However, some studies have suggested that this may be due to (1) alterations in brain structure, such as hippocampal atrophy and hippocampal neuron damage; (2) alterations in neurotransmitter signaling, such as norepinephrine, dopamine, and 5-HT systems, which are known to be affected in PD patients (and these neurotransmitters are also involved in mood regulation); (3) alterations in inflammation and brain-derived neurotrophic factor (BDNF) levels; and (4) psychosocial factors and pain, which may also contribute to the development of depression in PD patients [44]. This evidence concerns the gene BDNF and Parkinson disease.