[Radioinduced brain cyst: case report]. / Kyste radioinduit du cerveau: case report.

We present a case of intraparenchymal radioinduced cyst of the brain observed in our department. It is a rare and relatively benign pathology which is usually treated conservatively or by surgery. We emphasize long-term imaging follow up in patients treated by radiosurgery, which can lead to the demonstration of multiple adverse events such as tumefactive cyst formation.

NOAC and intracerebral bleeding--presentation of four cases and review of the literature.

AF might be a life threatening disease. Patients have been under oral antithrombotic treatment in order to avoid thrombotic events. Although this treatment proved to be effective in the last decades there was always the inconvenience of a regular blood control. In the last months NOACs have been flooding the market promising to be as effective as their older concurrents in certain circumstances and highlighting the fact that the control of INR has become obsolete. However, as there is no specific antidote up to date, NOACs might present a life threatening event in case of an intracerebral haemorrhage. The brain surgeons might find themselves in a difficult situation when they have to decide whether to operate on a patient with a compromised haemostasis or not. We present four patients who were treated with NOACs for AF. Three of them were admitted with intracerebral haemorrhage in our neurosurgical unit from January to October 2013. The fourth patient bled one week after stopping his treatment with NOAC. Furthermore we take a closer look to the existing literature and try to portray the issue from a neurosurgical point of view.

Superselective indocyanine green angiography for selective revascularization in the management of peripheral cerebral aneurysms.

This report describes the management of a fusiform peripheral middle cerebral artery aneurysm by endovascular parent artery occlusion under bypass protection. Localization of the recipient cortical artery was accomplished after craniotomy by superselective injection of diluted ICG dye via a microcatheter positioned proximal to the aneurysm. This report demonstrates that superselective ICG angiography can be a beneficial alternative technique to identify the best anastomosis site intraoperatively.

Ruptured carotid artery aneurysms of the ophthalmic (C6) segment: clinical and angiographic long term follow-up of a multidisciplinary management strategy.

BACKGROUND: The management of ruptured C6 aneurysms remains controversial. Detailed long-term outcome data are still lacking. Thus the present study provided a detailed long term follow-up for a multidisciplinary approach combining microsurgical clipping, endovascular embolisation and parent artery occlusion with/without bypass protection. METHODS: In our single centre analysis of 64 consecutive patients, indications for microsurgery were: superior aneurysm projection, giant/large or wide necked aneurysms and aneurysms at branching sites. Indications for embolisation were: narrow necks, neck calcification, close aneurysm relation to the clinoid process or adhesion to the distal dural ring, and aneurysm location in the concavity of the carotid siphon curve. RESULTS: 23 patients (35.9%) underwent microsurgery, 38 patients (59.4%) embolisation and three patients (4.7%) parent artery occlusion under bypass protection. Retreatment was required in 20.9% (surgery 8.7%, endovascular 31.6%). Procedure related transient complications occurred in 10.9% (surgery 13.0%, endovascular 10.5%). Procedure related permanent morbidities occurred in 6.3% (surgery 8.7%, endovascular 5.3%), including visual deficits in 4.7% (surgery 4.4%, endovascular 5.3%). One endovascular patient died. Angiographic follow-up (29.2 (SD 31.9) months) revealed total aneurysm occlusion in 94.4% of the surgical and 82.9% of the endovascular patients. Clinical follow-up (58.7 (SD 47.6) months) showed 73.4% of the population reaching Glasgow Outcome Scale 4-5, these data being equivalent to the International Subarachnoid Aneurysm Trial (ISAT) outcomes. CONCLUSIONS: Based on favourable neuroradiological and ophthalmological outcomes, microsurgery is recommended for superiorly projecting aneurysms, especially aneurysms involving the ophthalmic artery, and for giant/large or wide necked aneurysms. Based on stable aneurysm occlusion and excellent clinical outcomes, embolisation can be recommended for inferiorly/medially projecting small, narrow necked aneurysms.

Influence of bilateral Stn-stimulation on psychiatric symptoms and psychosocial functioning in patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. There is some evidence that subthalamic stimulation not only affects motor function, but also mood, behaviour and cognition. In the present study we investigated the effects of subthalamic stimulation on psychiatric symptoms and psychosocial functioning in a consecutive series of patients with Parkinson's disease. 33 patients were assessed three times prior to surgery and at three, nine weeks as well as three, six and twelve months after surgery. We found significant improvements in depression, anxiety, psychological symptoms and distress after surgery. In most cases the amelioration followed surgery and was stable in the course of time. Individual analysis indicated deterioration in three patients despite motor improvement. The results suggest that stimulation of the subthalamic nucleus has a positive influence on psychiatric symptoms, psychosocial functioning and distress. We observed a decline in a minority of patients.

Kinematic evaluation in Parkinson's disease using a hand-held position transducer and computerized signal analysis.

BACKGROUND: The objective of this work was to develop a device for quantification of akinesia in Parkinson's disease, for the use in home monitoring of PD patients, as a part of home telecare programs. For this purpose a simple movement task is to be preferred, and the measurement devices must be small, lightweight, and easy to use, so patients may perform the measurements unattended. Another intended application was optimisation of the electrode position during implantations of neuromodulation systems for treatment of Parkinson. METHOD: A hand held transducer was used to measure the position of the thumb while the patient repeatedly flexed and extended the thumb. The position data was sampled and stored on a personal computer with a plug in converter card and software. Measurements were performed on 15 PD patients and 6 age-matched controls. Signal analysis procedures were developed in order to automatically derive numerical parameters that quantify the movement performance. In order to select the most relevant parameters, they were correlated to Unified Parkinson Disease Rating Scale (UPDRS) motor scores (Spearman's rank, single sided, p < 0.05). FINDINGS: In reviews of the raw position signals the amplitude and frequency was found to be lower in patients than in controls. In patients the movement was frequently interrupted by short periods of hesitation. The calculated parameters of covered distance (correlation coefficient r = -0.63), hesitation (r = 0.64) and frequency (r = -0.6) were found to be most relevant, as they correlated best to the UPDRS hand pronation/supination score. DISCUSSION: The equipment proved to be fast to setup and easy to use. The signal analysis methods provided meaningful numerical parameters for quantification of akinesia, represented in hand pronation/supination. These results suggest that the described methods may be useful for telemedicine and intraoperative use.

Emergency Extracranial-to-Intracranial Bypass after Thromboembolic Occlusion of the Middle Cerebral Artery Following GDC Embolization of a Ruptured ACoA Aneurysm.

SUMMARY: We report a case of thromboembolic occlusion of the middle cerebral artery after endovascular treatment of a ruptured anterior communicating artery aneurysm. When fibrinolytic therapy failed to recanalize the occluded vessel, an emergency extracranial-to-intracranial bypass was performed. This intervention rescued our patient from cerebral infarction. This case demonstrates the importance of the offering this procedure at neurointerventional centers.

Influence of aortic blood flow velocity on changes of middle cerebral artery blood flow velocity during isoflurane and sevoflurane anaesthesia.

BACKGROUND AND OBJECTIVE: We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia. METHODS: Forty patients (age: isoflurane 24-62 years; sevoflurane 24-61 years; ASA I-III) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50-60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspiratory and end-expiratory concentrations of 0.75, 1.00, and 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvI). CSvI of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity. RESULTS: Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvI decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 +/- 25%/81 +/- 23%, 1.0 MAC: 79 +/- 19%/74 +/- 16%, 1.25 MAC: 71 +/- 16%/79 +/- 21%; [mean +/- SD] P = 0.0001). CONCLUSIONS: The reduction of the CSvI vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.

Changes in handwriting resulting from bilateral high-frequency stimulation of the subthalamic nucleus in Parkinson's disease.

High-frequency stimulation of the subthalamic nucleus (STN) is a promising therapeutic approach in patients with severely disabling Parkinson's disease (PD). Whereas STN stimulation improves the cardinal signs of PD, little is known about the effects of STN stimulation on fine manual skills like handwriting. Therefore, the present study investigated the changes in handwriting during bilateral STN stimulation in 12 patients with advanced PD. Dopaminergic medication was discontinued at least 12 hours before the study. The patients were asked to write a standardized sentence repetitively. Five samples of the patient's script were recorded during effective bilateral STN stimulation and 1 hour after both stimulators had been switched off. The movements of the tip of the pencil were recorded using a digitizing tablet. Handwriting movements were segmented into subsequent up- and down-strokes, and a stroke-based kinematic analysis of handwriting was performed. During high-frequency STN stimulation, handwriting movements became faster and smoother indicating a partial restoration of an "open-loop" automatic performance. In addition, STN stimulation gave rise to a significant increase in the mean vertical stroke length demonstrating a stimulation-related reduction in micrographia. The present data underscores the importance of the STN in "open-loop" performance of highly skilled sequential hand movements.

Increased diurnal plasma concentrations of dehydroepiandrosterone in depressed patients.

Activation of the hypothalamus-pituitary-adrenocortical system is a biological core symptom of depression. Although the regulation of cortisol secretion is well studied in this condition, there is no information about the diurnal activity of dehydroepiandrosterone (DHEA) secretion. Therefore, we studied 24-h DHEA plasma concentrations (every 30 min) in severely depressed patients (n = 26) and healthy controls (n = 33). We found depression to significantly increase diurnal minimal and mean DHEA plasma concentrations, whereas there was no effect on the diurnal maximal plasma concentration and the diurnal amplitude of DHEA. In particular, we found a parallel increase in mean DHEA (5.8 +/- 3.6 vs. 3.4 +/- 1.9 nmol/L; P < 0.003), cortisol (286 +/- 65 vs. 184 +/- 29 nmol/L; P < 0.0001) and ACTH (7.14 +/- 2.06 vs. 5.72 +/- 1.36 pmol/L; P < 0.002) plasma concentrations. The novel finding of parallel increases in diurnal DHEA and cortisol plasma concentrations in depressed patients has important implications for the regulation of the hypothalamus-pituitary-adrenocortical system in conditions of chronic stress and for the rationale of DHEA treatment in depressed patients.

Endurance training and its effect upon the activity of the GH-IGFs system in the elderly.

There is an age-associated decline in the activity of the GH-IGFs system. However, so far, it has not been studied, whether this decline in somatotrophic activity might be preventable by intensive exercising. We studied 11 elderly male (50-78 years) marathon runners and 10 age-matched male (52-73 years) sedentary controls to evaluate plasma concentrations of GH, total and free IGF-I and IGF-II and of IGF-binding protein-1 (IGFBP-1), IGFBP-2, IGFBP-3 and insulin. When comparing the two groups (runners vs controls) no differences were found in GH (1.0 +/- 1.2 vs 1.3 +/- 1.3 microg/l [mean +/- SD]), IGF-1 (115 +/- 23 vs 113 +/- 21 microg/l), IGF-II (961 +/- 192 vs 864 +/- 125 microg/l), free IGF-1 (227 +/- 80 vs 318 +/- 146 ng/l), free IGF-II (563 +/- 249 vs 492 +/- 108 ng/l), IGFBP-3 (2403 +/- 515 vs 2307 +/- 326 microg/l) or insulin (26 +/- 13 vs 27 +/- 18 mU/l). However, IGFBP-1 (4.44 +/- 2.61 vs 2.28 +/- 0.93 microg/l) and IGFBP-2 (493 +/- 143 vs 340 +/- 186 microg/l) were found to be significantly increased in marathon runners. In conclusion, our findings do not support the hypothesis that the age-associated decline in GH, IGF-1 and IGFBP-3 may be preventable by intensive endurance training. However, marathon running affects the regulation of the GH-IGFs system activity at the level of IGFBP-1 and -BP-2.

The combined dexamethasone/corticotropin-releasing hormone stimulation test is more closely associated with features of diurnal activity of the hypothalamo-pituitary-adrenocortical system than the dexamethasone suppression test.

BACKGROUND: The dexamethasone suppression test (DST) is a widely used endocrine test in psychiatry, but was reported to not allow reliable inferences with regard to the basal activity of the hypothalamo-pituitary-adrenocortical (HPA) system. We compared the association of the standard DST and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) challenge with parameters of diurnal cortisol profiles. METHODS: We performed a DEX/CRH challenge and 24-hour cortisol profiles in 25 depressed patients (mean age: 47.4 +/- 16.0 years) and 33 age-matched healthy controls (mean age: 51.4 +/- 19.3 years). RESULTS: A path analysis showed cortisol area under the curve (AUC) after CRH (= DEX/CRH status) to be dependent upon minimal 24-hour cortisol and evening frequency of pulsatile cortisol release. In contrast, postdexamethasone cortisol (= DST status) was related to 24-hour mean cortisol. Simple linear regressions supported an association of cortisol AUC with several parameters of the diurnal cortisol profiles, which was not true for the standard DST. CONCLUSIONS: We conclude that the combined DEX/CRH challenge test is more closely associated with the activity of the HPA system than the standard DST in healthy and depressed subjects.

Insulin-like growth factor-I (IGF-I) plasma concentrations are increased in depressed patients.

There is some evidence that the somatotrophic system in depression, as assessed by basal growth hormone (GH) concentrations and by GH releasing hormone (GHRH) challenge, might be dysfunctional. However, the rather limited data have been inconclusive so far and plasma concentrations of both insulin-like growth factor-1 (IGF-I) and binding proteins (IGFBP 1 to IGFBP-6) have not been measured simultaneously in depressed patients. We studied 24 severely depressed patients and 33 healthy controls and estimated 24-hour mean plasma cortisol, six-hour evening mean plasma growth hormone (GH), morning plasma IGF-I, IGFBP 2 and 3 and GH-binding protein (GH-BP). Twenty-four-hour mean cortisol (306 +/- 69 vs. 196 +/- 30 nmol/l, p < .001) and IGF-I (157 +/- 40 vs. 120 +/- 33 micrograms/l, p < .01) plasma concentrations were found to be significantly increased in depressed patients, while there was no difference in GH or binding proteins between both groups. MANOVA analysis revealed age and diagnosis to have main effects upon plasma IGF-I. Especially young age and a diagnosis of major depression are associated with higher plasma IGF-I. After treatment only patients in remission had attenuated IGF-I plasma concentrations. We conclude that plasma IGF-I is increased in acutely depressed patients similar to other states of hypercortisolemia.

Pulse-dosing and conventional application of doxepin: effects on psychopathology and hypothalamus-pituitary-adrenal (HPA) system.

It has been shown that a single pulse-dosing (PD) dose of clomipramine improves depressive symptoms. However, so far PD and conventional (CONV) application of antidepressants have never been directly compared for an extended period. We performed a double-blind study of PD and CONV application of doxepin (DOX) in depressed patients. After a 1-week placebo treatment, nine parents in the PD group received 250 mg of DOX every 6 days and placebo on the other days until day 39. Ten patients in the CONV group received increasing dosages of DOX until day 7 and 250 mg DOX on the other days for 39 days. Three dexamethasone (DEX)-suppression/corticotropin-releasing hormone (CRH)-stimulation tests were completed: (1)during the initial placebo period; (2)on day 9; and (3)on day 21. In the PD group, scores on the Hamilton Rating Scale for Depression (HAM-D) differed from baseline only after day 36 (17.1 +/- 7.0 vs. 22.7 +/- 2.8, p < 0.03). In the CONV group, however, HAM-D scores improved significantly after 2 days (22.8 +/- 7.2 vs. 26.5 +/- 5.7, p < 0.02) and continued to improve until day 39 (7.3 +/- 5.8). From day 25 to 39, there were significant differences between the HAM-D scores of the two groups. In the PD group, the decline of cortisol after DEX pretreatment was nonsignificant (NS) at both follow-up test occasions (35.9 +/- 40.7 vs. 24.0 +/- 20.7 vs. 23.6 +/- 26.6 micrograms/mL). In the CONV group, a significant decrease was observed at the second test (61.8 +/- 61.9 vs. 10.7 +/- 4.2 vs. 19.8 +/- 19 micrograms/mL, p < 0.05, respectively, NS). The area-under-the-curve cortisol response after CRH was attenuated in the PD group (5,667 +/- 2,910 vs. 1,883 +/- 2,178 vs. 2,239 +/- 2,583 [arbitrary unit], p < 0.01, respectively, p < 0.01) and in the CONV group (5,710 +/- 4,734 vs. 1,267 +/- 2,053 vs. 445 +/- 1,016 [arbitrary unit], NS, respectively, p < 0.02. We conclude that CONV application of DOX is clinically superior compared with PD and that both modes of application have attenuating effects on hypothalamus-pituitary-adrenal system activity.

Doxepin and its metabolites in plasma and cerebrospinal fluid in depressed patients.

Little information exists on the concentrations of antidepressants and their metabolites in CSF. We measured plasma and CSF levels of trans-doxepin (trans-DOX) and DOX metabolites in 12 depressed patients treated with DOX (250 mg/day) for 6 days. Spinal taps and blood samples were taken on day 7, 10 h after drug administration. Trans-DOX, cis-desmethyldoxepin (cis-DM-DOX), trans-desmethyldoxepin (trans-DM-DOX) and di-desmethyldoxepin (DDM-DOX) were analyzed in CSF and plasma samples by HPLC with column-switching. Although DOX was given as a mixture of 85% trans-DOX and 15% of the pharmacologically more active cis-DOX, we found similar amounts of cis-DM-DOX and trans-DM-DOX in plasma (59.8 +/- 45.1 versus 72.0 +/- 60.0 ng/ml; NS), suggesting that isomerization of DOX had taken place. Trans-DOX and DOX metabolites could be detected in CSF of most patients. Relatively low CSF concentrations of the active metabolite cis-DM-DOX were measured. Clinical efficacy, as assessed by HAMD scores, was not significantly related to plasma or CSF concentrations of trans-DOX or its metabolites. Trans-DOX and DOX metabolites were distributed differently between plasma and CSF. It is concluded that isomerization of DOX is not only relevant for neuronal uptake inhibition, but also for the transport of the metabolites.

Twenty-four hour cortisol release profiles in patients with Alzheimer's and Parkinson's disease compared to normal controls: ultradian secretory pulsatility and diurnal variation.

Endocrine abnormalities of the hypothalamic-pituitary-adrenal (HPA) system in patients with Alzheimer's disease (AD) and Parkinson's disease (PD) have been described repeatedly. However, no data are available on the diurnal cortisol secretory pattern in these major neurodegenerative disorders. Therefore, we studied 24-h pulsatile cortisol secretion in 12 patients with AD and 12 patients with PD compared to 10 normal community- and age-matched volunteers (NV). Twenty-four hour blood sampling was performed from 1800 h to 1800 h at 15-min intervals. Cortisol half-life, number of cortisol secretory bursts/24-h, interpulse interval, mass of cortisol secreted per burst, amplitude of cortisol secretory bursts, pulsatile cortisol production rate, 24-h mean, and integral cortisol concentrations were calculated by applying deconvolution analysis. Furthermore, the relative diurnal variation and the quiescent period were determined. Patients with AD and PD were found to have significantly higher total plasma cortisol concentrations (24-h pulsatile cortisol production rate: AD + 56%; PD + 52%/24-h integrated cortisol: AD + 37%; PD + 29%) compared to NV. This sustained hypercortisolism is due to a higher mass of cortisol secreted per burst (AD + 62%; PD + 79%), but not to increased cortisol half-life or secretory pulse frequency or amplitude. Despite these similarities between AD and PD patients, relative diurnal variation of cortisol secretion was significantly decreased in patients with PD (-22%), whereas the pattern of secretory curves was not different between NV and AD patients. This observation was indirectly supported by a reduction of the quiescent period in patients with PD (-74 min) compared to the NV and AD group. Based on these results and recently published animal data, we hypothesize that decreased expression of hippocampal mineralocorticoid receptors (MR) may account for the flattened diurnal cortisol secretory curve observed in PD patients, whereas the intact diurnal profile in AD patients may be due to a relative increase in MR compensating for the hippocampal neuronal loss commonly occurring in this disorder.

Diurnal activity and pulsatility of the hypothalamus-pituitary-adrenal system in male depressed patients and healthy controls.

There is only sparse and ambiguous information about circadian and pulsatile secretion features of the hypothalamus-pituitary-adrenocortical system in depression. We studied 15 severely depressed (Hamilton Depression Scale 30.4 +/- 6.7) male patients (age 22-72 yr; mean, 47.7 +/- 14.8) and 22 age-matched male controls (age 23-85 yr; mean, 53.1 +/- 18.2). Twenty-four-hour blood sampling from 0800-0800 h with 30-min sampling intervals was performed; from 1800-2400 h, blood was drawn every 10 min. Multivariate analysis of covariance, with the covariate being age, revealed mean 24-h cortisol (315.9 +/- 58.5 vs. 188.2 +/- 27.3 nmol/L) and mean ACTH (7.82 +/- 1.94 vs. 5.79 +/- 1.28 pmol/L) to be significantly increased in depressed patients. The frequency of cortisol (2.6 +/- 0.7 vs. 1.3 +/- 1.0 pulses/6 h) and ACTH (2.6 +/- 1.6 vs. 1.6 +/- 1.4 pulses/6 h) pulses during the evening were higher in patients compared to controls. The flattened circadian cortisol variation and reduced time of quiescence of cortisol secretory activity (140 +/- 116 vs. 305 +/- 184 min) in patients suggest disturbances of circadian functions. We conclude that increased hypothalamus-pituitary-adrenocortical activity in depression is related to a greater frequency of episodic hormone release, and we hypothesize that the observed circadian changes might be partly due to altered mineralocorticoid and glucocorticoid receptor capacity and function.

With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its diurnal amplitude flattens.

There is compelling evidence for feedback disturbances in the hypothalamus-pituitary-adrenal system associated with human aging as assessed by challenge tests. However, reports about age-related changes in human basal activity are ambiguous and to date little is known about changes in the pulsatile features of the HPA system. To investigate these changes we studied twenty-two healthy male and eleven healthy female subjects ranging from 23 to 85 and 24 to 81 years respectively. 24-hour blood sampling with 30 minute sampling intervals was performed. From 18.00 to 24.00 hours blood was sampled every 10 minutes for analysis of pulsatile features of HPA activity. Statistical analysis revealed that age in particular had major effects upon basal HPA-system activity: there was a significant age-associated increase in minimal (p < 0.0001) and mean (p < 0.02) cortisol plasma concentrations, but no alteration in pulsatile features. We found no age-cortisol correlation during daytime, but were able to demonstrate a strong impact of age upon cortisol plasma levels from 20.00 to 1.30 hours. The diurnal amplitude of cortisol (p < 0.005) and ACTH (p < 0.006), relative to the 24-hour mean of the hormones, showed an age-associated decline. Additionally, the evening cortisol quiescent period (p < 0.01) was shortened in the elderly, suggesting increasingly impaired circadian function in aging. Our results suggest an increased basal activity and a flattened diurnal amplitude of the HPA system in the elderly.

Corticosteroid-binding globulin is not decreased in depressed patients.

We studied corticosteroid-binding globulin (CBG) in 25 drug-free depressed patients and 33 healthy controls over a wide age-range. CBG was measured at 0800, 1400, 2000 and 2400 h in all subjects. Analysis of variance (ANOVA) with repeated measurement design revealed a significant effect of gender and time, but not of diagnosis (depressed patients vs healthy controls) or age group (< 50/> 50 years). In females, regardless of diagnosis, CBG plasma concentrations were significantly increased, when compared with their male counterparts. Although as a group depressed patients had significantly higher plasma cortisol concentrations (108.0 +/- 23.1 vs 70.7 +/- 10.9 micrograms/l), CBG levels did not differ between the two groups. Thus we did not find hypercortisolemia in depression to be paralleled by a decrease in CBG. However, the exaggerated activity of the hypothalamus-pituitary-adrenocortical system in healthy and depressed females is associated with an increase in plasma CBG.