Impaired Declarative Memory Consolidation During Sleep in Patients With Primary Insomnia: Influence of Sleep Architecture and Nocturnal Cortisol Release

BACKGROUND: A central cognitive function of sleep is to consolidate newly acquired memories for long-term storage. Here, we investigated whether the overnight consolidation of declarative memory in patients with chronic sleep disturbances is impaired, owing to less slow wave sleep (SWS) and an increased cortisol release. METHODS: Polysomnographic recordings, serum cortisol concentrations, and overnight memory consolidation in 16 patients with primary insomnia were compared with those of 13 healthy control subjects. RESULTS: Patients displayed distinctly less overnight consolidation of declarative memory (p < .05), which was significantly correlated with SWS in the control subjects (r = .69) but with rapid eye movement (REM) sleep in the patients (r = .56), who had a diminished amount of SWS (p < .05). Increased cortisol levels in the middle of the night were associated with impaired retrieval of declarative memory after sleep for both control subjects (r = -.52) and patients (r = -.46). CONCLUSIONS: Primary insomnia is associated with a diminished sleep-related consolidation of declarative memory. Efficient overnight consolidation of declarative memory is associated with high amounts of SWS and low serum cortisol levels during the early part of the night. Where SWS is decreased, REM sleep might play a partly compensatory role in the consolidation of declarative memory.     

Sleep and the cholinergic rapid eye movement sleep induction test in patients with primary alcohol dependence.

BACKGROUND: The present study investigated polysomnographically assessed sleep parameters in alcohol-dependent patients after withdrawal and in healthy control subjects during baseline and after a cholinergic stimulation paradigm. The aim of the study was to test whether sleep parameters, especially rapid eye movement (REM) sleep variables, may serve as predictors for relapse in alcohol-dependent patients. METHODS: Forty patients diagnosed with alcohol dependence were admitted to a specialized ward for alcohol withdrawal and were investigated by polysomnography at three time points: 2-3 weeks after withdrawal (T0) and at follow-up investigations 6 (T1) and 12 (T2) months after discharge from the hospital. A subgroup of patients (n = 17) was studied at T0 after challenge with galanthamine, a reversible cholinesterase inhibitor (cholinergic REM induction test, CRIT). Patients were compared with two control groups: a) 30 healthy control subjects (matched for age- and gender-distribution) for comparison at baseline conditions; and b) 17 age- and gender-matched control subjects for comparison with the CRIT. RESULTS: At baseline the patients showed significant disturbances of sleep continuity and sleep architecture (decreased slow-wave sleep, SWS) and exhibited an increase of "REM sleep pressure" (a combined index of REM latency, REM density, and REM sleep percent). Galanthamine provoked significant alterations of sleep continuity, sleep architecture (reduced SWS), and increased most of the components of REM pressure, taking patients and control subjects together. Apart from SWS %SPT (sleep period time) no significant drug-group interactions occurred. Patients who remained abstinent (n = 11) for at least 6 months at follow-up exhibited significantly less abnormalities of REM sleep at T0 compared to the group of patients that relapsed at 6 months follow-up. CONCLUSIONS: It is concluded that increased REM sleep pressure after alcohol withdrawal is a robust predictor of vulnerability to relapse. Thus, a subgroup of alcoholic patients appears to exhibit distinct neurobiological abnormalities assessable by polysomnography that are related to an increased vulnerability for alcoholism and early relapse.     

Night-time plasma cortisol secretion is associated with specific sleep stages

Polysomnographic recordings were obtained in 16 healthy male subjects in order to evaluate temporal interrelationships between concentrations of plasma cortisol and sleep at night. The pattern of nocturnal cortisol secretion appeared to be synchronized with the periodicity of sleep: rapid eye movement (REM) sleep was found to be primarily present when cortisol concentrations were decreasing, indicating a diminished or absent secretory activity of the adrenals at that time; wakefulness and Stage 1 sleep, by contrast, were associated with increasing plasma cortisol concentrations. Furthermore, the enhanced adrenal secretory activity usually preceded the occurrence of light sleep or wakefulness, which is in accord with a wakening effect of plasma cortisol. Just prior to the onset of the first pronounced rise in plasma cortisol during sleep, episodes of slow wave sleep (SWS) became more frequent. This suggests that the offset of episodes of SWS may act as a trigger for the first pronounced nocturnal rise in plasma cortisol.     

Clinical significance of sleep EEG abnormalities in chronic schizophrenia

This study aimed to investigate the relationship between measures of clinical symptom severity and sleep EEG parameters in a relatively diagnostically homogeneous group of patients with schizophrenia. We obtained sleep EEG data in 15 drug-free inpatients who met DSM-IV-R criteria for schizophrenia, undifferentiated type, with 15 age- and sex-matched normal controls over two consecutive night polysomnographic recordings. Clinical symptoms were assessed by the Positive and Negative Symptom Scale (PANSS) and Hamilton Rating Scale for Depression. Characteristic features of sleep disturbance were seen in patients with schizophrenia: profound difficulties in sleep initiation and maintenance, poor sleep efficiency, a slow wave sleep (SWS) deficit, and an increased REM density. SWS was inversely correlated with cognitive symptoms. REM density was inversely correlated with positive, cognitive, and emotional discomfort symptoms as well as PANSS total score. Our data demonstrate that drug-free patients with chronic undifferentiated type schizophrenia suffer from profound disturbances in sleep continuity and sleep architecture. Both the SWS deficit and cognitive impairment found in schizophrenics in this study may relate to similar underlying structural brain abnormalities.     

Cranial computed tomography findings in bulimia

In cranial computed tomography (CT), not only patients with anorexia nervosa but also patients suffering from bulimia, display enlarged external cerebrospinal fluid spaces. This was true for more than one third of the 28 bulimic patients studied, regardless of whether or not they had a past history of anorexia nervosa. As the bulimic patients had a near normal body weight, the observed structural changes cannot be attributed to underweight, as is commonly assumed to be the case in anorectic patients. These findings indicate that, in addition to underweight, other factors have to be considered as causing the morphological brain alterations present in patients with eating disorders.     

On the role of menopause for sleep-endocrine alterations associated with major depression

Aging and menopause are associated with alterations of the sleep EEG, while age-related changes of the hypothalamo-pituitary-adrenal (HPA) axis remain controversial. Major depression is also associated with typical sleep-endocrine changes, including enhanced activity of the HPA axis, while an influence of age and gender on these alterations is less clear. To test the hypothesis that after menopause sleep-endocrine alterations associated with major depression are accentuated, we examined the sleep EEG and nocturnal hormone secretion (ACTH, cortisol, GH, estradiol, LH, FSH, and leptin) in 16 drug-free female patients, mostly with the first episode of a major depressive disorder (seven pre- and nine postmenopausal subjects) and 19 female controls (10 subjects in the early follicular phase and nine postmenopausal subjects).Nocturnal cortisol secretion was increased in postmenopausal patients with depression, while a decrease was noted in postmenopausal controls. Sleep alterations typically associated with depression, namely a reduction in sleep continuity and slow wave sleep (SWS) and an increase in REM density, were prominent in post- but not in premenopausal patients. An inverse correlation was noted between the decline in SWS and sleep continuity and FSH secretion in patients with depression, suggesting a role of menopause for these sleep-endocrine alterations typically associated with major depression. In contrast, in premenopausal patients we noted primarily a shift in SWS and delta-EEG activity from the first to the second non-REM period, which was not related to age or hormone secretion.Though the relatively small number of subjects per group precludes a definitive conclusion, our data open up the possibility that the sleep-endocrine changes typically associated with major depression are most prominent in postmenopausal patients. Whether the predominant alteration of the distribution of SWS and delta EEG activity in younger patients with a first episode of major depression has a predictive value for the future course of the disease remains to be investigated.     

Polysomnography in patients with post‐traumatic stress disorder

Aims: The purpose of the present study was to investigate sleep structure in post‐traumatic stress disorder (PTSD) patients with and without any psychiatric comorbidities. The relationship between sleep variables and measurements of clinical symptom severity were also investigated. Methods: Sleep patterns of 24 non‐medicated male PTSD patients and 16 age‐ and sex‐matched normal controls were investigated on polysomnography on two consecutive nights. Six PTSD‐only patients and 15 PTSD patients with major depressive disorder (MDD) were also compared to normal controls. Sleep variables were correlated with PTSD symptoms. Results: Compared to the normal controls, the PTSD patients with MDD had difficulty initiating sleep, poor sleep efficiency, decreased total sleep time, decreased slow wave sleep (SWS), and a reduced rapid eye movement (REM) sleep latency. The PTSD patients without any comorbid psychiatric disorders had moderately significant disturbances of sleep continuity, and decreased SWS, but no abnormalities of REM sleep. REM sleep latency was inversely proportional to the severity of startle response. SWS was found to be inversely correlated with the severity of psychogenic amnesia. Conclusions: PTSD patients have disturbance of sleep continuity, and SWS deficit, without the impact of comorbid depression on sleep. The relationship between SWS and the inability to recall an important aspect of trauma may indicate the role of sleep in the consolidation of traumatic memories. The relationship between the severity of the startle response and REM latency may suggest that REM sleep physiology shares common substrates with the symptoms of PTSD.     

Visual and spectral analysis of sleep EEG in acute hemispheric stroke

BACKGROUND: Reports on the effects of focal hemispheric damage on sleep EEG are rare and contradictory. PATIENTS AND METHODS: Twenty patients (mean age +/- SD 53 +/- 14 years) with a first acute hemispheric stroke and no sleep apnea were studied. Stroke severity [National Institute of Health Stroke Scale (NIHSS)], volume (diffusion-weighted brain MRI), and short-term outcome (Rankin score) were assessed. Within the first 8 days after stroke onset, 1-3 sleep EEG recordings per patient were performed. Sleep scoring and spectral analysis were based on the central derivation of the healthy hemisphere. Data were compared with those of 10 age-matched and gender-matched hospitalized controls with no brain damage and no sleep apnea. RESULTS: Stroke patients had higher amounts of wakefulness after sleep onset (112 +/- 53 min vs. 60 +/- 38 min, p < 0.05) and a lower sleep efficiency (76 +/- 10% vs. 86 +/- 8%, p < 0.05) than controls. Time spent in slow-wave sleep (SWS) and rapid eye movement (REM) sleep and total sleep time were lower in stroke patients, but differences were not significant. A positive correlation was found between the amount of SWS and stroke volume (r = 0.79). The slow-wave activity (SWA) ratio NREM sleep/wakefulness was lower in patients than in controls (p < 0.05), and correlated with NIHSS (r = -0.47). CONCLUSION: Acute hemispheric stroke is accompanied by alterations of sleep EEG over the healthy hemisphere that correlate with stroke volume and outcome. The increased SWA during wakefulness and SWS over the healthy hemisphere contralaterally to large strokes may reflect neuronal hypometabolism induced transhemispherically (diaschisis).     

Cerebral and local cerebral metabolism in the cat during slow wave and REM sleep

[14C]2-deoxyglucose autoradiography was used to show cerebral and regional cerebral metabolism during slow-wave sleep (SWS) and rapid-eye-movement sleep (REM) in the cat. Lower levels of mean cerebral metabolism, reflecting cerebral energy conservation, were associated with SWS. A clear link between REM and mean cerebral metabolism was not observed. At the regional level, SWS was associated with markedly low metabolism in thalamic sensory relays and in cortex. REM was associated with relatively low metabolism in the cerebellum, but with relatively high metabolism in the hippocampus, and in some 'motor' regions including the trigeminal and red nuclei. Thus, SWS was linked to cerebral energy conservation and to particularly low levels of functional activity in cortical and sub-cortical sensory regions. REM was unlike SWS in that: REM did not appear to be strongly linked to cerebral energy conservation; REM was linked to metabolism in fewer brain regions than was SWS; and most REM-linked regions exhibited relatively high levels of metabolism. In addition, while SWS was most clearly associated with functional activity in sensory regions, REM was linked to functional activity in a small number of limbic and motor regions. In sum, SWS and REM are associated with distinctive cerebral metabolic and functional states.     

CSF somatostatin in anorexia nervosa and bulimia: relationship to the hypothalamic pituitary-adrenal cortical axis

The eating disorders, anorexia nervosa and normal weight bulimia, are associated with disturbances of hypothalamic-pituitary-adrenal cortical (HPA) and growth hormone function. Because somatostatin (SRIF) is one of the neuropeptides known to modulate feeding behavior and neuroendocrine systems, we measured cerebrospinal fluid (CSF) concentrations of this peptide in patients with eating disorders. CSF SRIF concentrations in patients with anorexia nervosa, both at low weight and after weight recovery, were similar to those in controls. When normal weight bulimic women stopped binging, they had a modest but significant increase in CSF SRIF. CSF SRIF was not related to plasma growth hormone concentrations but did show relationships to HPA axis hormones. Healthy volunteer women had a significant positive relationship between CSF SRIF and CSF corticotropin releasing hormone (CRH). In underweight anorectics, CSF SRIF was negatively related to both 24-hr urinary free cortisol and plasma cortisol concentrations after dexamethasone, but it was not significantly related to CSF CRH. These relationships more closely resembled those of healthy controls after weight correction. In bulimics, CSF SRIF was positively related to CSF CRH and negatively related to plasma cortisol. Our findings support a previously described relationship between CSF SRIF and HPA axis activity. The differences in SRIF-HPA relationships in anorectics and bulimics may constitute or reflect pathophysiological distinctions between these disorders.     

Correlation between eating disorders and sleep disturbances]

Anorectics and bulimics often complain sleep onset insomnia and disrupted sleep. During awakenings bulimics can have binges. Conversely, eating disorders can be a clinical expression of a concomitantly occurring sleep disorder. Two clinical entities have been recently described: the Night Eating Syndrome (NES) and the Sleep Related Eating Disorders. The main goal of this literature review was to better characterize the relationships between eating disorders and sleep disturbances. No specific EEG sleep pattern emerges in anorectic and bulimic patients. However, all studies include several methodological limitations: a few number of patients, heterogeneous patient groups, various diagnostic criteria. The results of studies evaluating the impact of depression on sleep EEG in eating disorder patients are also subject to controversy. The only study examining the relationship between sleep EEG and morphological alterations in anorectics and normal weight bulimics shows that patients with enlarged cerebrospinal fluid spaces spent more time in slow wave sleep and that the duration of rapid eye movement (REM) sleep was reduced. The ventricular brain ratio was negatively correlated with REM sleep. The Night Eating Syndrome consists in insomnia, binge eating and morning anorexia. Other criteria are proposed to characterize the NES: more than 50% of the daily energy intake is consumed after the last evening meal, awakenings at least once a night, repetition of the provisional criteria for more than 3 months, subjects do not meet criteria for bulimia nervosa or binge eating disorder. Patients have no amnesia nor alteration of alertness, and no other sleep disorder. There is no modification of sleep EEG except sleep maintenance. The prevalence of the NES is 1.5% in the general population. Some neuroendocrine disturbances have been found in the NES. The delimitation with eating disorders is not yet clearly established. If it shares the compulsive features with eating disorders, particularly the "Binge Eating Disorder", and occurs during full awakenings, the night eating syndrome may be recognized as a specific eating disorder. The sleep related eating syndrome is also characterized by compulsive binge eating during awakenings. But in this case, night eating is linked with a reduced consciousness and sleep disorders, mainly somnambulism. Patients never experience hunger, abdominal pain, nausea or hypoglycemia. Night-eating takes place invariant across weekdays, weekend and vacations. Patients consumed high caloric foods and fluids but never alcohol and purging does not occur. Diurnal bulimia is frequently associated with the sleep-related eating disorder. In conclusion, the sleep related eating disorder seems rather be a clinical subtype of sleep disorders whereas the NES could be considered as an eating disorder.     

Hypothalamic-pituitary-adrenal-cortical activity in anorexia nervosa and bulimia

We studied hypothalamic-pituitary-adrenal-cortical (HPA) activity in nine underweight women with anorexia nervosa, 12 women of normal body weight with bulimia, and nine control subjects. The measures of HPA activity were the pattern of plasma cortisol secretion over 24 hr and the responses of plasma cortisol to dexamethasone suppression and to low dose ACTH stimulation. The patients with anorexia nervosa had significantly elevated 24 hr concentrations of plasma cortisol compared to the controls and showed significantly less cortisol suppression following dexamethasone. There was no difference between patients with anorexia nervosa and controls in the rise in plasma cortisol following ACTH. On most measures of HPA activity, the normal weight patients with bulimia were indistinguishable from the controls. These results suggest that HPA activity is normal in most patients of normal body weight with bulimia and that the psychological and behavioral disturbances common to both anorexia nervosa and bulimia are, in the absence of significant weight loss, insufficient to produce major alterations in HPA activity.     

Sleep and the hypothalamo-pituitary-adrenocortical system

The intention of this review is to summarize the current knowledge on the bidirectional interaction between sleep EEG and the secretion of corticotropin (ACTH) and cortisol. The administration of various hypothalamic-pituitary- adrenocortical (HPA) hormones and their antagonists exerts specific sleep-EEG changes in several species including humans. It is well documented that corticotropin releasing hormone (CRH) impairs sleep and enhances vigilance. In addition, it may promote REM sleep. Changes in the growth hormone-releasing hormone (GHRH):CRH ratio in favour of CRH appear to contribute to shallow sleep, elevated cortisol levels and blunted GH in depression and ageing. On the other hand, in women GHRH appears to exert CRH-like effects on sleep. Acute cortisol administration increases slow-wave sleep (SWS) and GH, probably due to feedback inhibition of CRH, and inhibits REM sleep. With the mixed glucocorticoid and progesterone receptor antagonist mifepriston sleep is disrupted. Subchronic administration of the glucocorticoid agonist methylprednisolone desinhibited REM sleep. A synergism of elevated CRH and cortisol activity may contribute to REM disinhibition during depression. Also ACTH and vasopressin modulate sleep specifically but their physiological role remains unclear. For example acute icv vasopressin enhances wakefulness in rats, whereas its long-term administration increases SWS in the elderly. In various studies the interaction of sleep EEG and HPA hormones has been investigated at the baseline, after manipulation of sleep-wake behaviour and after environmental changes. Most studies agree that the circadian pattern of cortisol is relatively independent from sleep and environmental influences. Some data suggest a major effect of light on cortisol secretion. Sleeping is widely associated with blunting and awakenings are linked with increases of HPA hormones.     

Estimation of the dimensionality of sleep-EEG data in schizophrenics

Summary Deterministic chaos could be regarded as a healthy flexibility of the human brain necessary for correct neuronal operations. Several investigations have demonstrated that in healthy subjects the dimensionality of REM sleep is much higher than that of slow wave sleep (SWS). We investigated the sleep-EEG of schizophrenic patients with methods from nonlinear system theory in order to estimate the dynamic properties of CNS. We hypothesized that schizophrenics would reveal alterations of their dynamic EEG features indicating impaired information processing.In 11 schizophrenic patients, the EEG's dimensionality during sleep stages II and REM was reduced. We suggest that such lower dimensional chaotic processes might be associated with an overloading of neuronal networks during sleep and therefore the psychopathology of schizophrenics might be due to impaired complexity of their EEG's dynamics.     

18F]fluorodopa uptake in the upper brainstem measured with positron emission tomography correlates with decreased REM sleep duration in early Parkinson's disease

Sleep disturbances are common in patients with Parkinson's disease (PD). Previous studies have shown alterations of polysomnographic sleep parameters in PD, such as overall diminution of slow-wave and REM sleep duration, absence of muscle atonia during REM and increased occurrence of periodic leg movements during sleep. The pathogenesis of sleep dysregulation in PD is unknown. The aim of this study was to determine relations of abnormal polysomnographic sleep parameters and the dopaminergic function of the striatum and the upper brainstem measured with the use of positron emission and magnetic resonance tomography in 10 early-stage PD patients with a history of sleep disturbances. Our data demonstrated a significant inverse correlation of absolute and percentage REM sleep duration with the mesopontine [18F]6-fluorodopa (FDOPA) uptake in PD patients. Therefore, the results point to a REM inhibiting effect of increased monaminergic transmission within the upper brainstem in early-stage PD. This finding emphasises the pathophysiological significance of a disturbed neurotransmitter equilibrium in the rostral brainstem for REM sleep alterations in PD.     

The interaction between sleep and thermoregulation in adults and neonates

The interaction between sleep and thermoregulation leads to different thermoregulatory responses depending on the sleep stage and alterations in sleep when in a cool or warm environment. In the human adult, differences in thermoregulatory efficiency during rapid eye movement (REM) sleep and slow wave sleep (SWS) are less pronounced compared to other mammals: although thermoregulatory processes persist in REM sleep, they are less efficient than during SWS. Cold and warm loads disturb the efficiency and structure of sleep. The duration of REM sleep and (to a lesser extent) of SWS decreases. In contrast, pre-sleep warm loads enhance SWS and improve sleep continuity. This procedure may promote and maintain sleep in depressed patients, whose sleep and body temperature rhythms are modified. In contrast to adults, homeothermic processes in neonates are maintained or even enhanced during active sleep (AS) when compared to quiet sleep (QS). Sleeping in a cool environment increases the duration of AS at the expense of QS. As a result, the thermoregulatory function overcomes the need to conserve energy that would otherwise lead to increased QS. An interaction between sleep, respiration, and thermoregulation may be involved in Sudden Infant Death Syndrome: an alteration in the thermal balance may perhaps induce respiration instability, especially during AS.     

Sleep in depression: the influence of age,gender and diagnostic subtype on baseline sleep and the cholinergic REM induction test with RS 86

Summary One hundred and eight healthy controls and 178 patients with a major depressive disorder according to DSM-III were investigated in the sleep laboratory after a 7-day drug wash-out period. Subsamples of 36 healthy controls and 56 patients additionally took part in the cholinergic rapid eye movement (REM) sleep induction test with RS 86. Data analysis revealed that age exerted powerful influences on sleep in control subjects and depressed patients. Sleep efficiency and amount of slow wave sleep (SWS) decreased with age, whereas the number of awakenings, early morning awakening, and amounts of wake time and stage 1 increased with age. REM latency was negatively correlated with age only in the group of patients with a major depression. Statistical analysis revealed group differences for almost all parameters of sleep continuity with disturbed indices in the depressed group. Differences in SWS were not detected. REM latency and REM density were altered in depression compared to healthy subjects. Sex differences existed for the amounts of stage 1 and SWS. The cholinergic REM induction test resulted in a significantly more pronounced induction of REM sleep in depressed patients compared with healthy controls, provoking sleep onset REM periods as well in those depressed patients showing baseline REM latencies in the normal range. Depressed patients with or without melancholia (according to DSM-III) did not differ from each other, either concerning baseline sleep or with respect to the results of the cholinergic REM induction test. The results stress the importance of age when comparing sleep patterns of healthy controls with those of depressed patients. Furthermore they underline the usefulness of the cholinergic REM induction test for differentiating depressed patients from healthy controls and support the reciprocal interaction model of nonREM-REM regulation and the cholinergic-aminergic imbalance hypothesis of affective disorders.     

Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders

Recent evidence shows that the temporal alignment between the sleep-wake cycle and the circadian pacemaker affects self-assessment of mood in healthy subjects. Despite the differences in affective state between healthy subjects and patients with psychiatric disorders, these results have implications for analyzing diurnal variation of mood in unipolar and bipolar affective disorders and sleep disturbances in other major psychiatric conditions such as chronic schizophrenia. In a good proportion of patients with depression, mood often improves over the course of the day; an extension of waking often has an antidepressant effect. Sleep deprivation has been described as a treatment for depression for more than 30 years, and approximately 50% to 60% of patients with depression respond to this approach, especially those patients who report that their mood improves over the course of the day. The mechanisms by which sleep deprivation exerts its antidepressant effects are still controversial, but a reduction in rapid eye movement sleep (REM sleep), sleep pressure and slow-wave sleep (SWS), or a circadian phase disturbance, have been proposed. Although several studies support each of these hypotheses, none is sufficient to explain all observations reported to date. Unfortunately, the disturbed sleep-wake cycle or behavioural activities of depressed patients often explain several of the abnormalities reported in the diurnal rhythms of these patients. Thus, protocols that specifically manipulate the sleep-wake cycle to unmask the expression of the endogenous circadian pacemaker are greatly needed. In chronic schizophrenia, significant disturbances in sleep continuity, REM sleep, and SWS have been consistently reported. These disturbances are different from those observed in depression, especially with regard to REM sleep. Circadian phase abnormalities in schizophrenic patients have also been reported. Future research is expected to clarify the nature of these abnormalities.     

Structural brain abnormalities in patients with bulimia nervosa

Computed tomographic (CT) brain scans were performed in 50 inpatients with bulimia nervosa, 50 anorectic inpatients, and 50 age-matched control subjects. A number of patients with bulimia nervosa had enlarged ventricles and/or sulcal widening, but the degree and frequency of ventricular dilatation and sulcal widening were not so pronounced as in patients with anorexia nervosa. As the bulimic patients were of normal body weight, the CT abnormalities cannot be attributed to emaciation, which has often been suggested as the cause of abnormalities found in anorectic patients. Since many bulimic patients repeatedly attempt to lose weight by going on restrictive diets, the morphological brain alterations may reflect the endocrine and metabolic reactions to starvation--regardless of whether starvation has led to emaciation, as in the case of anorexia nervosa, or only counterbalanced the binges of high-caloric food. This assumption is supported by the finding that in both bulimic and anorectic patients ventricular size is inversely correlated with the plasma levels of triiodothyronine, a low concentration of which is an indicator for starvation.