Apathy, depression, and anxiety are among the most important non-motor signs of Parkinson's disease (PD). This may be encountered at early stages of illness and represent a major source of burden. Understanding their pathophysiology is a major prerequisite for efficient therapeutic strategies. Anatomical and metabolic imaging studies have enabled a breakthrough by demonstrating that widespread abnormalities within the limbic circuits notably the orbitofrontal and anterior cingulate cortices, amygdala, thalamus, and ventral striatum are involved in the pathophysiology of depression, anxiety, and apathy in PD. Functional imaging has further shown that mesolimbic dopaminergic but also serotonergic lesions play a major role in the mechanisms of these three neuropsychiatric manifestations, which has direct therapeutic implications.
Keywords: Anxiety; Apathy; Brain imaging; Depression; Dopamine; Limbic system; Serotonin.