Background: The uncinate fasciculus (UF) is the largest white matter association tract connecting the prefrontal cortex and the medial temporal lobe, and is the final major association tract to mature with myelination extending into the third decade of life. The UF is typically described as having a temporal stem, a body, and two prefrontal stems extending to the lateral and fronto-polar prefrontal cortex respectively. However, there is increasing evidence of fibers extending from the subgenual cingulate gyrus (Brodmann Area 25: BA25) to the amygdala, along the expected course of the UF. If these fibers are continuous with the UF, they may represent a separate medial subgenual stem. BA25 is implicated in mood disorder pathophysiology, whilst the lateral prefrontal cortex is implicated in the negative symptoms of psychosis.
Hypotheses: Given that the UF as a whole has reduced integrity in both mood and psychotic disorders, it is feasible that the lateral stem of the UF is more markedly affected in psychosis and the potential subgenual stem more markedly affected in depression. In addition, since the UF matures during the typical clinical onset age of these disorders, we hypothesize that such changes are present from first onset.
Methods: In a series of four manuscripts utilizing diffusion tensor imaging (DTI), the anatomy, anatomical variability, and stem-by-stem microstructural changes in depression and first-onset psychosis patients were investigated within the UF. The use of a stem-by-stem analysis within the UF was a common link across the four articles.
Results: A subgenual stem of the UF was consistently demonstrated. Significantly reduced integrity was shown in the subgenual and polar stems of the UF in depressed patients (in both the first-onset and chronic depression cohorts), and in the lateral and polar stems in first-onset psychosis patients.
Conclusion: We have demonstrated anatomically distinct patterns of white matter changes within the uncinate fasciculus in mood vs. psychotic disorders, present from the time of first clinical onset.