Neurobiology and Neuroanatomy of Psychiatric Symptoms in Parkinsonism

Abstract

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.