Evaluating the influence of nonproblematic alcohol intake on the outcome of major depression.

The effect of light or moderate alcohol intake on the outcome of patients with major depression taking antidepressants is a question that remains unanswered. The main objective of this study was to assess the association between light or moderate alcohol consumption and the acute response (efficacy and tolerability) to pharmacological treatment in unipolar major depression. Efficacy and tolerability analyses compared 8-week outcomes between three subgroups, abstainers, light drinkers and moderate drinkers, of patients with major depression using a prospective naturalistic single-blind design.

Lithium Augmentation Versus Citalopram Combination in Imipramine-Resistant Major Depression: A 10-Week Randomized Open-Label Study.

Purpose/background: According to available international clinical guides, tricyclic antidepressants are our first- or second-line treatment of choice for severe unipolar major depression. However, the therapeutic option after an unsuccessful response to a tricyclic antidepressant drug in unipolar major depression is still unclear.

Methods/procedures: This 10-week randomized open-label study assessed the effectiveness of add-on lithium (adjusted to plasma levels) compared with add-on citalopram (30 mg/d) in 104 severe unipolar major depressive patients after a 10-week unsuccessful imipramine (adjusted to plasma level).

Switching to Imipramine Versus Add-on Mirtazapine in Venlafaxine-Resistant Major Depression: A 10-Week Randomized Open Study.

Purpose/background: Newer-generation antidepressants used in monotherapy or in combination with other newer-generation antidepressants or other psychotropic drugs are usually preferred as first- or second-step treatment options in resistant depression. According to our clinical experience, tricyclic antidepressants still are one of our preferred first choices in treatment-resistant moderate to severe unipolar major depressive episodes.

Methods: This 10-week open-design randomized study assessed the effectiveness of switching to imipramine (adjusted to plasma levels) compared with add-on mirtazapine (30 mg/d) for treatment of moderate to severe unipolar major depressive episodes after a 10-week unsuccessful venlafaxine regimen (225-300 mg/d).

Escitalopram Impairs Thrombin-Induced Platelet Response, Cytoskeletal Assembly and Activation of Associated Signalling Pathways.

Background Serotonin reuptake inhibitors (SSRIs) may impair platelet function. Thrombin is a strong platelet agonist causing irreversible aggregation, release of granules' contents, cytoskeletal rearrangement and activation of signalling pathways. We investigated the effects of the SSRI escitalopram (SCIT) on thrombin-induced platelet response.

Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model.

There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24).

Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins.

Depressive disorders have been shown to be highly influenced by environmental pathogenic factors, some of which are believed to exert stress on human brain functioning via epigenetic modifications. Previous genome-wide methylomic studies on depression have suggested that, along with differential DNA methylation, affected co-twins of monozygotic (MZ) pairs have increased DNA methylation variability, probably in line with theories of epigenetic stochasticity. Nevertheless, the potential biological roots of this variability remain largely unexplored.

Polymorphic variation in the epigenetic gene DNMT3B modulates the environmental impact on cognitive ability: a twin study.

Background: Though cognitive abilities in adulthood are largely influenced by individual genetic background, they have also been shown to be importantly influenced by environmental factors. Some of these influences are mediated by epigenetic mechanisms. Accordingly, polymorphic variants in the epigenetic gene DNMT3B have been linked to neurocognitive performance.

DISC1-TSNAX and DAOA genes in major depression and citalopram efficacy.

Background: Major depressive disorder (MDD) is a common disease with high morbidity and still unsatisfying treatment response. Both MDD pathogenesis and antidepressant effect are supposed to be strongly affected by genetic polymorphisms. Among promising candidate genes, distrupted in schizophrenia 1 (DISC1), translin-associated factor X (TSNAX) and D-amino acid oxidase activator (DAOA) were suggested since their regulator role in neurodevelopment, neuroplasticity and neurotransmission, and previous evidence of cross-involvement in major psychiatric diseases.

Prothrombotic platelet phenotype in major depression: downregulation by antidepressant treatment.

Background: Serotonergic mechanisms have been suggested as a link between major depression and cardiovascular risk. We investigated the existence of a prothrombotic condition in depressed patients and its possible modulation during treatment with a selective serotonin-reuptake inhibitor (SSRI).

Methods: Modifications in a series of biomarkers of platelet and coagulation activation were evaluated in blood from 19 patients with a major depression disorder (MDD) at the time of diagnosis, and at 8 and 24 weeks of treatment with escitalopram.

Treatment and outcome of antidepressant treatment-associated hypomania in unipolar major depression: a 3-year follow-up study.

Background: The main aim of this study was to propose a standardized acute and maintenance/continuation treatment protocol for acute antidepressant treatment-associated hypomania (AAH) in major unipolar depression. The second objective was to describe outcomes at three-year follow-up in a cohort of patients with AAH who had been included in this standardized therapeutic protocol.

Methods: The study consisted of two distinct prospective phases: a 1-year follow-up first phase in which all consecutive patients with a diagnosis of moderate/severe unipolar depressive disorder received acute and continuation/maintenance antidepressant treatment; and a second phase, in which patients who had suffered AAH during the first phase were admitted to a 3-year follow-up with the authors-designed standardized acute and continuation/maintenance treatment protocol.

Association between symptomatic profile and remission following antidepressant treatment in unipolar major depression.

Background: To evaluate, in patients affected by an acute major depressive episode, what predictive value certain baseline psychopathological characteristics have with regard to expected therapeutic remission following biological antidepressant treatment (pharmacological/electroconvulsive; non-psychological).

Methods: Six predefined psychopathological characteristics in acute major depressive episode were evaluated using a logistic regression model through a protocolised antidepressant treatment to assess their predictive value with regard to expected remission rate.

Results: The final study sample consisted of 129 subjects affected by an acute major depressive episode.

Gene-environment interaction on cognition: a twin study of childhood maltreatment and COMT variability.

The functional variant Val(158)Met in the coding sequence of COMT gene is involved in the modulation of dopamine availability in the prefrontal cortex in both clinical and general population samples. It has been suggested that the interplay between this genotype and early environmental factors could be used to predict the observed variation in cognitive flexibility. However, other genetic variants and environmental factors may confound the association and produce the inconsistent results commonly found in the literature.

Brain effects of cognitive remediation therapy in schizophrenia: a structural and functional neuroimaging study.

Background: Cognitive remediation therapy positively affects cognition and daily functioning in patients with schizophrenia. However, studies on the underlying neurobiological mechanisms of this treatment are scarce. The aim of the current study was to investigate functional and structural connectivity brain changes in schizophrenia patients after cognitive remediation therapy using a whole-brain approach that combined functional magnetic resonance imaging and diffusion tensor imaging.

Psychosis-inducing effects of cannabis are related to both childhood abuse and COMT genotypes.

Objective: To test whether the association between childhood abuse, cannabis use and psychotic experiences (PEs) was moderated by the COMT (catechol-O-methyltransferase) gene.

Method: Psychotic experiences (PEs), childhood abuse, cannabis use and COMT Val158Met genotypes were assessed in 533 individuals from the general population. Data were analysed hierarchically by means of multiple linear regression models.

Regional gray matter reductions are associated with genetic liability for anxiety and depression: an MRI twin study.

Background: The influence of genetic and/or environmental factors on the volumetric brain changes observed in subjects affected by anxiety and depression disorders remains unclear. The current study aimed to investigate whether genetic and environmental liabilities make different contributions to abnormalities in gray matter volume (GMV) in anxiety and depression using a concordant and discordant MZ twin pairs design.

Methods: Fifty-three magnetic resonance imaging (3T) brain scans were obtained from monozygotic (MZ) twins concordant (6 pairs) and discordant (10 pairs) for lifetime anxiety and depression disorders and from healthy twins (21 subjects).

Screening genetic variability at the CNR1 gene in both major depression etiology and clinical response to citalopram treatment.

Rationale: The endocannabinoid system has been implicated in the pathogenesis of major depression (MD) as well as in the mediation of antidepressant drug effects.

Objectives: To analyze CNR1 gene variants in MD and clinical response to citalopram (selective serotonin re-uptake inhibitors [SSRI]).

Methods: The role of CNR1 gene (rs806368, rs1049353, rs806371, rs806377 and rs1535255) was investigated in 319 outpatients with MD and 150 healthy individuals.

TPH1, MAOA, serotonin receptor 2A and 2C genes in citalopram response: possible effect in melancholic and psychotic depression.

Background: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal.

Methods: 159 MDD patients treated with citalopram were genotyped and evaluated by the 21-item Hamilton Depression Rating Scale at the beginning and every 4 weeks during the 12-week follow-up. Four serotonin-related genetic variants were tested for association with treatment outcome: tryptophane hydroxylase 1 (TPH1) rs1800532, monoamine oxidase A µVNTR, serotonin 2A receptor rs6311 and serotonin 2C receptor rs6318.

Childhood adversity and psychosis: examining whether the association is due to genetic confounding using a monozygotic twin differences approach.

Purpose: To test whether the association between childhood adversity and positive and negative psychotic experiences is due to genetic confounding.

Method: Childhood adversity and psychotic experiences were assessed in an ongoing sample of 226 twins from the general population. A monozygotic (MZ) twin differences approach was used to assess possible genetic confounding.

Genetic variability in the endocannabinoid system and 12-week clinical response to citalopram treatment: the role of the CNR1, CNR2 and FAAH genes.

First line treatment of major depression is based on selective serotonin re-uptake inhibitors (SSRIs) that enhance serotonergic neurotransmission by blocking the serotonin transporter. However, clinical response is a complex phenomenon in which other systems such as the endocannabinoid system could be involved. Given the evidence for the role of the endocannabinoid system in the pathogenesis of depression as well as in the mediation of antidepressant drug effects, the aim of this study was to analyze genetic variability in the endocannabinoid system genes (CNR1, CNR2 and FAAH genes) and their role in clinical response (at week 4) and remission (at week 12) in SSRI (citalopram) treatment in a sample of 154 depressive outpatients, all of Spanish origin.

CRF test in melancholic depressive patients with partial versus complete relapses: a 2-year follow-up study.

Background: Patients with depressive disorders present abnormalities in the hypothalamic pituitary adrenal (HPA) axis. The effects of a partial relapse with regard to HPA axis has not been studied so far.

Aim: To assess whether patients with partial relapse have a different neuroendocrine profile compared with those with complete relapse and with those without relapse over a 2-year follow-up.