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

Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Neuroscience Research (Impact Factor: 1.94). 11/2010; 69(2):129-34. 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.

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    • "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. "
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    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.
    Gastroenterology Research and Practice 08/2014; 2014:424503. DOI:10.1155/2014/424503 · 1.75 Impact Factor
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    • "Moreover, 5-HT1A autoreceptor binding has been shown to be anti-correlated with PCC activation, while opposing effects were found for retrosplenial and medial prefrontal DMN regions [20]. A similar regionally-specific effect of serotonergic neurotransmission on DMN activity has been reported in a tryptophan depletion study [85]. Given the spatial co-occurrence between cortical regions of high 5-HTT densities and nodes of the DMN [23], [78] (Text S1 and Figure S8), it is interesting that 5-HT reuptake inhibition with escitalopram or combined 5-HT and norepinephrine inhibition with duloxetine have been demonstrated to decrease DMN coupling in human phMRI studies [16], [86]. "
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    ABSTRACT: The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA) to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD) activity and platelet Vmax. The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN) suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity. This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.
    PLoS ONE 03/2014; 9(3):e92543. DOI:10.1371/journal.pone.0092543 · 3.23 Impact Factor
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    • "in RS-fMRI studies [34] [35] [36] [37] [38] . Thus, we applied fALFF to investigate the low-frequency properties of brain activity during the RT-FFF and S-FFF states. "
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    ABSTRACT: Behavioral studies have suggested a low-frequency (0.05 Hz) fluctuation of sustained attention on the basis of the intra-individual variability of reaction-time. Conventional task designs for functional magnetic resonance imaging (fMRI) studies are not appropriate for frequency analysis. The present study aimed to propose a new paradigm, real-time finger force feedback (RT-FFF), to study the brain mechanisms of sustained attention and neurofeedback. We compared the low-frequency fluctuations in both behavioral and fMRI data from 38 healthy adults (19 males; mean age, 22.3 years). Two fMRI sessions, in RT-FFF and sham finger force feedback (S-FFF) states, were acquired (TR 2 s, Siemens Trio 3-Tesla scanner, 8 min each, counter-balanced). Behavioral data of finger force were obtained simultaneously at a sampling rate of 250 Hz. Frequency analysis of the behavioral data showed lower amplitude in the low-frequency band (0.004-0.104 Hz) but higher amplitude in the high-frequency band (27.02-125 Hz) in the RT-FFF than the S-FFF states. The mean finger force was not significantly different between the two states. fMRI data analysis showed higher fractional amplitude of low-frequency fluctuation (fALFF) in the S-FFF than in the RT-FFF state in the visual cortex, but higher fALFF in RT-FFF than S-FFF in the middle frontal gyrus, the superior frontal gyrus, and the default mode network. The behavioral results suggest that the proposed paradigm may provide a new approach to studies of sustained attention. The fMRI results suggest that a distributed network including visual, motor, attentional, and default mode networks may be involved in sustained attention and/or real-time feedback. This paradigm may be helpful for future studies on deficits of attention, such as attention deficit hyperactivity disorder and mild traumatic brain injury.
    Neuroscience Bulletin 08/2012; 28(4):456-67. DOI:10.1007/s12264-012-1254-2 · 2.51 Impact Factor
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