Modulation of default-mode network activity by acute tryptophan depletion is associated with mood change: A resting state functional magnetic resonance imaging study

ArticleinNeuroscience Research 69(2):129-34 · November 2010with29 Reads
DOI: 10.1016/j.neures.2010.11.005 · Source: PubMed
Recently, resting-state fMRI (R-fMRI) has attracted interest based on its ability to detect the default mode network. We examined the effect of acute tryptophan depletion (ATD) on the fractional amplitude of low-frequency fluctuation (fALFF) during the resting state, and the correlation between changes of mood and fALFF following ATD. We manipulated the central serotonergic levels of 21 right-handed healthy males (mean age=21.57±1.83 years) following ATD. A within-subjects, double-blind, placebo-controlled, and counter-balanced design was employed. Following ATD or sham depletion, subjects completed the Profile of Mood States (POMS) and underwent 5-min R-fMRI scans. Our findings show that the fALFF of the middle orbitofrontal cortex and precuneus was significantly decreased and the fALFF of the superior parietal lobule, paracentral lobule and precentral gyrus was significantly increased after ATD. The fALFF of the orbitofrontal cortex was negatively correlated with depressive mood. The fALFF of the superior parietal lobule was positively correlated with anger-hostility and the fALFF of the paracentral lobule was negatively correlated with vigor-activity. The middle orbitofrontal cortex plays a key role in serotonin depletion-induced brain changes and individual differences in depressive mood change. These results serve to further elucidate the mechanism of ATD-induced relapse in remitted MDD patients.
    • "Additionally, we identified our ROIs structurally based on established, standard coordinates; subject-specific functionallyidentified ROIs may have enabled individual specificity, but also would have limited generalizability of our results. Although this study does not examine neural networks directly, it supports past work demonstrating that ATD is a useful probe for modulating neural networks dependent on serotonergic innervation (Kahkonen et al., 2005; Evers et al., 2006; Merens et al., 2008; Roiser et al., 2009; Daly et al., 2010; Van der Veen et al., 2010; Booij and Van der Does, 2011; Kunisato et al., 2011). This study also extends this by indirectly demonstrating involvement of pontomesencephalic raphé. "
    [Show abstract] [Hide abstract] ABSTRACT: Depression remains a great societal burden and a major treatment challenge. Most antidepressant medications target serotonergic raphé nuclei. Acute tryptophan depletion (ATD) modulates serotonin function. To better understand the raphé's role in mood networks, we studied raphé functional connectivity in depression. Fifteen depressed patients were treated with sertraline for 12 weeks and scanned during ATD and sham conditions. Based on our previous findings in a separate cohort, resting state MRI functional connectivity between raphé and other depression-related regions (ROIs) was analyzed in narrow frequency bands. ATD decreased raphé functional connectivity with the bilateral thalamus within 0.025-0.05Hz, and also decreased raphé functional connectivity with the right pregenual anterior cingulate cortex within 0.05-0.1Hz. Using the control broadband filter 0.01-0.1Hz, no significant differences in raphé-ROI functional connectivity were observed. Post-hoc analysis by remission status suggested increased raphé functional connectivity with left pregenual anterior cingulate cortex in remitters (n=10) and decreased raphé functional connectivity with left thalamus in non-remitters (n=5), both within 0.025-0.05Hz. Reducing serotonin function appears to alter coordination of these mood-related networks in specific, low frequency ranges. For examination of effects of reduced serotonin function on mood-related networks, specific low frequency BOLD fMRI signals can identify regions implicated in neural circuitry and may enable clinically-relevant interpretation of functional connectivity measures. The biological significance of these low frequency signals detected in the raphé merits further study.
    Article · Sep 2015
    • "Kunisato et al. performed a resting-state fMRI study with 21 healthy men in which they showed that changes in some subscores of the POMS correlated with changes in orbitofrontal cortex (OFC) activity of the brain under ATD. Less activity of the OFC was associated with an increase of depressive mood during the depletion situation [38]. To the best of our knowledge, there are no imaging studies which investigate the influence of orally administered 5-HTP supplementation on the brain. "
    [Show abstract] [Hide abstract] ABSTRACT: Background. Fat affects gastric emptying (GE). 5-Hydroxythryptophan (5-HTP) is involved in central and peripheral satiety mechanisms. Influence of 5-HTP in addition to saturated or monounsaturated fatty acids (FA) on GE and hormone release was investigated. Subjects/Methods. 24 healthy individuals (12f : 12m, 22–29 years, BMI 19–25.7 kg/m²) were tested on 4 days with either 5-HTP + short-chain saturated FA (butter), placebo + butter, 5-HTP + monounsaturated FA (olive oil), or placebo + olive oil in double-blinded randomized order. Two hours after FA/5-HTP or placebo intake, a 13C octanoid acid test was conducted. Cortisol, serotonin, cholecystokinin (CCK), and ghrelin were measured, as were mood and GE. Results. GE was delayed with butter and was normal with olive (P < 0.05) but not affected by 5-HTP. 5-HTP supplementation did not affect serotonin levels. Food intake increased plasma CCK (F = 6.136; P < 0.05) irrespective of the FA. Ghrelin levels significantly decreased with oil/5-HTP (F = 9.166; P < 0.001). The diurnal cortisol profile was unaffected by FA or 5-HTP, as were ratings of mood, hunger, and stool urgency. Conclusion. Diverse FAs have different effects on GE and secretion of orexigenic and anorexigenic hormones. Supplementation of 5-HTP had no effect on plasma serotonin and central functions. Further studies are needed to explain the complex interplay.
    Full-text · Article · Aug 2014
    • "Therefore, non-specific signal components could be effectively suppressed by this technology, and the sensitivity and specificity in examining regional spontaneous brain activity could be significantly improved [19,20]. So far, this method has been successfully used to investigate the brain function in healthy subjects [21] and clinical populations22232425262728. The aim of the current study was to examine regional neural activity of the brain in SD patients by using the fALFF approach. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Patients with somatization disorder (SD) have altered neural activity in the brain regions of the default mode network (DMN). However, the regional alteration of the DMN in SD remains unknown. The present study was designed to investigate the regional alterations of the DMN in patients with SD at rest. Methods Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex-, education- matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI) scan. The fractional amplitude of low-frequency fluctuations (fALFF) was applied to analyze the data. Results Patients with SD showed a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the bilateral superior medial prefrontal cortex (MPFC, BA8, 9) and decreased fALFF in the left precuneus (PCu, BA7). Furthermore, significantly positive correlation was observed between the z values of the voxels within the bilateral superior MPFC and somatization subscale scores of the Symptom Check List (SCL-90) in patients with SD. Conclusions Our findings indicate that there is a dissociation pattern of the anterior and posterior DMN in first-episode, treatment-naive patients with SD. The results provide new insight for the importance of the DMN in the pathophysiology of SD.
    Full-text · Article · Jul 2014
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