Neural correlates of treatment outcome in major depression

Lisiecka, Danuta; Meisenzahl, Eva; Scheuerecker, Johanna; Schoepf, Veronica; Whitty, Peter; Chaney, Aisling M.; Moeller, Hans‐Juergen; Wiesmann, Martin; Frodl, Thomas

doi:10.1017/s1461145710001513

Cited by 74 publications

(67 citation statements)

References 73 publications

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“…With regard to studies of treatment effects, reductions in functional connectivity observed here encompass the region lesioned in anterior cingulotomy for severe treatment-resistant depressive disorder (17), those areas stimulated in rapid-rate transcranial magnetic treatment for depression (18), and parallel aspects of the impact of cognitive behavioral therapy (19). The observed effects were entirely intracortical [including changes in functional connectivity between the neocortex and limbic cortex (e.g., DLPFC, anterior cingulate)], in contrast to connectivity studies exploring chemical antidepressant therapy, where subcortical limbic structures are implicated (12,13). Strikingly, the medial areas to which connectivity has been reduced (Fig.…”

Section: Discussionmentioning

confidence: 92%

“…Although such regional findings tend to correspond anatomically to those brain areas maximally activated by diverse emotional tasks in normal individuals (10), the nature (over-or underactivity) of the dysfunction seen in depressed subjects has seemed contradictory at times and its significance uncertain. Several recent functional imaging studies have focused on the investigation of functional connectivity among cortical and corticolimbic networks rather than the description of stimulus-induced or task-related activity in individual regions of interest (11)(12)(13).…”

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confidence: 99%

“…Healthy volunteers taking chemical antidepressants have been shown to have reduced connectivity between the amygdala and frontal regions compared with subjects taking placebo (with different frontal connectivity patterns observed for serotonin and noradrenaline reuptake inhibitors) (13), and higher pretreatment orbitofrontal cortex connectivity levels may predict a positive response to antidepressants in depressed patients (12).…”

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confidence: 99%

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Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder

Perrin

Merz

Bennett

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

207

149

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To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. A comparison of pre-and posttreatment functional connectivity data in a group of nine patients revealed a significant cluster of voxels in and around the left dorsolateral prefrontal cortical region (Brodmann areas 44, 45, and 46), where the average global functional connectivity was considerably decreased after ECT treatment (P < 0.05, family-wise error-corrected). This decrease in functional connectivity was accompanied by a significant improvement (P < 0.001) in depressive symptoms; the patients' mean scores on the Montgomery Asberg Depression Rating Scale pre-and posttreatment were 36.4 (SD = 4.9) and 10.7 (SD = 9.6), respectively. The findings reported here add weight to the emerging "hyperconnectivity hypothesis" in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorder and a potential therapeutic target. T he treatment of depressive disorder is one of the most pressing issues in contemporary medical practice: The illness is a leading cause of significant disability worldwide (1). Current therapeutic strategies are imperfect, and there is an urgent need to develop more consistently effective and rapidly acting treatment solutions. Unfortunately, our understanding of the etiopathology of mood disorder is incomplete. As a result, the elucidation of the mechanisms of action of effective treatment has necessarily been less than secure and advance has been slow. Available treatments (e.g., chemical antidepressant therapy) were discovered serendipitously rather than designed, and insight into the biology of depressive disorder by study of antidepressant actions has been limited. In particular, the effectiveness of electroconvulsive therapy (ECT), the most potent and rapidly acting of all antidepressant agents (2), has eluded a coherent explanatory framework despite its regular use for more than 70 years. However, if the effects of ECT could be reproduced in a less invasive way, and with a more benign side-effect profile, the treatment of severe depression would be significantly enhanced. To achieve this, we need first to understand better how ECT influences brain function. Here, we show that ECT alters the functional architecture of frontal systems by strongly down-regulating connectivity in key circuits implicated in mood disorder.Efforts to delineate the neural substrate of mood disorder using functional brain imaging technology have generally identified abnormal frontal cortical and limbic activity in depressed patients (3-9). Although such regional findings tend to correspond anatomically to tho...

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Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

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confidence: 99%

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Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder

Perrin

Merz

Bennett

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

207

149

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“…The neural correlates of emotion processing and attention shifting evoked by our task were localized in areas that are usually not connected with response to antidepressant treatment in patients with MDD. [75][76][77] Owing to variability in the duration of treatment, it is also possible that some of the patients may not have responded to treatment yet.…”

Section: Figmentioning

confidence: 99%

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression

Lisiecka

Carballedo

Fagan

et al. 2013

J Psychiatry Neurosci

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IntroductionIndividuals with a first-degree relative who has major depressive disorder (MDD) are at a 2-to 3-fold greater risk for depression than those without a family history of MDD. 1 Rela tives of depressed patients, compared with individuals without family history of psychiatric disorders, are characterized by elevated neuroticism, depressive cognitions and rigidity 2 and by stability of these traits over time.3 Patients with MDD who had relatives with an affective disorder display greater neuroticism 4 and have an earlier age of onset of MDD. 5 Evidently, family history of MDD alters susceptibility to depression and to an acute MDD episode. The factor is clinically important since it involves mechanisms of elevated risk for MDD (relatives of patients with MDD compared with healthy controls), suggests relative resilience to the disease (relatives of patients with MDD compared with the patients themselves) and points to different endophenotypes of healthy controls and patients with MDD. A good understanding of these mechanisms should not be underestimated if diagnosis, therapy and prevention of the disorder are to be enhanced. Background: Family history of major depressive disorder (MDD) increases individuals' vulnerability to depression and alters the way depression manifests itself. Emotion processing and attention shifting are functions altered by MDD and family history of the disease; therefore, it is important to recognize the neural correlates of these functions in association with both factors. Methods: Our study determines neural correlates of emotion processing and attention shifting for healthy individuals and patients with MDD with and without family history of depression. We compared the performance and neural activity in a functional magnetic resonance imaging experiment examining emotion processing and attention shifting in all participants. Results: Our sample included 4 study groups: healthy controls without family history of depression (n = 25), patients with MDD without family history of the disease (n = 20), unaffected healthy first-degree relatives of patients with MDD (n = 21) and patients with MDD with family history of MDD (n = 30). Compared with healthy controls, unaffected first-degree relatives overactivate the somatosensory cortex and the attention controlling areas during both emotion processing and attention shifting. Patients with family history of MDD have stronger neural activation in subcortical areas during shifting attention from negative stimuli. Patients without family history of MDD have less activation in the paralimbic regions and more activation in core limbic areas, especially during emotion processing. Limitations: The conclusions about the intergroup differences in activation can be drawn only about neural areas engaged in the task. Conclusion: Unaffected first-degree relatives of patients with MDD overreact to external emotional cues and compensate for the vulnerability with increased involvement of executive control. Patients with a family history of MDD have le...

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“…Moreover, FCS reduction in the dorsomedial PFC was significantly associated with symptom improvement. However, since the treatment outcomes of the SSRI class of antidepressants cannot be extrapolated to norepinephrine reuptake inhibitors [88][89][90][91], another study focused on the treatment effect of duloxetine-a dual serotonin-norepinephrine reuptake inhibitor-in MDD using MRI [92]. This study showed a group-by-time interaction in the anterior DMN in which MDD patients presented increased functional connectivity with treatment, and that reduced baseline resting-state connectivity in the orbitofrontal component of the anterior DMN is a predictor of greater clinical response.…”

Section: Mr Imaging Of Resting-state Functional Connectivitymentioning

confidence: 99%

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

Zhang

Zhu

et al. 2016

Neurosci. Bull.

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Major depressive disorder (MDD) is a significant cause of morbidity and mortality worldwide, correlating with genetic susceptibility and environmental risk factors. Molecular, functional, and structural imaging approaches have been increasingly used to detect neurobiological changes, analyze neurochemical correlates, and parse pathophysiological mechanisms underlying MDD. We reviewed recent neuroimaging publications on MDD in terms of molecular, functional, and structural alterations as detected mainly by magnetic resonance imaging (MRI) and positron emission tomography. Altered structure and function of brain regions involved in the cognitive control of affective state have been demonstrated. An abnormal default mode network, as revealed by resting-state functional MRI, is likely associated with aberrant metabolic and serotonergic function revealed by radionuclide imaging. Further multi-modal investigations are essential to clarify the characteristics of the cortical network and serotonergic system associated with behavioral and genetic variations in MDD.

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Neural correlates of treatment outcome in major depression

Cited by 74 publications

References 73 publications

Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder

Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder

Recruitment of the left hemispheric emotional attention neural network in risk for and protection from depression

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

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