Kaija Huuhka

Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression.

SummarySeveral studies have linked 5-HT1A C1019G and BDNF G196A (Val66Met) gene polymorphisms to major depressive disorder (MDD) and the actions of antidepressants. We attempt to show that the interaction between 5-HT1A and BDNF polymorphism predicts the risk of treatment-resistant depression. The sample consists of 119 patients with treatment-resistant MDD and 392 controls. 5-HT1A C1019G and BDNF G196A (Val66Met) polymorphisms were studied. The combination of 5-HT1A GG and BDNF GA + AA genotypes is associated with an increased risk of depression.

Dopamine 2 receptor C957T and catechol-o-methyltransferase Val158Met polymorphisms are associated with treatment response in electroconvulsive therapy

Alterations in dopamine levels and dopamine receptors in brain are suggested to be associated with treatment response in electroconvulsive therapy (ECT). Dopamine 2 receptor gene (DRD2) polymorphism C957T (rs6277) and cathechol-o-methyltransferase (COMT) polymorphism Val158Met (rs4680) interaction was studied in 118 patients suffering from major depressive disorder (MDD) treated with ECT and 383 healthy controls. It was found that the combination of COMT Met allele and DRD2 T allele predicted more severe depression in those already affected but did not predict the risk of depression when compared to normal population. The genotype modified the response to ECT. The patients with TT genotype of D2 receptor gene C957T polymorphism combined with COMT gene polymorphism Met/Met genotype did not achieve remission as often as those with CC genotype of DRD2 C957T combined with COMT Val/Val genotype. Thus the interaction of these polymorphisms may be associated with response to ECT.

Interaction between TPH1 and GNB3 genotypes and electroconvulsive therapy in major depression

SummaryWe studied the association between tryptophan hydroxylase 1 (TPH1) A218C and G-protein beta-3 subunit (GNB3) C825T polymorphisms and treatment response in electroconvulsive therapy (ECT). The sample consisted of 119 patients with major depressive disorder (MDD) and 398 controls. Neither TPH1 nor GNB3 polymorphisms are associated with treatment response. However, subjects carrying TPH1 CC genotype are more likely to belong to the patient sample than to the controls. In female subjects, T-allele of GNB3 polymorphism increases the risk of being a treatment-resistant patient with MDD. Moreover, in females the combination of TPH1 CC and GNB3 CT + TT genotype is associated with an increased risk of belonging to the patient group.

Catechol-O-methyltransferase (COMT) polymorphisms predict treatment response in electroconvulsive therapy

Several lines of evidence suggest that catechol-O-methyltransferase (COMT) may be associated with treatment response in depression. We conducted a study on 119 patients with treatment-refractory depression admitted consecutively for electroconvulsive therapy (ECT). The COMT high/high genotype leads to a higher enzyme activity and thus lowers dopaminergic activity in the prefrontal cortex. In the present sample, those homozygous to high-active allele of COMT responded significantly more frequently to ECT.

Interaction between two HTR2A polymorphisms and gender is associated with treatment response in MDD.

The 5HT2A receptor gene (HTR2A) polymorphisms rs7997012 and rs6311 have in some earlier studies been associated with serotonin selective reuptake inhibitor (SSRI) treatment response in major depressive disorder (MDD), but the findings are inconsistent. The aim of the present study was to test for an association between two HTR2A polymorphisms (rs7997012 and rs6311), their interaction and the Montgomery and Åsberg Depression Rating Scale (MADRS) score change after ECT or SSRI treatment. The total number of patients was 218. All were treated in outpatient care. Of these, 119 subjects had treatment-resistant MDD and were treated with ECT and 99 were depressive patients treated with SSRI. Treatment response was assessed by MADRS. Patients scoring <8 on post-treatment MADRS were considered remitters. Neither rs7997012 nor rs6311 HTR2A polymorphism was significantly associated with MADRS score change alone, but the interaction between them and gender explained 14% of the variance in MADRS score change. The finding suggests an association between MADRS score change and interaction of HTR2A polymorphisms, rs7997012 and rs6311 and gender.

TPH2 polymorphisms may modify clinical picture in treatment-resistant depression.

The association of two tryptophan hydroxylase 2 (TPH2) polymorphisms and treatment response in electroconvulsive therapy (ECT) and the risk of depression was studied. The patient sample consisted of 119 subjects with treatment-resistant major depressive disorder who were treated with ECT. Treatment response was assessed by the Montgomery and Asberg Depression Rating Scale (MADRS) scores. Patients who had <8 scores in post-treatment MADRS were considered remitters; scores >15 indicated non-response. The polymorphisms studied (rs1386494 and rs1843809) were not associated with treatment response to ECT. However, TPH2 rs1386494 A/A genotype carrying patients had significantly higher MADRS scores before ECT than A/G+G/G genotype carriers (p<0.001). A/A genotype carriers also had a greater decline in MADRS scores than A/G+G/G genotype carriers during the course of ECT treatment (p=0.03). This polymorphism may be associated with the severity of treatment-resistant depression. ECT may able to counteract a putative genetically driven worse depressive phenotype.

ACE polymorphism and response to electroconvulsive therapy in major depression

The angiotensin I-converting enzyme gene (ACE) has been repeatedly suggested as a major gene affecting affective disorders and their treatment, but the study results have been ambiguous so far. The primary purpose of this study was to compare the effects of the ACE genotype distributions and treatment response to electroconvulsive therapy (ECT) in patients with major depressive disorder (MDD). The association in ACE genotypes and the age at onset of depression was also analyzed and these gene distributions were also compared between patients and healthy controls. The study included 119 treatment-resistant MDD patients who were referred to ECT treatment, and 392 voluntary blood donors as controls. All participants were tested for their ACE genotype, and all study patients were evaluated both before and after treatment. The Montgomery-Asberg Depression Scale (MADRS) was used as a primary efficacy evaluating method. The ACE genotype was not associated in treatment results for MDD. However, younger onset age of primary depression was associated with the I/D genotype in the whole patient group. The finding was partly gender dependent; in male patients the I allele carried a higher risk of earlier depression onset age, while in female patients the higher risk was seen only in the heterozygous I/D allele carriers. Distributions of these genotypes or alleles did not differ between patients and controls. The studied ACE genotype was not associated with ECT results but may be associated with age of onset of the illness in patients with MDD.

The apolipoprotein E polymorphism is not associated with response to electroconvulsive therapy in major depressive disorder.

Abstract: The apolipoprotein E (APOE) polymorphism is associated with neurodegenerative diseases. Its role regarding psychiatric disorders is controversial. It has been suggested to affect antidepressant treatment response and response to electroconvulsive therapy (ECT). In the present study, the association between APOE polymorphism and response to ECT in 119 patients with major depressive disorder was investigated. Moreover, a relation between APOE polymorphism and the age of onset of depression as well as the cognitive outcome of ECT was studied. In the whole population, no association was found between APOE polymorphism and response to ECT. However, in nonpsychotic patients, the ϵ2 allele tended to be more frequent in responders than nonresponders. Earlier onset of depression was observed in the patients with ϵ4 allele in late-life depression. There was no association between the APOE genotype and the cognitive change caused by ECT in the population as a whole. In women, however, ϵ2 allele may play a protective and ϵ4 allele a deleterious role in cognition during ECT.

RGS4 polymorphism and response to electroconvulsive therapy in major depressive disorder.

We studied the association between RGS4 (rs951436) polymorphism and treatment response in electroconvulsive therapy (ECT) as well as risk of treatment-resistant depression. The study sample consisted of 119 patients with major depressive disorder (MDD) and 384 healthy control subjects. RGS4 polymorphism was not associated with treatment response in ECT or risk of MDD. According to the present data, the impact of RGS4 genotype is not decisive in major depressive disorder. The results provide preliminary data on the impact of RGS4 polymorphism in treatment response in ECT.

One-year follow-up after discontinuing maintenance electroconvulsive therapy.

Objectives Electroconvulsive therapy (ECT) has been established as an effective method in the treatment of severe depressive or psychotic disorders. Its efficacy is greatest in severe major depressive disorder (MDD) with or without psychotic symptoms. However, maintaining remission after a successful course of short-term ECT is often difficult owing to resistance to medication in these patients. Therefore, the relapse rate after short-term ECT is high; 40% to 60% of patients relapse even with adequate antidepressant continuation therapy. The risk of relapse is greatest during the first months after discontinuation of short-term ECT. Continuation/maintenance (c/m) ECT is an option in maintaining remission, but systematic data and clinical guidelines are lacking. The point at which to discontinue this treatment has not been adequately established. Methods Altogether 45 consecutive patients treated with c/mECT after short-term ECT to prevent relapse were followed up 1 year after discontinuation of this treatment. Results Twenty (44%) of 45 patients relapsed during follow-up, all within the first 8 months. Patients having a diagnosis other than MDD (bipolar disorder, depressive episode type I, schizophrenia, and schizoaffective disorder) were more likely to relapse than MDD patients. Conclusions Almost half of the patients relapsed in 1 year after discontinuation of c/mECT, most of these within the first 3 months and all within the first 8 months. The risk of relapse is greater in the patients with diagnoses other than MDD. When discontinuing c/mECT, patients should be carefully followed up; and for those at risk of relapse, even permanent mECT should be considered. To the best of our knowledge, the present study is the first to report the prognosis of patients after discontinuing c/mECT.