Decreased synaptic and mitochondrial density in the postmortem anterior cingulate cortex in schizophrenia

Area of Science:

• Neuroscience
• Cell Biology
• Psychiatry

Background:

• Schizophrenia (SZ) is a complex mental illness characterized by psychosis, negative symptoms, and cognitive deficits.
• The anterior cingulate cortex (ACC) shows structural and functional abnormalities in SZ.
• Altered executive functions are a hallmark of SZ, suggesting underlying neurobiological changes.

Purpose of the Study:

• To compare synaptic organization and mitochondrial characteristics in postmortem ACC tissue from individuals with SZ and normal controls (NC).
• To investigate potential anatomical substrates for cognitive deficits observed in SZ.

Main Methods:

• Postmortem analysis of anterior cingulate cortex (ACC) tissue from SZ patients and normal controls (NC).
• Quantification of total synaptic density, including axospinous synapses (asymmetric/excitatory and symmetric/inhibitory).
• Assessment of mitochondrial number, density, morphology, and proportion within axon terminals and neuronal somata across different ACC layers.

Main Results:

• Total synaptic density in the ACC was reduced in SZ (72% of NC), primarily due to decreased axospinous synapses in layers 3 and 5/6.
• Mitochondrial density in axon terminals was significantly lower in SZ (64% of NC), with layer-specific reductions.
• Mitochondrial number per neuronal somata was decreased in SZ, particularly in layers 5-6, while mitochondrial size remained similar.

Conclusions:

• The study reveals significant alterations in synaptic organization and mitochondrial content within the ACC in schizophrenia.
• These neuroanatomical changes, particularly in synaptic and mitochondrial structures, may contribute to the executive function deficits seen in SZ.
• The findings provide preliminary but robust evidence supporting an anatomical basis for cognitive impairments in schizophrenia.