Neuroimaging of major depression in Parkinson's disease: Cortical thickness, cortical and subcortical volume, and spectroscopy findings
Introduction
Depression is the most common psychiatric disorder in patients with Parkinson's disease (PD) (Reijnders et al., 2008) and has a significant impact on the quality of life of these individuals (Chagas et al., 2011). Currently, it is known that non-motor symptoms may arise many years before the appearance of the classic motor symptoms of PD and provide important clues for diagnosis (Meissner, 2012).
Regarding the possible causes of depressive symptoms in PD patients, these can be attributed to the functional impairments caused by motor symptoms, to neurodegeneration caused by deposition of alpha-synuclein in brain regions associated with depression, and to a possible dopaminergic deficit in the brain reward system. This fact may contribute to the different response rates to antidepressants found in clinical trials with PD patients (Liu et al., 2013). Many psychotropic drugs are used to treat depressive symptoms in PD, including tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, and dopamine agonists. These multiple options of pharmacological treatment may reflect the complex mechanisms involved in the etiology of depression in PD. In addition, the use of dopamine agonists and monoamine oxidase B inhibitors as alternative treatments strengthens the role of neurodegenerative processes in the emergence of depressive symptoms in PD patients even before the onset of the classical motor signs. This heterogeneous overview can also be responsible for the differences found in the results of neuroimaging studies on depression in PD (Chagas et al., 2013).
One way to study the pathophysiology of psychiatric disorders is through neuroimaging techniques. Most of the neuroimaging studies on depression in PD used techniques based on radiotracers (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]), which were mainly focused on the dopaminergic and serotonergic systems (Chagas et al., 2013). In a brief review, we found seven studies to date that have used structural neuroimaging techniques to explore the relationship between depression and PD (Cardoso et al., 2009, Feldmann et al., 2008, Huang et al., 2013, Huang et al., 2015, Kostić et al., 2010, Surdhar et al., 2012, van Mierlo et al., 2015), but none of them analyzed cortical thickness.
The technique of magnetic resonance spectroscopy (H1-MRS) can provide information on the levels of neurotransmitters and neuronal integrity by measuring metabolites in brain regions, including N-acetyl-aspartate (NAA), considered to be a neuronal marker; choline (Cho), which is involved in the synthesis and degradation of cell membranes; and creatine (Cre), which reflects the energetic activity of cells and is generally stable. The measure of brain metabolites by magnetic resonance imaging (MRI) is thought to provide an indirect measure of neuronal viability. Although depression in PD has been extensively studied using several neuroimaging techniques, no studies to date used H1-MRS with the primary objective of evaluating this association.
The aim of this study, therefore, was to compare patients with depression and PD divided in three groups with current Major Depressive Disorder (MDD), previous MDD without current MDD, and no MDD in the lifetime (control group) in terms of cortical thickness, cortical and subcortical volume, and brain metabolite levels measured through H1-MRS.
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Sample
Participants were selected among attendants of the Movement Disorders Outpatient Clinic of the Ribeirão Preto Medical School University Hospital after assessment by a neurologist and a psychiatrist. The recruitment occurred from February 2011 to November 2012. A total of 43 PD patients were selected and divided into three groups: (i) current diagnosis of MDD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria (current MDD group, n = 15); (ii) previous
Results
The 43 PD patients evaluated had no statistically significant differences in age, years of education, gender, age of onset of PD or disease severity between groups (Table 1). Antidepressant use was higher in the lifetime MDD group than in the other groups. Only three patients with current MDD were in treatment at the moment of the diagnostic interview. The antidepressants in use were sertraline 50 mg (n = 2), escitalopram 20 mg (n = 2), fluoxetine 20 mg, paroxetine 30 mg, venlafaxine 150 mg,
Discussion
We found no differences between the groups in relation to the NAA/Cre and Cho/Cre ratios in the areas of interest as measured with H1-MRS. Only a weak correlation between HAM-D scores and the NAA/Cre ratio in the right putamen was found.
No neuroimaging studies to date assessed depression in PD using H1-MRS. Studies comparing PD patients and healthy controls are also relatively scarce, possibly due to the difficulties involved in performing MRI scans in PD patients because of motor symptoms. In
Conclusion
Current and lifetime MDD have an impact on volume and cortical thickness in PD patients. Alterations were found in the anterior cingulate cortex, amygdala, frontotemporal regions, and cerebellar white matter. The nucleus accumbens should be investigated in future studies involving larger samples and other techniques for more detailed explanation of its role in depression in PD.
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