Elevated Excitatory Input to the Nucleus Accumbens in Schizophrenia: A Postmortem Ultrastructural Study

Area of Science:

• Neuroscience
• Psychiatry
• Cell Biology

Background:

• The etiology of schizophrenia (SZ) remains unclear, with pathology involving widespread brain dysfunction rather than a single region.
• Understanding disrupted inter-regional brain communication is crucial for advancing SZ research.
• The nucleus accumbens (NAcc) integrates information from SZ-altered brain areas and is a key region of interest.

Purpose of the Study:

• To investigate synaptic abnormalities in the nucleus accumbens (NAcc) in individuals with schizophrenia (SZ).
• To compare the morphology of synaptic connections in the NAcc core and shell between SZ subjects and healthy controls.

Main Methods:

• Pilot study utilizing electron microscopy to examine synaptic structures.
• Comparison of NAcc core and shell synaptic densities and postsynaptic density morphology.
• Analysis of asymmetric (excitatory) and symmetric (inhibitory) synapses in 6 SZ subjects and 8 matched controls.

Main Results:

• A 19% increase in the density of asymmetric synapses was observed in the NAcc core of SZ subjects compared to controls.
• No significant difference in symmetric synapse density was found between groups.
• The postsynaptic density area of asymmetric synapses was 22% smaller in the NAcc core of SZ subjects.

Conclusions:

• Findings suggest increased excitatory input to the NAcc core in SZ, potentially impacting dopamine neurotransmission and cortico-striatal-thalamic circuits.
• Reduced postsynaptic density size indicates impaired synaptic signaling.
• These results highlight the NAcc's role in SZ pathophysiology and the interplay of glutamatergic and dopaminergic abnormalities.