Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes (original) (raw)
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Regional patterns of brain tissue loss associated with depression in Parkinson disease
Neurology, 2010
Objective: To investigate, using MRI and voxel-based morphometry (VBM), whether specific patterns of gray matter (GM) and white matter (WM) loss are associated with depression in patients with Parkinson disease (PD). Methods: Forty patients with PD and 26 healthy subjects were studied. Patients were diagnosed with depression using DSM-IV criteria. The Hamilton Depression Rating Scale (HDRS) was administered to patients. The topographic distribution of brain tissue loss in patients with PD and controls was assessed using VBM as implemented in Statistical Parametric Mapping (SPM5). Results: Twenty-four patients with PD were diagnosed as nondepressed (PD-NDep) and 16 as having depression (PD-Dep). Patient groups were similar in terms of clinical findings, except for the HDRS score (p Ͻ 0.001). Compared to controls, patients with PD showed common GM loss in the right anterior cingulate (AC) cortex and insula, and in the left middle frontal and angular gyri (p Ͻ 0.001). No regions of WM loss common to PD-NDep and PD-Dep patients relative to healthy controls were found. PD-Dep vs PD-NDep patients showed WM loss in the right AC bundle and inferior orbitofrontal (OF) region (p Ͻ 0.001). In patients with PD, HDRS score correlated with WM loss in the right inferior OF region (r ϭ Ϫ0.51, p Ͻ 0.05). Conclusions: Tissue loss in several WM regions within the cortical-limbic network occurs in PD-Dep vs PD-NDep patients. Such pattern of brain atrophy overlaps with key regions involved in major depressive disorders, suggesting an increased vulnerability of this neural circuit in PD. This may partially account for the high prevalence of depression in PD. Neurology ® 2010;75:857-863 GLOSSARY AC ϭ anterior cingulate; ACC ϭ anterior cingulate cortex; AES ϭ Apathy Evaluation Scale; DARTEL ϭ diffeomorphic anatomic registration using exponentiated lie algebra; DE ϭ dual-echo; DSM-IV ϭ Diagnostic and Statistical Manual of Mental Disorders, 4th edition; DT ϭ diffusion tensor; FOV ϭ field of view; GM ϭ gray matter; HARS ϭ Hamilton Anxiety Rating Scale; HDRS ϭ Hamilton Depression Rating Scale; MMSE ϭ Mini-Mental State Examination; OF ϭ orbitofrontal; OFC ϭ orbitofrontal cortex; PD ϭ Parkinson disease; PD-Dep ϭ patients with Parkinson disease and depression; PD-NDep ؍ patients with Parkinson disease without depression; SPM ϭ Statistical Parametric Mapping; TE ϭ echo time; TR ϭ repetition time; VBM ϭ voxel-based morphometry; WM ϭ white matter; WMH ϭ white matter hyperintensity.
Neuroimage, 2009
Depression is the most frequent psychiatric disorder in Parkinson's disease (PD). Although evidence suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontal cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation.
Journal of psychiatric research, 2017
Depression is the most common psychiatric disorder in Parkinson's disease (PD). The aim of this study was to compare PD patients with current Major Depressive Disorder (MDD), lifetime MDD, and no MDD using three neuroimaging techniques. A total of 43 PD patients were selected and divided into three groups: (i) current MDD (n = 15), (ii) previous MDD without current MDD (n = 10); and (iii) control group (no current or lifetime MDD; n = 18). All participants underwent magnetic resonance imaging to evaluate cortical thickness, cortical and subcortical volume, and spectroscopy in the bilateral putamen and cingulate cortex. Volumetric analysis showed volume decreases in frontal and temporal areas, bilateral amygdala, and left cerebellar white matter in the lifetime MDD group compared to the control group. Furthermore, the volumes of the anterior cingulate cortex, right amygdala, and left cerebellar white matter were smaller in the group with current MDD compared to the control group....
The neuropathological basis for depression in Parkinson's disease
Parkinsonism & Related Disorders, 2009
Depression is found in 30-40% of all patients with Parkinson's disease (PD), but its etiology is unclear. Using neuropathology as a signpost for neurotransmitter function, we investigated the prevalence of pathological features found at postmortem and sought to uncover differences between depressed (n = 11) and non-depressed (n = 9) elderly PD patients. The results indicate a higher prevalence of pathological features in depressed compared to non-depressed PD patients, particularly in catecholamine areas of the brain; the locus coeruleus (neuronal loss: odds ratio = 7.2, p = 08; gliosis: odds ratio = 18.0, p = 008); dorsal vagus nerve (gliosis: odds ratio = 7.63, p < 0.05), and substantia nigra pars compacta (gliosis: odds ratio 2.85, ns). However, neuropathological differences were absent in the dorsal raphe nuclei, amygdala, and cortical regions. Our evidence suggests that depression in PD is related more to catecholaminergic than serotonergic system dysfunction.
Neuroimaging of depression in Parkinson's disease: a review
International Psychogeriatrics, 2013
ABSTRACTBackground:Depression is the most common psychiatric manifestation in patients with Parkinson's disease (PD). In addition, depressive symptoms may be considered to be a prodromal manifestation of PD. In recent years, the association between PD and depression has been the focus of neuroimaging studies using functional and structural techniques.Methods:The aim of this study was to review the main neuroimaging studies assessing the comorbidity between depression and PD. Literature searches were conducted to find the major neuroimaging studies that consider primarily the comorbidity between depression and PD using the indices Web of Science and Lilacs.Results:In total, 296 papers were identified, and 18 of these studies were selected for the current review. The principal neuroimaging technique used was SPECT. The structural neuroimaging studies that have evaluated the impact of current or previous bouts of depression on the neurodegenerative process of PD are scarce and incl...
Neuroanatomical correlates of depressive symptoms in newly diagnosed Parkinson ’ s disease patients
2018
Objective: Depression is the most frequent neuropsychiatric manifestation in Parkinson’s disease (PD). Although evidence suggests that depression in PD is related to the degenerative process that underlies the disease, a complete understanding of neural substrates has yet to be achieved. To investigate the neuroanatomical changes underlying depression in PD, we conducted a surface-based morphometry (SBM) study in de novo, drug-naïve Parkinson’s disease patients with and without depression. Methods: We studied thirty-one patients with idiopathic, de novo, drug-naïve PD. Patient clinical characteristics, including age, sex, disease duration, Hoehn and Yahr stage, UPDRS part III, and brief neuropsychological testing, were assessed. Sixteen Parkinson’s disease patients with depression (PD-D) were defined as patients with abnormal geriatric depressions scales (> 17 points), and fifteen patients had Parkinson’s disease without depression (PD-ND). The SBM analysis of cortical thickness ...
Depressive Symptoms are Frequent in Atypical Parkinsonian Disorders CLINICAL PRACTICE
Background: The objective of this study was to compare the incidence and prevalence of depressive symptoms in atypical parkinsonian (APD) syndromes versus Parkinson disease (PD). Methods: In a large, retrospective patient cohort, the authors analyzed the incidence and prevalence of depressive symptoms using the Beck Depression Inventory and evaluated patients longitudinally on subsequent visits. For individuals who were followed at subsequent visits, incidence rates were calculated in person-years as a measure of incidence. Results: In total, 361 patients were identified who had APD syndromes, including progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and dementia with Lewy bodies; and 2352 patients with PD were used as a control group. The mean Beck Depression Inventory values were significantly higher in patients with APD (F = 14.19; P < 0.001). A significantly higher proportion of those with APD screened positive for depressive symptoms both at the initial visit and on subsequent visits (P < 0.001), and depressive symptoms appeared to be more severe in the APD subgroups. Unified Parkinson's Disease Rating Scale motor scores and disease duration were correlated with depressive symptoms. Conclusions: The current results suggest that the incidence and prevalence of depressive symptoms are higher in patients with APD syndromes and also appear to be more severe than those in patients with PD. Depressive symptoms in APD are common and affect patients regardless of disease duration or motor severity. Neuropsychiatric symptoms are common in patients with Parkinson's disease (PD) and atypical parkinsonian disorders (APDs), and they may be more severe and challenging to treat than motor symptoms. Among the neuropsychiatric comorbidi-ties, depression is 1 of the most common nonmotor symptoms in PD; it can present in the premotor stage of the disease and affects nearly one-half of all patients with PD. 1 In addition, associated suicidal ideations are prevalent, ranging from 11% to 23%, 1,2 with a suicide-specific mortality rate of 5.3%. 2 Despite the extensive literature on depression in PD, 3-10 there are relative few studies in APD 11-15 and a paucity of information about incidence or prevalence in these disorders. In progressive supranuclear palsy (PSP), depression is estimated to affect over 50% of patients 16,17 and has been identified as a possible predic-tor of a shorter survival. 18 Depression also has been reported in 80% of patients with multiple system atrophy (MSA) 19 and in over 70% of patients with corticobasal degeneration (CBD). 20 Neuroimaging and postmortem studies suggest that mesolimbic dopaminergic pathways and basal ganglia dysfunction may be associated with depression, findings also encountered in patients with PD or APD who have depression. 21-24 However, structural and functional differences between PD and APD syndromes, including PSP, MSA, dementia with Lewy body (DLB), and CBD, have not been fully described.
Psychiatry Research, 2007
Severity of Parkinson's disease (PD) and frontal impairment are positively correlated. Testing frontal functions in depressed/ nondepressed PD patients with different severity stages may reveal whether depression leads to this impairment. We aimed to relate severity of PD to frontal functional impairment and to test if negative stimuli/depressive symptoms interfered with frontal tasks. The Stroop test and the Emotional Stroop test were performed by 46 PD patients, 18 of whom were depressed. The Hoehn and Yahr scale assessed severity of the disease. We calculated the difference in seconds for each Stroop card and the interference index (C/D) between depressed and nondepressed patients sharing the same severity of disease. The differences among the groups (depressed and nondepressed) according to the severity of the disease (mild and moderate) were compared using the Mann-Whitney test. The depressed patients had a poorer performance on the test than the nondepressed PD patients, although the difference was not statistically significant. In conclusion, there is a clinically relevant but not statistically significant difference on the performance of frontal tasks between depressed and nondepressed PD patients. Neither depression nor the severity of the disease were determinant to the poorer performance on the Stroop and the Emotional Stroop tests.
Aging and disease, 2018
Positron emission tomography (PET) scan with tracer [ 18 F]-fluorodeoxy-glucose (18 F-FDG) is widely used to measure the glucose metabolism in neurodegenerative disease such as Idiopathic Parkinson's disease (IPD). Previous studies using 18 F-FDG PET mainly focused on the motor or non-motor symptoms but not the severity of IPD. In this study, we aimed to determine the metabolic patterns of 18 F-FDG in different stages of IPD defined by Hoehn and Yahr rating scale (H-Y rating scale) and to identify regions in the brain that play critical roles in disease progression. Fifty IPD patients were included in this study. They were 29 men and 21 women (mean±SD, age 57.7±11.1 years, disease duration 4.0±3.8 years, H-Y 2.2±1.1). Twenty healthy individual s were included as normal controls. Following 18 F-FDG PET scan, image analysis was performed using Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST). The metabolic feature of IPD and regions-of-interests (ROIs) were determined. Correlation analysis between ROIs and H-Y stage was performed. SPM analysis demonstrated a significant hypometabolic activity in bilateral putamen, caudate and anterior cingulate as well as left parietal lobe, prefrontal cortex in IPD patients. In contrast, hyperme tabol i s m was observed in the cerebellum and vermis. There was a negative correlation (p=0.007, r=-0.412) between H-Y stage and caudate metabolic activity. Moreover, the prefrontal area also showed a negative correlation with H-Y (P=0.033, r=-0.334). Thus, the uptake of FDG in caudate and prefrontal cortex can potentially be used as a surrogate marker to evaluate the severity of IPD.
Depression, intellectual impairment, and Parkinson disease
Neurology, 1981
To the Editor: Dr. Mayeux and his colleagues make an interesting contribution to the study of intellectual and emotional disturbances in patients with subcortical disease.I However, I would like to comment on several issues, with particular reference to the specificity of their findings to Parkinson disease. For example, 67% of a sample of consecutively admitted neurological patients' showed evidence of cognitive deficit, emotional disturbance, or both, using instruments similar to those employed by Mayeux et al. This figure is considerably higher than for the general medical populations and may account, in part, for the fact that "when equally disabled patients with other medical diseases were used for comparison, the prevalence of depression in PD was always significantly higher" (page 6471.' As the authors pointed out, attention and memory are frequently impaired in depressed patients; this is a common observation even when the cognitive disturbance is not severe enough to warrant a diagnosis of "dementia syndrome with depression." In addition, we have frequently encountered disturbances in calculations, constructional ability, and memory in patients with early Alzheimer disease, when language, praxis, and gnostic functions were still intact. In practice, the "characteristic" symptoms of "subcortical dementia" seem to describe many patients with mild cognitive impairment of diverse etiology (e.g., atherosclerotic or demyelinating disease). Adequate description of this impairment requires more than the correlation of single items from the mental status examination. The most striking aspect of the intellectual and emotional disturbances in PD appears to be their surprisingly strong correlations with akinesia and rigidity.l Mayeux et a1 suggest that the degeneration of dopaminergic neurons in the substantia nigra and locus ceruleus cannot account for this finding; yet, they do not consider the possible contribution of the mesolimbic and mesocortical dopamine systems, both of which may be affected in PD,56 and which might account for the observed relation between the movement and psychologic disorders. Their alternative hypothesis of neuronal loss in the tuberal and posterolateral hypothalamus merits further consideration, although one might then expect to observe a relationship between cognitive/emotional status and autonomic vegetative symptoms in these patients. Further exploration of these factors would surely enhance the specificity and value of their findings.