Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease
ABSTRACT We studied whether the (123)I-FP-CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 +/- 12.7 years) underwent the (123)I-FP-CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and (123)I-FP-CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with (123)I-FP-CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia.
SourceAvailable from: Marcos Hortes N. Chagas[Show abstract] [Hide abstract]
ABSTRACT: ABSTRACT Background: 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 inclusive. The instruments that were used to evaluate depression differed among the studies. Several brain regions appear to be involved in depression, particularly the limbic system and the basal ganglia. In addition, the serotonergic, dopaminergic, and noradrenergic systems also appear to be associated with depressive symptoms in PD. Conclusion: Several brain regions and neurotransmitter systems are involved in depression in PD; however, the variety of criteria used to evaluate depressive symptoms precludes more specific conclusions.International Psychogeriatrics 09/2013; 25(12):1-9. DOI:10.1017/S1041610213001427 · 1.89 Impact Factor
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ABSTRACT: Depression is a frequent comorbid disorder in Parkinson's disease and may antedate its motor symptoms. However, mechanisms underlying Parkinson's disease-associated depression are unknown and its current medication is insufficient. The aim of the present study was to compare antidepressant-like effects of imipramine, fluoxetine and pramipexole in a model of preclinical stages of Parkinson's disease in rats. 6-Hydroxydopamine was bilaterally injected into the ventrolateral region of the caudate-putamen in rats. This treatment induced moderate decreases in the levels of dopamine and its metabolites in the caudate-putamen, nucleus accumbens and frontal cortex and reduced the density of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta and ventral tegmental area. The lesion increased immobility measured in the forced swimming test without influencing locomotor activity. Chronic (13 days) administration of pramipexole (1mg/kg sc/twice a day) reversed prolongation of the immobility time in lesioned animals but did not stimulate their locomotion. Chronic pramipexole activated dopaminergic transmission in the brain structures which might contribute to its effectiveness in the forced swimming test. In contrast, the 13-day administration of imipramine (10mg/kg ip/day) and fluoxetine (10mg/kg ip/day) did not shorten the immobility time in lesioned rats but reduced their locomotion. The present study seems to indicate that already a moderate lesion of dopaminergic neurons induces "depressive-like" behaviour in animals which is reversed by chronic administration of the antiparkinsonian drug, pramipexole.Behavioural Brain Research 06/2014; 271. DOI:10.1016/j.bbr.2014.06.029 · 3.39 Impact Factor
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ABSTRACT: Depression and impulse control disorders (ICD) are two common neuropsychiatric features in Parkinson's disease (PD). Studies have revealed that both phenomena are associated with aberrations in ventral striatal dopamine signaling and concomitant dysfunction of the reward-related (limbic) cortico-striatal-thalamocortical (CSTC) circuit. Depression in PD seems associated with decreased activity in the limbic CSTC circuit, whereas ICD seems associated with increased limbic CSTC circuit activity, usually after commencing dopamine replacement therapy (DRT). Not all DRT using PD patients, however, develop symptoms of ICD, suggesting an additional underlying neurobiological susceptibility. Furthermore, the symptoms of depression and ICD frequently coincide even though they are related to seemingly contrasting limbic CSTC circuit activation states. The aim of this review is to provide an overview of the currently available literature on the neurobiology of PD-related depression and ICD and discusses possible susceptibility factors. Finally, we propose a neurobiological model that identifies ventral striatal dopaminergic denervation as a common underlying neurobiological substrate of depression and ICD and subsequent dysfunction of reward and motivation-related brain areas.Neuroscience & Biobehavioral Reviews 11/2013; DOI:10.1016/j.neubiorev.2013.11.001 · 10.28 Impact Factor