具象単語の意味処理における感覚処理システムの関与

広島大学(Hiroshima University)博士(心理学)Philosophy in Psychologydoctora

DLPFC and KYN in MDD treatment response

Aim: To establish treatment response biomarkers that reflect the pathophysiology of depression, it is important to use an integrated set of features. This study aimed to determine the relationship between regional brain activity at rest and blood metabolites related to treatment response to escitalopram to identify the characteristics of depression that respond to treatment. Methods: Blood metabolite levels and resting-state brain activity were measured in patients with moderate to severe depression (n = 65) before and after 6–8 weeks of treatment with escitalopram, and these were compared between Responders and Nonresponders to treatment. We then examined the relationship between blood metabolites and brain activity related to treatment responsiveness in patients and healthy controls (n = 36). Results: Thirty-two patients (49.2%) showed a clinical response (>50% reduction in the Hamilton Rating Scale for Depression score) and were classified as Responders, and the remaining 33 patients were classified as Nonresponders. The pretreatment fractional amplitude of low-frequency fluctuation (fALFF) value of the left dorsolateral prefrontal cortex (DLPFC) and plasma kynurenine levels were lower in Responders, and the rate of increase of both after treatment was correlated with an improvement in symptoms. Moreover, the fALFF value of the left DLPFC was significantly correlated with plasma kynurenine levels in pretreatment patients with depression and healthy controls. Conclusion: Decreased resting-state regional activity of the left DLPFC and decreased plasma kynurenine levels may predict treatment response to escitalopram, suggesting that it may be involved in the pathophysiology of major depressive disorder in response to escitalopram treatment

Altered Gamma-Band Activity in Recovered Depression

Background: The neurophysiological mechanisms of cognitive reactivity, the primary vulnerability factor of major depressive disorder (MDD) recurrence, remain unclear in individuals with recovered MDD (rMDD). Because gamma-band responses (GBRs) can be used to measure cognitive processing, they may also be useful for elucidating the mechanisms underlying cognitive reactivity. Identifying these mechanisms may permit the development of an index for predicting and preempting MDD recurrence. Here, to identify the neurophysiological mechanisms of cognitive reactivity, we examined the characteristics of the GBRs evoked/induced by emotional words in participants with and without rMDD after inducing a negative mood. Methods: Thirty-three healthy control participants and 18 participants with rMDD completed a lexical emotion identification task during electroencephalography along with assessments of cognitive reactivity after negative mood induction. Results: No between-group differences were identified for the task reaction times; however, the rMDD group had significantly higher cognitive reactivity scores than did the control group. Furthermore, the power of late GBRs to positive words was significantly greater in the rMDD group, with the greater power of late GBRs being related to higher cognitive reactivity. Limitations: Considering the population studied, our findings cannot be completely generalized to populations other than adolescents, people with rMDD, and those without a history of co-morbid disorders and early life stress. Conclusions: Our findings indicate that the dysfunction of neural circuits related to higher-order processes like memory and attention might underlie cognitive reactivity. Altered late GBRs to positive information may be persistent biomarkers of the depression recurrence risk

Increased amygdala reactivity following early life stress : a potential resilience enhancer role

Background: Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. Methods: Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. Results: Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. Conclusions: Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events

Altered Gamma-Band Activity as a Potential Biomarker for the Recurrence of Major Depressive Disorder

Background: The neurophysiological mechanisms of cognitive reactivity, the primary vulnerability factor of major depressive disorder (MDD) recurrence, remain unclear in individuals with recovered MDD (rMDD). Because gamma-band responses (GBRs) can be used to measure cognitive processing, they may also be useful for elucidating the mechanisms underlying cognitive reactivity. Identifying these mechanisms may permit the development of an index for predicting and preempting MDD recurrence. Here, to identify the neurophysiological mechanisms of cognitive reactivity, we examined the characteristics of the GBRs evoked/induced by emotional words in participants with and without rMDD after inducing a negative mood.Methods: Thirty-three healthy control participants and 18 participants with rMDD completed a lexical emotion identification task during electroencephalography along with assessments of cognitive reactivity after negative mood induction.Results: No between-group differences were identified for the task reaction times; however, the rMDD group had significantly higher cognitive reactivity scores than did the control group. Furthermore, the power of late GBRs to positive words was significantly greater in the rMDD group, with the greater power of late GBRs being related to higher cognitive reactivity.Limitations: Considering the population studied, our findings cannot be completely generalized to populations other than adolescents, people with rMDD, and those without a history of co-morbid disorders and early life stress.Conclusions: Our findings indicate that the dysfunction of neural circuits related to higher-order processes like memory and attention might underlie cognitive reactivity. Altered late GBRs to positive information may be persistent biomarkers of the depression recurrence risk

Effects of behavioural activation on the neural circuit related to intrinsic motivation

[Background] Behavioural activation is an efficient treatment for depression and can improve intrinsic motivation. Previous studies have revealed that the frontostriatal circuit is involved in intrinsic motivation; however, there are no data on how behavioural activation affects the frontostriatal circuit. [Aims] We aimed to investigate behavioural activation-related changes in the frontostriatal circuit. [Method] Fifty-nine individuals with subthreshold depression were randomly assigned to either the intervention or non-intervention group. The intervention group received five weekly behavioural activation sessions. The participants underwent functional magnetic resonance imaging scanning on two separate occasions while performing a stopwatch task based on intrinsic motivation. We investigated changes in neural activity and functional connectivity after behavioural activation. [Results] After behavioural activation, the intervention group had increased activation and connectivity in the frontostriatal region compared with the non-intervention group. The increased activation in the right middle frontal gyrus was correlated with an improvement of subjective sensitivity to environmental rewards. [Conclusions] Behavioural activation-related changes to the frontostriatal circuit advance our understanding of psychotherapy-induced improvements in the neural basis of intrinsic motivation. [Declaration of interest] None.This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas from Japan Society for the Promotion of Science, JSPS (grants 16H06395 and 16H06399), and grant 23118004 from the Ministry of Education, Culture, Sports, Science and Technology, Japan. This work was partially supported by the programme for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) by Japan Agency for Medical Research and Development, AMED (grant 15dm0207012h0002) and Integrated Research on Depression, Dementia and Development Disorders by AMED (grant 16dm0107093h0001). The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation or review of the manuscript or decision to submit the manuscript for publication