RESUMO
BACKGROUND: Many factors are involved in the pathogenesis of depression. This article provides an overview of the results given in the thesis entitled 'Linking Depression', in which some putative underlying neurobiological and genetic mechanisms of depression are examined. AIM: To gain more insight in brain activity as endophenotype for depression. METHOD: As part of the Netherlands Study of Depression and Anxiety (nesda), 301 people, including patients with depression and/or anxiety and healthy volunteers, underwent functional magnetic resonance imaging (fmri) and genotyping. RESULTS: During the processing of negative emotions, patients with depression showed a pattern of heightened limbic activation but less prefrontal activation. The same pattern, but in reverse, was seen during the processing of positive emotions. We showed that the disc1, comt and npy genes were associated with brain activation patterns comparable to those seen in patients with depression. In addition, in cases of depression, there was a different kind of relationship between these genes and brain activation. CONCLUSION: Depression is characterised by the disturbed processing not only of negative emotions but also of positive emotions. In addition, the studies we describe contribute to our insight into the neurobiology of depression and relevant genetic influences because the results demonstrate that depression alters the relationship between genes and brain activation.
Assuntos
Encéfalo/fisiologia , Depressão/genética , Emoções/fisiologia , Encéfalo/metabolismo , Depressão/etiologia , Genótipo , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Insufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more targeted treatment strategies to reduce suffering. We therefore explored whether baseline alterations within and between resting state functional connectivity networks could serve as markers of insufficient response to antidepressant treatment in two years of follow-up. We selected MDD patients (Nâ¯=â¯17) from the NEtherlands Study of Depression and Anxiety (NESDA), who received ≥ two antidepressants, indicative for insufficient response, during the two year follow-up, a group of MDD patients who received only one antidepressant (Nâ¯=â¯32) and a healthy control group (Nâ¯=â¯19) matched on clinical characteristics and demographics. An independent component analysis (ICA) of baseline resting-state scans was conducted after which functional connectivity within the components was compared between groups. We observed lower connectivity of the right insula within the salience network in the group with ≥ two antidepressants compared to the group with one antidepressant. No difference in connectivity was found between the patient groups and healthy control group. Given the suggested role of the right insula in switching between task-positive mode (activation during attention-demanding tasks) and task-negative mode (activation during the absence of any task), we explored whether right insula activation differed during switching between these two modes. We observed that in the ≥2 antidepressant group, the right insula was less active compared to the group with one antidepressant, when switching from task-positive to task-negative mode than the other way around. These findings imply that lower right insula connectivity within the salience network may serve as an indicator for prospective insufficient response to antidepressants. This result, supplemented by the diminished insula activation when switching between task and rest related networks, could indicate an underlying mechanism that, if not sufficiently targeted by current antidepressants, could lead to insufficient response. When replicated, these findings may contribute to the identification of biomarkers for early detection of insufficient response.
Assuntos
Antidepressivos/uso terapêutico , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Adulto , Antidepressivos/administração & dosagem , Biomarcadores , Mapeamento Encefálico , Córtex Cerebral/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/efeitos dos fármacos , Resultado do TratamentoRESUMO
Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene--involved in monoaminergic neurotransmission--as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging (fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD.