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Shigeto Yamawaki

Publications and source records attributed to Shigeto Yamawaki.

At least 19 recordsLinked to original sources
PubMed2007

Antidepressants increase glial cell line-derived neurotrophic factor production through monoamine-independent activation of protein tyrosine kinase and extracellular signal-regulated kinase in glial cells.

Recent studies show that neuronal and glial plasticity are important for therapeutic action of antidepressants. We previously reported that antidepressants increase glial cell line-derived neurotrophic factor (GDNF) production in rat C6 glioma cells (C6 cells). Here, we found that amitriptyline, a tricyclic antidepressant, increased both GDNF mRNA expression and release, which were selectively and completely inhibited by mitogen-activated protein kinase kinase inhibitors. Indeed, treatment of amitriptyline rapidly increased extracellular signal-regulated kinase (ERK) activity, as well as p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase activities. Furthermore, different classes of antidepressants also rapidly increased ERK activity. The extent of acute ERK activation and GDNF release were significantly correlated to each other in individual antidepressants, suggesting an important role of acute ERK activation in GDNF production. Furthermore, antidepressants increased the acute ERK activation and GDNF mRNA expression in normal human astrocytes as well as C6 cells. Although 5-hydroxytryptamine (serotonin) (5-HT), but not noradrenaline or dopamine, increased ERK activation and GDNF release via 5-HT2A receptors, ketanserin, a 5-HT2A receptor antagonist, did not have any effect on the amitriptyline-induced ERK activation. Thus, GDNF production by amitriptyline was independent of monoamine. Both of the amitriptyline-induced ERK activation and GDNF mRNA expression were blocked by genistein, a general protein tyrosine kinase (PTK) inhibitor. Actually, we found that amitriptyline acutely increased phosphorylation levels of several phosphotyrosine-containing proteins. Taken together, these findings indicate that ERK activation through PTK regulates antidepressant-induced GDNF production and that the GDNF production in glial cells may be a novel action of the antidepressant, which is independent of monoamine.

Amitriptyline↗
PubMed2007

Factors related to anxiety and depression in women with breast cancer and their husbands: role of alexithymia and family functioning.

GOALS OF WORK: The purpose of this study was to explore alexithymia, family functioning, and other factors that might affect anxiety and depression levels in women with breast cancer and in their husbands. PATIENTS AND METHODS: A cross-sectional study was undertaken in 46 postsurgical ambulatory women with breast cancer and their husbands. Documented informed consent for the study was obtained from each subject. All subjects completed the Zung self-rating anxiety scale (SAS), the Zung self-rating depression scale (SDS), the 20-item Toronto alexithymia scale (TAS-20), and the family assessment device (FAD). MAIN RESULTS: Multiple regression analysis revealed that a high degree of alexithymia in patients correlated with a high degree of patient anxiety. Patient perceptions of inappropriate affective responsiveness among family members correlated with a high degree of depression. Among husbands, a high degree of anxiety was correlated with their own high level of alexithymia or low level of education, and with the occurrence of adjuvant therapy in their wives. Husband perceptions of inappropriate sharing of roles among family members, their own low education level, and a large number of family members correlated with high degrees of depression among them. CONCLUSIONS: The present study revealed that alexithymia and family functioning are associated with anxiety and depression, respectively, in both women with breast cancer and in their husbands. Individual traits such as alexithymia and family functioning should be taken into account when we intervene to treat anxiety and depression in breast cancer patients and their husbands.

Affective Symptoms↗
PubMed2006

Post-stroke affective or apathetic depression and lesion location: left frontal lobe and bilateral basal ganglia.

This study was designed to examine the correlation between damage to the basal ganglia or frontal lobe and depression status (both affective and apathetic dimensions) in 243 stroke patients. We assessed the affective dimension in post-stroke depression (PSD) using the Zung Self-rating Depression Scale (SDS) and the apathetic dimension in PSD using the apathy scale (AS). We classified basal ganglia or frontal lobe damage into four groups: no damage, damage to the left side only, damage to the right side only, and damage to both sides. Affective and/or apathetic PSD was found in 126 patients (51.9%). The severity of affective depression (SDS score) was associated with left frontal lobe (but not basal ganglia) damage, and that of apathetic depression (AS score) was related to damage to the bilateral basal ganglia (but not to the frontal lobe). The anatomical correlates of PSD differ depending on the PSD dimension (affective or apathetic) and may explain interstudy differences regarding the association between lesion location and type of PSD.

Aged↗
PubMed2006

Effect of paroxetine on enhanced contextual fear induced by single prolonged stress in rats.

RATIONALE: Single prolonged stress (SPS) is an animal model of posttraumatic stress disorder (PTSD) that can reproduce enhanced hypothalamo-pituitary-adrenal negative feedback. OBJECTIVES: We examined whether SPS can produce an enhanced psychophysiological reactivity to laboratory stressors unrelated to trauma and whether paroxetine (PRX) can alleviate the enhanced anxiety and fear response in rats subjected to SPS. Furthermore, the effect of PRX on pain sensitivity was examined in rats with and without SPS. METHODS: Rats were subjected to SPS (restraint for 2 h, forced swim for 20 min, and ether anesthesia) and then kept undisturbed for 14 days. After that, contextual fear response was assessed. Twenty-four hours after foot shock conditioning, freezing behavior was measured during reexposure to the shock environment for 3 min. Pain sensitivity was assessed by the flinch-jump test. PRX (0.01, 0.03, or 0.1 mg/mL) was chronically administered orally in drinking water. RESULTS: Rats subjected to SPS showed a significant increase in contextual freezing compared to rats without SPS. Chronic administration of PRX at concentrations of 0.03 and 0.1 mg/mL (which produced serum concentrations similar to those that are clinically relevant) caused significant suppression of the enhanced contextual freezing. Acute administration of PRX at a dose producing clinically relevant serum concentrations did not affect the enhanced freezing. CONCLUSIONS: Our results suggest that SPS can reproduce behavioral alteration similar to that observed in patients with PTSD, and this elevated fear response can be alleviated by the chronic administration of PRX at doses producing clinically relevant serum concentrations.

Animals↗
PubMed2006

Factors related to posttraumatic stress in adolescent survivors of childhood cancer and their parents.

GOALS OF WORK: The purpose of this study was to investigate factors related to severe posttraumatic stress symptoms (PTSS) in adolescent survivors of childhood cancer and their parents. MATERIALS AND METHODS: Eighty-nine families (88 adolescent survivors of childhood cancer, 87 mothers, 72 fathers) completed a self-report questionnaire. Multivariate logistic regression analyses were performed using the following risk factors for severe PTSS: trait anxiety, family functioning, demographic and medical variables. MAIN RESULTS: Severe PTSS were reported by 10.9% (n=9) of the survivors, 20.7% (n=18) of the mothers, and 22.2% (n=16) of the fathers. Preliminary analyses found significant correlations of PTSS between mother-survivor (Spearman's gamma=0.377, p<0.01) and mother-father (Spearman's gamma=0.483, p<0.01). The results of multivariate analyses indicated that higher trait anxiety [odds ratio (OR):1.16; 95% confidence interval (CI): 1.03-1.31; p<0.05] and having medical sequelae (OR: 5.85; 95% CI:1.02-33.72; p<0.05) were significant factors related to PTSS for survivors. For mothers, the significant PTSS-related factors were: higher trait anxiety (OR:1.13; 95% CI:1.04-1.23; p<0.01); 5- to 9-year interval from the first diagnosis to the present investigation, compared to more than a 10-year interval (OR: 6.45; 95% CI:1.67-24.89; p<0.01); and a relatively lower rating on "roles" of family functioning (OR: 12.34; 95% CI:1.11-136.97; p<0.05). For fathers, trait anxiety was a significant related factor (OR: 1.07; 95% CI:1.01-1.14; p<0.05). CONCLUSIONS: Survivors and their parents suffered from PTSS after long interval from completion of treatment, and PTSS-related factors varied for each family member. Appropriate allocation of responsibility for family functioning may promote the ability to decrease PTSS, especially for mothers.

Adaptation, Psychological↗
PubMed2006

Brain mechanism of reward prediction under predictable and unpredictable environmental dynamics.

In learning goal-directed behaviors, an agent has to consider not only the reward given at each state but also the consequences of dynamic state transitions associated with action selection. To understand brain mechanisms for action learning under predictable and unpredictable environmental dynamics, we measured brain activities by functional magnetic resonance imaging (fMRI) during a Markov decision task with predictable and unpredictable state transitions. Whereas the striatum and orbitofrontal cortex (OFC) were significantly activated both under predictable and unpredictable state transition rules, the dorsolateral prefrontal cortex (DLPFC) was more strongly activated under predictable than under unpredictable state transition rules. We then modelled subjects' choice behaviours using a reinforcement learning model and a Bayesian estimation framework and found that the subjects took larger temporal discount factors under predictable state transition rules. Model-based analysis of fMRI data revealed different engagement of striatum in reward prediction under different state transition dynamics. The ventral striatum was involved in reward prediction under both unpredictable and predictable state transition rules, although the dorsal striatum was dominantly involved in reward prediction under predictable rules. These results suggest different learning systems in the cortico-striatum loops depending on the dynamics of the environment: the OFC-ventral striatum loop is involved in action learning based on the present state, while the DLPFC-dorsal striatum loop is involved in action learning based on predictable future states.

Brain↗
PubMed2006

Importance of early environment in the development of post-traumatic stress disorder-like behaviors.

A number of clinical studies in which early adversities were defined retrospectively, demonstrated that early adverse experiences increased the morbidity rate of post-traumatic stress disorder (PTSD) in later life. However, no prospective studies have yet been conducted to elucidate whether early adversity affects the risk or severity of PTSD. Thus, we examined whether early adversity would strengthen the severity of PTSD symptoms in later life by using neonatal isolation (NI) and single prolonged stress (SPS) as an animal model of PTSD. We measured anxiety-like behavior in the elevated plus maze (EPM), contextual freezing in the contextual fear (CF) test, and analgesia in the flinch-jump and hot-plate tests in four groups of adult rats (sham, NI, SPS, and NI+SPS). NI significantly enhanced the SPS-induced decrease in the percentage of open arm time and open arm entries in the EPM, enhanced the SPS-induced increase in contextual freezing, and strengthened SPS-induced analgesia, without any changes in locomotor activity in the open field locomotor test. In addition, we examined the effect of environmental enrichment (EE). Repeated exposure to EE ameliorated the NI-induced enhancement of contextual freezing, but not anxiety-like behavior or analgesia, in response to SPS. The results of the present study demonstrated that while early adversity strengthened PTSD-like symptoms, EE alleviated the enhanced contextual freezing by NI and SPS. These findings suggest that early adversity may worsen dysfunction of the amygdala and hippocampus in PTSD, and an early intervention may alleviate the early adversity-mediated enhancement of hippocampal dysfunction in PTSD.

Age Factors↗
PubMed2006

Neonatal isolation changes the expression of IGF-IR and IGFBP-2 in the hippocampus in response to adulthood restraint stress.

Early adverse experiences are thought to contribute to the development of stress vulnerability, and to increase the onset of stress-related psychiatric disorders in stressful environments in adulthood. One plausible molecular mechanism of stress vulnerability is the modulation of neurotrophic factor signal transduction in the hippocampus by early adversity. In the present study we investigated the influence of neonatal isolation (NI) with or without adulthood single restraint stress (SRS) on the expression of several growth factor-related genes in the rat hippocampus using a cDNA microarray, real-time quantitative PCR, and Western blot. We found that hippocampal insulin-like growth factor-I receptor (IGF-IR) mRNA levels and immunoreactivity, and IGF binding protein-2 (IGFBP-2) mRNA levels were significantly lower in response to SRS in NI rats compared with rats without NI. Immunohistochemical analyses revealed that hippocampal IGF-IR immunoreactivity in the CA1 and CA3 pyramidal cell layers, and in the dentate gyrus granule cell layer of NI rats subjected to SRS was significantly lower compared with rats subjected to SRS. In addition, the hippocampal levels of IGF-IR mRNA were significantly lower in adult rats subjected to NI. These findings indicate that NI down-regulates IGF signal transduction under basal and stressful conditions in later life. Since the activation of IGF signalling plays a role in the development and neuroprotection of the central nervous system, the down-regulation of IGF signal transduction induced by NI may be, at least in part, involved in the development of adulthood stress vulnerability, which in turn precipitates the onset of depression.

Actins↗
PubMed2006

Anticipation of affective image modulates visual evoked magnetic fields (VEF).

We investigated the interaction between anticipation of positive and negative affective images and visual evoked magnetic fields (VEF). Participants (n = 13) were presented emotionally positive or negative images under different anticipatory conditions, and their subsequent brain responses were recorded by magnetoencephalography (MEG). In the Affective Cue conditions, the cue stimulus indicated the emotional valence of the image, which followed 2 s later. In the Null Cue conditions, the cue stimulus did not include any information about the valence of the image. In the No Cue conditions, the affective image was suddenly presented, without a cue stimulus. The VEF amplitude for the negative image in the Affective Cue condition was smaller than that of the positive image in the Affective Cue condition and that of the negative image in the Null Cue condition. This result suggests that anticipation of the valence of affective images modulates the processes of the visual cortex.

Adult↗
PubMed2006

[Influence of stress on the activation of CaMKII in the brain].

Stress can affect signal transduction in the brain, possibly resulting in the development of certain psychiatric disorders, such as depression and posttraumatic stress disorder. Calcium/calmodulin-dependent protein kinase (CaMK) II is one of the protein kinases abundantly expressed in the brain, especially in the hippocampus, which plays an important role in synaptic plasticity, and is therefore involved in memory formation. Here, we provide a brief overview of the effects of stress on the levels of CaMKII and phosphorylation (activation) of CaMKII in the rat hippocampus through the glutamatergic system, alpha-amino-3-hydro-5-methyl-4-isoxazolepropionate (AMPA) receptors. Furthermore, we highlight the possible links between stress-mediated CaMKII modulation and the pathophysiology of psychiatric disorders.

Animals↗
PubMed2005

Decreased levels of whole blood glial cell line-derived neurotrophic factor (GDNF) in remitted patients with mood disorders.

Recent post-mortem and imaging studies provide evidence for a glial reduction in different brain areas in mood disorders. This study was aimed to test whether glial cell line-derived neurotrophic factor (GDNF), a member of transforming growth factor (TGF)-beta superfamily, in blood levels was associated with mood disorders. We measured GDNF and TGF-beta levels in whole blood in remitted patients with mood disorders [n=56; major depressive disorders (MDD) 39, bipolar disorders (BD) 17] and control subjects (n=56). GDNF and TGF-beta were assayed with the sandwich ELISA method. Total GDNF levels were significantly lower in MDD and in BD than in control subjects (MDD, p=0.0003; BD, p=0.018), while no significant difference in total TGF-beta1 or total TGF-beta2 levels was found in these groups. Our study suggests that lower GDNF levels might be involved in the pathophysiology of mood disorders, although this preliminary study has several limitations.

Adult↗
PubMed2005

Distorted images of one's own body activates the prefrontal cortex and limbic/paralimbic system in young women: a functional magnetic resonance imaging study.

BACKGROUND: Our aim was to study the gender differences in brain activation upon viewing visual stimuli of distorted images of one's own body. METHODS: We performed functional magnetic resonance imaging on 11 healthy young men and 11 healthy young women using the "body image tasks" which consisted of fat, real, and thin shapes of the subject's own body. RESULTS: Comparison of the brain activation upon performing the fat-image task versus real-image task showed significant activation of the bilateral prefrontal cortex and left parahippocampal area including the amygdala in the women, and significant activation of the right occipital lobe including the primary and secondary visual cortices in the men. Comparison of brain activation upon performing the thin-image task versus real-image task showed significant activation of the left prefrontal cortex, left limbic area including the cingulate gyrus and paralimbic area including the insula in women, and significant activation of the occipital lobe including the left primary and secondary visual cortices in men. CONCLUSIONS: These results suggest that women tend to perceive distorted images of their own bodies by complex cognitive processing of emotion, whereas men tend to perceive distorted images of their own bodies by object visual processing and spatial visual processing.

Adult↗
PubMed2005

Psychiatric disorders following first breast cancer recurrence: prevalence, associated factors and relationship to quality of life.

OBJECTIVE: The purpose of this study was to investigate the prevalence of and factors associated with psychiatric disorders and the impact on quality of life (QOL) in patients with first breast cancer recurrence. METHODS: We analyzed the baseline data on 50 consecutively enrolled recurrent breast cancer patients, participating in a feasibility study of multifaceted psychosocial intervention. Psychiatric disorders, including major depressive disorder (MDD), dysthymic disorder, panic disorder, post-traumatic stress disorder (PTSD), generalized anxiety disorder and adjustment disorders (AD), were evaluated according to the Structured Clinical Interview for the DSM-III-R and IV. The patients' demographic data, biomedical factors, social support, mental adjustment to cancer, personality traits and QOL were also evaluated. RESULTS: Eleven (22%) met the DSM-III-R and IV criteria for MDD, PTSD or AD (MDD, 2%; PTSD, 2%; AD, 20%). Univariate analysis indicated that current doxorubicin/cyclophosphamide, presence of a confidant, past history of MDD, helplessness/hopelessness and neuroticism were significantly associated with psychiatric disorders. On multivariate logistic regression analysis, past history of MDD and helplessness/hopelessness were significant associated factors. Psychiatric disorders were significantly associated with lower functional scales ('emotional functioning', 'body image' and 'future perspective') and higher symptom scales ('appetite loss', 'diarrhea', 'fatigue' and 'nausea-vomiting') in QOL. CONCLUSIONS: The result suggests that asking about history of depression and appropriate intervention, including psycho-education, are needed for patients with first breast cancer recurrence in order to detect and manage psychological distress. Although further studies are needed to clarify causal links between psychiatric disorders and QOL, patients' psychiatric disorders were associated with QOL.

Adaptation, Psychological↗
PubMed2005

Reduced activation of posterior cingulate cortex during imagery in subjects with high degrees of alexithymia: a functional magnetic resonance imaging study.

BACKGROUND: Although the brain areas involved in imagery have been reported, the neural bases of individual differences in imagery remain to be elucidated. People with high degrees of alexithymia (HDA) are known to have constricted imaginal capacities. The purpose of this study was to investigate neural correlates of imagery disturbance in subjects with HDA. METHODS: A functional magnetic resonance imaging (fMRI) study was undertaken in 10 subjects with HDA and 10 subjects with low degrees of alexithymia (LDA), who were selected according to their scores on the 20-item Toronto Alexithymia Scale (TAS-20). The two groups' regional cerebral activation was compared during various imagery conditions. In those conditions, the subjects imaged a past happy (PH) event, a past sad (PS) event, a past neutral (PN) event, a future happy (FH) event, a future sad (FS) event, and a future neutral (FN) event. The activation levels during these conditions were compared with those during a rest condition (REST). RESULTS: The t tests showed that the mean subjective ratings of both the vividness of the imagery and the intensity of emotion during the imagery were higher in the subjects with LDA than in those with HDA for the PS and FS imagery conditions. On the other hand, relative to the LDA group, the HDA group showed significantly less activation in the posterior cingulate cortex (PCC) during the PH and FH imagery conditions compared with REST and during the FH imagery condition compared with the FN imagery condition. CONCLUSION: The present results suggest an association between an HDA and reduced activation of the PCC during happy imagery. Given the function of this brain region, these results might be related to a dysfunction of episodic memory retrieval during happy imagery in subjects with HDA.

Adult↗
PubMed2005

Family functioning and psychological distress among Japanese breast cancer patients and families.

GOALS OF WORK: The purpose of this study was to develop a typology of family functioning in the families of breast cancer patients. PATIENTS AND METHODS: Seventy-four families (189 individuals: 74 patients, 54 spouses, 46 offspring, and 15 other relatives) completed self-report questionnaires. Perception of family functioning was assessed using the family relationship index (FRI) and its three dimensions (cohesiveness, expressiveness, and conflict) and was classified into groups by a cluster analytic approach. Psychological distress was assessed using the Zung self-rating depression scale (SDS) and the Zung self-rating anxiety scale (SAS). MAIN RESULTS: Cluster analysis yielded three groups of patients and their family members: one cluster with high cohesiveness, high expressiveness, and low conflict ("supportive" type: n=64); a second group with low cohesiveness, low expressiveness, and high conflict ("conflictive" type: n=65); and a third group with limited cohesiveness, limited expressiveness, and low conflict ("intermediate" type: n=60). Analysis of variance revealed that conflictive families manifested the highest level of depression and anxiety among these clusters. CONCLUSIONS: Typology of family functioning can identify psychologically at-risk families. A family-focused approach can help to reduce psychological distress, especially in conflictive families.

Adult↗
PubMed2005

Gender differences in brain activity toward unpleasant linguistic stimuli concerning interpersonal relationships: an fMRI study.

Women are more vulnerable to psychosocial stressors such as interpersonal conflicts than men, and are more susceptible to some psychiatric disorders. We hypothesized that there are differences in the brain activity of men and women while perceiving unpleasant linguistic stimuli concerning interpersonal relationships, and that they underlie the different sensitivity toward these stressful stimuli. We carried out a functional magnetic resonance imaging (fMRI) study on 13 young female adults and 13 young male adults who performed an emotional decision task including sets of unpleasant words concerning interpersonal relationships and sets of neutral words. In the women, the unpleasant words more significantly activated the bilateral caudate nuclei and left putamen than the neutral words. However, among the men, there was no difference in the level of activation of any brain area induced by the unpleasant or neutral word stimuli. Upon performing the task, there was a significant gender difference in brain activation. Moreover, among the female subjects, the activation in the bilateral caudate nuclei and left thalamus was negatively correlated with the average rating of pleasantness of the words concerning interpersonal conflicts by the subject. These results demonstrate gender differences in brain activity in processing unpleasant linguistic stimuli related to interpersonal conflicts. Our data suggest that the bilateral caudate nuclei and left putamen play an important role in the perception of words concerning interpersonal conflicts in women. The bilateral caudate nuclei and left thalamus may regulate a woman's sensitivity to unpleasant information about interpersonal difficulties.

Adult↗
PubMed2005

Development of an Impact Thermometer for use in combination with the Distress Thermometer as a brief screening tool for adjustment disorders and/or major depression in cancer patients.

Screening cancer patients for adjustment disorders and major depression is important, because both are prevalent and often underrecognized. The purpose of this study was to validate the Distress and Impact Thermometer, a 2-item questionnaire, which we newly developed as a brief screening tool for detection of adjustment disorders and/or major depression. Two hundred ninety-five cancer patients completed the Distress and Impact Thermometer and the Hospital Anxiety and Depression Scale (HADS), and were examined by psychiatrists based on DSM-IV criteria. Using cutoff points for detection of adjustment disorders and major depression of "3/4" on "distress" score and "2/3" on "impact," the sensitivity and specificity were 0.82 and 0.82, respectively. Screening performance of the Distress and Impact Thermometer was comparable to that of the Hospital Anxiety and Depression Scale. Its brevity and good performance suggest that the Distress and Impact Thermometer is an effective tool for routine screening in clinical oncology settings.

Adaptation, Psychological↗