Effects of weight gain and resumption of menses on reduced bone density in patients with anorexia nervosa.

The bone mineral density (BMD) of the lumbar vertebrae (L2-L4) and of the whole body were measured in cross-sectional and longitudinal studies in female patients with eating disorders, using dual photon absorptiometry before and after weight gain with or without resumption of menses. In the cross-sectional study, the low-body-weight anorectic patients, with or without bulimia nervosa, were found to have lower BMD of the lumbar vertebrae associated with severe weight loss, low physical activity, and earlier onset and longer duration of amenorrhea. In the longitudinal study, 11 patients attained subnormal body weight (70%SBW < or = approximately < 85% SBW), 10 patients attained normal body weight (> or = 85%SBW, 6 patients of them resumed regular menses) after treatment. The BMD of the lumbar vertebrae was found to increase with weight gain, but not to the control level. The BMD was further increased with the resumption of menses in patients with anorexia nervosa. These results suggest that resumption of menses, in addition to weight gain, is essential to normalize reduced bone mineral density.

Thyrotropin, prolactin, and growth hormone responses to thyrotropin-releasing hormone in anorexia nervosa and bulimia.

Serum thyrotropin (TSH), prolactin (PRL), and growth hormone (GH) levels were measured before and after stimulation with thyrotropin-releasing hormone (TRH) in 10 patients with bulimia, 7 with features of the restricting subtype of anorexia nervosa, and 6 with bulimic subtype of anorexia nervosa. The mean basal levels of TSH, PRL, and GH did not differ among the three groups. A delayed TSH response was found in 86% of the restricting anorectics, 80% of the bulimic anorectics, and 22% of the bulimics. The PRL response was normal in all patients, with no significant difference among the three groups. Elevated basal GH levels were found in 29% of the restricting anorectics, 33% of the bulimic anorectics, and 33% of the bulimics. An abnormal GH increase after TRH stimulation was observed in 50% of the restricting anorectics, 20% of the bulimic anorectics, and 13% of the bulimics. These results suggest that some patients with bulimia, and some with anorexia nervosa, have a hypothalamic dysfunction. These neuroendocrine abnormalities do not appear to be due solely to low weight or to metabolic changes resulting from binge eating and are not associated with depressive symptoms.

Lymphocyte subset, lymphocyte proliferative response, and soluble interleukin-2 receptor in anorexic patients.

BACKGROUND: Despite a prominent malnourished state, anorexics are unexpectedly free from infection. Several studies have shown that the cell-mediated immunity of anorexics might be well preserved, but results are conflicting. METHODS: Lymphocyte subsets, lymphoproliferative response to phytohemagglutinin, and soluble interleukin-2 receptor (sIL-2R) were measured in 7 patients with anorexia nervosa restricting type (RAN), 6 with anorexia nervosa binge-eating/purging type (ANBP), and 8 controls (C). RESULTS: Compared with controls, significantly elevated percentage of CD4 and CD4/CD8 ratio in ANBP was found. Although there was no significant difference in lymphoproliferative response among the three groups, sIL-2R in RAN was significantly lower than that in the C group, but not in ANBP. CONCLUSIONS: Although detail mechanism still remains to be unknown, some kinds of compensatory mechanism for cell-mediated immunity is working, especially in chronic underweight anorexic patients.

Prefrontal and striatal dopamine metabolism during enhanced rebound hyperphagia induced by space restriction--a rat model of binge eating.

BACKGROUND: Several lines of evidence indicate that abnormalities in brain dopamine and serotonin metabolism may play an important role in bulimia nervosa. However, the regional neurochemical mechanism of the binge eating is poorly understood. Our purpose was to elucidate brain neurochemical mechanisms of binge eating using a rat model. METHODS: The dopamine release and metabolism in the prefrontal cortex (PFC) and in the ventrolateral striatum (VLS) of rats were studied using microdialysis during enhanced rebound hyperphagia induced by space restriction (an animal model of binge eating). RESULTS: The rats showed rebound hyperphagic state when they were released from scheduled feeding (2 hours/day feeding for 7 days). The hyperphagia was further enhanced when they were put in a space-restricted cage where their mobility was restricted. Dopamine release and metabolism were increased both in the PFC and in the VLS during the enhanced rebound hyperphagia. CONCLUSIONS: These results tentatively suggest that increased dopamine release and metabolism in the PFC and in the VLS may be related to space restriction and to activation of motor function involved in feeding behavior, respectively. The enhanced rebound hyperphagia induced by space restriction may be useful as an animal model of binge eating.

TRH test and DST in schizoaffective mania, mania, and schizophrenia.

The thyrotropin-releasing hormone (TRH) test and the Dexamethasone Suppression Test (DST) were given to 10 patients who met Research Diagnostic Criteria (RDC) for schizoaffective disorder, manic type, 9 who met the criteria for mania, and 27 who met the criteria for schizophrenia. A blunted thyrotropin (TSH) response to TRH was observed in 3 of the 10 schizoaffective manics, 4 of the 9 manics, and 3 of the 27 schizophrenics. Nonsuppression on the DST was observed in 5 of the 10 schizoaffective manics, 2 of the 9 manics, and 2 of 22 schizophrenics. The schizoaffective manic and the manic patients had similar rates of TSH blunting and DST nonsuppression, and these were significantly higher than the rates in the schizophrenic patients. This difference was not attributable to baseline TSH and cortisol levels or to neuroleptic treatment. It is suggested that patients with RDC schizoaffective mania and mania have more disturbance in the hypothalamic-pituitary adrenal and thyroid axes than patients with schizophrenia.

Effect of maternal separation on feeding behavior of rats in later life.

Effects of maternal separation on feeding behavior, particularly on rebound hyperphagia, in adult rats were examined. Time-restricted scheduled feeding (2 h per day for 6 days), was given at the age of 3, 6, 9 or 12 weeks in rats that were maternal separated from postnatal days (PD) 1-21 and control rats. Following the time-restricted scheduled feeding, rats were fed freely for 24 h (rebound hyperphagia). Body weight, daily normal food consumption and food consumption during time-restricted scheduled feeding and rebound hyperphagia were measured. Body weight of 3-week-old maternally separated rats were less than those of control rats. There was no significant difference in normal daily food consumption. Food consumption during rebound hyperphagia was significantly increased in 6- to 9-week-old female maternally separated rats, but there was no difference observed in males. Postnatal maternal separation enhanced rebound hyperphagia of female rats in later life. These results indicate that postnatal maternal separation made rats more vulnerable to the development of abnormal feeding behavior in response to food restriction in later life.

Effects of fluvoxamine on food intake during rebound hyperphagia in rats.

We examined the effects of fluvoxamine on food intake during rebound hyperphagia induced by a time-restricted feeding schedule in rats. Rats were allowed access to food for only 2 h daily for 7 days, and then had free access to food for 7 consecutive days. The daily food intake of the rats was dramatically increased, by 42.5% (rebound hyperphagia), for 7 days of the free-feeding period. Intraperitoneal injection of fluvoxamine decreased food intake significantly in a dose-dependent manner for the first 3 h of feeding during 7 days. When rats were allowed access to one of the standard, carbohydrate-, fat-, or protein-rich diets in the free-feeding period following the time-restricted feeding schedule, fluvoxamine significantly decreased food intakes of standard, carbohydrate- and fat-rich diets on all days, and the protein-rich diet after the 2nd day of the free-feeding period. These results indicate that fluvoxamine, irrespective of the diet composition, suppresses rebound hyperphagia induced by a time-restricted feeding schedule, but that its effect is short-lived.

Scheduled feeding caused activation of dopamine metabolism in the striatum of rats.

The effects of a time-restricted feeding schedule on dopamine (DA) release and its metabolites output in the striatum of freely moving rats were studied. Rats had access to food for only 2 h daily for 7 successive days. On the 1st or 7th day, the extracellular concentrations of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the ventrolateral striatum were measured by in vivo brain microdialysis during 2 h of exposure to food-related stimuli followed by 2 h of access to food. Extracellular concentrations of DA and its metabolites did not change during the period of exposure to food-related stimuli or during feeding on the 1st day. On the 7th day, extracellular DOPAC and HVA concentrations increased significantly during 2 h of feeding, but not during exposure to food-related stimuli, compared with basal levels. Extracellular DA concentration did not change significantly. These results indicate that scheduled feeding caused activation of DA metabolism in the ventrolateral striatum and facilitate feeding-related motor activity in feeding behavior.

Multi-impulsivity of Japanese patients with eating disorders: primary and secondary impulsivity.

Several studies have noted that multi-impulsive bulimia nervosa tends to be refractory to treatment. However, it is not known whether these impulsivities are an expression of more fundamental psychopathology or simply the consequence of chaotic eating behaviors. Studies of the temporal relationship between the onset of eating disorder and the occurrence of impulsive behaviors will facilitate a better understanding of these issues. Subjects consisted of 60 patients with anorexia nervosa restricting type (AN-R), 62 patients with anorexia nervosa binge-eating/purging type (AN-BP), 114 patients with bulimia nervosa purging type (BN) and 66 control subjects. Impulsive behaviors and childhood traumatic experiences were assessed by self-report questionnaire. Multi-impulsivity (defined by at least three of the following: heavy regular alcohol drinking; suicide attempt; self-mutilation; repeated shoplifting of items other than food; sexual relationships with persons not well known to the subject) was found in 2% of AN-R, 11% of AN-BP, 18% of BN and 2% of control subjects. Eighty percent of BN patients with multi-impulsivity had a history of suicide attempts or self-mutilation history prior to the onset of bulimia nervosa. In BN patients, there tended to be a relationship between childhood parental loss or borderline personality disorder and multi-impulsivity. In conclusion, primary impulsivity (chronological prior occurrence of impulsive behaviors) does exist even in a very different culture, although the number of patients of this type is very limited.

A comparative study of clinical features between pure checkers and pure washers categorized using a lifetime symptom rating method.

The current study assessed lifetime obsessive-compulsive disorder (OCD) symptoms in 156 Japanese patients with OCD in order to investigate clinical differences between pure lifetime checkers and pure lifetime washers. Fifty subjects (32%), who had no lifetime history of washing or checking compulsions, or who had a principal symptom other than washing or checking compulsions, were initially excluded. The remaining 106 subjects were divided into three groups: 43 pure lifetime washers (W), 33 pure lifetime checkers (C) and 30 subjects who had experienced both checking and washing compulsions over their lifetime (WC). No differences in clinical characteristics were observed between the W and C groups, suggesting that the lifetime washer-checker distinction may not be useful in subtyping OCD. However, subjects in the WC group differed from other subjects in a number of respects including poorer level of insight, more severe psychopathology and global dysfunction. Thus, they can be generally distinguished by more pervasive and severe psychopathological features, and may constitute a valid subgroup of OCD. Further work from a multidimensional perspective is required to verify the clinical significance of a typology based on lifetime symptoms.

Prevalence of binge-eating and bulimia among adolescent women in Japan.

This study examined by questionnaire the prevalence of binge-eating and bulimia among 220 women at a school of nursing and 236 women at a junior college, all from 18 to 21 years old, in two different areas of Japan. Binge-eating more than once a week was found in 14 (6.5%) of the nursing school students and 21 (9.1%) of the college women. Self-induced vomiting and use of purgatives were found in 19 (8.7%) and 12 (5.5%) of the nursing school students, and 19 (8.1%) and 9 (3.8%) of the college women, respectively. The difference between these two groups was not significant. The prevalence of binge-eating more than once a week, together with self-induced vomiting or purgative use, was 3.6% in the nursing school students, 2.1% in the college women, and 2.9% in the total sample. These women appeared to meet both DSM-III criteria for bulimia and Russell's criteria for bulimia nervosa.

D2 receptors in the ventrolateral striatum are involved in feeding behavior in rats.

To study the role of dopamine D1 and D2 receptors in the ventrolateral striatum in feeding behavior, a D1 receptor agonist (CY 208-243), a D1 receptor antagonist (SCH 23390), a D2 receptor agonist (quinpirole), and a D2 receptor antagonist [(-)-sulpiride] were perfused via a microdialysis probe into the ventrolateral striatum of rats fasted for 22 h. Then the rats were allowed to feed freely for 6 h. Sulpiride perfusion at a high concentration suppressed food and water intake significantly, whereas dopamine release and the levels of DOPAC and HVA were increased at all concentrations. In contrast, quinpirole perfusion at a high concentration increased food intake by 41%. Dopamine release and the levels of DOPAC and HVA were decreased at all concentrations. On the other hand, neither CY 208-243 nor SCH 23390 changed food intake or dopamine release, but both drugs decreased water intake. These results suggest that D2 receptors in the ventrolateral striatum have a more important role than D1 receptors in the feeding behavior of rats.

Bromocriptine enhances feeding behavior without changing dopamine metabolism.

Bromocriptine is an ergot derivative and has been thought to act as a selective D2 receptor agonist, but its effects on dopamine release in vivo have not been confirmed. We administered bromocriptine into the striatum of rats and studied the effects on feeding behavior and dopamine release. Bromocriptine was perfused via a microdialysis probe into the ventrolateral striatum of rats fasted for 22 h, and the rats were then allowed to feed freely for 6 h. Bromocriptine perfusion increased food intake in a dose-dependent manner, whereas the extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) did not change. Perfusion of (-) sulpiride, a selective D2 receptor antagonist, decreased food intake, but increased dopamine release and the levels of DOPAC and HVA. Pretreatment with (-)sulpiride perfusion for 1 h prior to bromocriptine perfusion inhibited the increase of food intake induced by bromocriptine, and it increased dopamine release and the levels of DOPAC and HVA. These findings suggest that bromocriptine directly perfused into the ventrolateral striatum acts selectively on postsynaptic D2 receptors and enhances feeding behavior.

A single-blind study of clocapramine and sulpiride in hospitalized chronic schizophrenic patients.

The therapeutic effects, safety and side-effects of clocapramine and sulpiride were evaluated in 52 hospitalized chronic schizophrenic patients using a single-blind method during an 8-week trial period. While the final global improvement rating showed clocapramine to be superior to sulpiride, the differences were not statistically significant. The time course of the total psychiatric rating scales (PRS) showed a progressive decline during treatment for both drugs, and at the end of treatment clocapramine proved significantly lower in total PRS than did sulpiride. In the improvement of psychotic symptoms, clocapramine seemed to be superior to sulpiride with respect to motor retardation, delusion, hallucination or disturbance of self-consciousness, social isolation or withdrawal, and recreation or work. Side-effects appeared more frequently with clocapramine than with sulpiride, but abnormal laboratory-test results appeared less in clocapramine-treated patients than in sulpiride-treated ones. Neither side-effects nor abnormal laboratory-test results induced by the two drugs were severe enough to terminate administration. Clocapramine is concluded to have a more favourable effect on negative symptoms, as well as on some positive symptoms of chronic schizophrenia, than sulpiride.

The clinical effect of bifemelane hydrochloride on dementia in aged patients.

The effect of bifemelane hydrochloride on dementia in the elderly was studied in thirty-one patients having cerebrovascular disorders. Alzheimer's disease, Parkinsonism and related diseases. The drug (150 mg) was administered orally three times daily for 10 weeks. The final global improvement rating was 77.4% for all patients. The rates of improvement for Alzheimer's disease were higher than those for cerebrovascular disorders, suggesting that this drug affects Alzheimer's disease through a cholinergic potentiating action. Psychotic, neurological and subjective symptoms, and the activity of daily life, were rated before, during and after treatment. All mean rates of improvement were based on observations made in the 4th week after the start of treatment. Improvement rates for global symptoms were more than 80% for emotional incontinence and prejudice or querulous attitudes toward the nurses, and in headache, tinnitus and dizziness among the subjective symptoms. The improvement in intellectual function was evaluated by the dementia rating scale for the elderly (DRSE), and a significant increase was found in DRSE after treatment with this drug. Side effects attributable to the drug were noted in one patient developing urticaria. It is thus suggested that bifemelane hydrochloride is useful in the treatment of different symptoms of dementia.

Study on the mental health of patients with atopic dermatitis in adults.

General Health Questionaire of 60 symptoms proposed by Goldberg was used to study psychiatric condition of 74 patients with severe atopic dermatitis. The patients were composed of 26 males and 48 females. A matched healthy control was obtained from 65 persons of 22 males and 43 females. The patients showed remarkably higher scores than the healthy control in the sum of all morbid ratings and all four scales for somatic symptoms, anxiety and worry, social dysfunction and despondency and depressed mood. The results obtained indicate that atopic dermatitis could be not only disease of dermatology but also accompanied with psychiatric disturbances and even social disease. Then, we propose that intense provision of psychiatric support will be important and necessary to those patients with atopic disease.

The importance of mental support to the patients with adult atopic dermatitis.

To study mental condition of the patients with severe adult atopic dermatitis, the General Health Questionnaire of 60 symptoms proposed by Goldberg was completed by 64 patients composed of 22 males and 42 females twice (before the start of the treatment and following improvement or reduction of their skin symptoms), and also 65 healthy persons as a matched healthy control. The patients were much more markedly disturbed in the sum of all morbid ratings and all four scales for somatic symptoms, anxiety and worry, social dysfunction and despondency and depressed mood before the start of the treatment than the healthy control. However, the patients showed remarkably reduced scores in all measured scales with improvement of their skin symptoms lower than healthy control. These depressed mental conditions reflected on their daily and social activities. The results obtained indicated that atopic dermatitis could be not only a disease of dermatology but also a disease of mental and even social disease. The results endorsed importance and necessity to provide for dermatologists, the patients family and even nurses concerned mental support to those patients with adult atopic dermatitis.