Basal ganglia pathology in schizophrenia: dopamine connections and anomalies

Abstract

Schizophrenia is a severe mental illness that affects 1% of the world population. The disease usually manifests itself in early adulthood with hallucinations, delusions, cognitive and emotional disturbances and disorganized thought and behavior. Dopamine was the first neurotransmitter to be implicated in the disease, and though no longer the only suspect in schizophrenia pathophysiology, it obviously plays an important role. The basal ganglia are the site of most of the dopamine neurons in the brain and the target of anti-psychotic drugs. In this review, we will start with an overview of basal ganglia anatomy emphasizing dopamine circuitry. Then, we will review the major deficits in dopamine function in schizophrenia, emphasizing the role of excessive dopamine in the basal ganglia and the link to psychosis.

Figure 1

Electron micrographs of tyrosine hydroxylase (TH) immunocytochemistry in postmortem human caudate nucleus. Several synaptic arrangements are shown. Note that the synapses formed by the TH-labeled synapses are short in length and non-perforated. A) TH-labeled axons (straight black arrows outlined in black) are adjacent to unlabeled axon terminals (at) that are forming asymmetric synapses (black arrows). A TH-labeled terminal makes a symmetric synapse (curved white arrow outlined in black). B) Boxed area in panel A is enlarged to show the symmetric synapse. C) Three TH-labeled boutons (black arrow with white outline) are adjacent to a spine which receives a symmetric TH-labeled synapse (curved white arrow outlined in black) and an asymmetric synapse (black arrow) from an unlabeled terminal (at). D) TH-labeled axon makes a symmetric synapse (arrow) en passant with a dendrite (den). Sp, spines. Scale bars in A-D: 0.5µm. Figures A, B and D are modifications of our previously published figure 1 from Roberts et al., (2009), while Figure C is a modification of our previously published figure 4 from Kung et al., (1998).