The role of neuropeptide Y, orexin-A, and ghrelin in differentiating unipolar and bipolar depression: a preliminary study.

BACKGROUND: When depressive symptoms in bipolar and unipolar patients were compared, a number of studies reported that atypical vegetative features such as hypersomnia and hyperphagia were more common in bipolar patients. Moreover, neuropeptides such as orexin-A (ORX-A), ghrelin (GRL), and neuropeptide Y (NPY) are involved in the regulation of these vegetative functions. MATERIALS AND METHODS: A total of 45 unipolar and 24 bipolar depressive patients, and 36 euthymic healthy controls were included in the study. The groups were compared in terms of peripheral blood samples of ORX-A, GRL, and NPY levels, as well as HAM-D, Epworth Sleepiness Scale, Three-Factor Eating Questionnaire-Revised, and Suicide Probability Scale scores. RESULTS: Both unipolar and bipolar patients had lower ORX-A, GRL, and NPY levels compared to the controls, whereas NPY levels of bipolar patients were lower than unipolar patients. There was a negative correlation between NPY levels and emotional eating in the bipolar group. CONCLUSION: While lower ORX-A, GRL, and NPY levels are associated with depressive episodes regardless of the diagnosis; NPY levels also differ in bipolar and unipolar depression patients.

Serum N-Desmethylcitalopram Concentrations are Associated with the Clinical Response to Citalopram of Patients with Major Depression.

OBJECTIVE: Citalopram (CITA) is a widely used and well-tolerated selective serotonin reuptake inhibitor. The aim of the study was to evaluate the possible influences of serum concentrations of CITA and its major metabolite n-desmethylcitalopram (NDCITA) on the efficacy and tolerability of CITA in patients with major depressive disorder. METHODS: The study included 46 outpatients with major depressive disorder who received CITA. The efficacy and tolerability were assessed for 6 weeks. Serum CITA and NDCITA levels were measured at the 4th week. RESULTS: The HDRS17 total scores of the patients with high NDCITA and CITA & NDCITA concentrations showed a more significant reduction compared to the patients with expected and low serum NDCITA and CITA & NDCITA concentrations. However, we did not observe a correlation between the serum concentrations and the side effects of CITA, NDCITA, and CITA & NDCITA. CONCLUSION: Our results suggested the potential contribution of NDCITA to the antidepressant effect of CITA. Further studies involving larger clinical samples are required to confirm the impact of serum NDCITA concentrations on the efficacy of CITA.

ABCB1 C3435T polymorphism is associated with susceptibility to major depression, but not with a clinical response to citalopram in a Turkish population.

BACKGROUND: The ATP-binding cassette sub-family B member 1 (ABCB1) gene, which encodes the p-glycoprotein at the blood-brain barrier, is investigated for patients' susceptibility to major depressive disorder (MDD) and their therapeutic response to antidepressants. However, there is an inconsistency between the studies of different ethnic groups. The current study aimed to determine the potential correlations of the ABCB1 gene C3435T polymorphism with the susceptibility to MDD and the therapeutic response to citalopram in a Turkish population. METHODS: Fifty-four patients with MDD who received citalopram and 70 controls from the Turkish population were genotyped for ABCB1 C3435T polymorphism. To assess the therapeutic response to citalopram, all patients were rated baseline, first, second, fourth and sixth weeks according to the 17-item Hamilton Rating Scale for Depression (HAMD-17). RESULTS: There was a significant correlation between the patient and control groups for ABCB1 C3435T polymorphism. Distribution of CC genotype and C allele frequency were higher in the patients than in the control group (p = 0.006, p = 0.020, respectively). However, no correlation between ABCB1 C3435T polymorphism and a therapeutic response to citalopram was observed. CONCLUSION: Our results suggested that C3435T polymorphism in the ABCB1 gene may be an indicator of the susceptibility to major depression, without a likely treatment response to citalopram in a Turkish population. These findings should be replicated in studies on larger patient groups with different ethnicities.

The effects of the estrus cycle and citalopram on anxiety-like behaviors and c-fos expression in rats.

In rats, hormonal fluctuations during the estrus cycle may have numerous behavioral and neurobiological consequences. The aim of this study was to investigate the effects of estrus cycles and citalopram on behavior, ultrasonic vocalizations, anxiety levels, and c-fos expression in rats. With this aim, the rats were grouped into two: (1) a control group (n=16) and (2) a citalopram group (n=16), which received daily intraperitoneal 20mg/kg citalopram from baseline (D0) to the 10th day (D10). Behavioral analysis and ultrasonic vocalization (USV) recordings were made on D0 and D10. Next, the rats were further subgrouped according to estrus phases identified through a vaginal smear (8 proestrus rats and 8 non-proestrus rats, in each group). The rat's anxiety levels were analyzed with an elevated plus maze (EPM), and their c-fos expression was measured at the cingulate cortex, the amygdala, and the paraventricular thalamic nucleus. Our results showed that the citalopram group showed significantly more grooming behaviors on D10 than the control group (p=0.002). USVs on D0, D10 and during the EPM did not show any significant differences between the groups. Proestrus rats in the control group showed significantly less anxiety-like behavior during the EPM than the non-proestrus rats in the control group (p=0.028 for time spent in open arms, and p=0.011 for entries into open arms). There was no significant difference in anxiety-like behavior between the control and citalopram groups, and between the proestrus and non-estrous rats in the citalopram group. C-fos expression at the amygdala (p=0.013) and the paraventricular thalamic nucleus (p=0.014) was significantly inhibited in the citalopram group. We concluded that estrus cycles have a significant effect on anxiety levels in rats, which may be suppressed behaviorally and neurobiologically by citalopram.

Effects of the adverse life events and Disrupted in Schizophrenia-1 (DISC1) gene polymorphisms on acute symptoms of schizophrenia.

The aim of this study was to evaluate the effects of traumatic childhood events and recent adverse life events, as well as the Disrupted in Schizophrenia-1 (DISC1) gene polymorphisms on types of last acute symptoms of patients with schizophrenia. Hundred patients with schizophrenia were given the Childhood Trauma Questionnaire, the Social Readjustment Rating Scale, Scale for Assessment of Positive Symptoms (SAPS), Scale for Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), and Calgary Depression Scale for Schizophrenia (CDSS). The patients' and healthy controls' DISC1 gene was evaluated for the -274G>C, c.791G>A, and c.2110A>T polymorphisms. There was no statistically significant difference with regard to the DISC1 gene polymorphisms between patient and healthy control groups. No significant relationship was found between the -274G>C, c.791G>A, and c.2110A>T haplotypes and development of different acute symptoms of schizophrenia. Having a recent stressful life event significantly affected SAPS (95% confidence interval [CI]=-67.547, -21.473; p=0.00) and BPRS-1 scores (95% CI=-51.405, -6.885; p=0.01), whereas emotional abuse at childhood significantly affected SANS scores (95% CI=-37.300, -10.401; p=0.00). This study shows that features of acute symptoms in schizophrenia are not influenced by the polymorphisms on the DISC1 gene, but are influenced by recent adverse life events and emotional abuse at childhood.

Serotonin transporter gene polymorphisms and sertraline response in major depression patients.

Major depression (MD) has a complex multifactorial etiology with genetic and environmental factors contributing to the disorder. As with all antidepressant treatments, there is variability in drug response due to heredity, generally focusing on genetic polymorphism of the drug-metabolizing transporter genes. The serotonin transporter (5-HTT) gene is a particularly important candidate for genetic involvement in MD disorders owing to its key role in the regulation of serotonergic transmission and is therefore considered to be an interesting candidate in the mechanism of antidepressant drugs. In this study, we have focused on the associations between genetic polymorphisms in two regions of the 5-HTT gene (5-HTTLPR and VNTR) related to sertraline responses. Our sample consisted of 64 unrelated Turkish subjects who strictly met DSM-IV and CGI scores. There was no significant difference between the frequency of the SS, LS, LL, 9/10, 10/10, 9/12, 10/12, and 12/12 genotypes and responses to sertraline. However, the number of patients can be increased and different drugs can be studied in order to find a specific pharmacogenetic relation.

Acute and chronic tianeptine treatments attenuate ethanol withdrawal syndrome in rats.

Effects of acute and chronic tianeptine treatments on ethanol withdrawal syndrome were investigated in rats. Ethanol (7.2% v/v) was given to adult male Wistar rats by a liquid diet for 30 days. Acute or chronic (twice daily) tianeptine (5, 10 and 20 mg/kg) and saline were administered to rats intraperitoneally. Acute and last chronic tianeptine injections and saline were done 30 min before ethanol withdrawal testing. After 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs which included locomotor hyperactivity, agitation, tremor, wet dog shakes, stereotyped behavior and audiogenic seizures were recorded or rated. Locomotor activity in naive (no ethanol-dependent rats) was also tested after acute tianeptine treatments. Acute but not chronic tianeptine treatment attenuated locomotor hyperactivity and agitation in ethanol-dependent rats. Both acute and chronic tianeptine treatment produced some significant inhibitory effects on tremor, wet dog shakes, stereotyped behaviors and audiogenic seizures during the ethanol withdrawal. Our results suggest that acute or chronic tianeptine treatment attenuates ethanol withdrawal syndrome in ethanol-dependent rats and this drug may be useful for treatment of ethanol-type dependence.