample.

Smoking in Schizophrenia: an Updated Review.

Patients with schizophrenia continue to have the highest rate of both smoking and heavy nicotine dependence. The interaction between smoking and schizophrenia is complex. There is evidence of the shared genetic background. Recent preclinical and clinical research has further investigated self-medication hypothesis, given that nicotine might alleviate cortical dysfunction. While prior research indicated some favorable effects of smoking on cognitive performance, particulatly on attention/vigilance, recent studies did not confirm those findings. Lower severity of negative symptoms in smokers was not confirmed across studies. Cigarette smoking decreases clozapine and olanzapine concentrations. There is no consistent evidence of favorable effects of nicotine on symptoms in schizophrenia, but the evidence of detrimental effects of smoking on general health is highly consistent. Smoking cessation should be a priority in patients with schizophrenia.

Latent Toxoplasma gondii infection is associated with decreased serum triglyceride to high-density lipoprotein cholesterol ratio in male patients with schizophrenia.

BACKGROUND: Previous studies suggested a complex association between Toxoplasma gondii (TG) infection and host lipid metabolism. Both TG infection and metabolic disturbances are very common in patients with schizophrenia, but this relationship is not clear. METHODS: In this cross-sectional study, we evaluated the association between TG seropositivity, serum lipid levels, body mass index (BMI) and metabolic syndrome (MetS) in 210 male inpatients with schizophrenia. RESULTS: In our sample of schizophrenia patients, with the mean age of 43.90 ±â€¯12.70 years, the rate of TG seropositivity was 52.38% and the prevalence of MetS was 17%. Patients with the TG antibodies had lower serum triglyceride levels and body weight compared to TG seronegative patients, despite having more frequently received antipsychotics (clozapine, olanzapine risperidone and quetiapine), which are well known to induce weight gain and metabolic abnormalities. However, the only significant change in metabolic parameters, observed in TG seropositive patients with schizophrenia, was decreased serum triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio. No associations were observed between TG seropositivity and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose levels, waist circumference, BMI and the rate of MetS. CONCLUSION: This is the first report of the association between TG infection and decreased serum triglyceride to HDL-C ratio in a sample of carefully selected men with chronic schizophrenia.

Nicotine dependence in Croatian male inpatients with schizophrenia.

BACKGROUND: Patients with schizophrenia have the highest known rates of cigarette smoking, but less is known about their smoking behavior and the differences across geographical regions, including Croatia. The aim of this study was to compare patterns of nicotine dependence between patients with schizophrenia and healthy individuals, and to determine the relationship between clinical presentation and the severity of smoking. METHODS: This cross-sectional study included 182 recently hospitalized male inpatients and 280 healthy males, who were daily smokers. All participants have fulfilled the Fagerstrom Test for Nicotine Dependence (FTND). Patients were also evaluated by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients had higher FTND total score (p = 0.010), smoked their first cigarette earlier in the morning (p = 0.000), consumed higher number of cigarettes (p = 0.000), while healthy subjects had more difficulties to refrain from smoking in places where it is forbidden (p = 0.000) and smoked more even when they were sick (p = 0.000). While severe dependence was more prevalent in the patient group, light dependence was more frequent in control subjects (p = 0.04). Smoking behavior was not associated with either PANSS total score or any of its subscales and items. CONCLUSIONS: Smokers with schizophrenia differ from healthy smokers in both smoking behavior and level of dependence. Longitudinal studies are needed to shed more light on the complex relationship between smoking and psychopathology in schizophrenia.

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.

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.

Brain-derived neurotrophic factor serum and plasma levels in the treatment of acute schizophrenia with olanzapine or risperidone: 6-week prospective study.

Antipsychotics have been the mainstay of the treatment of schizophrenia, and their potential role in neuroprotection could be related to brain-derived neurotrophic factor (BDNF). So far different effects on both serum and plasma levels of BDNF were reported related to the various antipsychotic treatments. Aim of this study was to investigate the influence of olanzapine or risperidone on both plasma and serum levels of BDNF in patients with acute schizophrenia. For 50 participants with acute episode of schizophrenia both plasma and serum BDNF, along with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale, were assessed pretreatment and post treatment - after 6 weeks of either risperidone or olanzapine. Results show that a weak correlation between pretreatment plasma and serum levels of BNDF was found no longer significant after 6 weeks of treatment. Antipsychotics, olanzapine and risperidone showed no significant effect on post treatment plasma and serum levels of BDNF. Pretreatment plasma level of BDNF and PANSS positive subscale were positively correlated. Post treatment serum level of BDNF and Clinical Global Impression were negatively correlated. In conclusion, plasma and serum BDNF levels could be different markers to some extent with regard to clinical symptoms, response to therapy and outcome. The interrelation between serum and plasma BDNF should be established in further studies.

Do spirituality and religiousness differ with regard to personality and recovery from depression? A follow-up study.

BACKGROUND: The studies show that both spirituality and religiousness are protective for mental health. Personality is related with course and outcome of depression, as well as spirituality and religiousness, and their relations toward to recovery from depression are underresearched. This study followed influence of spirituality and religiousness on course and outcome of depression in patients with depressive episode, controlled for personality dimensions. METHODS: The patients were assessed with self-report measures of depression (Beck Depression Inventory), spirituality (WHO-Quality of Life-Spiritual, Religious, Personal Beliefs), religiousness (Duke University Religion Index) and personality (Temperament and Character Inventory). Ninety nine patients finished a year long follow up. RESULTS: Higher spirituality influenced recovery of depression in patients with depressive episode, but religiousness did not show to be significant predictor of recovery for depression. Dimension harm avoidance was significant predictor of improvement of depression in all points of measurement. LIMITATIONS: Some limitations of this research are small sample size, usage of the self-report measures of depression in follow-up period, and the predominantly Catholic affiliation of the participants that can impact the generalizability of our data to other denominations. CONCLUSION: Spirituality and dimension harm avoidance are significant predictors of recovery from depression during a year long follow up.

A prospective, longitudinal study of platelet serotonin and plasma brain-derived neurotrophic factor concentrations in major depression: effects of vortioxetine treatment.

BACKGROUND: Various antidepressants occupy brain serotonin transporter (SERT), decrease platelet serotonin (5-HT) concentration, and normalize reduced plasma brain-derived neurotrophic factor (BDNF) concentrations in depressed patients. Vortioxetine is a recently introduced antidepressant with a multimodal mechanism of action. In addition to SERT inhibition, vortioxetine acts via different 5-HT receptors. To further elucidate its mechanism of action, we have investigated the effects of vortioxetine on platelet 5-HT and plasma BDNF concentrations in patients with major depression. METHODS: Platelet 5-HT and plasma BDNF concentrations were determined in 44 healthy subjects at baseline and in 44 depressed patients before and after 4 weeks of treatment with vortioxetine (5-15 mg daily). Platelet 5-HT concentration was determined using the ortho-phthalaldehyde-enhanced fluorometric method, and plasma BDNF concentration using a commercial enzyme-linked immunosorbent assay (Quantikine ELISA, R&D Systems). RESULTS: At baseline, platelet 5-HT concentrations did not differ between depressed and control subjects, but plasma BDNF values were lower (p = 0.011; ω = 0.80) in depressed patients than in healthy subjects. Vortioxetine treatment significantly (p < 0.0001; ω = 0.80) decreased platelet 5-HT concentration and significantly (p = 0.004; ω = 0.80) increased plasma BDNF concentration in depressed patients compared to their baseline values. Age, gender, and smoking were not significantly associated with platelet 5-HT and plasma BDNF concentrations. CONCLUSION: Despite a novel mechanism of action, vortioxetine shares some common effects with other antidepressants. This study is the first to show that, in addition to clinical improvement, 4 weeks of treatment with vortioxetine (5-15 mg daily), decreased platelet 5-HT and increased plasma BDNF concentrations in depressed patients.

The role of dehydroepiandrosterone (DHEA) in schizophrenia.

Neurosteroid dehydropiandrosterone (DHEA) and its sulphate (DHEAS) are reported to have modulatory effects on neuronal excitabillity and synaptic plasticity. DHEA and DHEAS are synthesized in central and peripheral nervous system from cholesterol or steroidal precursors imported from peripheral sources. There is accumulating evidence that alterations in DHEA(S) levels may be involved in the pathophysiology of schizophrenia. The possible effects of DHEA(S) as augmentation therapy in schizophrenia, related to psychological and somatic aspects of this disease, are discussed.

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-R's relations with the abovementioned psychological measures. RESULTS: The TCI-R scales showed adequate internal consistencies, with Cronbach's 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).