Sex-specifics of ECT outcome.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression: a longitudinal neuroimaging study.

Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement. We assessed 12 patients with treatment-resistant depression (TRD) at four time points (pre-treatment, after the first ECT session, after the ninth ECT session and 15 days after ECT course completion) and 10 healthy participants at two time points, 5 weeks apart. Patients with TRD showed bilateral medial temporal lobe (MTL) and perigenual anterior cingulate cortex volume increases. Left MTL volume increase was associated with (i) a hippocampal N-acetylaspartate concentration decrease, (ii) a hippocampal Glutamate+Glutamine concentration increase and (iii) significant clinical improvement. The observed findings are, in part, compatible with both neuroplastic and neuroinflammatory changes induced by ECT. We postulate that such phenomena may be interrelated, therefore reconciling the neuroplasticity and neuroinflammatory hypotheses of ECT action.

Improving survival and growth of planted Austrocedrus chilensis seedlings in disturbed patagonian forests of Argentina by managing understory vegetation.

This study was aimed at determining, under field conditions, early interactions between planted cypress seedlings and their associated shrubs in a mesic area of Andean Patagonia and, in a nursery, the effects of increasing light availability on cypress performance when soil water was not a limiting factor. The field experiment was performed in a former cypress-coihue mixed forest (42°02'S, 71°33'W), which was replaced in the 1970s by a plantation of radiata pine. In 2005, 800 cypress seedlings were planted under maqui shrubs in a clear-cut area of the pine stand. In 2007, two treatments were set: no-competition treatment ([NCT] i.e., the surrounding aboveground biomass was removed) and competition treatment ([CT] i.e., without disturbance). The nursery experiment (42°55'S, 71°21'W) consisted of two groups: "shade" (grown under shade cloth) and "sun" (grown at full sun) cypress seedlings. After one growing season, seedling survival and stem growth (in height and diameter) were determined at both sites. Furthermore, the growth rate of leaves, stems, and roots was determined in the nursery. In the field experiment, height growth and survival in NCT were significantly greater than in CT, and a competition process occurred between cypress and surrounding shrubs. In the nursery, sun plants grew more in diameter and increased root weight more than shade plants. Results also showed that in mesic areas of Patagonia, decreasing competition and increasing light levels produced stouter seedlings better adapted to support harsh environmental conditions. Therefore, the removal of protecting shrubs could be a good management practice to improve seedling establishment.

A haplotype of glycogen synthase kinase 3ß is associated with early onset of unipolar major depression.

Recent findings suggest that glycogen synthase kinase 3ß (GSK3ß) may play a role in the pathophysiology and treatment of mood disorders. Various genetic studies have shown the association of GSK3ß polymorphisms with different mood disorder phenotypes. We hypothesized that genetic variants in the GSK3ß gene could partially underlie the susceptibility to mood disorders. We performed a genetic case-control study of 440 psychiatrically screened control subjects and 445 mood disorder patients [256 unipolar major depressive disorder (MDD) and 189 bipolar disorder (BD)]. We genotyped a set of 11 single nucleotide polymorphisms (SNPs) and determined the relative frequency of a known copy number variant (CNV) overlapping the GSK3ß by quantitative real-time polymerase chain reaction (PCR). We found no evidence of association with MDD or BD diagnosis, and we further investigated the age at onset (AAO) of the disorder and severity of depressive index episode. We found that rs334555, located in intron 1 of GSK3ß, was nominally associated with an earlier AAO of the disease in MDD (P = 0.001). We also identified a haplotype containing three SNPs (rs334555, rs119258668 and rs11927974) associated with AAO of the disorder (permutated P = 0.0025). We detected variability for the CNV, but we could not detect differences between patients and controls for any of the explored phenotypes. This study presents further evidence of the contribution of GSK3ß to mood disorders, implicating a specific SNP and a haplotype with an earlier onset of the disorder in a group of well-characterized patients with unipolar MDD. Further replication studies in patients with the same phenotypic characteristics should confirm the results reported here.

[Circadian rhythms and depression]. / Ritmos circadianos y depresión.

Some core symptoms of major depression show a circadian rhythm in their clinical manifestations or are intimately linked to the circadian system functioning, such as sleep-wake cycle. Moreover, abnormalities in circadian rhythms of core body temperature and some endocrine-metabolic parameters have been detected in depressive patients compared to healthy controls. The circadian rhythm disturbances described in depressive states as well as the efficacy and fast onset of action of chronobiological based treatments point out the circadian system as an therapeutic target in the treatment of depression. The aim of this work is to review the biological and clinical data that link major depression to circadian rhythm abnormalities, the mechanisms that may underlie the abnormalities of circadian rhythm physiology seen in depressive states and the different therapeutic approaches to depression that involve the circadian system in their mechanisms of action.

A brain-derived neurotrophic factor (BDNF) haplotype is associated with antidepressant treatment outcome in mood disorders.

Brain-derived neurotrophic factor (BDNF) has been studied extensively in relation to the susceptibility to mood disorders (MD), although it remains to be clarified whether BDNF is a susceptibility locus for MD phenotypes, including therapeutic response to antidepressants. We have performed a single-marker and haplotype association study of eight TagSNPs polymorphisms in the genomic region containing the BDNF gene in 342 control subjects and 374 patients with MD, and have tested the association with antidepressant treatment outcome. None of the eight single nucleotide polymorphisms (TagSNPs) was significantly associated with MD phenotype after Bonferroni correction. In the single-marker analysis, a SNP was found to be associated with the patient's state of 'remitter' after adequate trial with a single antidepressant phenotype (odds ratio (OR)=2.95; P=0.0025). We also identified a haplotype associated with this phenotype. This study supports the implication of BDNF in antidepressant treatment outcome in MD, with specific association with 5' upstream region of BDNF gene.

Auditory event-related potentials in 50 melancholic patients: increased N100, N200 and P300 latencies and diminished P300 amplitude.

BACKGROUND: To investigate whether there are some differences in Event-Related Potentials (ERP) between melancholic patients and healthy controls. To establish whether there is a relationship between abnormalities of ERP and severity of depression and psychomotor retardation. METHOD: Melancholic depressed patients (N=50) and normal comparison subjects (N=31) were assessed for latencies and interlatencies of N100, N200, N400, latency and amplitude of P300. The ERPs were studied with an 'oddball paradigm' in the auditory modality. Severity of depression was measured by the Hamilton Depression Rating Scale (HDRS) and psychomotor retardation with the Depressive Retardation Rating Scale (DRRS). RESULTS: The melancholic group showed a significantly higher latency in N100 (P<0.001), N200 (P<0.001) and P300 (P<0.001) and a significantly lower P300 amplitude (P<0.001) than healthy controls. No other differences were found either in the latencies of the N400 or in their interlatencies. HDRS and DRRS do not have any significant correlations with amplitude or latency measures. LIMITATIONS: The subjects of this study are inpatients, with a severe subcategory of depression and high average age. It is difficult to generalize these findings. CONCLUSIONS: The principal finding of this study is the increase in three of the four latencies measured (N100, N200 and P300) and in the decreased P300 amplitude in melancholic patients compared to normal controls. There is no association between these abnormalities and clinical variables.

Loss of the circadian variation of platelet [3H]imipramine binding in delusional compared with non-delusional endogenously depressed patients.

BACKGROUND: The circadian variations of the serotonin reuptake sites were studied in 16 patients meeting DSM-IV criteria for major depression with melancholia, either with (n=8) or without (n=8) psychotic symptomatology. METHOD: The [3H]imipramine binding sites were measured in platelet samples. RESULTS: While no statistically significant difference was found between the morning (09:00 h) and evening (21:00 h) [3H]imipramine B(max) values in the control group, both the non-delusional and delusional melancholic patients showed higher evening than morning B(max) values, which were only statistically significant in the former. When both diagnostic groups were compared, the delusional patients showed significantly lower [3H]imipramine binding values than the non-delusional patients both in the morning and evening samples. Within the non-delusional depressed patients, those individuals with mood circadian variation, assessed by the 18th item of the HDRS, showed significantly lower B(max) values than those without mood variation. Lowest morning and evening B(max) values were noted in the delusional depressed group without mood variations. CONCLUSIONS: These results suggest that delusional depressions might have a different neurobiological substrate with loss of chronobiological rhythms.

Altered 5-HT(2A) binding sites and second messenger inositol trisphosphate (IP(3)) levels in hippocampus but not in frontal cortex from depressed suicide victims.

The binding parameters of 5-HT(2A) and levels of its second messenger, 1,4,5-trisphosphate (IP(3)), were simultaneously studied in frontal cortex and hippocampus from the brains of 18 control subjects and 18 depressed suicide victims. All suicides met DSM-III-R criteria for depressive symptoms, suffered a violent death and had not taken any antidepressant drugs for at least 6 months prior to death. A significant decrease in the number of 5-HT(2A) binding sites (154+/-22 vs. 254+/-36 fmol/mg), together with a significantly lower apparent affinity constant (1.02+/- 0.08 vs. 1. 36+/-0.09 nM), was detected in hippocampus but not in frontal cortex from the depressed suicides compared to the control subjects. Furthermore, IP(3) concentrations were significantly increased in hippocampus (3.2+/-0.3 vs. 2.1+/-0.3 pmol/g) but not in frontal cortex (1.3+/-0.3 vs. 2.7+/-0.5 pmol/g) from the suicide victims. The reported results may indicate a significant hypersensitivity of the 5-HT(2A) postsynaptic receptor located in the hippocampus from depressed suicide victims, giving rise to an enhancement of its intracellular signaling system with higher IP(3) production.

Seasonal variability in blood platelet 3H-imipramine binding in healthy controls: age and gender effects.

Binding of 3H-imipramine to blood platelet membranes was determined four times (once each season) in 26 healthy volunteers (11 men and 15 women), over the course of 1 year to determine possible seasonal variations. Blood platelets were obtained in April-May, July-August, October-November, and January-February. Significant seasonal variations in the maximum number of binding sites were found in women but not in men, with circannual peak in summer and a nadir in spring. The pattern of seasonal variations was not the same in men and women. The present results highlight the importance of monitoring for gender and season in binding studies. We found no significant correlation between 3H-imipramine binding parameters and age.

Growth hormone response to growth hormone releasing hormone in non-delusional and delusional depression and healthy controls.

Growth hormone (GH) responses to growth hormone releasing hormone (GHRH) of 53 in-patients meeting DSM-III-R criteria for major depressive episode with melancholia (24 non-delusional and 23 delusional depression) were compared with those of 19 healthy controls. No significant differences in basal GH were found between the control and either the non-delusional or the delusional groups. The whole group of depressed patients showed a significantly lower response than the control patients at all points of the GH response to GHRH curve as well as a lower area under curve. When the three groups (control, delusional, and non-delusional depressed) were compared, it was found that only the non-delusional depressed patients had a significantly lower area under curve and lower values at +60, +90 and +120 min than the controls. The only significant difference between the two groups of depressed patients was that the delusional group showed a delayed appearance of the maximum response peak and a more prolonged response.

[The Melkersson-Rosenthal syndrome. Apropos 2 cases]. / Síndrome de Melkersson-Rosenthal. A propósito de dos observaciones.

Melkersson-Rosenthal syndrome is classically defined as facial palsy, oedema facial and plication of the tongue, constituting one rare cause of facial palsy. The primary care physician must include this syndrome in the differential diagnosis of Bell's palsy. We report two cases of this syndrome, one in a young man, another in a 56 aged woman, and also a succinct literature review.