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. The treatment strategy was adapted from a local clinical guideline. Antidepressants prescribed were escitalopram, venlafaxine extended-release and imipramine; benzodiazepines and antipsychotics could be prescribed as needed. The final sample consisted of 614 severe unipolar major depressive inpatients and outpatients aged 18 years or older. Notably, no significant differences in efficacy or tolerability (including all subscores assessed) were found between the abstainer and nonproblematic drinker subgroups. Without ever forgetting the serious implicit risks associated with the inappropriate use of alcohol, in conclusion, our results suggest that nonproblematic alcohol consumption does not influence the outcome of patients diagnosed with an acute severe major depressive episode.

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). Efficacy analyses examined changes in the severity of depression symptoms from baseline visit to endpoint and the comparative remission rate between treatment subgroups. FINDINGS/RESULTS: The randomized sample consisted of 104 imipramine-resistant severe unipolar major depressed patients. Both, the percentage of remitters (40.4% vs 21.1%, P = 0.034) and the mean reduction of the Hamilton Depression Rating Scale score (58.8% vs 42.5%, P = 0.005) were significantly greater in the add-on citalopram subgroup at endpoint visit. IMPLICATIONS/CONCLUSIONS: Although we should be cautious about generalizing these results to patients with a less severe unipolar major episode, results from the present study suggest that add-on citalopram is a very effective treatment option in unipolar major depressive episodes after an unsuccessful imipramine regimen.

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). Efficacy analyses examined the change in depressive symptoms severity from baseline visit to endpoint and the comparative remission rate between treatment subgroups. FINDINGS/RESULTS: The randomized sample consisted of 112 venlafaxine-resistant moderate to severe unipolar major depressed patients. Both the percentage of remitters (71.43% vs 39.28%) and the mean reduction of the Hamilton Depression Rating Scale score (76.94% vs 50.72%) were significantly larger in the imipramine subgroup. IMPLICATIONS/CONCLUSIONS: Even though we should be cautious about generalizing these results to patients with a less severe unipolar major episodes, our study suggest that switching to imipramine is a very effective treatment option in unipolar major depressive episodes after an unsuccessful venlafaxine regimen.

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. Methods Isolated platelets were exposed to SCIT and activated with thrombin. We evaluated (1) platelet response by aggregometry and flow cytometry; (2) modifications in cytoskeleton proteins and signalling pathways by electrophoresis and Western blot; and (3) ultrastructural changes in platelets by electron microscopy. Results SCIT inhibited platelet response to thrombin, measured as platelet aggregation and expression of activation markers CD62-P and CD63 from platelet granules. Platelet aggregation decreased in a dose-dependent manner, reaching statistical significance with SCIT ≥32 µg/mL (65.4 ± 6.8% vs. 77.7 ± 2.5% for controls; p < 0.05). Expression of activation markers was statistically reduced with SCIT ≥20 µg/mL (p < 0.05). SCIT impaired the polymerization of the actin cytoskeleton and association of contractile proteins during activation with thrombin (p < 0.05 with SCIT ≥50 µg/mL). Resting platelets incubated with SCIT became most spherical, with increased platelet roundness (p < 0.01, SCIT 50 µg/mL vs. control). SCIT interfered with signalling pathways modulated by thrombin (RhoA, PKC, Erk1/2 and PI3K/AKT). Conclusions Our data indicate that SCIT inhibits thrombin-induced platelet response and interferes with cytoskeletal assembly and related signalling pathways, thus resulting in compromised release of granules' contents, reduced platelet activation and aggregation. These mechanisms may explain the antithrombotic benefits observed in patients treated with this SSRI, and could become new therapeutic targets for future antithrombotic strategies.

El debate emoción y cognición en neurociencias. Avances en la comprensión de los dominios sintomáticos de la depresión unipolar / The cognition-emotion debate in neuroscience. Advances in the understanding of symptom domains in unipolar depression

El trastorno depresivo mayor (TDM) se caracteriza por respuestas biológicas, cognitivas y conductuales desreguladas durante el procesamiento emocional. Las teorías cognitivas de vulnerabilidad del TDM postulan que los individuos con riesgo elevado se caracterizan por sesgos cognitivos negativos, incluyendo autoevaluaciones negativas y el sesgo atencional hacia los estímulos positivos. Más de 3 décadas de investigación sobre los factores cognitivos en la depresión han proporcionado un impresionante apoyo de las formulaciones cognitivas de la depresión. Los primeros estudios demostraron principalmente que las personas deprimidas y no deprimidas difieren en el contenido de sus pensamientos y en las maneras de manejarlos. Investigaciones recientes, sin embargo, han comenzado a explorar la naturaleza de los déficits cognitivos y sesgos en el procesamiento de información que caracterizan a la depresión. Mientras que los estudios iniciales utilizaron una variedad de medidas de autoinforme, los estudios sobre los sesgos cognitivos vienen utilizado una amplia variedad de tareas experimentales. Estas investigaciones han proporcionado un apoyo general a la formulación de que la depresión se caracteriza por pensamientos negativos automáticos y sesgos en la atención, la interpretación y la memoria (AU)

Major depressive disorder (MDD) is characterized by dysregulated biological, cognitive and behavioural responses during emotional processing. Cognitive theories of vulnerability to MDD postulate that individuals at high risk are characterized by negative cognitive biases, including negative self-assessments and attentional bias toward positive stimuli. More than 3 decades of research on cognitive factors in depression have provided impressive support for cognitive formulations of depression. Early studies mainly showed that depressed and non-depressed people differ in the content of their thoughts and in how they manage them. Recent research, however, has begun to explore the nature of cognitive deficits and biases in the information processing that characterize depression. While initial studies used a variety of self-report measures, studies on cognitive biases are used in a wide variety of experimental tasks. These studies have provided general support for the view that depression is characterized by automatic negative thoughts and biases in attention, interpretation and memory (AU)

¿En qué consiste el efecto procognitivo de los antidepresivos? / What is the pro-cognitive effect of antidepressants?

La disfunción cognitiva en el trastorno depresivo mayor (TDM) abarca varios dominios incluyendo, pero no limitados, a la función ejecutiva, la memoria verbal y la atención. Por otra parte, la disfunción cognitiva es una manifestación residual frecuente en la depresión y puede persistir durante la fase de remisión de los síntomas afectivos y somáticos. Los déficits cognitivos también pueden impedir la recuperación funcional incluyendo la capacidad de recuperación laboral, social y familar. Los nuevos antidepresivos como vortioxetina parecen conseguir una importante mejoría en dominios cognitivos alterados en el TDM y superan el efecto antidepresivo a este nivel de los antidepresivos convencionales y los antidepresivos selectivos. Los objetivos generales de este artículo de opinión son evaluar críticamente los efectos de los antidepresivos disponibles, así como las nuevas dianas terapéuticas sobre la disfunción neurocognitiva en el TDM (AU)

Cognitive dysfunction in major depressive disorder (MDD) spans multiple domains, including-but not limited to-executive function, verbal memory and attention. Moreover, cognitive dysfunction is a common residual manifestation in depression and may persist during the remission phase of affective and somatic symptoms. Cognitive deficits can also prevent functional recovery, including the ability to work, and social and familar recovery. New antidepressants such as Vortioxetine seem to achieve a significant improvement in the cognitive domains that are altered in MDD, thus providing additional benefits over conventional and selective antidepressants. The general objectives of this article are to critically assess the effects of available antidepressants and to discuss new therapeutic targets on neurocognitive dysfunction in MDD (AU)

Introducción: Detección y manejo clínico de los dominios cognitivos en la depresión

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Dominios cognitivos en la depresión unipolar. Teorías multimodales y nuevas perspectivas terapéuticas / Cognitive domains in unipolar depression. Multimodal theories and new therapeutic perspectives

El trastorno depresivo mayor (TDM) se considera el prototipo de alteración del grupo heterogéneo de trastornos depresivos (DSM-5). El TDM es una patología pleomórfica, poligénica y multisistémica que emerge de los diferentes niveles de interacción entre genes y factores ambientales. Por desgracia el aumento del costo de la depresión y de los trastornos afectivos relacionados no ha ido acompañado de mejoras en la eficacia del tratamiento antidepresivo. Los retos actuales se centran en la búsqueda de dianas terapéuticas capaces de modular diferentes niveles fisiopatológicos desde el genoma, variables metabólicas sistémicas, hasta los mecanismos cognitivos de orden superior (p.ej. funciones ejecutivas). Esta breve revisión tiene como objetivo analizar los términos neuropsicológicos que consideramos necesarios en la evaluación clínica de los pacientes afectos de un TDM así como ciertos mecanismos neurobiológicos y nuevos antidepresivos que pretender superar las limitaciones clínicas actuales (AU)

Major depressive disorder (MDD) is considered the prototype of pathology heterogeneous group of Depressive Disorders (DSM-5). The MDD is a pleomorphic pathology and multisystem polygenic disorder emerging from different levels of interacting genes and environmental factors. Unfortunately, the increasing cost of depression and related affective disorders has not been paralleled by improvements in the efficacy of antidepressant treatment. Current challenges are focused on finding therapeutic targets capable of modulating different pathophysiological levels from the genome (eg. histone deacetylase inhibitors), and systemic metabolic variables (eg. drugs that interact at the level of oxidative and inflammatory phenomena), to higher order cognitive mechanisms (eg. executive functions). This brief review aims to analyze the neuropsychological terms we considered necessary in the clinical assessment of patients with MDD and the pathophysiological mechanisms and new therapeutic seeking to overcome current limitations (AU)

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. METHODS: The present paper investigated the role of 13 SNPs within the reported genes in MDD susceptibility through a case-control (n=320 and n=150, respectively) study and in citalopram efficacy (n=157). Measures of citalopram efficacy were response (4th week) and remission (12th week). Pharmacogenetic findings were tested in the STAR(⁎)D genome-wide dataset (n=1892) for replication. RESULTS: Evidence of association among rs3738401 (DISC1), rs1615409 and rs766288 (TSNAX) and MDD was found (p=0.004, p=0.0019, and p=0.008, respectively). A trend of association between remission and DISC1 rs821616 and DAOA rs778294 was detected, and confirmation was found for rs778294 by repeated-measure ANOVA (p=0.0008). In the STAR(⁎)D a cluster of SNPs from 20 to 40Kbp from DISC1 findings in the original sample was associated with citalopram response, as well as rs778330 (12,325bp from rs778294). LIMITATIONS: Relatively small size of the original sample and focus on only three candidate genes. CONCLUSIONS: The present study supported a role of DISC1-TSNAX variants in MDD susceptibility. On the other hand, genetic regions around DAOA rs778294 and DISC1 rs6675281-rs1000731 may influence citalopram efficacy.

Delusional disorder: no gender differences in age at onset, suicidal ideation, or suicidal behavior

Objective: To investigate gender differences in age at onset, psychopathology, and suicidal behavior rates in delusional disorder (DD). Methods: We conducted a prospective longitudinal study of 97 patients with DD. Demographic and clinical data at baseline were recorded. Gender differences were investigated by applying analysis of covariance, using age at onset and age at first psychiatric consultation as dependent variables, comorbid depression and gender as between-subject factors, and employment status, social support, and DD types as covariates. Results: Seventy-six percent of the patients were women. The average age at onset was 48.76±12.67 years, mean age at first psychiatric consultation was 54.13±13.67 years, and men were more likely to be employed than women (p = 0.041). Despite the earlier age at onset and at first psychiatric consultation in men, these differences tended to disappear when adjusted for potential confounders. There were no significant gender differences in depressive comorbidity, presence of suicidal ideation and behavior, or compliance rates at follow-up. Conclusions: Our findings could not confirm that male and female DD patients differ in age at onset, age at first psychiatric consultation, or suicidal ideation and behavior, even after controlling for potential confounders. .

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. Response of blood aliquots recirculated through a thrombogenic surface was assessed in a thrombosis model. Results were compared with those of 20 healthy-matched controls. RESULTS: In comparison with controls, platelets from MDD patients showed elevated volumes (p<0.01), significantly enhanced aggregating response to arachidonic acid and augmented expression of GPIb, fibrinogen, factor V, and anionic phospholipids by flow cytometry (p<0.05). Clot firmness and procoagulant activity of platelet-associated tissue factor were also significantly elevated (p<0.05). Studies with circulating blood revealed increased fibrin formation in early diagnosed patients (71.1±9.5% vs. 45.8±5.3%; p<0.05 vs. controls). After 24 weeks of treatment with escitalopram, the majority of the alterations observed were normalized, except for a residual increased expression of GPIIbIIIa (p<0.05) and persistent alterations in thromboelatometic parameters. LIMITATIONS: Despite the reduced number of followed-up patients our findings were consistent reaching statistical significance. CONCLUSIONS: Our results reveal a prothrombotic phenotype in MDD patients. While continuous treatment with an SSRI downregulated the majority of the biomarkers analyzed, alterations in viscoelastic parameters of clot formation remained unaffected by the antidepressant treatment.

Delusional disorder: no gender differences in age at onset, suicidal ideation, or suicidal behavior.

OBJECTIVE: To investigate gender differences in age at onset, psychopathology, and suicidal behavior rates in delusional disorder (DD). METHODS: We conducted a prospective longitudinal study of 97 patients with DD. Demographic and clinical data at baseline were recorded. Gender differences were investigated by applying analysis of covariance, using age at onset and age at first psychiatric consultation as dependent variables, comorbid depression and gender as between-subject factors, and employment status, social support, and DD types as covariates. RESULTS: Seventy-six percent of the patients were women. The average age at onset was 48.76 ± 12.67 years, mean age at first psychiatric consultation was 54.13 ± 13.67 years, and men were more likely to be employed than women (p = 0.041). Despite the earlier age at onset and at first psychiatric consultation in men, these differences tended to disappear when adjusted for potential confounders. There were no significant gender differences in depressive comorbidity, presence of suicidal ideation and behavior, or compliance rates at follow-up. CONCLUSIONS: Our findings could not confirm that male and female DD patients differ in age at onset, age at first psychiatric consultation, or suicidal ideation and behavior, even after controlling for potential confounders.

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. RESULTS: In our patient sample, the reintroduction of antidepressant treatment according to the proposed protocol was not accompanied by new AAH episodes following 11-36 months of pharmacological antidepressant treatment. The second notable result was that no subject presented manic episodes or spontaneous hypomania (once antidepressant maintenance treatment had finished) during three years of follow-up. LIMITATIONS: We should be cautious when generalizing these results to patients with mild major depressive episode or other type of unipolar affective disorder. CONCLUSIONS: Based on these results, we should not refuse the prescription of antidepressant drugs to patients with unipolar depression and subsequent AAH. The treatment protocol which we describe in this study can serve as a basis for future studies and, in anticipation of future consensus, as a practical proposal for clinical psychiatrists.

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. From the baseline evaluation of the anguish/restlessness, reduced emotional reactivity, reduced attention, reduced motor response, feeling of worthlessness, and mood characteristics items, it was possible to correctly classify 88.1% of the sample as remitter/non-remitter with sensitivity of 0.77 and specificity of 0.96. Addition of the 17-item HRSD baseline variable to the regression model increased the capacity for correct classification of the baseline sample by only 0.09%. LIMITATIONS: Protocolised antidepressant treatment was used. The results of this study may not be generalisable to pharmacological treatments not included in this protocol. CONCLUSIONS: The results of this study suggest that certain baseline psychopathological characteristics (and perhaps other clinical variables too) of the acute major depressive episode may be of great use in establishing patient subgroups according to expected clinical remission to the administration of biological antidepressant treatment. This could have considerable consequences for individualised therapeutic decision-making and for future researches (clinical trials included).

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. METHODS: A randomized controlled trial with 30 schizophrenia outpatients and 15 healthy volunteers. A strategy-learning-based treatment was used as a cognitive remediation therapy. A social skills training that provides useful information about illness management was used as an active control. We investigated changes in the pattern of functional connectivity assessed during an n-back task by tensorial independent component analysis as implemented in the multivariate exploratory linear decomposition into independent components and in the fractional anisotropy index of white matter integrity using tract-based spatial statistics. RESULTS: Brain networks activation pattern significantly changed in patients exposed to the cognitive treatment in the sense of normalizing toward the patterns observed in healthy control subjects. Additionally, in white matter, they showed an increase in fractional anisotropy index in the anterior part of the genu of the corpus callosum. Cognitive improvement, functional, and also structural changes showed statistically significant correlations. CONCLUSIONS: Improvement in brain functioning detected after cognitive remediation therapy in schizophrenia patients might be based on an increase of the interhemispheric information transfer between the bilateral prefrontal cortexes via the corpus callosum.

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. In the present study we aimed at testing putative interaction mechanisms between childhood maltreatment and COMT genotypic variability that might explain a proportion of the observed variability of cognitive flexibility in the population. Our design was based on a sample of adult monozygotic twins, which allowed us to test these effects free from potential genetic and shared-environmental confounding factors. Results showed that unique environmental effects of childhood maltreatment significantly impacted cognitive performance among Met/Met subjects. Interestingly, the direction of the association indicated that exposure to early stressful experiences was associated with enhanced cognitive flexibility in this genotype group. These results suggest that COMT may operate as a plasticity gene that provides differential cognitive capacity to respond to environmental stressors.

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. A subsample of 155 depressive patients were treated with citalopram and evaluated for response (fourth week) and remission (12th week) by the 21-item Hamilton Depression Rating Scale (HDRS). RESULTS: We observed a higher frequency of rs806371 G carriers in MD patients with both presence of melancholia (p = 0.018) and psychotic symptoms (p = 0.007) than in controls. Haplotype frequency distributions between MD sample and controls showed a significant difference for Block 1 (rs806368-rs1049353-rs806371) (p = 0.008). This haplotype finding was consistent when we compared controls with MD subsample stratified by melancholia (p = 0.0009) and psychotic symptoms (p = 0.014). The TT homozygous of the rs806368 and rs806371 presented more risk of no Remission than the C carriers (p = 0.008 and 0.012, respectively). Haplotype frequency distributions according to Remission status showed a significant difference for Block 1 (p = 0.032). Also, we observed significant effect of time-sex-genotype interaction for the rs806368, showing that the C carrier men presented a better response to antidepressant treatment throughout the follow-up than TT homozygous men and women group (p = 0.026). CONCLUSIONS: These results suggest an effect of CNR1 gene in the etiology of MD and clinical response to citalopram.

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). We applied voxel-based morphometry to analyse GMV differences. Concordant affected twins were compared to healthy twins and within-pairs comparisons were performed in the discordant group. RESULTS: GMV reductions in bilateral fusiform gyrus and amygdala were observed in concordant affected twins for anxiety and depression compared to healthy twins. No intrapair differences were found in GMV between discordant affected twins and their healthy co-twins. LIMITATIONS: The sample size was modest. This might explain why no intrapair differences were found in the discordant MZ twin group. CONCLUSIONS: As concordant affected MZ twins are believed to have a particularly high genetic liability for the disorder, our findings suggest that fusiform gyrus and amygdala gray matter reductions are related to a genetic risk for anxiety and depression. Discrepancies in regard to brain abnormalities in anxiety and depression may be related to the admixture of patients with GMV abnormalities mainly accounted for by genetic factors with patients presenting GMV mainly accounted for by environmental factors.

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. METHODS: The adrenocorticotropin hormone (ACTH) and cortisol responses to corticotrophin releasing factor (CRF) stimulation was assessed in 62 outpatients diagnosed with unipolar depressive disorder with melancholic features according to DSM-IV. Twenty-three healthy controls were included in the study for comparison. Monthly follow-up visits were performed over a 2-year period after remission; partial and complete relapses were established using the Hamilton Depression Rating Scale (HDRS) and according to Frank's criteria. Fifty-four patients completed the study. A comparative statistical analysis was performed. RESULTS: Stratifying the net area under cortisol curve (NAUCC) (µg/ml/min) at three levels-< 150, 150-350 and ≤ 350-significant differences appear between the three depressive groups of patients (non-relapsers, partial relapsers and complete relapsers). Particularly, there are more patients with a NAUCC ≤ 350 who show partial or complete relapses than patients with a NAUCC ≤ 350 who do not relapse (P ≤ 0.05). CONCLUSIONS: Our results show an increasingly altered HPA axis in those depressive patients with complete or partial relapses compared with those who did not relapse or with healthy controls, but there are not differences in HPA axis between partial and complete relapsers.