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BACKGROUND: Pathophysiologic processes supporting abnormal emotion regulation in major depressive disorder (MDD) are poorly understood. We previously found abnormal inverse left-sided ventromedial prefrontal cortical-amygdala effective connectivity to happy faces in females with MDD. We aimed to replicate and expand this previous finding in an independent participant sample, using a more inclusive neural model, and a novel emotion processing paradigm. METHODS: Nineteen individuals with MDD in depressed episode (12 females), and 19 healthy individuals, age, and gender matched, performed an implicit emotion processing and automatic attentional control paradigm to examine abnormalities in prefrontal cortical-amygdala neural circuitry during happy, angry, fearful, and sad face processing measured with functional magnetic resonance imaging in a 3-T scanner. Effective connectivity was estimated with dynamic causal modeling in a trinodal neural model including two anatomically defined prefrontal cortical regions, ventromedial prefrontal cortex, and subgenual cingulate cortex (sgACC), and the amygdala. RESULTS: We replicated our previous finding of abnormal inverse left-sided top-down ventromedial prefrontal cortical-amygdala connectivity to happy faces in females with MDD (p = 0.04), and also showed a similar pattern of abnormal inverse left-sided sgACC-amygdala connectivity to these stimuli (p = 0.03). These findings were paralleled by abnormally reduced positive left-sided ventromedial prefrontal cortical-sgACC connectivity to happy faces in females with MDD (p = 0.008), and abnormally increased positive left-sided sgACC-amygdala connectivity to fearful faces in females, and all individuals, with MDD (p = 0.008; p = 0.003). CONCLUSION: Different patterns of abnormal prefrontal cortical-amygdala connectivity to happy and fearful stimuli might represent neural mechanisms for the excessive self-reproach and comorbid anxiety that characterize female MDD.
ABSTRACT
BACKGROUND: Bipolar disorder is frequently misdiagnosed as major depressive disorder, delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation might therefore help discriminate bipolar from major depressive disorder. METHODS: Thirty-one depressed individuals-15 bipolar depressed (BD) and 16 major depressed (MDD), DSM-IV diagnostic criteria, ages 18-55 years, matched for age, age of illness onset, illness duration, and depression severity-and 16 age- and gender-matched healthy control subjects performed two event-related paradigms: labeling the emotional intensity of happy and sad faces, respectively. We employed dynamic causal modeling to examine significant among-group alterations in effective connectivity (EC) between right- and left-sided neural regions supporting emotion regulation: amygdala and orbitomedial prefrontal cortex (OMPFC). RESULTS: During classification of happy faces, we found profound and asymmetrical differences in EC between the OMPFC and amygdala. Left-sided differences involved top-down connections and discriminated between depressed and control subjects. Furthermore, greater medication load was associated with an amelioration of this abnormal top-down EC. Conversely, on the right side the abnormality was in bottom-up EC that was specific to bipolar disorder. These effects replicated when we considered only female subjects. CONCLUSIONS: Abnormal, left-sided, top-down OMPFC-amygdala and right-sided, bottom-up, amygdala-OMPFC EC during happy labeling distinguish BD and MDD, suggesting different pathophysiological mechanisms associated with the two types of depression.
Subject(s)
Amygdala/physiopathology , Bipolar Disorder/diagnosis , Bipolar Disorder/physiopathology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/physiopathology , Prefrontal Cortex/physiopathology , Adult , Case-Control Studies , Diagnosis, Differential , Emotions/physiology , Facial Expression , Female , Humans , Male , Models, Neurological , Neural Pathways/physiopathologyABSTRACT
INTRODUÇÃO: O processamento emocional pelo cérebro humano tem sido atualmente investigado através do uso de ressônancia magnética funcional (RMf). A RMf possibilita o estudo in vivo e não invasivo de mudanças na atividade cerebral regional em voluntários humanos saudáveis. O processamento emocional pode ser modulado através do uso de antidepressivos que influenciam sistemas neurais relacionados ao processamento emocional, através da modulação da ação de neurotransmissores como a serotonina e a noradrenalina. A clomipramina, um antidepressivo tricíclico, tem sido relacionada com efeitos de resposta clínica mesmo em voluntários saudáveis. Estudos utilizando a RMf permitem a investigação do efeito de antidepressivos nos sistemas neurais envolvidos no processamento emocional em indivíduos saudáveis que apresentam resposta ao uso destes medicamentos comparados a sujeitos que não apresentam resposta ao tratamento. MÉTODOS: Nesta tese, dezoito voluntários saudáveis foram investigados em relação a mudanças de atividade neural em resposta à indução emocional através da apresentação de fotografias do International Affective Pictures System (IAPS). Foram estudadas particularmente as emoções de raiva, felicidade e medo. Os voluntários foram submetidos ao tratamento prolongado com doses baixas de clomipramina por quatro semanas. A amostra foi subdividida em respondedores (n=6) e não respondedores (n=12) ao tratamento com clomipramina. A atividade neural foi estimada com o uso da RMf, através da mensuração do efeito blood oxygenation level dependent (BOLD). As imagens foram processadas e analisadas usando o programa Statistical Parametric Mapping (SPM). Indivíduos não respondedores foram comparados sob o efeito e na ausência de efeito da clomipramina, através de comparações planejadas utilizando t-teste pareado. Indivíduos respondedores foram comparados com os não respondedores sob o efeito da clomipramina através de t-teste não pareado. RESULTADOS: Nos voluntários...
INTRODUCTION: The emotional processing by the human brain has now been investigated through the use of functional magnetic resonance imaging (fMRI). The fMRI technique allows the noninvasive study of in vivo changes in regional brain activity in healthy human volunteers. The emotional processing may be modulated through the use of antidepressants that influence neural systems linked to emotional processing, by modulating the action of neurotransmitters such as serotonin and norepinephrine. Clomipramine, a tricyclic antidepressant, has been reported to elicit clinical response even in healthy volunteers. Studies using fMRI allow the investigation of the effect of antidepressants on neural systems involved in emotional processing in healthy subjects showing response to the use of antidepressant drugs compared to subjects who do not respond to treatment. METHODS: In this thesis, eighteen healthy volunteers were investigated in relation to changes in neural activity in response to emotional induction through the presentation of photos of the International Affective Picture System (IAPS). We studied especially the emotions of anger, happiness and fear. The volunteers were subjected to prolonged treatment with low doses of clomipramine for four weeks. The sample was divided into responders (n = 6) and non-responders (n = 12) to treatment with clomipramine. The neural activity was estimated by using fMRI, by measuring the blood oxygenation level dependent effect (BOLD). Images were processed and analyzed using the Statistical Parametric Mapping (SPM) program. Non-responders were compared under two conditions: when using clomipramine, and after drug washout, using paired t-tests. Individuals who responded to clomipramine treatment were compared with non-responders under the effect of the drug by independent t-test. RESULTS: In volunteers not responding to clomipramine, a comparison between the non-medicated versus medicated states showed less neural activity...
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Basal Ganglia , Clomipramine , Expressed Emotion , Humans , Limbic System , Magnetic Resonance ImagingABSTRACT
A nova lei dos transplantes, sancionada em 1997, trouxe grandes mudanças na forma de doaçäo de órgäos, transformando todos os brasileiros maiores de 21 anos em doadores, a menos que se manifestem contra em documento de identidade ou habilitaçäo. Isto tem gerado grande polêmica sobre a liberdade de escolha, utilizaçäoadequada de tecidos e órgäos e conceito de morte encefálica. Era a impressäo geral que a populaçäo näo estaria bem informada a respeito da nova lei e que as religiöes seriam contra a doaçäo de órgäos. Este estudo teve como objetivos verificar a compreensäo da populaçäo e dos dirigentes das principais religiöes frenteà nova lei, definindo o perfil da populaçäo, verificando a influência das religiöes na anuência da lei assim como o impacto dos conceitos religiosos na aceitaçäo dos transplantes. Para isto foi aplicado um questionário para 150 membros da comunidade, escolhidos ao acaso em um shopping center do Grande ABC e outro para dirigentes das seguintes religiöes. Adventista do 7 dia, Católica Apostólica Ortodoxa, Católica Apostólica Romana, Episcopal Anglicana, Espírita kardexista, Judaica, Luterana do Brasil, Presbiteriana, Testemunhas de Jeová e Universal do Reino de Deus. Todas as religiöes se mostraram favoráveis à nova lei exceto a Adventista, que tinha restriçöes. Apenas a Luterana, a Presbiteriana, a Espírita e a Testemunha de Jeová divulgavam o assunto em cultos. Em conclusäo, a maioria da populaçäo é favorável à nova lei e doaria seus órgäos independentemente da mesma; os dirigentes religiosos näo influenciam a opiniäo dos fiéis e a nova lei näo vai alterar, a curto prazo, a situaçäo dos transplantes no Brasil porque o problema é mais amplo, incluindo a falta de infra estrutura, integraçäo e verbas do Sistema de Saúde
