ABSTRACT
In major depressive disorder (MDD) patients, life stress events represent a risk factor for a severe, early-onset, treatment-resistant and chronic endophenotype. Treatment-resistant depression (TRD) patients who have experienced traumatic events could benefit from evidence-based trauma-focused psychotherapies. Because this topic has never been investigated, the aim of this pilot trial was to evaluate whether trauma-focused cognitive-behavioural therapy (TF-CBT) and/or eye movement desensitization and reprocessing (EMDR) can help achieve depressive symptom remission in TRD patients. We carried out a single-blind randomized controlled trial with TRD patients and we compared EMDR (N = 12) with TF-CBT (N = 10). Patients received 3 individual sessions per week over a period of 8 weeks. The symptomatological assessments were performed at 4 timepoints: baseline (T0), 4 (T4), 8 (T8) and 12 (T12) weeks. After 24 weeks, a clinical interview was carried out by phone. All TRD patients showed a significant improvement in depressive symptomatology; however, post hoc comparisons showed a significant difference between the two treatment groups, with lower depressive symptom scores in the EMDR than in the TF-CBT group at the follow-up (T12). This effect was partly maintained at 24 weeks. This pilot study suggests that evidence-based trauma-focused psychotherapies, particularly EMDR, can represent effective interventions to treat TRD patients.
Subject(s)
Cognitive Behavioral Therapy/methods , Depressive Disorder, Major/therapy , Depressive Disorder, Treatment-Resistant/therapy , Eye Movement Desensitization Reprocessing/methods , Stress Disorders, Post-Traumatic/therapy , Adolescent , Adult , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Depressive Disorder, Treatment-Resistant/diagnosis , Depressive Disorder, Treatment-Resistant/psychology , Female , Humans , Male , Middle Aged , Pilot Projects , Psychotherapy/methods , Single-Blind Method , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/psychology , Treatment OutcomeABSTRACT
BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) genetic variations have been widely studied in major depressive disorder (MDD) and antidepressants outcome. An interaction with catechol-O-methyltransferase (COMT) has also been proved affecting depression. The aim of this study was to clarify the role of the most commonly studied single nucleotide polymorphisms (SNPs) of MTHFR gene in MDD and in treatment response mechanisms, along with the impact of the interaction with COMT. METHODS: A total of 613 MDD patients, of whom 389 were classified as having treatment resistant depression (TRD), and 463 controls were enrolled. The A1298C, C677T and COMT Val158Met were genotyped. Genetic data were integrated with a transcriptional level analysis in peripheral blood cells (PBCs) and fibroblasts. RESULTS: The A1298C CC homozygotes were more frequent in MDD patients compared to controls in women, increasing twice the genetic risk to develop depression. Moreover this genotype resulted in epistasis with COMT Met carriers in association with MDD. No significant effects were obtained concerning response to treatment. Transcriptional analyses highlighted a strong correlation between the mRNA levels of MTHFR in fibroblasts and COMT genotypes whereas no significant association with MDD was found. PBCs results revealed relevant influences of environmental factors. LIMITATION: We did not measure folate and homocisteine levels. CONCLUSION: This study showed the involvement of A1298C, Val158Met and their interaction in MDD. The transcriptional analyses supported the participation of COMT in the folate pathway, which partakes in the complex network of gene×gene and gene×environment interactions of MDD etiopathogenesis.
Subject(s)
Catechol O-Methyltransferase/genetics , Depressive Disorder, Major/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Female , Genetic Variation , Genotype , Humans , Middle Aged , Risk FactorsABSTRACT
BACKGROUND: A recent genome-wide association study on Major Depressive Disorder (MDD) identified a specific association with a non-synonymous polymorphism (rs2522833) of a gene encoding the presynaptic protein piccolo (PCLO). A high percentage of patients who develop MDD have particular temperamental traits, such as passivity, pessimism, indecisiveness, and low self-esteem, which are related to the subsequent development of depression. The aims of this study were to perform a replicate case-control study and to conduct the first association study between the rs2522833 polymorphism and depression-related personality traits using the Temperament and Character Inventory (TCI) in a healthy subject sample. METHODS: A total of 522 MDD patients and 375 healthy volunteers were enrolled in the study. Two hundred and forty-six controls agreed to fill out the TCI. RESULTS: The results showed that rs2522833 CC homozygotes were more frequent among the depressed patients than in the controls (p<0.01). The C allele distribution showed a trend in the same direction (p=0.08). Among controls, we found that the C allele carriers were associated with personality traits increasing vulnerability to depression, including higher Harm Avoidance (HA) and lower in Novelty Seeking (NS). In particular, C allele carriers were more fearful (HA2) and fatigable (HA4), and less impulsive/more deliberate (NS2) and less extravagant/more frugal (NS3). LIMITATIONS: The absence of possible epistatic interaction effect. CONCLUSIONS: These results provide further support for the involvement of the PCLO gene in MDD and show that this effect may be mediated by influencing personality traits that increase the risk of major depression.
