Brain Abnormalities In Patients Research Articles

Increased duration of illness is associated with reduced volume in right medial temporal/anterior cingulate grey matter in patients with chronic schizophrenia

It is unclear whether the neuroanatomical abnormalities associated with schizophrenia change over the course of the disorder. We addressed this issue by examining whether the magnitude of structural brain abnormalities in patients with chronic schizophrenia was related to their duration of illness. Thirty-nine subjects with schizophrenia (34 male, 5 female, range of illness duration 2–31 years) were scanned using magnetic resonance imaging. Images were segmented into grey and white matter, cerebrospinal fluid and dura/blood vessels using the Structural Magnetic Resonance Toolkit (SMaRT). Voxel-based analysis identified brain areas whose volume varied significantly with time since the first onset of psychosis. Right medial temporal, medial cerebellar and bilateral anterior cingulate grey matter volume, and white matter volume in the right posterior limb of the internal capsule, were all negatively correlated with illness duration ( p<0.002). Conversely, illness duration was positively correlated with the volume of the right globus pallidus ( p<0.002). These correlations were not a function of chronological age or age at illness onset. The inverse correlation between right frontal, temporal and cerebellar volumes and the time since the onset of schizophrenia could reflect progressive tissue loss following the first episode of the disorder.

Focal features in patients with idiopathic generalized epilepsy

Purpose: The stringent dichotomy between focal and generalized epilepsies has become a contentious issue, since neuropathological studies as well as structural and functional imaging data hypothesized the existence of focal brain abnormalities in patients with well-documented idiopathic generalized epilepsy. The aim of our study was to investigate whether clinical and EEG features generally considered typical for a focal seizure disorder also occur in patients with generalized epilepsies to further support the hypothesis of a more continuous transition between focal and generalized epilepsies in contrast to the present concept of a stringent pathophysiologic dichotomy. Methods: We retrospectively studied 20 consecutive patients with idiopathic generalized epilepsy who underwent video EEG monitoring either because of uncertainty of their epilepsy syndrome or because of a difficult to treat epilepsy. We determined the incidence of (a) focal interictal epileptiform discharges (IEDs), (b) intermittent temporal slow waves, and (c) clinical signs that are widely accepted as typical for a focal seizure onset, i.e. version, tonic/dystonic unilateral posturing, postictal hemiparesis, postictal nose wiping and figure of 4. Results: Focal IEDs occurred in seven patients (35.0%), intermittent temporal slow waves in six (30%), and clinical signs pointing towards a focal seizure onset were found in seven patients (35%). Conclusion: Our study of EEG and clinical data supports the more sophisticated previous investigations in which structural and functional imaging as well as histopathological data suggested the presence of focal brain abnormalities in patients with ‘generalized’ epilepsies. Furthermore we emphasize the cautious use of isolated focal EEG abnormalities and certain clinical signs to prevent a premature diagnosis of focal epilepsy in patients who may indeed suffer from a generalized seizure disorder.

Evidence of brain abnormality in patients with psychogenic nonepileptic seizures

Markers of brain abnormalities in patients with psychogenic nonepileptic seizures (PNES) were studied to explore whether physical brain disorder is associated with an increased risk of PNES. Evidence of epileptiform EEG changes, MRI abnormalities, and neuropsychological (NPS) deficits was obtained from the records of 329 consecutive patients in whom the diagnosis of PNES was established at our center between 1991 and 2001. Two hundred six patients had PNES alone, and 123 PNES and epilepsy (PNES + E). In the PNES-only group, at least one marker of brain disorder was detected in 22.3% of patients (epileptiform potentials in 8.7%, MRI changes in 9.7%, NPS deficits in 9.7%). The actual prevalence of abnormalities is likely to be higher because 54.9% of the patients with only psychogenic seizures did not undergo MRI or neuropsychological testing. Evidence of brain abnormality was found more frequently in the PNES + E group (epileptiform potentials in 70.7%, MRI changes in 60.2%, NPS deficits in 52.8%). Although markers of brain abnormality were detected much less commonly in the PNES than in the PNES + E group, they were still found in a substantial proportion of patients with PNES alone. This suggests that physical brain disease plays a role in the development of PNES. Markers of physical abnormality were not more common in the right hemisphere.

Structural brain abnormalities in patients with schizophrenia and 22q11 deletion syndrome

Background: 22q11 Deletion Syndrome is a genetic syndrome associated with an increased risk for developing schizophrenia. Brain abnormalities have been reported in 22q11 Deletion Syndrome, but little is known about whether differences in brain structure underlie the psychotic disorders associated with this syndrome. In the current study, we used magnetic resonance imaging to characterize the structural brain abnormalities found in adults who have both 22q11 Deletion Syndrome and schizophrenia. Methods: Magnetic resonance imaging brain scans of 14 adults (7 male, 7 female) with 22q11 Deletion Syndrome and schizophrenia and 14 age- and gender-matched healthy volunteers were analyzed to derive measures of gray matter, white matter, and cerebrospinal fluid. Differences between the two groups were tested using student t tests. Results: 22q11 Deletion Syndrome and schizophrenia subjects had significantly smaller total gray matter volume ( t = 2.88, p < .01) and larger lateral ventricles ( t = 4.08, p < .001) than healthy controls. Gray matter deficits were most prominent in the frontal and temporal lobes. Total white matter volumes did not differ between the two groups. Conclusions: Findings from this 22q11 Deletion Syndrome and schizophrenia study are similar to those reported in other patients with schizophrenia, but only partially consistent with those reported in nonpsychotic children with 22q11 Deletion Syndrome. 22q11 Deletion Syndrome may provide a valuable genetic neurodevelopmental model for investigating the relationship between abnormalities in brain development and the expression of schizophrenia.

Structural brain abnormalities in patients with schizophrenia, epilepsy, and epilepsy with chronic interictal psychosis

Chronic interictal psychotic syndromes, often resembling schizophrenia, develop in some patients with epilepsy. Although widespread brain abnormalities are recognized as characteristic of schizophrenia, prevailing but controversial hypotheses on the co-occurrence of epilepsy and psychosis implicate left temporal lobe pathology. In this study, quantitative MRI methods were used to address the regional specificity of structural brain abnormalities in patients with epilepsy plus chronic interictal psychosis (E+PSY, n=9) relative to three comparison groups: unilateral temporal lobe epilepsy without chronic psychosis (TLE, n=18), schizophrenia (SCZ, n=46), and healthy control subjects (HC, n=57). Brain measures, derived from a coronal spin-echo MRI sequence, were adjusted for age and cerebral volume. Relative to HC, all patient groups had ventricular enlargement and smaller temporal lobe, frontoparietal, and superior temporal gyrus gray matter volumes, with the extent of these abnormalities greatest in E+PSY. Only TLE had temporal lobe white matter deficits, as well as smaller hippocampi, which were ipsilateral to the seizure focus. Structural brain abnormalities in E+PSY are not restricted to the left temporal lobe. The confluence of cortical gray matter deficits in E+PSY and SCZ suggests salience to chronic psychosis.

79. Subcortical brain abnormalities in patients with schizophrenia: an MRI morphometric study

79. Subcortical brain abnormalities in patients with schizophrenia: an MRI morphometric study

The contribution of fast-FLAIR MRI for lesion detection in the brain of patients with systemic autoimmune diseases.

Fast fluid-attenuated inversion recovery (fFLAIR) is more sensitive that conventional or fast spin echo T2-weighted magnetic resonance imaging (MRI) for detecting lesions in the brain of patients with ischemic, inflammatory, or demyelinating diseases of the CNS. We investigated whether the use of fFLAIR also increases the sensitivity of brain MRI assessment in patients with systemic autoimmune disorders. Turbo spin echo (TSE) dual-echo and fFLAIR scans of the brain were obtained from patients affected by systemic lupus erythematosus (SLE) with (NSLE, n = 9) and without clinical CNS involvement (n = 15), Behçet disease (n = 5), Wegener granulomatosis (n = 9), and antiphospholipid antibody syndrome (n = 6). Brain hyperintense lesions were counted and classified according to their size and their location by two observers by consensual agreement. The total lesion volume was measured using a semiautomated technique for lesion segmentation on both TSE and fFLAIR scans. The imaging modalities showed brain hyperintense lesions in all 9 SLE patients with CNS involvement, 5 of 15 SLE patients without CNS involvement, 5 of 9 patients with Wegener granulomatosis, 1 of 5 with Behçet disease, and 3 of 6 with antiphospholipid antibody syndrome. A total of 342 lesions were seen on both sequences; 88 were seen only on TSE and 54 only on fFLAIR scans. The average number of brain lesions per scan was higher on TSE than on fFLAIR, since significantly more discrete (P<0.002) and small (P = 0.004) lesions were seen on TSE than on fFLAIR. The median total lesion volume, however, was similar on TSE and fFLAIR. Our study indicates that the use of fFLAIR does not improve the sensitivity of fast dual-echo MRI for detecting brain abnormalities in patients with systemic autoimmune disorders.

Changes in cerebral metabolism are detected prior to perfusion changes in early HIV-CMC: A coregistered (1)H MRS and SPECT study.

Human immunodeficiency virus-cognitive motor complex (HIV-CMC), a common complication of the acquired immunodeficiency syndrome (AIDS), is characterized by progressive cognitive impairment and motor dysfunction. Functional imaging methods, such as single-photon emission computed tomography (SPECT) and proton magnetic resonance spectroscopy ((1)H-MRS), have been applied to assess the severity of brain injury. However, it is unclear which of these two methods is more sensitive in detecting brain abnormalities in patients with early HIV-CMC. Twenty-four HIV-CMC patients were compared with 34 healthy subjects; each had quantitative SPECT ((133)Xenon-calibrated (99m)Tc-HMPAO) and quantitative (1)H-MRS. Both modalities were co-registered in order to assess regional cerebral blood flow (rCBF) and metabolite concentrations within the same voxel of interest in four brain regions (midfrontal and midparietal gray matter, temporoparietal white matter, and basal ganglia). On SPECT, only the temporoparietal white matter showed a trend for decreased rCBF in HIV-CMC patients (-13%, P = 0.06). On MRS, HIV-CMC patients showed significantly reduced creatine concentration in the basal ganglia (-8%, P = 0.008), as well as increased myoinositol concentrations in the basal ganglia (+25%, P = 0.01) and the temporoparietal white matter (+18%, P = 0.08). There was no significant correlation between SPECT and MRS variables in the patients in any region. (1)H MRS showed abnormal neurochemistry in the basal ganglia, whereas rCBF on SPECT was normal in the same region. This finding suggests that metabolite concentrations on (1)H MRS are better surrogate markers than rCBF measurements with SPECT for the evaluation of brain injury in early HIV-CMC. J. Magn. Reson. Imaging 2000;12:859-865.

STRUCTURAL BRAIN IMAGING IN SCHIZOPHRENIA

The subtle pathomorphology of schizophrenia is gradually being unraveled through the application of increasingly sophisticated brain imaging techniques. There is now compelling evidence of subtle brain abnormalities in patients with schizophrenia. It less clear, however, whether these reflect a widespread cortical involvement, or more selective involvement among interconnected neural systems, or more focal pathology. The extent of brain changes, their etiopathologic significance, and putative clinical correlates are reviewed in this article.

Neurological manifestations of antiphospholipid antibody syndrome.

Thrombosis, thrombocytopenia, recurrent fetal loss and a variety of non-thrombotic neurological disorders have all been associated with antiphospholipid antibodies (aPL). Cerebral ischemia associated with aPL is the most common arterial thrombotic manifestation. Depression, cognitive dysfunction, depression and psychosis have all been associated with aPL. The presumed pathophysiologic mechanism underlying these manifestations is thought to be a result of cerebral ischemia in some, but not all cases. Seizures, chorea and transverse myelitis all appear to be associated with aPL. An interaction between aPL and central nervous system cellular elements rather than aPL-associated thrombosis seems to be a more plausible mechanism for these clinical manifestations. Migraine on the other hand, does not appear to be associated with aPL in either lupus or non-lupus populations. Neuroimaging studies show an increased frequency of brain abnormalities in patients with aPL, but none appear to be specific. The best treatment strategy for preventing neurological manifestations of aPL is not fully defined. For thrombotic manifestations, both antiplatelet and anticoagulant therapies have been suggested. In some patients, immunosuppressant therapy has been used. For non-thrombotic manifestations, some combination of immunosuppressant therapy and symptomatic treatment may be warranted.

The study of mitochondrial diseases using magnetic resonance spectroscopy.

Mitochondrial function in muscle in vivo can be quantitatively evaluated using 31P magnetic resonance spectroscopy. In resting muscle the concentrations of ions (e.g., H+, Na+) and two of the major bioenergetic components (inorganic phosphate and creatine) are determined by regulated transcellular transport process. During recovery after exercise the kinetics and control of mitochondrial ATP synthesis can be established. During exercise the relative contributions to ATP of phosphocreatine conversion, anaerobic glycogenolysis and oxidative phosphorylation are dissected and have been shown to change with time. Thus the quantitative consequences of mitochondrial lesions and dysfunctions on these processes can be evaluated [1]. Studies of patients with mitochondrial disorders have been reported by many groups, including our own. For example, we used 31P-MRS to examine the skeletal muscle in 29 patients with mitochondrial myopathy [2]. Gastroncnemius was investigated in 15 patients and 30 normal subjects and finger flexor muscle in 24 patients and 35 normal controls. Results were abnormal in all but two patients. In 86% abnormalities were detected in resting muscle (mostly low phosphocreatine/ATP ratio, high [ADP] and low phosphorylation potential). Exercise and recovery increased the sensitivity of MRS in detecting abnormal metabolism. Nearly all patients (93%) showed abnormalities during recovery from exercise (slow phosphocreatine resynthesis, high [ADP] and its delayed recovery, providing increased drive for oxidative phosphorylation). Recovery of intracellular pH after exercise was significantly faster than normal, consistent with upregulation of proton efflux. Recently, the relationship between the nature of mitochondrial mutations and muscle bioenergetics is beginning to be examined, for example, in non-affected carriers of 11,778 mtDNA mutation [3] and in Leber’s hereditary optic neuropathy patients and carriers with the 14,484, 3460 and 11,778 mtDNA mutations [4]. Muscle mitochondrial abnormalities might also be present in other disorders such as familial hemiplegic migraine [5] and alternating hemiplegia of childhood [6]. MRS has also been used to study brain abnormalities in patients with mitochondrial disorders (e.g., MELAS) [4,5,7].

Prefrontal Cortical and Hippocampal Modulation of Dopamine-Mediated Effects

With the advent of new technologies and more sensitive tools to study brain function there is rapidly growing evidence of structural abnormalities in brains of patients with schizophrenia. Both brain imaging and postmortem neuroanatomical studies show morphometric changes in the cerebral cortices of schizophrenics. In addition to structural abnormalities, functional imaging studies indicate cortical malfunction and suggest functional disorganization of prefrontal-temporal-limbic cortical connectivity, perhaps consistent with evidence of a developmental cortical defect. Recent clinical and basic research data suggest that schizophrenia is related to subtle maldevelopment of prefrontal-temporal-limbic cortices and abnormal dopamine (DA) function. This chapter summarizes some experimental approaches to model some aspects of schizophrenia in the animal. The results indicate that neonatal hippocampal lesions result in behavioral abnormalities that resemble negative symptoms of schizophrenia, such as cognitive impairments and social withdrawal, and that these deficits appear relatively early in development. Taken together, the results of these studies demonstrate that a similar lesion induced later in development or in adulthood results not only in a different temporal profile of changes, but also in qualitative differences in behavioral abnormalities, as compared with the lesion induced early in life. The results of this series of studies indicate that some behavioral abnormalities associated with the neonatal hippocampal lesion and corresponding to positive symptoms of schizophrenia remain relatively quiet until a certain time in development, while others appear soon after the lesion. The profile of changes depends on the age at which damage is induced.

Experimental model: change in the posterior fossa with surgically induced spina bifida aperta in mouse.

On the basis of experimental studies on mouse embryos in which spina bifida development of the brain ventricular system. Mouse embryos were exposed and surgically treated at gestation day 12 to produce spina bifida aperta, and operated embryos were cultured exo utero in the peritoneal cavity of the pregnant dam. Embryos were harvested at gestation day 14. Open neural tube defects resulted in 7 out of 10 embryos surviving surgery. Histological examination revealed that the sizes of ventricles in both the supra- and infratentorial compartments were greatly reduced in embryos with spina bifida aperta compared with control embryos. This result supports the hypothesis that leakage of cerebrospinal fluid through the opening of the caudal spine may be a major cause of brain abnormalities in patients with myelomeningocele.

Brain development, gender and IQ in children. A volumetric imaging study.

Normal brain development during childhood is a complex and dynamic process for which detailed scientific information is lacking. MRI techniques, combined with methods for advanced image analysis, offer the potential to begin to construct a quantitative map of normal paediatric brain development in vivo. In this study we utilize volumetric analysis of high resolution brain images obtained from MRI to describe cerebral development and morphology in 85 normal children and adolescents ranging in age from 5 to 17 years. The results show that total cerebral volume is 10% larger in boys compared with girls. However, both boys and girls show little change in total cerebral volume after the age of 5 years. Increased cortical grey matter is the primary contributor to larger brain volume in boys, thus supporting the hypothesis that gender associated differences in brain size are related to differences in cortical neuronal density. Prominent, age-related changes in grey matter, white matter and CSF volumes are evident during childhood and appear to reflect ongoing maturation and remodelling of the CNS. Both boys and girls show a similar pattern of cerebral asymmetry; a rightward prominence of cortical and subcortical grey matter and a leftward prominence of CSF is observed. IQ is positively correlated with total cerebral volume in children, in particular, with the volume of cortical grey matter in the prefrontal region of the brain. Subcortical grey matter also contributes to the variance in IQ, although to a lesser extent than cortical grey volume. Quantitative knowledge of the developing human brain will play an increasingly greater role in improving sensitivity and specificity in the interpretation of brain abnormalities in patients within the clinical environment, as well as in groups of children with suspected brain dysfunction in the research setting.

Phosphorylation of paired helical filament tau in Alzheimer's disease neurofibrillary lesions: focusing on phosphatases.

The major brain abnormalities in patients with Alzheimer's disease (AD) include extracellular deposits of beta-amyloid, intraneuronal neurofibrillary lesions, and the massive loss of specific subsets of telencephalic neurons. Neurofibrillary lesions contain paired helical filaments (PHFs) that accumulate in the perikarya (e.g., neurofibrillary tangles) and processes (e.g., dystrophic neurites, neuropil threads) of selectively vulnerable telencephalic neurons. The subunits of PHFs are derivatized forms of central nervous system (CNS) tau proteins (CNS tau) known collectively as PHFtau. Until very recently it was thought that the aberrant phosphorylation of PHFtau was the most salient difference between normal human CNS tau and PHFtau. However, this view required modification when it was shown that fetal and biopsy-derived human CNS tau proteins were phosphorylated at nearly all of the same sites found in PHFtau, albeit to a lesser extent. More significantly, these and other studies may be interpreted to suggest that the abnormal phosphorylation of PHFtau may result from the failure of protein phosphatases (i.e., PP2A and 2B) to dephosphorylate PHFtau. In this review, we summarize current understanding of the role of kinases and phosphatases in pathogenesis of PHFtau. We then consider how the formation PHFtau in neurons could disrupt the microtubule network, impair axonal transport, and compromise the viability of neurons, thereby contributing to the onset and progression of AD.

Head trauma: use of SPECT.

Brain damage inflicted by head trauma may not be visible on computed tomography or magnetic resonance imaging. This is true not only for mild head trauma, but also for moderate and severe head trauma. Perfusion imaging with single-photon emission computed tomography has proved in several controlled studies to be more sensitive than either computed tomography or magnetic resonance imaging in detecting brain abnormalities in patients with head trauma.

Familial risk of schizophrenia and ventricular size on CT

evidence that patients with schizophrenia as a group have structural brain abnormalities including enlarged ventricles and cortical sulci as well as deficits in cortical gray matter volumes. Whether patients with other psychiaffic disorders have similar structural brain abnormalities has yet to be fully clarified. This study was undertaken to investigate structural brain abnormalities in patients with chronic schizophrenia using MR! and to determine whether a comparison group of patients with bipolar disorder would also differ on the structural brain measures. Twenty-three patients meeting DSM-IlI-R criteria for Chronic Schizophrenia and 14 patients m~ting DSM-IlI-R criteria for Bipolar Disorder were compared to a conerol ~oup consisting of 17 healthy community volunteers. All subjects were scanned using a i.5 Tesla General Electric Signa MR! scanner. A spin echo sequence was used to obtain early and late echo images with 5 nun. thickness and 2.5 ram. intersection skip. A total of 8 axial sections were chosen for this analysis. Axial images were read from computer storage medium into Macintosh workstations and analyzed using NIH Image (Rasband 1992). Images were processed using routines based on the methods of Lira and Pfefferbaum (J Comput Assist Tomogr. 1989). The lateral ventricles were quantified over all sections where they were present. Gray matter, white matter and cerebrospinal fluid volumes were quantified over the upper seven sections. The schizophrenia group had larger cortical sulci than controls (ig.05, one-tailed) while the bipolar group had larger ventricles than controls (p<.05, one-tailed). The schizophrenia group had significant deficits in cortical gray matter volumes compared to controls (p<.05). The results of this MRI study replicate previous work demonstrating increased cortical sulcal volumes with diminished cortical gray matter volumes in patients with schizophrenia as well as increased ventricular volumes in patients with bipolar disorder. Analysis of regional cortical gray matter volumes in these two patient samples will be presented. 379. FAMILIAL RISK OF SCHIZOPHRENIA AND VENTRICULAR SIZE ON CT

Neuropsychological sequelae of methyl bromide: A case study

Methyl bromide (MB) is a pesticide used primarily as a fumigating agent for homes, storage vehicles and soil. Chronic exposure to MB is known to cause damage to the central nervous system and other organs. Previously published post-mortem studies have also revealed significant brain abnormalities in patients whose deaths were attributed to MB. Only one study to date has examined the neuropsychological effects of this potential neurotoxin. The present case report documents the events surrounding an incident of acute and subacute MB exposure following home fumigation and the neuropsychological after-effects associated with that exposure. Behavioural and cognitive correlates of CNS dysfunction revealed by the neuropsychological testing included impairments in concentration, information processing, learning and memory. Emotional sequelae appeared to be a secondary problem associated with fears over physical well-being and impaired cognition. The cognitive symptomatology did not abate after completion of litigation and award of compensation.

Brain magnetic resonance imaging in coronary artery bypass grafts: a pre- and postoperative assessment.

We undertook a study to determine (1) the frequency and prognostic significance of preexisting MRI brain abnormalities in patients undergoing coronary artery bypass grafts (CABG) and (2) whether MRI can detect surgery-related brain damage in 31 neurologically asymptomatic CABG patients (mean age, 61.0 +/- 6.6 years). MRIs were performed within 7 days before and 8 to 17 days after surgery. When we compared the preoperative images with those of 31 age- and risk factor-matched neurologically asymptomatic controls free of cardiac disease (mean age, 60.3 +/- 6.1 years), higher rates of thromboembolic infarcts (16% versus 0%), lacunes (58.1% versus 32.3%), and brainstem lesions (22.6% versus 3.8%) were noted. Subjective rating demonstrated significantly larger ventricles in patients than in controls (p = 0.002). CABG candidates also had significantly increased ventricular-to-intracranial cavity ratios (VICR) as determined by semiquantitative volumetric measurements (6.9 +/- 2.5% versus 4.9 +/- 1.6%; p = 0.0004). Eleven patients had postsurgical complications, with eight having symptoms consistent with diffuse encephalopathy. The only MRI finding that separated encephalopathic from complication-free patients was ventricular size (VICR 9.0 +/- 2.5% versus 4.9 +/- 1.6%; p = 0.006). This difference remained statistically significant after adjustment for the effects of age (p = 0.04). Postoperative MRI consistently failed to demonstrate surgery-related brain damage responsible for the encephalopathy.

The dexamethasone suppresion test and quantitative cerebral anatomy in depression

To determine whether structural brain abnormalities in patients with depression are related to cortisol state, we examined the relationship between the dexamethasone suppression test (DST) and brain magnetic resonance imaging (MRI) in 40 inpatients with severe depression referred for electroconvulsive therapy (ECT). Prior to ECT, 27 (68%) of the patients exhibited nonsuppression on the DST. Frontal lobe volume was negatively correlated with peak post-dexamethasone cortisone (r= −0.37) and was 13% smaller in DST nonsuppressors than suppressors; these findings were no longer significant after adjustments for age, geneder, and cranial size. Lateral and third ventricular volumes were also correlated with peak postdexamethasone cortisol (r = 0.34 and 0.33, respectively), but not after adjustments for age, gender, and cranial size. Subcortical hyperintensity was associated with peak postdexamethasone cortisol and was more common in DST nonsuppressors than suppressors. Again these findings were no longer significant after adjustments for age. Finally, longitudinal DST and brain MRI studies in 11 of these patients revealed no changes in regional brain volumes nor in postdexamethasone cortisol up to six months after ECT. However, within individual patients, postdexamethasone cortisol was positively (and significantly) correlated with frontal lobe volume.