technetium-tc-99m-exametazime and Depressive-Disorder--Major

Alterations of regional cerebral blood flow (rCBF) in prefrontal cortex and the anterior cingulate cortex are conspicuous imaging findings in patients with major depression (MD). While these rCBF changes have been suggested as functional disease markers, data in large patient samples examining treatment response prediction to antidepressant therapy are limited. This study examined the predictive value of Tc-99m-HMPAO-SPECT for subsequent treatment response to antidepressant therapy with citalopram in an unprecedented large collective of patients. Ninety-three patients with MD were examined with Tc-99m-HMPAO-SPECT twice, at the beginning of citalopram-treatment (T1) and after 4 weeks of treatment (T2). To determine the impact of rCBF changes associated with treatment response, the patient sample was divided into two subgroups: responders (44 patients) and non-responders (49 patients). A two-sample t-test was used to determine group-specific rCBF-differences. Age, gender and initial Hamilton Rating Scale for Depression (HRSD) were treated as regressors of no interest. The responder group revealed significant relative rCBF increases at T1 in a large region en-compassing predominantly prefrontal and temporal cortices as well as subgenual cingulate cortex. No relative rCBF decreases were detected in this group. The comparison between T1 and T2 revealed trends of rCBF decreases in inferior frontal gyrus and rCBF increases in premotor cortex in the responder group. Our data show that rCBF measurements with TC-99M-HMPAO-SPECT provide a predictor estimate for subsequent treatment response in depressed patients undergoing antidepressant therapy with citalopram. This effect is highly significant and, most notably, independent of the initial HRSD score.

Topics: Antidepressive Agents, Second-Generation; Cerebral Cortex; Citalopram; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Radiopharmaceuticals; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Previous regional cerebral blood flow (rCBF) studies on patients with unipolar major depressive disorder (MDD) have analysed clusters of voxels or single regions and yielded conflicting results, showing either higher or lower rCBF in MDD as compared to normal controls (CTR). The aim of this study was to assess rCBF distribution changes in 68 MDD patients, investigating the data set with both volume of interest (VOI) analysis and principal component analysis (PCA). The rCBF distribution in 68 MDD and 66 CTR, at rest, was compared. Technetium-99m d, l-hexamethylpropylene amine oxime single-photon emission tomography was performed and the uptake in 27 VOIs, bilaterally, was assessed using a standardising brain atlas. Data were then grouped into factors by means of PCA performed on rCBF of all 134 subjects and based on all 54 VOIs. VOI analysis showed a significant group x VOI x hemisphere interaction ( P<0.001). rCBF in eight VOIs (in the prefrontal, temporal, occipital and central structures) differed significantly between groups at the P<0.05 level. PCA identified 11 anatomo-functional regions that interacted with groups ( P<0.001). As compared to CTR, MDD rCBF was relatively higher in right associative temporo-parietal-occipital cortex ( P<0.01) and bilaterally in prefrontal ( P<0.005) and frontal cortex ( P<0.025), anterior temporal cortex and central structures ( P<0.05 and P<0.001 respectively). Higher rCBF in a selected group of MDD as compared to CTR at rest was found using PCA in five clusters of regions sharing close anatomical and functional relationships. At the single VOI level, all eight regions showing group differences were included in such clusters. PCA is a data-driven method for recasting VOIs to be used for group evaluation and comparison. The appearance of significant differences absent at the VOI level emphasises the value of analysing the relationships among brain regions for the investigation of psychiatric disease.

Topics: Algorithms; Brain; Brain Mapping; Cerebrovascular Circulation; Depressive Disorder; Depressive Disorder, Major; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Principal Component Analysis; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The aim of the present study was to search for differences between subtypes of major depression with the use of single photon emission tomography.. Fifty (50) patients aged 21-60 years suffering from Major Depression according to DSM-IV took part in the study. The SCAN v 2.0 was used to assist clinical diagnosis. The psychometric assessment included the HDRS, the HAS, the GAF, the Newcastle scales and the Diagnostic Melancholia Scale (DMS). Single Photon Emission Computerized Tomography (HMPAO SPECT) was used to assess regional cerebral blood flow. The methods of analysis included chi-square test, ANCOVA, and Discriminant Function Analysis.. Forty one (82%) depressed patients had abnormal SPECT findings. The most consistent finding in all patients across all subtypes was a global brain hypoperfusion, which did not include the frontal lobes. The most impressive finding was the relative increase of right frontal lobe perfusion in atypicals, in contrast to the relative decrease of perfusion in both the melancholic and the 'undifferentiated' patients in that particular region. The reverse was true for the right occipital lobe.. The results of the current study provide support for the old hypothesis on the existence of two distinct types of depression, characterized by different underlying psychopathologies, but also provide strong evidence for a neurobiological abnormality underlying atypical depression, the subtype closer to the old concept of 'neurotic' depression, which was considered to be psychological or reactive in origin.

Topics: Adult; Brain Chemistry; Cerebrovascular Circulation; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

To elucidate the neural mechanisms of depression.. Despite extensive study, the neurophysiology of the brain's state(s) corresponding to depression remains uncertain.. HMPAO single photon emission computed tomographic (SPECT) scans were obtained from eight adults diagnosed with major depression resistant to medication (average age 51 years; 4 men) before and immediately after 10 days of 20 Hz repetitive transcranial magnetic stimulation (rTMS) (2000 stimuli/daily 30' treatment). To maximize the likelihood that SPECT scans reflected the state of depression, rather than uncontrolled responses of patients to poorly constrained environments, HMPAO was administered while subjects performed a simple task involving continuous monitoring of the direction of a large arrow on a computer screen and continuously tapping with the left or right index finger according to the direction of the arrow. Mean baseline Beck Depression Inventory (BDI) score was 27.4 (SD = 8.3) and mean posttreatment BDI score was 17.5 (SD = 8.5).. Treatment responders (defined by reduction in BDI score of > or = 30%) had significantly less pretreatment blood flow in the left amygdala compared with nonresponders. Responders demonstrated two patterns of change in regional blood flow with treatment: a reduction in orbitofrontal blood flow and/or a reduction in anterior cingulate blood flow. Nonresponders did not demonstrate any regional changes in blood flow with treatment.. These results suggest that there may be either more than one state of depression, or that depression may be associated with more than one pattern of psychologic activity, which in turn defines the depressive experience for individual patients.

Topics: Adult; Aged; Brain; Depressive Disorder, Major; Electromagnetic Fields; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Radiopharmaceuticals; Severity of Illness Index; Skull; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Transcranial Magnetic Stimulation; Treatment Outcome

Neuroimaging studies in major depressive disorder (MDD) have indicated dysregulation in a network involving prefrontal cortex, subgenual cingulate and the amygdalae, which is known to be modulated by serotonin. The serotonergic system is the principal target for pharmacological treatment in MDD and the functional variable serotonin promoter polymorphism (5-HTTLPR) influences susceptibility, course and treatment response of MDD. Using data from a previously published sample of 89 MDD-patients, we examined post hoc the effect of 5-HTTLPR status on resting state perfusion, as measured with (99m)Tc-HMPAO-SPECT. MDD patients were stratified according to receptor polymorphism, both using a bi-allelic (group A: L/L vs. group B: S/S and S/L genotype) and a tri-allelic approach (Group A': LA/LA vs. Group B': non-LA/LA genotype). There were no significant differences between both subgroups regarding age, gender, severity of depression, medication, or treatment response (p > 0.1). Using the bi-allelic approach, Group B, compared to group A, revealed a significantly higher resting state perfusion in medial prefrontal cortex (p(voxel) (FWE) < 0.05). Additional ROI analyses showed relative overactivity of the amygdalae in group B (p(voxel) (FWE) < 0.05). Similar effects were observed in the tri-allelic approach. The opposite contrasts (Group A > Group B) revealed no significant effects. We demonstrate that in patients with MDD, 5-HTTLPR gene polymorphism modulates resting state perfusion in key structures of mood processing. While the clinical impact of these findings will need to be further investigated in larger cohort studies, the necessity to monitor and to account for individual 5-HTTLPR-status in future MDD imaging studies is highly recommended.

Topics: Adult; Analysis of Variance; Brain; Brain Mapping; Depressive Disorder, Major; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Polymorphism, Genetic; Psychiatric Status Rating Scales; Radiopharmaceuticals; Rest; Retrospective Studies; Serotonin Plasma Membrane Transport Proteins; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

White matter hyperintensities on T2-weighted images (WMH T2-WI) are prevalent in depressed, particularly elderly, patients. In an earlier study we used structural magnetic resonance imaging (MRI) to study 37 depressed and 27 healthy control subjects to show that prevalence of WMH T2-WI is higher in depressed patients and that severity of depression and cognitive impairment is associated with presence of WMH T2-WI in basal ganglia. The occurrence of WMH T2-WI in depression may also be associated with cerebrovascular deficiency, although this association has not been adequately studied. We therefore performed single photon emission computed tomography (SPECT) with Technetium-99m hexamethylpropyleneamineoxime (Tc-99m HMPAO) as tracer in this same sample to seek an association between presence/location of WMH T2-WI and cerebral perfusion deficits. In addition, we examined the relationship between presence/location of WMH T2-WI and treatment response. We found that severely depressed, cognitively compromised patients with WMH T2-WI in the basal ganglia display more profuse cerebral perfusion deficits than less depressed patients with WMH T2-WI in other regions or with no WMH T2-WI but are not less responsive to antidepressant treatment. WMH T2-WI in depression are associated with cerebral perfusion deficits, although not necessarily located in the same regions as the MRI findings. Clinical symptoms are largely reversible even in depressed patients with WMH T2-WI in basal ganglia.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents; Basal Ganglia; Brain Mapping; Cerebral Cortex; Depressive Disorder, Major; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Psychiatric Status Rating Scales; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Young Adult

Although patients suffering from major depression respond to antidepressant treatment within several weeks, full reinstatement of premorbid capabilities requires much longer. Nevertheless, most research in major depression seeking the pathophysiological correlates of remission has focused upon the acute post-treatment period. Brain imaging research offers no exception. We have recently shown that cerebral perfusion in depressed patients responding to 6-wk antidepressant medication increases in parieto/cerebellar regions and becomes similar to that of healthy control subjects. We now present technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (99mTc-HMPAO SPECT) data collected from 11 of these patients 2 years in remission. Images were analysed using Statistical Parametric Mapping. After 2 years, perfusion normalization found immediately after treatment was maintained, with further increases in frontal and decreases in parieto/cerebellar regions. These findings suggest that perfusion increases in parieto/cerebellar regions may be involved in acute response to treatment whereas increases in frontal regions may be related to its consolidation.

Topics: Adult; Aged; Antidepressive Agents; Brain Mapping; Cerebral Cortex; Depressive Disorder, Major; Female; Humans; Image Processing, Computer-Assisted; Longitudinal Studies; Male; Middle Aged; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Hypothyroidism and major depressive disorder (MDD) share neuropsychiatric features. Cerebral perfusion deficits are found in both disorders. We compared regional cerebral blood flow (rCBF) in hypothyroidism and MDD to determine if clinical similarities are mediated by common neurocircuitry. Ten hypothyroid and 10 depressed patients underwent 99mTc-HMPAO-SPECT and clinical evaluation before and after response to respective treatments. Ten healthy controls underwent a similar, single, evaluation. Before treatment, rCBF in hypothyroid and depressed patients was lower than in controls, in posterior and anterior aspects of the brain respectively. rCBF in hypothyroidism was lower than in MDD in right posterior cingulate and parieto/occipital regions, and higher in frontal, prefrontal and sub-genual regions. Reduced rCBF in pre- and post-central gyri was found in both groups. Following treatment, rCBF in depressed patients increased and normalized, but remained unchanged in hypothyroidism. Affective symptoms in hypothyroidism may be mediated by neurocircuitry different from that of major depression.

Topics: Adult; Aged; Antidepressive Agents; Brain; Case-Control Studies; Cerebrovascular Circulation; Cohort Studies; Depressive Disorder, Major; Female; Humans; Hypothyroidism; Male; Middle Aged; Pilot Projects; Radiopharmaceuticals; Severity of Illness Index; Technetium Tc 99m Exametazime; Thyroxine; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Regions of seizure onset and propagation in human generalized tonic-clonic seizures are not well understood. Cerebral blood flow (CBF) measurements with single photon emission computed tomography (SPECT) during electroconvulsive therapy (ECT)-induced seizures provide a unique opportunity to investigate seizure onset and propagation under controlled conditions.. ECT stimulation induces a typical generalized tonic-clonic seizure, resembling spontaneous generalized seizures in both clinical and electroencephalogram (EEG) manifestations. Patients were divided into two groups based on timing of ictal (during seizure) SPECT tracer injections: 0 s after ECT stimulation (early group), and 30 s after ECT (late group). Statistical parametric mapping (SPM) was used to determine regions of significant CBF changes between ictal and interictal scans on a voxel-by-voxel basis.. In the early injection group, we saw increases near the regions of the bitemporal stimulating electrodes as well as some thalamic and basal ganglia activation. With late injections, we observed increases mainly in the parietal and occipital lobes, regions that were quiescent 30 s prior. Significant decreases occurred only at the later injection time, and these were localized to the bilateral cingulate gyrus and left dorsolateral frontal cortex.. Activations in distinct regions at the two time points, as well as sparing of intermediary brain structures, suggest that ECT-induced seizures propagate from the site of initiation to other specific brain regions. Further work will be needed to determine if this propagation occurs through cortical-cortical or cortico-thalamo-cortical networks. A better understanding of seizure propagation mechanisms may lead to improved treatments aimed at preventing seizure generalization.

Topics: Brain Mapping; Cerebral Cortex; Cerebrovascular Circulation; Depressive Disorder; Depressive Disorder, Major; Electric Stimulation; Electroconvulsive Therapy; Electroencephalography; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Functional Laterality; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Technetium Tc 99m Exametazime; Thalamus; Tomography, Emission-Computed, Single-Photon

Compromised regional cerebral blood flow (rCBF) in major depressive disorder may be partly reversed by successful antidepressant treatment. However, it is not known if the reversal of rCBF compromise is dependent on the mode of antidepressant treatment. The current study aimed to address this question.. Thirty-three patients (19 women and 14 men; mean age +/- SD, 53 +/- 16 y) with moderate major depressive disorder were studied before 6 wk of treatment with tricyclic antidepressants, selective serotonin reuptake inhibitors, or a course of electroconvulsive therapy, and 31 of these patients were also studied afterward. A comparison group of 25 healthy volunteers (13 women and 12 men; mean age, 49 +/- 15 y) were studied once. rCBF was assessed using 99mTc-hexamethylpropyleneamine oxime SPECT. Images were analyzed using globally normalized statistical parametric mapping localized to the Montreal Neurologic Institute brain atlas.. Baseline rCBF was lower in depressed patients than in controls in the frontal cortex and subcortical nuclei bilaterally. A response to medication was associated with normalization of rCBF deficits, whereas a response to electroconvulsive therapy was associated with an additional rCBF decrease in the parietotemporal and cerebellar regions bilaterally.. Hypoperfusion in major depressive disorder largely normalizes after a response to pharmacotherapy. Perfusion changes after a response to electroconvulsive therapy may follow a different course.

Topics: Adult; Aged; Antidepressive Agents; Cerebrovascular Circulation; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Little is known about the evolution of brain perfusion alterations in patients with major depression, and still less about the changes in functional neuroimage produced by different antidepressant biological treatments.. Between January 2001 and December 2003, long-term follow-up frontal brain perfusion was compared in 2 subgroups of elderly patients (>or= 60 years) treated for severe unipolar major depression (DSM-IV): one subgroup of 16 patients administered electroconvulsive therapy, and another of 26 patients receiving pharmacologic treatment. All patients were remitters. A medication-free brain single photon emission computed tomography was performed in baseline conditions and after a minimum period of 12 months of euthymia. Twenty-eight age- and sex-matched healthy controls were also assessed.. No significant differences were found between the 2 subgroups in frontal uptake ratios after a 12-month follow-up period of euthymia. During the acute episode, patients presented significant anterior hypofrontality; 12 months later the hypofrontality had disappeared.. The long-term evolution of frontal perfusion in elderly major depressives who respond to antidepressant biological treatment is essentially the same in those who receive electroconvulsive therapy and in those who receive medication.

Topics: Aged; Antidepressive Agents; Depressive Disorder; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Follow-Up Studies; Frontal Lobe; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Regional Blood Flow; Severity of Illness Index; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

The current clinical practice of reporting images obtained with single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropylene amine oxime (99mTc HMPAO) images was examined by having 16 experts evaluate the appearance of SPECT images in patients with probable Alzheimer type dementia (ATD), patients with major depressive episode (DSM-IV), and healthy volunteers. The experts rated diagnostic criteria of scan appearance in respect of importance for their individual diagnostic practice. Experts were nuclear medicine specialists, psychiatrists and physicists taking part in a European multi-centre collaborative project. They examined 158 perfusion scans and then the same perfusion scans together with statistical parametric maps (SPMs). The sensitivity of experts' diagnostic judgments was significantly and negatively correlated with the importance they attributed to reduced regional perfusion in the parietal lobes. A corresponding positive correlation was observed for diagnostic specificity against depressed and healthy volunteers. Similar results were observed with SPMs, where in addition area under the receiver operating characteristic (ROC) curve was significantly reduced with raters' increased diagnostic reliance on frontal lobe perfusion deficits. Sensitivity was greater with SPM for patients younger than 70 years and with dementia severity. The more importance experts placed on parietal (symmetrical) perfusion deficits, the less sensitive and the more specific their diagnostic judgment was. Using multiple raters in large patient samples may provide a way of identifying successful explicit diagnostic strategies for clinical image analysis.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Brain; Brain Ischemia; Cerebral Cortex; Depressive Disorder, Major; Diagnosis, Differential; Dominance, Cerebral; Female; Humans; Image Processing, Computer-Assisted; Male; Mental Status Schedule; Middle Aged; Parietal Lobe; Personality Inventory; ROC Curve; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

A mitochondrial disease might be considered when depressive disorder is associated with diabetes mellitus or other symptoms commonly found in mitochondrial disease. Scattered regional cerebral blood flow (rCBF) decreases and increases have been reported in depressive and mitochondrial disorders. A 61-year-old male patient with early adult onset of depressive disorder and a slowly developing multiorgan syndrome including diabetes mellitus was investigated.. 99mTc-HMPAO rCBF SPECT and muscle biopsy to assess mitochondrial functions were performed in the patient.. Alterations of rCBF were found in the patient, with the most pronounced decreases in the left dorsolateral frontal and inferior parietal lobes, and the most pronounced increases in the bilateral superior parietal lobes. Muscle biopsy revealed myopathy and decrease of mitochondrial adenosine triphosphate production rates (MAPRs).. The MAPRs decreases support the suspicion of mitochondrial dysfunction in the patient. A subgroup of depressed patients may have mitochondrial dysfunctions.

Topics: Brain; Depressive Disorder, Major; Diabetes Complications; Humans; Male; Middle Aged; Mitochondrial Myopathies; Radiopharmaceuticals; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Brain imaging studies have shown that repetitive transcranial magnetic stimulation (rTMS) is biologically active. The aim of the present study was to investigate the patterns of the regional cerebral glucose uptake rate (rCMRGlu) and regional (99m)Tc HMPAO uptake rate (regional cerebral blood flow; rCBF) during a series of therapeutic rTMS sessions at low frequency. Four drug-resistant depressed patients underwent 10 rTMS sessions as an add-on measure over 14 days. One day before and 1 day after the TMS series, 511-keV SPECT with simultaneous (18)F-fluorodeoxyglucose and (99m)Tc HMPAO measurements were carried out. All patients showed a good clinical outcome. Statistically significant common changes in rCBF and rCMRGlu patterns were found in the upper frontal regions bilaterally in terms of increased uptake rates and in the left orbitofrontal cortex in terms of decreased uptake rates of both isotopes compared to controls. However, the lateralization patterns of rCBF and rCMRGlu after rTMS treatment revealed marked differences. Thus, although no relevant changes in lateralization of the glucose uptake were observed, a clear right-sided preponderance of rCBF also in areas remote from the stimulation site was described. Therapeutic rTMS seems to influence distinct cortical regions, affecting rCBF and rCMRGlu in a homogeneous manner as well as in different ways, which are probably region dependent and illness related. The role of the stimulation coil placement site should be taken into account.

Topics: Adult; Brain; Case-Control Studies; Cerebrovascular Circulation; Depressive Disorder, Major; Drug Resistance; Electric Stimulation Therapy; Female; Fluorodeoxyglucose F18; Glucose; Humans; Male; Middle Aged; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Transcranial Magnetic Stimulation; Treatment Outcome

Topics: Cerebral Cortex; Depressive Disorder, Major; Electroconvulsive Therapy; Electrodes; Electroencephalography; Humans; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The aim of this preliminary study is to investigate the regional blood flow in response to ECT (electroconvulsive therapy) and to identify any responsive-pattern to the treatment.. Single longitudinal prospective study of cohorts.. For this preliminary study ten patients, female sex, mean age 70.8 years with major mood disorder (CID-10 investigation criteria) were studied after signature consent.. The intervention consisted in the administration of bilateral brief pulse ECT three times a week, during 6 to 12 sessions according to the standards of the Psychiatric Department of the Santiago Hospital in Victoria.. Clinical evaluation of depression was evaluated by Hamilton Depression Scale, Montgomery and Asberg Scale, Newcastle Scale and regional cerebral blood flow (rCBF) using the HMPAO-SPECT.. The pattern of distribution on the regional cerebral flow during the ECT showed changes from the basal pattern in all patients. All patients had a relative increased perfusion of the temporal lobes and basal ganglia. Other changes from the basal study were areas of decreased perfusion of the occipital lobe (6 patients) and parietal lobe (3 patients).. Brain perfusion SPECT study of the patients with major depression shows changes during ECT. Further analysis are needed to understand the relationship between mechanisms of treatment and recovery in affective illness.

Topics: Aged; Blood Flow Velocity; Cerebral Cortex; Depressive Disorder, Major; Dominance, Cerebral; Electroconvulsive Therapy; Female; Humans; Personality Inventory; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Baseline regional cerebral blood flow of thirty unmedicated late-onset unipolar major depressed patients over the age of 60 years and 20 sex-, age-, and vascular risk factor-matched healthy controls was imaged with single photon emission computed tomography, using technetium-99m hexamethylpropylene amine oxime as a tracer. To avoid errors of diagnosis--in particular, confusion between major depression and organic cognitive impairment--only treatment responders were included in the final sample. Statistically significant differences were observed in both left and right anterior frontal regions, with reduced uptake in depressed patients; these differences were more pronounced in the left hemisphere. Among patients, there was no correlation between regional cerebral blood flow and the severity of baseline symptoms. Our results support the hypothesis that certain neuroanatomic regions of the central nervous system may be functionally involved in elderly unipolar major depression, particularly in the late-onset subgroup.

Topics: Aged; Brain Ischemia; Depressive Disorder, Major; Dominance, Cerebral; Female; Frontal Lobe; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Depression is a recognized feature of epilepsy. This study tested the hypothesis that depression arising in patients with epilepsy would be associated with decreased activity in brain regions previously demonstrated to be hypoperfused both in primary depression and in depression secondary to movement disorders. Two groups of patients with temporal lobe epilepsy were studied, one of which also met DSM IV criteria for a major depressive episode. All underwent a SPECT scan using the blood flow marker,(99m)Tc-HMPAO. An automated voxel-based analysis demonstrated no regions of relatively decreased activity in the depressed compared with the non-depressed patients. Sites of relative hyperactivity in the depressed group were concentrated in the left hemisphere, particularly in dorsolateral prefrontal cortex, striatum, thalamus and temporo-parietal regions. Comparison of these data with normal population data revealed that in the depressed epilepsy group regional activities were within the normal range whilst corresponding results from the non-depressed group were below it. Depressed patients with epilepsy have cerebral regions with greater perfusion than non-depressed people with epilepsy, although they are not hyperperfused compared with normals. Our results suggest that depression in people with epilepsy may arise from a mechanism which differs from that underlying the development of depression in patients with movement disorders.

Topics: Adult; Brain; Depressive Disorder, Major; Electroencephalography; Epilepsy; Female; Humans; Male; Movement Disorders; Psychiatric Status Rating Scales; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Psychomotor slowing is a fundamental clinical feature of severe depression and is thought to reflect dysfunction within prefrontal-subcortical circuits. This study utilised a split-dose single photon emission computerised tomography (SPECT) scanning technique in association with a two-stage test of psychomotor speed. Twenty-five patients with primary depressive disorders were injected with technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) whilst performing each component of a two-stage psychomotor task. The first stage, 'simple reaction time' (RT) and the second stage, 'choice reaction time' (CRT), were each followed by 30-min SPECT scans. Regions of interest (ROIs) corresponding to the left and right neo-striatum (caudate-putamen) were drawn, and regional cerebral blood flow (rCBF) values were calculated. Importantly, the change in rCBF measure in the left neo-striatum was inversely correlated with RT (r = -0.48, P < 0.05). That is, the patients with the greatest psychomotor slowing initially showed the least increase in rCBF during the CRT condition. This effect was independent of age. The study demonstrates that a simple two-stage motor paradigm can be used to elicit rCBF correlates of psychomotor slowing in patients with primary depression. Such rCBF findings may implicate the neo-striatum in the neurobiology of major depression.

Topics: Adult; Aged; Corpus Striatum; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Prefrontal Cortex; Psychomotor Disorders; Radiopharmaceuticals; Reaction Time; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Basal Ganglia; Brain; Brain Mapping; Cerebral Cortex; Depressive Disorder, Major; Diagnosis, Differential; Dominance, Cerebral; Feasibility Studies; Humans; Image Processing, Computer-Assisted; Mathematical Computing; Middle Aged; Reference Values; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and 99mTc-hexamethylpropylenamine oxime (99mTc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-refractory subgroup, rCBF decreased significantly in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression.

Topics: Aged; Brain; Brain Mapping; Caudate Nucleus; Cerebral Cortex; Chronic Disease; Depressive Disorder, Major; Dominance, Cerebral; Female; Gyrus Cinguli; Humans; Limbic System; Male; Middle Aged; Recurrence; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Relative regional cerebral blood flow was measured with single photon emission computed tomography (SPECT) using 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) in 16 patients with major depression while they were in the depressed state as well as in remission. All patients were closely matched with regard to medication status. In the depressed state, significant reductions in tracer uptake were found in the left superior frontal, bilateral parietal and right lateral temporal cortex. During remission, significant increases in uptake were found in the left superior frontal, right parietal and right lateral temporal cortex. There were no significant differences in tracer uptake between patients in remission and controls. These findings suggest that the regional decreases in tracer uptake observed in the depressed state might be a state-related abnormality.

Topics: Adult; Amoxapine; Antidepressive Agents, Tricyclic; Brain; Cerebral Cortex; Clomipramine; Depressive Disorder, Major; Dominance, Cerebral; Female; Follow-Up Studies; Humans; Male; Middle Aged; Personality Inventory; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Single photon emission tomography (SPECT) with 99mTc-HMPAO was used to compare regional cerebral blood flow (rCBF) in patients with unipolar and bipolar depression. The study group consisted of 10 unipolar depressed patients and seven bipolar depressed patients who met the DSM-III-R criteria for major depressive disorder (MDD). Nine physically and mentally healthy volunteers served as control subjects. SPECT images were obtained in the patients at two time points: (1) during the major depressive episode before patients had received medication; and (2) at the beginning of the remitted state while patients were receiving antidepressant medication. During the depressive episode, unmedicated unipolar depressed patients showed relatively increased left frontal rCBF compared both with the control subjects and the bipolar patients (P < 0.05). No significant differences in rCBF emerged between the bipolar patients and the control subjects. The data suggest that unipolar depressed patients, unlike bipolar patients, have relatively increased rCBF in the left frontal lobes during the depressive episode, but these differences tend to disappear during the period of remission.

Topics: Adult; Aged; Bipolar Disorder; Brain; Brain Mapping; Depressive Disorder, Major; Dominance, Cerebral; Female; Frontal Lobe; Humans; Male; Middle Aged; Regional Blood Flow; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

We wished to explore the relationships between waking HMPAO uptake and visually scored polysomnography. We hypothesized that HMPAO activity would correlate positively with slow wave sleep measures the same night. Eight unmedicated unipolar patients with current DSM-IV major depression (17-item Hamilton Depression Rating Scale score 21.5+/-2.9) and seven control subjects received polysomnography on 2 consecutive nights. On the afternoon following the adaptation night, subjects received cerebral SPECT, with 15 mCi Tc-99m-HMPAO injected while subjects performed the Continuous Performance Task. Patients and control subjects did not significantly differ on demographic, polysomnographic, and SPECT variables. Slow wave sleep measures correlated positively (Spearman's) with global and regional tracer activity for depressed (n = 8), control (n = 7) and combined groups (n = 15); in other words, the greater the global or regional afternoon HMPAO uptake, the greater the slow wave sleep measures were the same night. In addition, the greater the waking afternoon global or regional HMPAO activity, the faster subjects fell asleep and the less Stage 2% they had. In patients, global and regional HMPAO activity correlated positively with REM density. Positive correlations between waking tracer activity and subsequent slow wave measures are consistent with previous hypotheses linking slow wave sleep with brain energy conservation and restoration. Further study is needed to determine whether these functional relationships differ in depression.

Topics: Adult; Brain; Brain Mapping; Circadian Rhythm; Delta Rhythm; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Polysomnography; Reference Values; Sleep Stages; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Wakefulness

Single photon emission computed tomography (SPECT) with technetium-99m-d,l-hexamethyl-propylene amine oxime (99Tcm-HMPAO) was carried out in 20 melancholic patients before and after total sleep deprivation. Findings in 11 responders to total sleep deprivation (defined by > or = 40% improvement on the Hamilton Rating Scale for Depression) were compared with findings in nine nonresponders. On the basis of a semiquantitative evaluation of SPECT findings, responders showed relative hyperperfusion before sleep deprivation in the right anterior cingulate cortex and in the right and left fronto-orbital cortex and basal cingulate gyrus. Responders who showed > or = 50% improvement also showed hippocampal overactivation before sleep deprivation. It is possible that limbic overactivation may characterize depressed responders to total sleep deprivation as a distinct subtype. Another possibility is that the pattern of limbic hyperactivation reflects the increased number of bipolar patients in the responder group, with response to total sleep deprivation being only a covariate of this bipolar-unipolar distinction.

Topics: Adult; Brain Mapping; Depressive Disorder; Depressive Disorder, Major; Dominance, Cerebral; Female; Frontal Lobe; Gyrus Cinguli; Hippocampus; Humans; Limbic System; Male; Middle Aged; Personality Inventory; Regional Blood Flow; Sleep Deprivation; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Treatment Outcome