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26.  Effects of Kampo on functional gastrointestinal disorders 
This article reviews the effectiveness of Kampo (traditional Japanese herbal medicine) in the treatment of functional gastrointestinal disorders, especially functional dyspepsia (FD) and irritable bowel syndrome (IBS). The results of four randomized, controlled trials (RCTs) suggested the usefulness of rikkunshito in relieving the subjective symptoms of patients with FD. Rikkunshito significantly improved not only gastric symptoms, such as epigastiric discomfort, but also extra-gastric symptoms, such as general fatigue, when compared with control drugs. The therapeutic effects of rikkunshito were more evident when it was prescribed to patients with “kyosho”, i.e., low energy. Two RCTs suggested the efficacy of keishikashakuyakuto for IBS.
Basic research studies have demonstrated that these Kampo medicines have multiple sites of action to improve subjective symptoms. For example, rikkunshito improves gastric motility dysfunction, including impaired adaptive relaxation and delayed gastric emptying, gastric hypersensitivity, and anorexia via facilitation of ghrelin secretion. It also exhibits anti-stress effects, i.e., it attenuates stress-induced exacerbation of gastric sensation and anorexia, as well as the hypothalamic-pituitary-adrenocortical axis and sympathetic activation. Keishikashakuyakuto exhibited not only an antispasmodic effect on intestinal smooth muscle, but also antidepressant-like effects. Case series suggest that other Kampo prescriptions are also effective for FD and IBS. However, further studies are necessary to evaluate their efficacy.
PMCID: PMC3906900  PMID: 24447839
Kampo; Rikkunshito; Keishikashakuyakuto; Functional dyspepsia; Irritable bowel syndrome
27.  Acupuncture therapy: mechanism of action, efficacy, and safety: a potential intervention for psychogenic disorders? 
Scientific bases for the mechanism of action of acupuncture in the treatment of pain and the pathogenic mechanism of acupuncture points are briefly summarized. The efficacy and safety of acupuncture therapy is discussed based on the results of German clinical trials. A conclusion on the role for acupuncture in the treatment of psychogenic disorders could not be reached.
PMCID: PMC3996195  PMID: 24444292
Acupuncture therapy; Action mechanism; Polymodal receptor; Efficacy; Safety; Randomized controlled trials; Systematic review; Psychogenic disorders
28.  Is it possible to bridge the Biopsychosocial and Biomedical models? 
PMCID: PMC3898026  PMID: 24422973
29.  Effect of 12 weeks of yoga training on the somatization, psychological symptoms, and stress-related biomarkers of healthy women 
Previous studies have shown that the practice of yoga reduces perceived stress and negative feelings and that it improves psychological symptoms. Our previous study also suggested that long-term yoga training improves stress-related psychological symptoms such as anxiety and anger. However, little is known about the beneficial effects of yoga practice on somatization, the most common stress-related physical symptoms, and stress-related biomarkers. We performed a prospective, single arm study to examine the beneficial effects of 12 weeks of yoga training on somatization, psychological symptoms, and stress-related biomarkers.
We recruited healthy women who had no experience with yoga. The data of 24 participants who were followed during 12 weeks of yoga training were analyzed. Somatization and psychological symptoms were assessed before and after 12 weeks of yoga training using the Profile of Mood State (POMS) and the Symptom Checklist-90-Revised (SCL-90-R) questionnaires. Urinary 8-hydroxydeoxyguanosine (8-OHdG), biopyrrin, and cortisol levels were measured as stress-related biomarkers. The Wilcoxon signed-rank test was used to compare the stress-related biomarkers and the scores of questionnaires before and after 12 weeks of yoga training.
After 12 weeks of yoga training, all negative subscale scores (tension-anxiety, depression, anger-hostility, fatigue, and confusion) from the POMS and somatization, anxiety, depression, and hostility from the SCL-90-R were significantly decreased compared with those before starting yoga training. Contrary to our expectation, the urinary 8-OHdG concentration after 12 weeks of yoga training showed a significant increase compared with that before starting yoga training. No significant changes were observed in the levels of urinary biopyrrin and cortisol after the 12 weeks of yoga training.
Yoga training has the potential to reduce the somatization score and the scores related to mental health indicators, such as anxiety, depression, anger, and fatigue. The present findings suggest that yoga can improve somatization and mental health status and has implications for the prevention of psychosomatic symptoms in healthy women.
Trial registration
University Hospital Medical Information Network (UMIN CTR) UMIN000007868.
PMCID: PMC3892034  PMID: 24383884
Yoga; Somatization; Psychological symptom; Stress; Biomarker; Anxiety; Depression; Anger; Hostility; Fatigue
30.  A clinical study of the efficacy of a single session of individual exercise for depressive patients, assessed by the change in saliva free cortisol level 
The efficacy of physical exercise as an augmentation to pharmacotherapy with antidepressants for depressive patients has been documented. However, to clarify the effectiveness of exercise in the treatment of depression, it is necessary to distinguish the effect of the exercise itself from the effect of group dynamics. Furthermore, an objective measurement for estimation of the effect is needed. Previous reports adopted a series of group exercises as the exercise intervention and mainly psychometric instruments for the measurement of effectiveness. Therefore, this clinical study was done to examine the effectiveness of a single session of individual exercise on depressive symptoms by assessing the change in saliva free cortisol level, which reflects hypothalamic-pituitary-adrenocortical axis function that is disturbed in depressive patients.
Eighteen medicated patients, who met the DSM-IV-TR criteria for major depressive disorder, were examined for the change in saliva free cortisol levels and the change in subjective depressive symptoms before and after pedaling a bicycle ergometer for fifteen minutes. Within a month after the exercise session, participants conducted a non-exercise control session, which was sitting quietly at the same time of day as the exercise session.
Depressed patients who participated in this study were in remission or in mild depressive state. However, they suffered chronic depression and had disturbed quality of life. The saliva free cortisol level and subjective depressive symptoms significantly decreased after the exercise session. Moreover, the changes in these variables were significantly, positively correlated. On the other hand, although the subjective depressive symptoms improved in the control session, the saliva free cortisol level did not change.
For the first time in depressive patients, we were able to show a decrease in the saliva free cortisol level due to physical exercise, accompanied by the improvement of subjective depressive symptoms. This identified a possible influence of exercise on the hypothalamic-pituitary-adrenal axis in depression.
These results suggest the utility of assessing the effect of physical exercise by saliva free cortisol level in depressive patients who suffer from bio-psycho-social disability.
PMCID: PMC4029195  PMID: 24314124
Depression; Physical exercise; Saliva free cortisol level; Augmentation therapy; Quality of life
31.  The role of perceived well-being in the family, school and peer context in adolescents’ subjective health complaints: evidence from a Greek cross-sectional study 
During adolescence children are usually confronted with an expanding social arena. Apart from families, schools and neighbourhoods, peers, classmates, teachers, and other adult figures gain increasing importance for adolescent socio-emotional adjustment. The aim of the present study was to investigate the extent to which Greek adolescents’ perceived well-being in three main social contexts (family, school and peers) predicted self-reported Subjective Health Complaints.
Questionnaires were administered to a Greek nation-wide, random, school-based sample of children aged 12–18 years in 2003. Data from 1.087 adolescents were analyzed. A hierarchical regression model with Subjective Health Complaints as the outcome variable was employed in order to i) control for the effects of previously well-established demographic factors (sex, age and subjective economic status) and ii) to identify the unique proportion of variance attributed to each context. Bivariate correlations and multicollinearity were also explored.
As hypothesized, adolescents’ perceived well-being in each of the three social contexts appeared to hold unique proportions of variance in self-reported Subjective Health Complaints, after controlling for the effects of sex, age and subjective economic status. In addition, our final model confirmed that the explained variance in SHC was accumulated from each social context studied. The regression models were statistically significant and explained a total of approximately 24% of the variance in Subjective Health Complaints.
Our study delineated the unique and cumulative contributions of adolescents’ perceived well-being in the family, school and peer setting in the explanation of Subjective Health Complaints. Apart from families, schools, teachers and peers appear to have a salient role in adolescent psychosomatic adjustment. A thorough understanding of the relationship between adolescents’ Subjective Health Complaints and perceived well-being in their social contexts could not only lead to more effective tailored initiatives, but also to promote a multi- and inter-disciplinary culture in adolescent psychosomatic health.
PMCID: PMC4175490  PMID: 24283390
Subjective Health Complaints (SHC); Adolescence; Family; School; Peers; Well-being; Psychosomatic health; Subjective perceptions; Subjective economic status
32.  The role of traditional Japanese medicine (Kampo) in the practice of psychosomatic medicine: the usefulness of Kampo in the treatment of the stress-related symptoms of women, especially those with peri-menopausal disorder 
A serious problem currently plaguing the medical field is the widening gap between academic medicine, which studies the features and causes of illness, and the medical care that patients desire. An example of this gap can be observed in the practice of psychotherapy, which is effective only for certain patients. Kampo medicine that combines the advantages of Western medicine with those of traditional Japanese medicine is currently undergoing a revival in the healthcare sector. The therapeutic policies underlying Kampo medicine are based on the physical constitution and current symptoms of each patient. For this reason, Kampo medicine is referred to as “tailor-made medicine” and has properties similar to “mind and body” or psychosomatic medicine. Some women exhibit multiple undefined stress-related symptoms during the peri-menopausal period. In order to accurately diagnose and provide patient-specific treatment, physicians should not only investigate the various stress factors in patients’ lives but should also provide a Sho, or a Kampo diagnosis. The therapeutic approach in Kampo medicine is aimed at harmonizing the mind, body, and spirit; this practice involves the use of narrative and holistic medication that treats the entire being of the patient, resulting in an increased number of specialized treatment plans.
There are many Kampo prescriptions tailored to treat women who exhibit various stress-related symptoms. Both Kampo and psychosomatic medicine are based on the principles of narrative-based medicine, and by integrating these two medical systems, an ideal system can be devised to better cope with the various needs of patients. This new medical system established by integrating and harmonizing Western and Eastern medicine can be used for the treatment of women with stress-related symptoms.
PMCID: PMC4016593  PMID: 24148283
Kampo medicine; Stress-related symptoms; Undefined symptoms; Pre-menopausal disorder; Tailor-made medicine
33.  Spiritual and religious beliefs: do they matter in the medication adherence behaviour of hypertensive patients? 
Medication non-adherence is often a predominant problem in the management of hypertension and other chronic conditions. In explaining health behaviours, social determinants like spirituality and religiosity are increasingly identified to impact health and treatment. Although a number of researchers have found spirituality and religiosity to be primary resources among persons dealing with chronic disability and illness, studies relating this specifically to medication adherence have been limited.
Our study sought to examine the interrelationship between spirituality/ religiosity and medication adherence among 400 hypertensive patients 18 years old and above. Spiritual Perspective Scale, Duke Religion Index, and the Morisky Medication Adherence Scale were used to determine spirituality, religiosity and medication adherence respectively.
The majority (93.25%) of patients poorly adhered to their medications. While high spiritual and religious beliefs formed core components of the lifestyles of patients, spirituality (p = 0.018) and not religiosity (p = 0.474) related directly with medication non-adherence. Likewise, after controlling for demography and other medical co-morbidities, patients with high spirituality were 2.68 times more likely to be poorly adherent than patients who place lower emphasis on the association between spirituality and health.
Our study suggests that while spirituality/ religiosity was dominant among hypertensive patients, these spiritual attachments of patients with a supreme being potentially increased their trust in the expectation of divine healing instead of adhering adequately with their anti-hypertensive medications.
PMCID: PMC3854617  PMID: 24138844
Spirituality; Religiosity; Medication non-adherence; Co-morbidity; Ghana
34.  TEACCH-based group social skills training for children with high-functioning autism: a pilot randomized controlled trial 
Although social skills training programs for people with high-functioning autism (HFA) are widely practiced, the standardization of curricula, the examination of clinical effectiveness, and the evaluation of the feasibility of future trials have yet to be done in Asian countries. To compensate for this problem, a Japanese pilot randomized controlled trial (RCT) of the Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH)-based group social skills training for children with HFA and their mothers was conducted.
Eleven children with HFA, aged 5–6 years, and their mothers were randomly assigned to the TEACCH program (n=5) or a waiting-list control group (n=6). The program involved comprehensive group intervention and featured weekly 2-hour sessions, totaling 20 sessions over six months. The adaptive behaviors and social reciprocity of the children, parenting stress, and parent–child interactions were assessed using the Strengths and Difficulties Questionnaire (SDQ), Parenting Stress Index (PSI), Beck depression inventory-II (BDI-II), and Interaction Rating Scale (IRS).
Through this pilot trial, the intervention and evaluation of the program has been shaped. There were no dropouts from the program and the mothers’ satisfaction was high. The outcome measurements improved more in the program group than in the control group, with moderate effect sizes (SDQ, 0.71; PSI, 0.58; BDI-II, 0.40; and IRS, 0.69). This pilot trial also implied that this program is more beneficial for high IQ children and mothers with low stress than for those who are not.
We have standardized the TEACCH program, confirmed the feasibility of a future trial, and successfully estimated the positive effect size. These findings will contribute to a larger trial in the future and to forthcoming systematic reviews with meta-analyses.
Trial registration
PMCID: PMC3850504  PMID: 24083413
Randomized controlled trial; Autism; Social skills training; TEACCH (Treatment and Education of Autistic and related Communication Handicapped Children)
35.  Family issues and family functioning of Japanese outpatients with type 2 diabetes: a cross-sectional study 
Previous studies confirmed that the control of diabetes is related to family functioning, but the validity of the tools used to assess family functioning in these studies is questionable. Few studies have focused on family issues. In this study, we used a new assessment tool to evaluate family functioning and family issues of patients with type 2 diabetes.
A cross-sectional questionnaire was given to outpatients with type 2 diabetes at a community hospital in Aichi, Japan, between August 2001 and March 2002. First, the patients were asked to answer FACESKGIV-16, which measures cohesion and adaptability, questions regarding family issues, daily lifestyle, and HAD. Physical and serological data were measured. Family functioning, family issues, and relationships between each parameter and family functioning or family issues were analyzed.
Of the 133 participants, 121 (33.3%) had some sort of family issue. Family issues included “Health problems of family members” (40.9%), “Family life cycle issues” (22.7%), and others.
The best fit multiple regression model (Adjusted R2: 0.494, p = 0.020) included Plasma Glucose as an independent variable, and the squared value of cohesion score, depression score of HAD, Total calorie intake, Exercise time, Housekeeping time, and BMI were dependent variables. The results show that extremes of family cohesion with either too many or too few issues related to family functioning are correlated with the plasma glucose level.
Family issues were common among patients with type 2 diabetes, and the extremes of family cohesion were associated with the glucose level, in contrast to the common wisdom that a well balanced family leads to good control of diabetes.
PMCID: PMC3700776  PMID: 23799927
Family; Family Research; Diabetes Mellitus; Family Relations; Family Characteristics; Family Members
36.  Does lavender aromatherapy alleviate premenstrual emotional symptoms?: a randomized crossover trial 
A majority of reproductive-age women experience a constellation of various symptoms in the premenstrual phase, commonly known as premenstrual syndrome (PMS). Despite its prevalence, however, no single treatment is universally recognized as effective, and many women turn to alternative approaches, including aromatherapy, a holistic mind and body treatment. The present study investigated the soothing effects of aromatherapy on premenstrual symptoms using lavender (Lavandula angustifolia), a relaxing essential oil, from the perspective of autonomic nervous system function.
Seventeen women (20.6 ± 0.2 years) with mild to moderate subjective premenstrual symptoms participated in a randomized crossover study. Subjects were examined on two separate occasions (aroma and control trials) in the late-luteal phases. Two kinds of aromatic stimulation (lavender and water as a control) were used. This experiment measured heart rate variability (HRV) reflecting autonomic nerve activity and the Profile of Mood States (POMS) as a psychological index before and after the aromatic stimulation.
Only a 10-min inhalation of the lavender scent significantly increased the high frequency (HF) power reflecting parasympathetic nervous system activity in comparison with water (aroma effect: F = 4.50, p = 0.050; time effect: F = 5.59, p = 0.017; aroma x time effect: F = 3.17, p = 0.047). The rate of increase in HF power was greater at 10–15 min (p = 0.051) and 20–25 min (p = 0.023) in the lavender trial than in the control trial with water. In addition, POMS tests revealed that inhalation of the aromatic lavender oil significantly decreased two POMS subscales—depression–dejection (p = 0.045) and confusion (p = 0.049)—common premenstrual symptoms, in the late-luteal phase, as long as 35 min after the aroma stimulation.
The present study indicated that lavender aromatherapy as a potential therapeutic modality could alleviate premenstrual emotional symptoms, which, at least in part, is attributable to the improvement of parasympathetic nervous system activity. This study further implies that HRV could evaluate the efficacy of aromatherapy using various fragrances to relieve premenstrual symptoms, and ultimately, support the mind and body health of women.
PMCID: PMC3674979  PMID: 23724853
37.  Changes in P300 following alternate nostril yoga breathing and breath awareness 
This study assessed the effect of alternate nostril yoga breathing (nadisuddhi pranayama) on P300 auditory evoked potentials compared to a session of breath awareness of equal duration, in 20 male adult volunteers who had an experience of yoga breathing practices for more than three months. Peak amplitudes and peak latencies of the P300 were assessed before and after the respective sessions. There was a significant increase in the P300 peak amplitudes at Fz, Cz, and Pz and a significant decrease in the peak latency at Fz alone following alternate nostril yoga breathing. Following breath awareness there was a significant increase in the peak amplitude of P300 at Cz. This suggests that alternate nostril yoga breathing positively influences cognitive processes which are required for sustained attention at different scalp sites (frontal, vertex and parietal), whereas breath awareness brings about changes at the vertex alone.
PMCID: PMC3679963  PMID: 23721252
Alternate nostril yoga breathing; P300; Breath awareness; Cognitive processes
38.  Psychosocial and cognitive function in children with nephrotic syndrome: association with disease and treatment variables 
To investigate possible differences in emotional/behavioral problems and cognitive function in children with nephrotic syndrome compared to healthy controls and to examine the effect of disease-specific and steroid treatment-specific characteristics on the abovementioned variables.
Forty-one patients with nephrotic syndrome (23 boys, age range: 4.4-15.2 years) and 42 sex- and age-matched healthy control subjects (20 boys, age range: 4.1-13.4 years) were enrolled in the study. Disease (severity, age of diagnosis, duration) and steroid treatment (total duration, present methylprednisolone dose and duration of present dose) data were collected. In order to assess children’s emotional/behavioral problems, the Child Behavior Checklist was administered. The Wechsler Intelligence Scale for Children – Third Edition was administered to assess Full-Scale, Verbal, and Performance intelligence quotient (IQ) scores.
The patients presented with more internalizing problems (P = 0.015), including withdrawal (P = 0.012) and somatic complaints (P = 0 .011), but not more anxiety/depression or externalizing problems. A significant association was found between severity of disease and somatic complaints (P = 0.017) as well as externalizing problems (P = 0.030). Years of illness were significantly more in those presenting with abnormal anxiety/depression (P = 0.011). Duration of steroid medication was significantly higher among those presenting with abnormal anxiety/depression (P = 0.011) and externalizing problems (P = 0.039). IQ was not associated significantly with disease or steroid treatment variables.
Psychosocial factors and outcomes may be important correlates of children’s nephrotic syndrome and potential targets of thorough assessment and treatment.
PMCID: PMC3652787  PMID: 23618427
Children; Cognitive; Nephrotic syndrome; Psychosocial; Steroids
39.  Prolonged post-hyperventilation apnea in two young adults with hyperventilation syndrome 
The prognosis of hyperventilation syndrome (HVS) is generally good. However, it is important to proceed with care when treating HVS because cases of death following hyperventilation have been reported. This paper was done to demonstrate the clinical risk of post-hyperventilation apnea (PHA) in patients with HVS.
Case presentation
We treated two patients with HVS who suffered from PHA. The first, a 21-year-old woman, had a maximum duration of PHA of about 3.5 minutes and an oxygen saturation (SpO2) level of 60%. The second patient, a 22-year-old woman, had a maximum duration of PHA of about 3 minutes and an SpO2 level of 66%. Both patients had loss of consciousness and cyanosis. Because there is no widely accepted regimen for treating patients with prolonged PHA related to HVS, we administered artificial ventilation to both patients using a bag mask and both recovered without any after effects.
These cases show that some patients with HVS develop prolonged PHA or severe hypoxia, which has been shown to lead to death in some cases. Proper treatment must be given to patients with HVS who develop PHA to protect against this possibility. If prolonged PHA or severe hypoxemia arises, respiratory assistance using a bag mask must be done immediately.
PMCID: PMC3637146  PMID: 23594702
Post-hyperventilation apnea; PHA; Hyperventilation syndrome; HVS; Hypocapnia; Hypoxemia
40.  Neuroimaging studies of alexithymia: physical, affective, and social perspectives 
Alexithymia refers to difficulty in identifying and expressing one’s emotions, and it is related to disturbed emotional regulation. It was originally proposed as a personality trait that plays a central role in psychosomatic diseases. This review of neuroimaging studies on alexithymia suggests that alexithymia is associated with reduced neural responses to emotional stimuli from the external environment, as well as with reduced activity during imagery, in the limbic and paralimbic areas (i.e., amygdala, insula, anterior/posterior cingulate cortex). In contrast, alexithymia is also known to be associated with enhanced neural activity in somatosensory and sensorimotor regions, including the insula. Moreover, neural activity in the medial, prefrontal, and insula cortex was lowered when people with alexithymia were involved in social tasks. Because most neuroimaging studies have been based on sampling by self-reported questionnaires, the contrasted features of neural activities in response to internal and external emotional stimuli need to be elucidated. The social and emotional responses of people with alexithymia are discussed and recommendations for future research are presented.
PMCID: PMC3621096  PMID: 23537323
Alexithymia; fMRI; PET; Neuroimaging study; Interoception; Psychosomatic medicine; Emotional awareness
41.  Psychological stress contributed to the development of low-grade fever in a patient with chronic fatigue syndrome: a case report 
Low-grade fever is a common symptom in patients with chronic fatigue syndrome (CFS), but the mechanisms responsible for its development are poorly understood. We submit this case report that suggests that psychological stress contributes to low-grade fever in CFS.
Case presentation
A 26-year-old female nurse with CFS was admitted to our hospital. She had been recording her axillary temperature regularly and found that it was especially high when she felt stress at work. To assess how psychological stress affects temperature and to investigate the possible mechanisms for this hyperthermia, we conducted a 60-minute stress interview and observed the changes in the following parameters: axillary temperature, fingertip temperature, systolic blood pressure, diastolic blood pressure, heart rate, plasma catecholamine levels, and serum levels of interleukin (IL)-1β and IL-6 (pyretic cytokines), tumor necrosis factor-α and IL-10 (antipyretic cytokines). The stress interview consisted of recalling and talking about stressful events. Her axillary temperature at baseline was 37.2°C, increasing to 38.2°C by the end of the interview. In contrast, her fingertip temperature decreased during the interview. Her heart rate, systolic and diastolic blood pressures, and plasma levels of noradrenaline and adrenaline increased during the interview; there were no significant changes in either pyretic or antipyretic cytokines during or after the interview.
A stress interview induced a 1.0°C increase in axillary temperature in a CFS patient. Negative emotion-associated sympathetic activation, rather than pyretic cytokine production, contributed to the increase in temperature induced by the stress interview. This suggests that psychological stress may contribute to the development or the exacerbation of low-grade fever in some CFS patients.
PMCID: PMC3599992  PMID: 23497734
Chronic fatigue syndrome; Stress-induced hyperthermia; Psychogenic fever; Stress interview; Cytokine
42.  Reviewer acknowledgement 2012 
The editors of BioPsychoSocial Medicine would like to thank all our reviewers who have contributed to the journal in Volume 6 (2012).
PMCID: PMC3579750  PMID: 23369529
43.  A randomized, double-masked, placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption 
Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism.
This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS), the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA), and a profile of mood states (POMS) and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase). In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption.
There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism.
Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the next morning. These effects were not caused by an increase in acute alcohol metabolism.
PMCID: PMC3583691  PMID: 23414576
Ornithine; Residual alcohol effects; Salivary cortisol; Flusher
44.  Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study 
Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome. 38 CFS patients aged 12–18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007). Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04). In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.
PMCID: PMC3570350  PMID: 23388153
Adolescents; Chronic fatigue syndrome; Autonomic cardiovascular control; Diagnostic criteria
45.  Younger and older chronic somatoform pain patients in psycho-diagnostics, physician-patient relationship and treatment outcome 
Patients with chronic pain are found with highly variable clinical presentation and differing physical complaints. They are seen as a heterogenic group. Based on clinical observations, elderly patients seem to differ from younger patients with chronic pain. We examined whether there were systematic differences between young and old pain patients.
As part of a routine evaluation of university hospital care, a newly developed psychosomatic treatment model for chronic somatoform pain disorders was examined. The basis for treatment efficacy was a target-oriented, specific somatic and psychological intervention that included a stable physician-patient relationship. Particular attention was paid to differences in treatment outcome with regard to changes in both physical and psychopathological symptom levels. We hypothesised that younger pain patients had higher psychological burden and benefitted more from our treatment than older pain patients.
Overall, 179 inpatients (57.5% women) with chronic pain were examined (age between 16 and 79 years). The group as a whole yielded high scores on the somatisation dimension (SCL-90) and showed a considerable amount of psychopathological symptoms, such as depressive mood and anxiety (HADS) and a great emotional instability (FPI-R). Age differences were only found with regards to patients’ degree of aggression (SCl-90): younger patients showed higher aggressive tendencies than older ones (p< 0.05). The treatment offered helped patients in both age groups especially with regard to reduction of depressive mood (HADS, p< 0.01) and anxiety levels (HADS, p< 0.01). Regression analysis showed different age groups and gender as significant predictors of anxiety reduction under therapy (R2=.108; model: p< 0.01).
Discussion and conclusion
Results show that younger chronic pain patients suffer more from a considerable amount of psychological distress than older ones, but our treatment approach was equally effective in both groups. However, age and gender differences, as well as the patient’s baseline level of anxiety influenced the outcome. These factors need to be studied in future research.
PMCID: PMC3573985  PMID: 23379640
Chronic somatoform pain; Age; Psychosomatic in-patient treatment; Attachment style
46.  New year address on the state of psychosomatic medicine in Japan 
PMCID: PMC3577672  PMID: 23363730
47.  The alexithymic brain: the neural pathways linking alexithymia to physical disorders 
Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala) and the prefrontal cortex when alexithymics attempt to feel other people’s feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT) was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The neural machinery in alexithymia is therefore activated more on the physiologic, motor-expressive level and less in the cognitive-experiential domains of the emotional response system. Affects may play an important role in alleviating intrinsic physiologic reactions and adapting to the environment. Deficient development of emotional neural structures may lead to hypersensitivity to bodily sensations and unhealthy behaviors, a possible mechanism linking alexithymia to psychosomatic disorders.
PMCID: PMC3563604  PMID: 23302233
Affect; Alexithymia; Emotional dysregulation; Neuroimaging; Psychosomatic disorders
48.  Alexithymia as a prognostic risk factor for health problems: a brief review of epidemiological studies 
The number of articles on alexithymia has been steadily increasing since the word “alexithymia” was coined in the 1970s to denote a common characteristic that is observed among classic psychosomatic patients in whom therapy was unsuccessful. Alexithymia, a disorder of affect regulation, has been suggested to be broadly associated with various mental and physical health problems. However, most available evidence is based on anecdotal reports or cross-sectional observations. To clarify the predictive value of alexithymia for health problems, a systematic review of prospective studies was conducted. A search of the PubMed database identified 1,507 articles on “alexithymia” that were published by July 31, 2011. Among them, only 7 studies examined the developmental risks of alexithymia for health problems among nonclinical populations and 38 studies examined the prognostic value of alexithymia among clinical populations. Approximately half of the studies reported statistically significant adverse effects, while 5 studies demonstrated favorable effects of alexithymia on health outcomes; four of them were associated with surgical interventions and two involved cancer patients. The studies that showed insignificant results tended to have a small sample size. In conclusion, epidemiological evidence regarding alexithymia as a prognostic risk factor for health problems remains un-established. Even though alexithymia is considered to be an unfavorable characteristic for disease control and health promotion overall, some beneficial aspects are suggested. More prospective studies with sufficient sample sizes and follow-up period, especially those involving life course analyses, are needed to confirm the contribution of alexithymia to health problems.
PMCID: PMC3546882  PMID: 23244192
Systematic review; Prospective study; Epidemiology
49.  Effects of personality traits on the manifestations of irritable bowel syndrome 
Previous studies have reported that patients with irritable bowel syndrome (IBS) show high neuroticism. However, the precise association between the IBS subtypes and the degree of neuroticism in younger populations is largely unknown. We tested our hypothesis that subjects with diarrhea-predominant IBS may have a higher degree of neuroticism than subjects without IBS or those with other subtypes of IBS. We also verified the additional hypothesis that the severity of neuroticism might be correlated with the severity of IBS in younger populations.
We conducted a cross-sectional survey of 557 university students, ranging in age from 18 to 21 years. Presence/ absence of IBS and determination of the IBS subtype was by the Rome II Modular Questionnaire, while the severity of IBS was determined by the IBS severity index (IBS-SI). The degree of neuroticism was evaluated using the Maudsely Personality Inventory (MPI). The presence/absence of psychological distress was measured with the K6 scale.
Neuroticism scores in the subjects with diarrhea-predominant IBS were significantly higher than those in the non-IBS subjects or subjects with constipation-predominant IBS. The neuroticism scores were significantly correlated with the IBS-SI scores in all subjects with IBS.
These results suggest that neuroticism is involved in the pathophysiology of IBS in young subjects, especially in that of the diarrhea-predominant subtype.
PMCID: PMC3523040  PMID: 23110762
Personality; Irritable bowel syndrome; Depression; Neuroticism; Brain- gut interactions
50.  Illness perception among patients with chest pain and palpitations before and after negative cardiac evaluation 
Patients with chest pain or palpitations often have poor outcomes following a negative cardiac evaluation, with symptom persistence, limitations in everyday activities, and reduced health-related quality of life. The aims of this study were to evaluate illness perceptions before and after negative cardiac evaluations and measure the ability of a self-report questionnaire to predict outcomes.
Patients (N = 138) referred for chest pain or palpitations to a cardiac outpatient clinic were assessed before and six months after a negative cardiac evaluation. In addition to Brief Illness Perception Questionnaire (BIPQ), all patients completed the Beck Depression Inventory and SF-36 Health Survey.
The emotional reactions to and understanding of symptoms had not improved six months after a negative cardiac evaluation. A stronger correlation between illness perceptions and health at follow-up than before the cardiac evaluation might explain the tendency for poor outcomes among these patients. Most of the eight BIPQ item scores before the negative cardiac evaluation were predictive of the outcome six months later. A single question asking about the perceived consequences of the complaints (BIPQ Item 1) rated before the cardiac evaluation was collapsed into a dichotomous variable with a cut-off at ≥4 which yields a sensitivity of 51%, a specificity of 85%, a positive predictive value of 71%, a negative predictive value of 69%, and an odds ratio of 5.7 (r = .38, p < .001) in predicting poor outcomes.
Assessing illness perceptions is important in patients with negative cardiac tests for understanding and predicting outcomes.
PMCID: PMC3538579  PMID: 23017128
Non-cardiac chest pain; Benign palpitations; Negative cardiac evaluation; Psychosomatic medicine; Illness perception

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