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Comparison of structural connectivity in Parkinson's disease with depressive symptoms versus non-depressed: a diffusion MRI connectometry study

  • Mina Ansari (a1) (a2), Sahand Adib Moradi (a1) (a2), Farzaneh Ghazi Sherbaf (a1) (a2), Abozar Hedayatnia (a1) and Mohammad Hadi Aarabi (a1) (a2)...

Research on psychobiological markers of Parkinson's disease (PD) remains a hot topic. Non-motor symptoms such as depression and REM sleep behavior disorder (RBD) each attribute to a particular neurodegenerative cluster in PD, and might enlighten the way for early prediction/detection of PD. The neuropathology of mood disturbances remains unclear. In fact, a few studies have investigated depression using diffusion magnetic resonance imaging (diffusion MRI).


Diffusion MRI of PD patients without comorbid RBD was used to assess whether microstructural abnormalities are detectable in the brain of 40 PD patients with depression compared to 19 patients without depression. Diffusion MRI connectometry was used to carry out group analysis between age- and gender-matched PD patients with and without depressive symptoms. Diffusion MRI connectometry is based on spin distribution function, which quantifies the density of diffusing water and is a sensitive and specific analytical method to psychological differences between groups.


A significant difference (FDR = 0.016129) was observed in the left and right uncinate fasciculi, left and right inferior longitudinal fasciculi, left and right fornices, left inferior fronto-occipital fasciculus, right corticospinal tract, genu of corpus callosum, and middle cerebellar peduncle.


These results suggest the prominent circuits involved in emotion recognition, particularly negative emotions, might be impaired in comorbid depressive symptoms in PD.

Corresponding author
Correspondence should be addressed to: Mohammad Hadi Aarabi, Neuroimaging Network (NIN), Universal Scientific Education and Research Network (USERN) Office, Children's Medical Center Hospital, Dr. Qarib Street, Keshavarz Blvd, Tehran 14194, Iran. Phone: +98-21-6692-9234. Email:
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Mina Ansari and Sahand Adib Moradi contributed equally to this work.

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Ansari, M., Rahmani, F., Dolatshahi, M., Pooyan, A. and Aarabi, M. H. (2017). Brain pathway differences between Parkinson's disease patients with and without REM sleep behavior disorder. Sleep Breath, 21, 155161.
Ashtari, M. (2012). Anatomy and functional role of the inferior longitudinal fasciculus: a search that has just begun. Development Medicine Child Neurology, 54, 67.
Bach, M. et al. (2014). Methodological considerations on tract-based spatial statistics (TBSS). NeuroImage, 100, 358369.
Bagga, D. et al. (2014). Decreased white matter integrity in fronto-occipital fasciculus bundles: relation to visual information processing in alcohol-dependent subjects. Alcohol, 48, 4353.
Balestrino, R. and Martinez-Martin, P. (2017). Neuropsychiatric symptoms, behavioural disorders, and quality of life in Parkinson's disease. Journal of the Neurological Sciences, 373, 173178.
Berg, D. et al. (2015). MDS research criteria for prodromal Parkinson's disease. Movement Disorders, 30, 16001611.
Bohnen, N. I., Kaufer, D. I., Hendrickson, R., Constantine, G. M., Mathis, C. A. and Moore, R. Y. (2007). Cortical cholinergic denervation is associated with depressive symptoms in Parkinson's disease and parkinsonian dementia. Journal Neurological, Neurosurgery, and Psychiatry, 78, 641643.
Buchy, L., Luck, D., Czechowska, Y., Malla, A., Joober, R. and Lepage, M. (2012). Diffusion tensor imaging tractography of the fornix and belief confidence in first-episode psychosis. Schizophrenia Research, 137, 8084.
Chaudhuri, K. R., Healy, D. G. and Schapira, A. H. (2006). Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurology, 5, 235245.
Chen, P.-H. and Cheng, S.-J. (2008). Depression in Parkinson disease: current understanding and treatment. International Journal of Gerontology, 2, 172182.
Cole, J. et al. (2012). White matter abnormalities and illness severity in major depressive disorder. The British Journal of Psychiatry, 201, 3339.
de Kwaasteniet, B. et al. (2013). Relation between structural and functional connectivity in major depressive disorder. Biological Psychiatry, 74, 4047.
Delaparte, L. et al. (2017). A comparison of structural connectivity in anxious depression versus non-anxious depression. Journal of Psychiatric Research, 89, 3847.
Duffy, S. L., Paradise, M., Hickie, I. B., Lewis, S. J., Naismith, S. L. and Lagopoulos, J. (2014). Cognitive impairment with and without depression history: an analysis of white matter microstructure. Journal of Psychiatry & Neuroscience, 39, 135143.
Emsell, L. et al. (2013). Limbic and callosal white matter changes in euthymic bipolar I disorder: an advanced diffusion magnetic resonance imaging tractography study. Biological Psychiatry, 73, 194201.
Foster, P. S. et al. (2011). Anxiety and depression severity are related to right but not left onset Parkinson's disease duration. Journal of Neurological Sciences, 305, 131135.
Fujishiro, H. et al. (2017). REM sleep without atonia in middle-aged and older psychiatric patients and Lewy body disease: a case series. International Journal of Geriatric Psychiatry, 32, 397406.
Gallagher, D. A. and Schrag, A. (2012). Psychosis, apathy, depression and anxiety in Parkinson's disease. Neurobiology Disease, 46, 581589.
Greicius, M. D. et al. (2007). Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biological Psychiatry, 62, 429437.
Hau, J. et al. (2016). Cortical terminations of the inferior Fronto-Occipital and uncinate fasciculi: anatomical stem-based virtual dissection. Frontiers in Neuroanatomy, 10, 58.
Hettema, J. M. et al. (2012). Pilot multimodal twin imaging study of generalized anxiety disorder. Depression and Anxiety, 29, 202209.
Hollocks, M. J. et al. (2015). Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes. Brain, 138, 38033815.
Hoogenboom, W. S. et al. (2014). Limbic system white matter microstructure and long-term treatment outcome in major depressive disorder: a diffusion tensor imaging study using legacy data. The World Journal of Biological Psychiatry, 15, 122134.
Huang, P. et al. (2014). Disrupted white matter integrity in depressed versus non-depressed Parkinson's disease patients: a tract-based spatial statistics study. Journal of Neurological Sciences, 346, 145148.
Ishihara, L. and Brayne, C. (2006). A systematic review of depression and mental illness preceding Parkinson's disease. Acta Neurologica Scandinavica, 113, 211220.
Kemp, A. et al. (2013). Age of onset and corpus callosal morphology in major depression. Journal of Affective Disorder, 150, 703706.
Koenigs, M. and Grafman, J. (2009). The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex. Behavioural Brain Research, 201, 239243.
Kummer, A., Cardoso, F. and Teixeira, A. L. (2009). Suicidal ideation in Parkinson's disease. CNS Spectrums, 14, 431436.
Lai, C. H. and Wu, Y. T. (2014). Alterations in white matter micro-integrity of the superior longitudinal fasciculus and anterior thalamic radiation of young adult patients with depression. Psychological Medicine, 44, 28252832.
Lai, C. H. and Wu, Y. T. (2016). The white matter microintegrity alterations of neocortical and limbic association fibers in major depressive disorder and panic disorder: the comparison. Medicine (Baltimore), 95, e2982.
Lemke, M. (2008). Depressive symptoms in Parkinson's disease. European Journal of Neurology, 15, 2125.
Li, W., Liu, J., Skidmore, F., Liu, Y., Tian, J. and Li, K. (2010). White matter microstructure changes in the thalamus in Parkinson disease with depression: a diffusion tensor MR imaging study. American Journal of Neuroradiology, 31, 18611866.
Liao, Y. et al. (2013). Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD. Journal of Psychiatry & Neuroscience, 38, 4956.
Lou, Y. et al. (2015). Altered brain network centrality in depressed Parkinson's disease patients. Movement Disorders, 30, 17771784.
Mahajan, A. et al. (2014). REM sleep behavior and motor findings in Parkinson's disease: a cross-sectional analysis. Tremor and Other Hyperkinetic Movements (NY), 4, 245.
Marsh, L. (2013). Depression and Parkinson's disease: current knowledge. Current Neurology and Neuroscience Reports, 13, 409.
Marsh, L., McDonald, W. M., Cummings, J. and Ravina, B. (2006). Provisional diagnostic criteria for depression in Parkinson's disease: report of an NINDS/NIMH work group. Movement Disorders, 21, 148158.
Matsui, H. et al. (2007). Depression in Parkinson's disease. Diffusion tensor imaging study. Journal of Neurology, 254, 11701173.
Phan, K. L. et al. (2009). Preliminary evidence of white matter abnormality in the uncinate fasciculus in generalized social anxiety disorder. Biological Psychiatry, 66, 691694.
Reijnders, J. S., Ehrt, U., Weber, W. E., Aarsland, D. and Leentjens, A. F. (2008). A systematic review of prevalence studies of depression in Parkinson's disease. Movement Disorders, 23, 183189; quiz 313.
Rogers, M. A. et al. (2004). Executive and prefrontal dysfunction in unipolar depression: a review of neuropsychological and imaging evidence. Neuroscience Research, 50, 111.
Scheuerecker, J. et al. (2010). Orbitofrontal volume reductions during emotion recognition in patients with major depression. Journal of Psychiatry & Neuroscience, 35, 311320.
Schrag, A. (2006). Quality of life and depression in Parkinson's disease. Journal of the Neurological Sciences, 248, 151157.
Schrag, A. et al. (2007). Depression rating scales in Parkinson's disease: critique and recommendations. Movement Disorders, 22, 10771092.
Sheline, Y. I. (2000). 3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity. Biological Psychiatry, 48, 791800.
Shiba, M. et al. (2000). Anxiety disorders and depressive disorders preceding Parkinson's disease: a case-control study. Movement Disorders, 15, 669677.
Storch, A. et al. (2008). Depression in Parkinson's disease. Part 1: epidemiology, signs and symptoms, pathophysiology and diagnosis. Fortschritte der Neurologie-Psychiatrie, 76, 715724.
Sveinbjornsdottir, S. (2016). The clinical symptoms of Parkinson's disease. Journal of Neurochemistry, 139 (Suppl. 1), 318324.
Tham, M. W., San Woon, P., Sum, M. Y., Lee, T.-S. and Sim, K. (2011). White matter abnormalities in major depression: evidence from post-mortem, neuroimaging and genetic studies. Journal of Affective Disorders, 132, 2636.
Thobois, S., Prange, S., Sgambato-Faure, V., Tremblay, L. and Broussolle, E. (2017). Imaging the etiology of apathy, anxiety, and depression in Parkinson's disease: implication for treatment. Current Neurology Neuroscience Reports, 17, 76.
Torbey, E., Pachana, N. A. and Dissanayaka, N. N. (2015). Depression rating scales in Parkinson's disease: a critical review updating recent literature. Journal of Affective Disorders, 184, 216224.
Tromp, D. P. et al. (2012). Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. Archives of General Psychiatry, 69, 925934.
van Mierlo, T. J., Chung, C., Foncke, E. M., Berendse, H. W. and van den Heuvel, O. A. (2015). Depressive symptoms in Parkinson's disease are related to decreased hippocampus and amygdala volume. Movement Disorders, 30, 245252.
Weintraub, D. et al. (2005). Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease. The Journal of Nuclear Medicine, 46, 227232.
Wen, M. C., Chan, L. L., Tan, L. C. and Tan, E. K. (2016). Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies. European Journal of Neurology, 23, 10011019.
Williams, M. R., Sharma, P., Fung, K. L., Pearce, R. K., Hirsch, S. R. and Maier, M. (2015). Axonal myelin increase in the callosal genu in depression but not schizophrenia. Psychological Medicine, 45, 21452155.
Yamada, S. et al. (2015). Microstructural abnormalities in anterior callosal fibers and their relationship with cognitive function in major depressive disorder and bipolar disorder: a tract-specific analysis study. Journal of Affective Disorders, 174, 542548.
Yeh, F. C., Badre, D. and Verstynen, T. (2016). Connectometry: a statistical approach harnessing the analytical potential of the local connectome. NeuroImage, 125, 162171.
Yesavage, J. A. et al. (1983). Development and validation of a geriatric depression screening scale: a preliminary report. Journal of Psychiatric Research, 17, 3749.
Zhang, Y. and Schuff, N. (2014). Differential patterns of white matter degradation in relation to cognitive and motor deficits in Parkinson's disease (P2.004). Neurology, 82, P2.004.
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International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
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