Global hippocampal atrophy in major depressive disorder: a meta-analysis of magnetic resonance imaging studies / Atrofia global do hipocampo no transtorno depressivo maior: uma metanálise de estudos com ressonância magnética

Abstract Introduction: Major depressive disorder (MDD), an incapacitating mental disorder, is characterized by episodes of at least 2 weeks of apparent changes in mood, cognition, and neurovegetative functions. Many neuroimaging studies using magnetic resonance imaging (MRI) have examined morphometric changes in patients with MDD, but the results are not conclusive. This study aims to review the literature and perform a meta-analysis on hippocampal volume (HcV) in patients with MDD. Methods: Studies on HcV in patients with MDD diagnosis were identified from major databases (MEDLINE, EMBASE, The Cochrane Library, Scopus, PsycINFO, and SciELO) using the search terms depression, major depressive disorder, MDD, unipolar, magnetic resonance imaging, MRI, and hippocampus. Results: A meta-analysis of 29 studies fulfilling specific criteria was performed. The sample included 1327 patients and 1004 healthy participants. The studies were highly heterogeneous with respect to age, sex, age of onset, and average illness duration. However, the pooled effect size of depression was significant in both hippocampi. MDD was associated with right (-0.43; 95% confidence interval [95%CI] −0.66 to −0.21) and left (-0.40; 95%CI −0.66 to −0.15) hippocampal atrophy. Conclusions: MDD seems to be associated with global HcV atrophy. Larger longitudinal follow-up studies designed to analyze the influence of sociodemographic variables on this relationship are required to yield better evidence about this topic.

Resumo Introdução: O transtorno depressivo maior (TDM) é uma doença mental incapacitante caracterizada por episódios de pelo menos 2 semanas de mudanças claras no afeto, cognição e funções neurovegetativas. Vários estudos de neuroimagem, realizados através de imagem de ressonância magnética (IRM), examinaram mudanças morfométricas em pacientes com TDM, com resultados não conclusivos. Este estudo tem como objetivo revisar a literatura e realizar uma metanálise sobre o volume do hipocampo (VHc) em pacientes com TDM. Métodos: Estudos de VHc em pacientes com TDM foram identificados a partir dos principais bancos de dados (MEDLINE, EMBASE, The Cochrane Library, Scopus, PsycINFO e SciELO) usando os seguintes termos: depression, major depressive disorder, MDD, unipolar, magnetic resonance imaging, MRI e hippocampus. Resultados: Foi realizada uma metanálise de 29 estudos que preencheram os critérios específicos. A amostra foi composta por 1327 pacientes e 1004 indivíduos saudáveis. Os estudos foram altamente heterogêneos em relação a idade, gênero, idade do primeiro episódio e duração média da doença, mas o efeito combinado da depressão foi significativo em ambos os hipocampos. O TDM foi associado à atrofia do hipocampo à direita [-0,43; intervalo de confiança de 95% (IC95%) −0,66 a −0,21] e à esquerda (-0,40; IC95% −0,66 a −0,15). Conclusões: O TDM parece estar associado à atrofia global do VHc. Estudos longitudinais com maior tempo de seguimento, projetados para analisar a influência dos fatores sociodemográficos nessa relação, são necessários para obter evidências mais robustas.

Interaction between polymorphisms in SLC6A4 and BDNF on major depressive disorder in a sample of the argentinean population / Interacción entre polimorfismos en SLC6A4 y BDNF en el trastorno depresivo mayor en una muestra de la población argentina

The dysfunction in the serotoninergic neurotransmission has been classically associated with major depressive disorder (MDD); however, other pathways and processes seem to have a role in this illness, such as neurogenesis and related molecules: the Brain-Derived Neurotrophic Factor (BDNF) and the Apolipoprotein E (APOE). There are many reports that indicate an association between certain polymorphism in these genes and MDD. The aim of our study was to analyze the possible association between MDD and polymorphisms in HTR2A (5-hydroxytryptamine receptor 2A), BDNF and APOE genes in a sample of the Argentinean population previously studied for 2 polymorphisms in SLC6A4 (Solute Carrier Family 6 Member 4) gene. Five polymorphisms were studied (rs6311 and rs6313 in HTR2A; rs429358 and rs7412 in APOE, and rs6265 in BDNF) in 95 MDD patients and 107 non-related controls. No statistically significant differences were observed between groups when analyzing the association with a single marker using logistic regression; however, when a possible combinatory effect of the polymorphisms (including previously studied polymorphisms in SLC6A4 gene) was analyzed using a dominant model for the risk alleles, the genotypes L/S_10/12_G/A (OR=3.57(95%CI=1.43-8.93); p=0.004, adjusted p-value=0.01) in SLC6A4 and BDNF genes and L/S_10/12_T/C_3/3_G/A in SLC6A4, HTR2A, APOE and BDNF genes (OR=5.99(95%CI=1.66-21.56); p=0.002, adjusted p-value=0.07), were more prevalent in patients than in controls (20%vs.6% and 15%vs.3%, respectively). Even though it is necessary to replicate these findings in a larger population, our results suggest a possible interaction between molecules involved in neurogenesis (BDNF and APOE), serotoninergic neurotransmission (SLC6A4 and HTR2A) and the pathogenesis of MDD. (AU)

La disfunción en la neurotransmisión serotoninérgica ha sido clásicamente asociada con el trastorno depresivo mayor (TDM); sin embargo, otras vías y procesos parecerían tener un rol en esta enfermedad, como la neurogénesis y moléculas asociadas: el factor neurotrófico derivado del cerebro (BDNF) y la apoliproteína E (APOE). Existen reportes en los que se establecen asociaciones entre polimorfismos en estos genes y el TDM. El objetivo de nuestro trabajo fue analizar la posible asociación entre el TDM y polimorfismos en los genes HTR2A (receptor 5-hidroxitriptamina 2A), BDNF y APOE en una muestra de la población argentina previamente estudiada para 2 polimorfismos en el gen SLC6A4 (transportador soluble familia 6 miembro 4). Se estudiaron 5 polimorfismos (rs6311 y rs6313 en HTR2A; rs429358 y rs7412 en APOE; rs6265 en BDNF) en 95 pacientes con TDM y 107 controles no relacionados. No se observaron diferencias significativas entre grupos al analizar la asociación por regresión logística con un único marcador; cuando se analizó el posible efecto combinatorio de polimorfismos (incluyendo los previamente estudiados para el gen SCL6A4) usando un modelo dominante para los alelos de riesgo, los genotipos L/S_10/12_G/A (OR=3,57(95%CI=1,43-8,93); p=0,004, valor-p-ajustado=0,01) en SLC6A4 y BDNF y L/S_10/12_T/C_3/3_G/A en SLC6A4, HTR2A, APOE y BDNF (OR=5,99(95%CI=1,66-21,56); p=0,002, valor-p-ajustado=0,07), fueron más prevalentes en pacientes que controles (20%vs.6% y 15%vs.3% respectivamente). Si bien es necesario replicar estos hallazgos en una población más grande, nuestros resultados sugieren una posible interacción entre moléculas involucradas en la neurogénesis (BDNF y APOE), la neurotransmisión serotoninérgica (SLC6A4 y HTR2A) y la patogenia de la depresión mayor. (AU)

Association of interleukin-10 levels with age of onset and duration of illness in patients with major depressive disorder

Objective: To investigate peripheral levels of interleukin-10 (IL-10) in patients with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the relationship between IL-10, age of disease onset, and duration of illness. Methods: Case-control study nested in a population-based cohort of 231 individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul, Brazil. Participants were screened for psychopathology using the Mini-International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially available immunoassay kits. Results: Peripheral levels of IL-10 were not significantly different in individuals with MDD or BD as compared to controls. However, higher IL-10 levels were found in MDD patients with a later disease onset as compared with controls or early-onset patients. In addition, IL-10 levels correlated negatively with illness duration in the MDD group. In the BD group, age of onset and duration of illness did not correlate with IL-10 levels. Conclusion: Higher levels of IL-10 are correlated with late onset of MDD symptoms. Moreover, levels of this cytokine might decrease with disease progression, suggesting that an anti-inflammatory balance may be involved in the onset of depressive symptoms and disease progression in susceptible individuals.

El circuito cerebral de la recompensa en los trastornos afectivos / Brain Reward Circuitry in Affective Disorders

Los síntomas conductuales de la depresión son numerosos y variados, cubriendo los dominios emocionales, motivacionales, cognitivos y fisiológicos. Estudios recientes en modelos animales de depresión y en pacientes depresivos utilizando técnicas neuropsicológicas combinadas con imagenología funcional muestran que grandes subgrupos de estos pacientes presentan deficiencias en el procesamiento de las recompensas a los estímulos emocionales positivos, que son nucleares en depresión. La proteína Rac 1, un regulador crítico de la actina del citoesqueleto, se reduce en el NAcc tanto en depresión como en modelos animales de adicción, lo que lleva al crecimiento de espinas dendríticas inmaduras en las MSNs del NAcc y esto es consecuencia de modificaciones epigenéticas selectivas en esta región, del gen que codifica Rac 1, tanto en modelos de estrés en roedores como en humanos depresivos (estudios post-mortem). El gran desarrollo de algunos de los modelos experimentales de depresión que cuentan con evidencias moleculares, sistémicas y conductuales no se han traducido en nuevos medicamentos pero al avanzar en la comprensión patofisiológica del trastorno y sus correlatos neuroimagenológicos, permitirán, junto a las modernas técnicas de investigación, buscar marcadores biológicos de los endofenotipos diferentes que se combinan para generar un trastorno que posee múltiples subtipos que los agrupan en clusters diferentes

The behavioral symptoms of depression are numerous and varied, and encompass the emotional, motivational and physiologic domains. Recent studies in animal models of depression and depressive patients, which used neuropsychological techniques combined with functional imaging, show that large subgroups of these patients display deficiencies in the processing of rewards to positive emotional stimuli, which are nuclear in depression. Rac 1 protein, a critical regulator of cytoskeleton actin, is reduced in the NAcc, both in depression as well as in animal models of addiction, which leads to the growth of immature dendritic spines in the MSNs of the NAcc, and this is the result of selective epigenetic alterations in this region, of the gene that codifies Rac1, both in models of stress in rodents as well as in depressive human beings (post-mortem studies). The great development of some of the experimental models of depression that provide molecular, systemic and behavioral evidences have not translated into new medications, but the progressive pathophysiological understanding of the disorder and its neuroimaging correlates will enable, together with the modern investigations techniques, to search for biological markers of the different endophenotypes that combine to generate a disorder which has multiple subtypes that gather in different clusters

Prevalência de transtorno depressivo maior em centro de referência no tratamento de hipertensão arterial / Prevalence of major depressive disorders in a reference center for the treatment of hypertension

OBJETIVO: Investigar a prevalência de transtorno depressivo maior em pacientes hipertensos matriculados em um centro de referência universitário para tratamento de hipertensão arterial e fatores de risco cardiovascular. MÉTODOS: Estudo transversal, descritivo, em amostra aleatória representativa, obtida de forma sistemática, de pacientes em atendimento contínuo na Liga de Hipertensão Arterial da Universidade Federal de Goiás. Aplicou-se o Inventário de Depressão de Beck para rastreamento de sintomas depressivos e a Entrevista Estruturada para o Manual de Diagnóstico e Estatística das Perturbações Mentais - Transtornos do Eixo I para avaliação diagnóstica de transtorno depressivo maior. Foram constituídos um grupo com pacientes portadores de depressão maior, denominado grupo-estudo, e um grupo com pacientes não-portadores de depressão maior, denominado grupo-controle. Avaliou-se variáveis sociodemográficas, pressão arterial e bioquímica sangüínea no momento da coleta de dados. RESULTADOS: Foram entrevistados 285 pacientes, tendo sido encontrada prevalência de 20 por cento de depressão maior na população investigada. A idade média foi significativamente menor para o grupo-estudo, com predomínio do sexo feminino. A prática de atividade física regular foi também significativamente menor entre os pacientes do grupo-estudo, que também apresentaram valores mais elevados de pressão arterial diastólica e de colesterolemia. CONCLUSÕES: Foi encontrada uma prevalência de transtorno depressivo maior em pacientes hipertensos superior àquela encontrada na população geral. Isso aponta para uma necessidade de maior atenção ao diagnóstico dos transtornos depressivos em pacientes hipertensos em atendimento primário e ambulatorial.

OBJECTIVE: To investigate the prevalence of major depression disorders in hypertensive patients enrolled in a university reference center for treatment of hypertension and other cardiovascular risk factors. METHODS: Cross-sectional, descriptive study of a representative randomized sample of patients, obtained according to a systematic protocol, among individuals enrolled for continuous treatment at the Hypertension League of Universidade Federal de Goiás. The Beck Depression Inventory was administered to detect depressive symptoms, and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders for diagnostic classification of major depressive disorders. Two groups were formed, one with patients with major depressive disorder, called study group, and another with patients without major depression, called control group. Sociodemographic variables, blood pressure and plasma biochemistry were evaluated at the time of data collection. RESULTS: A total of 285 patients were evaluated and results indicated a 20 percent prevalence of major depression in the population included in the study. Mean age was significantly lower for the study group, in which female patients were predominant. Regular physical activity was significantly lower among patients in the study group, and higher diastolic blood pressure values as well as cholesterolemia were also found in this group. CONCLUSIONS: These results show a higher prevalence of major depressive disorder among these hypertensive patients, compared with the general population. More attention should be paid to establishing an adequate diagnosis for depressive disorders in hypertensive patients, both in primary care facilities and in outpatient clinics.

The functioning and quality of life of depressive patients with 12 weeks of psychiatric care.

OBJECTIVES: The purpose of this study was to obtain data about the functional status of depressive patients with 12 weeks of psychiatric care and find out if there is any correlation between improvement of clinical and functioning status. MATERIAL AND METHOD: A prospective descriptive study was conducted and quality of life instruments (SF-36) were used to assess 96 depressive patients with 12 weeks follow up. RESULTS: There was prominent functional disability with depressive patients. The response rate of depressive patients with 3-month psychiatric care was 67.7%. The correlation between improvement in clinical status and quality of life of this group of patients did not significantly correlate. CONCLUSION: Depressive disorder is treatable with a very good response rate but no significant correlation between clinical improvement and quality of life. There is limitations in psychological and role functioning of depressive patients after 3 months of care. It is recommended that continuing of care should be considered for quality of life improvement.

Late-life depression, heart failure and frontal white matter hyperintensity: a structural magnetic resonance imaging study

The relevance of the relationship between cardiac disease and depressive symptoms is well established. White matter hyperintensity, a bright signal area in the brain on T2-weighted magnetic resonance imaging scans, has been separately associated with cardiovascular risk factors, cardiac disease and late-life depression. However, no study has directly investigated the association between heart failure, major depressive symptoms and the presence of hyperintensities. Using a visual assessment scale, we have investigated the frequency and severity of white matter hyperintensities identified by magnetic resonance imaging in eight patients with late-life depression and heart failure, ten patients with heart failure without depression, and fourteen healthy elderly volunteers. Since the frontal lobe has been the proposed site for the preferential location of white matter hyperintensities in patients with late-life depression, we focused our investigation specifically on this brain region. Although there were no significant group differences in white matter hyperintensities in the frontal region, a significant direct correlation emerged between the severity of frontal periventricular white matter hyperintensity and scores on the Hamilton scale for depression in the group with heart failure and depression (P = 0.016, controlled for the confounding influence of age). There were no significant findings in any other areas of the brain. This pattern of results adds support to a relationship between cardiovascular risk factors and depressive symptoms, and provides preliminary evidence that the presence of white matter hyperintensities specifically in frontal regions may contribute to the severity of depressive symptoms in cardiac disease.

Volumetric MRI analysis of the amygdala and hippocampus in subjects with major depression / 华中科技大学学报（医学）（英德文版）

In order to explore the MRI volume of the amygdala and hippocampus in patients with major depression, quantitative MRI of the amygdala and hippocampus were studied in 22 patients with major depression and compared with 13 age-matched controls. The results showed that both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The volume of the bilateral hippocampus was significantly smaller in the major depression group than that in control group. The patients had significant asymmetry of the amygdalar volumes (right smaller than left). No correlation was found between hippocampal volume abnormalities and ill duration. It was concluded that the hippocampus and amygdala within limbic-cortical networks may play a crucial role in the pathogenesis of major depression.