Neurobiology and neuroanatomy of psychiatric symptoms in parkinsonism.

The present article aims to review state-of-the-art evidence of altered neurobiology and neuroanatomy underlying psychiatric symptoms in parkinsonism. This issue covers a wide range of symptoms encompassing anxiety, mood disorders, psychosis as well as substance abuse and specific compulsive behaviors. Such a complex nosography makes it impossible to deal with the neurobiology and neuroanatomy of each psychopathological condition per se, unless offering a trivial list of symptoms joined with brief explanations reporting potential causal mechanisms. This approach would only provide a rough synthesis of what previously reported without adding neither novel concepts nor evidence to improve our insight into the neurobiology of parkinsonism as a psychiatric condition. Therefore, the analytical description of each psychiatric symptom associated with parkinsonism will be avoided but it will be referenced instead. In contrast, the present article will focus on the mechanisms why such a class of nonmotor symptoms clusters in parkinsonian patients. In addition, we will seek to establish the relationship between the occurrence of a given psychiatric condition and specific parkinsonian phenotypes. Again, an emphasis will be given to the occurrence of behavioral fluctuations in parkinsonism where both motor and psychiatric symptoms may possess a specific timing. The timing of these fluctuations will be related to the timing of dopamine substitution therapy and involvement of multiple neurotransmitters and brain regions as well. We provide evidence showing that specific parkinsonian phenotypes (and genotypes) possess a widespread neuropathology, which in turn associates to a fairly specific psychopathology. In contrast, other phenotypes (and genotypes) bring to very selective neuronal degeneration where the occurrence of psychiatric symptoms is rare if not absent at all. These clinical pathological phenotypes associate with specific molecular mechanisms in the dynamics of neurobiology of disease.