Brain Responses to Emotional Stimuli after Eicosapentaenoic Acid and Docosahexaenoic Acid Treatments in Major Depressive Disorder: Toward Personalized Medicine with Anti-Inflammatory Nutraceuticals.

N-3 polyunsaturated fatty acid supplements improve the symptoms of major depressive disorder (MDD) in randomized-controlled trials and meta-analyses, with the higher efficacy from anti-inflammatory eicosapentaenoic acid (EPA) than brain-dominant docosahexaenoic acid (DHA). To investigate the specific brain mechanisms of the anti-inflammatory anti-depressant nutraceutical compounds, we recruited 24 MDD subjects in this double-blind, head-to-head study with a 12-week EPA or DHA treatment (clinical trial registration number: NCT03871088). The depression severity was assessed by Hamilton depression rating scale (HAM-D). Brain responses to emotional stimuli were measured by a 3-Tesla MRI. The correlation between HAM-D scores and brain responses also were tested. Compared to 18 healthy controls, the brain responses of untreated 24 MDD patients mainly revealed hypoactivity in the regions associated with emotion perception and emotion control when processing positive emotion. After treatment, more remitted MDD patients have been observed in the EPA as compared to the DHA groups. In addition, the EPA, but not DHA, treatment revealed increased activity in the regions associated with emotion perception and cognitive control when processing positive emotion. The correlation analysis further revealed negative correlation between HAM-D scores and brain responses in cognitive control regions. The results of this study may imply the compensatory brain responses of cognitive and emotion controls by EPA but not DHA and underpin personalized medicine with anti-inflammatory nutraceuticals toward depression treatments.

Alterations in Brain Structure and Amplitude of Low-frequency after 8 weeks of Mindfulness Meditation Training in Meditation-Naïve Subjects.

Increasing neuroimaging evidence suggests that mindfulness meditation expertise is related to different functional and structural configurations of the default mode network (DMN), the salience network (SN) and the executive network at rest. However, longitudinal studies observing resting network plasticity effects in brains of novices who started to practice meditation are scarce and generally related to one dimension, such as structural or functional effects. The purpose of this study was to investigate structural and functional brain network changes (e.g. DMN) after 40 days of mindfulness meditation training in novices and set these in the context of potentially altered depression symptomatology and anxiety. We found overlapping structural and functional effects in precuneus, a posterior DMN region, where cortical thickness increased and low-frequency amplitudes (ALFF) decreased, while decreased ALFF in left precuneus/posterior cingulate cortex correlates with the reduction of (CES-D) depression scores. In conclusion, regional overlapping of structural and functional changes in precuneus may capture different components of the complex changes of mindfulness meditation training.

State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect.

The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.