Reduced CA2–CA3 Hippocampal Subfield Volume Is Related to Depression and Normalized by l-DOPA in Newly Diagnosed Parkinson’s Disease

Abstract

Hippocampal dysfunctions may play an important role in the non-motor aspects of Parkinson’s disease (PD), including depressive and cognitive symptoms. Fine structural alterations of the hippocampus and their relationship with symptoms and medication effects are unknown in newly diagnosed PD. We measured the volume of hippocampal subfields in 35 drug-naïve, newly diagnosed PD patients without cognitive impairment and 30 matched healthy control individuals. Assessments were performed when the patients did not receive medications and after a 24-week period of l-DOPA treatment. We obtained a T1-weighted 3D magnetization-prepared rapid acquisition gradient echo image at each assessment. FreeSurfer v6.0 was used for image analysis. Results revealed a selectively decreased CA2–CA3 volume in non-medicated PD patients, which was normalized after the 24-week treatment period. Higher depressive symptoms were associated with smaller CA2–CA3 volumes. These results indicate that the CA2–CA3 subfield is structurally affected in the earliest stage of PD in the absence of cognitive impairment. This structural anomaly, normalized by l-DOPA, is related to depressive non-motor symptoms.

Impaired long contact white matter fibers integrity is related to depression in Parkinson's disease

“…Studies using T1-weighted imaging have shown the depressed PD patients had decreased gray matter (GM) volumes in the prefrontal, parietal, and insular regions as well as the limbic system (anterior cingulate cortices and amygdala). [19][20][21][22][23] These structural abnormalities were found to further support our DTI findings. As we know, the prefrontal cortex and limbic systems are the main brain regions for emotion regulation.…”

Fast serotonin voltammetry as a versatile tool for mapping dynamic tissue architecture: I. Responses at carbon fibers describe local tissue physiology

“…To investigate these diseases, brain regions other than the SNr are thought to play important roles. For example, the hippocampus is heavily implicated in emotion and memory, and as such is often the focus of depression studies (Gyorfi et al ). Similarly, the amygdala, nucleus accumbens, and hypothalamus are investigated for their roles in depression and anxiety (Nestler et al ; Gina et al, ).…”

“…When it comes to interest in serotonin's actions in the brain, however, there is much focus on psychiatric, cognitive, and developmental disorders (Owens and Nemeroff ; Abi‐Dargham et al ; Volkow and Fowler ; Oades ; Muller et al ) which implicate brain regions other than the SNr. These brain regions include the hippocampus (Gyorfi et al ), amygdala (Schumann et al ), hypothalamus (Nestler et al ), and prefrontal cortex (PFC) (Jin et al ). Our own research interests incline us toward the hippocampus and medial prefrontal cortex (mPFC).…”

Hippocampal and Amygdalar Volume Changes in Major Depressive Disorder: A Targeted Review and Focus on Stress

“…9 Previous studies that have identified changes in various other hippocampal substructures, however, have failed to demonstrate CA1 changes. 59 Failure to do so may be accounted by the well-documented methodological issues with previous versions of automated segmentation that have underestimated the size of CA1. 51 The CA1 region has a particularly high expression of multiple 5-HT receptor subtypes 60 and is the most vulnerable hippocampal substructure to excitotoxicity.…”