Transcriptome profiling as a biological marker for bipolar disorder sub-phenotypes.

PURPOSE: Bipolar affective disorder (BP) causes major functional impairment and reduced quality of life not only for patients, but also for many close relatives. We aimed to investigate mRNA levels in BP patients to find differentially expressed genes linked to specific clinical course variants; assuming that several gene expression alterations might indicate vulnerability pathways for specific course and severity of the disease. MATERIALS: We searched for up- and down-regulated genes comparing patients with diagnosis of BP type I (BPI) vs type II (BPII), history of suicide attempts, psychotic symptoms, predominance of manic/hypomanic episodes, and history of numerous episodes and comorbidity of substance use disorders or anxiety disorders. RNA was extracted from peripheral blood mononuclear cells and analyzed with use of microarray slides. RESULTS: Differentially expressed genes (DEGs) were found in all disease characteristics compared. The lowest number of DEGs were revealed when comparing BPI and BPII patients (18 genes), and the highest number when comparing patients with and without psychotic symptoms (3223 genes). Down-regulated genes identified here with the use of the DAVID database were among others linked to cell migration, defense response, and inflammatory response. CONCLUSIONS: The most specific transcriptome profile was revealed in BP with psychotic symptoms. Differentially expressed genes in this variant include, among others, genes involved in inflammatory and immune processes. It might suggest the overlap of biological background between BP with a history of psychotic features and schizophrenia.

Is Venlafaxine More Effective than Escitalopram and Nortriptyline in the Management of Painful Symptoms in Patients with Major Depression?

BACKGROUND: Conflicting data regarding the efficacy of antidepressants of different mechanism of action on unexplained painful physical symptoms (UPPS) in depression have been published so far. OBJECTIVE: The aim of this study was to compare the impact of escitalopram (ESC), nortriptyline (NOR), and venlafaxine (VEN) on UPPS in patients with major depression. MATERIALS AND METHODS: Sixty patients, participants in the GENDEP study, with a diagnosis of depression according to the ICD-10 criteria were randomly assigned to treatment with ESC (10-30 mg, mean dose 15.2, standard deviation [SD]±9.2) or NOR (50-150 mg, mean dose 106.2, SD±8.2). Additionally, 30 patients who were treated with VEN (75-225 mg, mean dose 181.3, SD±8.8) were included. Before inclusion (day 0) and throughout the study (days 14, 28, 42, 56), the severity of pain was monitored using the visual analog scale. RESULTS: The patients treated with ESC, NOR, and VEN did not differ in the intensity of pain at days 0, 14, 28, 42, and 56. CONCLUSION: Our results do not support the hypothesis suggesting the superiority of VEN over ESC and NOR in the management of UPPS in major depression.

Unexplained Painful Physical Symptoms in Patients with Major Depressive Disorder: Prevalence, Pathophysiology and Management.

Patients with major depression often report pain. In this article, we review the current literature regarding the prevalence and consequences, as well as the pathophysiology, of unexplained painful physical symptoms (UPPS) in patients with major depressive disorder (MDD). UPPS are experienced by approximately two-thirds of depressed patients. The presence of UPPS makes a correct diagnosis of depression more difficult. Moreover, UPPS are a predictor of a poor response to treatment and a more chronic course of depression. Pain, in the course of depression, also has a negative impact on functioning and quality of life. Frequent comorbidity of depression and UPPS has inspired the formulation of an hypothesis regarding a shared neurobiological mechanism of both conditions. Evidence from neuroimaging studies has shown that frontal-limbic dysfunction in depression may explain abnormal pain processing, leading to the presence of UPPS. Increased levels of proinflamatory cytokines and substance P in patients with MDD may also clarify the pathophysiology of UPPS. Finally, dysfunction of the descending serotonergic and noradrenergic pathways that normally suppress ascending sensations has been proposed as a core mechanism of UPPS. Psychological factors such as catastrophizing also play a role in both depression and chronic pain. Therefore, pharmacological treatment and/or cognitive therapy are recommended in the treatment of depression with UPPS. Some data suggest that serotonin and noradrenaline reuptake inhibitors (SNRIs) are more effective than selective serotonin reuptake inhibitors (SSRIs) in the alleviation of depression and UPPS. However, the pooled analysis of eight randomised clinical trials showed similar efficacy of duloxetine (an SNRI) and paroxetine (an SSRI) in reducing UPPS in depression. Further integrative studies examining genetic factors (e.g. polymorphisms of genes for interleukins, serotonin transporter and receptors), molecular factors (e.g. cytokines, substance P) and neuroimaging findings (e.g. functional studies during painful stimulation) might provide further explanation of the pathophysiology of UPPS in MDD and therefore facilitate the development of more effective methods of treatment.

Comparison of the effects of escitalopram and nortriptyline on painful symptoms in patients with major depression.

OBJECTIVE: Unexplained painful physical symptoms are commonly reported by depressed patients. The evidence suggests that dual-action antidepressants are potent in relieving pain in depression. However, a direct comparison of the effects of selective serotonergic and selective noradrenergic antidepressants on painful symptoms has not been investigated so far. METHOD: Sixty patients who participated in the Genome-based Therapeutic Drugs for Depression study with a diagnosis of moderate or severe episodes of depression according to the International Classification of Diseases, 10th Revision, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were involved. All the participants were randomly allocated to receive nortriptyline or escitalopram. The severity of depression was measured using the Montgomery-Åsberg Depression Rating Scale, the Hamilton Depression Rating Scale and the Beck Depression Inventory at weeks 0, 2, 4, 6 and 8. The intensity of pain was measured on the Visual Analog Scale at the same points of the study. RESULTS: At "week 0," 83.3% of the patients later randomized to treatment with escitalopram and 86.7% of those treated with nortriptyline reported at least one painful symptom. A significant decrease of pain intensity was observed after 2 weeks of treatment. The two groups did not differ in degree of pain reduction at weeks 2, 4, 6 and 8 in comparison to baseline values. A 50% reduction in pain intensity preceded the 50% reduction of depression severity. The intensity of pain at "week 0" did not differ in remitted or nonremitted patients at week 8. CONCLUSION: Both selective serotonergic and selective noradrenergic antidepressants are equally effective in alleviations of painful physical symptoms of depression. The presence of painful symptoms before the onset of treatment did not determine the final response.

[Lack of association between the insertion/deletion polymorphism in the serotonin transporter gene and schizophrenia]. / Brak asocjacji pomiedzy polimorfizmem insercyjnodelecyjnym promotorowego odcinka genu transportera serotoniny a schizofrenia.

AIM: The authors analyzed the association between polymorphism of serotonin transporter gene and schizophrenia. This polymorphism is characterised by a 44-bp insertion or deletion in the promoter region of the gene which influences its transcriptional activity. METHOD: 349 not related patients with paranoid schizophrenia were included in this study. Using the SCID (Structured Clinical Interview for DSM-IV Axis I Disorders) a consensus diagnosis, according to the DSM-IV criteria was made by two independent psychiatrists for each patient. The control group consisted of 372 persons who have not been examined by psychiatrists. Genomic DNA was extracted from whole blood leukocytes using a salting out method. The polymorphism was amplified by the polymerase chain reaction (PCR). We received two products of PCR: 406 base pairs (short allele) and 450 base pairs (long allele). RESULTS: We analyzed genotypes and alleles of the 5-HTTLPR polymorphism in the group of patients and in the control group. We also divided our sample according to their gender and early onset of schizophrenia. The analysis did not show any significant differences between the studied groups. CONCLUSIONS: In the present study no association between 5-HTTLPR polymorphism and schizophrenia was found.