Locus coeruleus connectivity alterations in late-life major depressive disorder during a visual oddball task

The Locus Coeruleus (LC) is the major source of noradrenergic neurotransmission. Structural alterations in the LC have been observed in neurodegenerative disorders and at-risk individuals, although functional connectivity studies between the LC and other brain areas have not been yet performed in these populations. Patients with late-life major depressive disorder (MDD) are indeed at increased risk for neurodegenerative disorders, and here we investigated LC connectivity in late-life MDD in comparison to individuals with amnestic type mild cognitive impairment (aMCI) and healthy controls (HCs). We assessed 20 patients with late-life MDD, 16 patients with aMCI, and 26 HCs, who underwent a functional magnetic resonance scan while performing a visual oddball task. We assessed task-related modulations of LC connectivity (i.e., Psychophysiological Interactions, PPI) with other brain areas. A T1-weighted fast spin-echo sequence for LC localization was also obtained. Patients with late-life MDD showed lower global connectivity during target detection in a cluster encompassing the right caudal LC. Specifically, we observed lower LC connectivity with the left anterior cingulate cortex (ACC), the right fusiform gyrus, and different cerebellar clusters. Moreover, alterations in LC-ACC connectivity correlated negatively with depression severity (i.e., Geriatric Depression Scale and number of recurrences). Reduced connectivity of the LC during oddball performance seems to specifically characterize patients with late-life MDD, but not other populations of aged individuals with cognitive alterations. Such alteration is associated with different measures of disease severity, such as the current presence of symptoms and the burden of disease (number of recurrences)

Locus coeruleus connectivity alterations in late-life major depressive disorder during a visual oddball task

The Locus Coeruleus (LC) is the major source of noradrenergic neurotransmission. Structural alterations in the LC have been observed in neurodegenerative disorders and at-risk individuals, although functional connectivity studies between the LC and other brain areas have not been yet performed in these populations. Patients with late-life major depressive disorder (MDD) are indeed at increased risk for neurodegenerative disorders, and here we investigated LC connectivity in late-life MDD in comparison to individuals with amnestic type mild cognitive impairment (aMCI) and healthy controls (HCs). We assessed 20 patients with late-life MDD, 16 patients with aMCI, and 26 HCs, who underwent a functional magnetic resonance scan while performing a visual oddball task. We assessed task-related modulations of LC connectivity (i.e., Psychophysiological Interactions, PPI) with other brain areas. A T1-weighted fast spin-echo sequence for LC localization was also obtained. Patients with late-life MDD showed lower global connectivity during target detection in a cluster encompassing the right caudal LC. Specifically, we observed lower LC connectivity with the left anterior cingulate cortex (ACC), the right fusiform gyrus, and different cerebellar clusters. Moreover, alterations in LC-ACC connectivity correlated negatively with depression severity (i.e., Geriatric Depression Scale and number of recurrences). Reduced connectivity of the LC during oddball performance seems to specifically characterize patients with late-life MDD, but not other populations of aged individuals with cognitive alterations. Such alteration is associated with different measures of disease severity, such as the current presence of symptoms and the burden of disease (number of recurrences)

Lower Locus Coeruleus MRI intensity in patients with late-life major depression

Background: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. Methods: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. Results: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). Conclusion: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons

Lower Locus Coeruleus MRI intensity in patients with late-life major depression

Background: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity. Methods: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables. Results: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs). Conclusion: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons.Peer ReviewedObjectius de Desenvolupament Sostenible::9 - Indústria, Innovació i InfraestructuraObjectius de Desenvolupament Sostenible::4 - Educació de QualitatObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version