Cerebral metabolism and depression in patients with complex partial seizures.

Twenty-three patients with complex partial seizures were evaluated with 18F-2-deoxyglucose positron emission tomography and with the Beck Depression Inventory. Five of 10 patients with left and zero of eight with right temporal electroencephalographic foci had depressive symptoms; one of five patients with poorly localized electroencephalographic foci also scored in the depressed range. Temporal, frontal, caudate, and thalamic normalized glucose metabolic rates among five patients with depressive symptoms and well-localized left temporal epileptogenic regions were compared with five patients without depressive symptoms but with similar electroencephalographic characteristics. Multifactorial analysis of variance yielded a significant nonlateralized mood by region interaction. Of nine individual regions compared, only inferior frontal cortex showed a significant difference in normalized regional metabolic rate between depressed and nondepressed patients. Metabolism in this region also distinguished patients with depressive symptoms from normal control subjects. Depressive symptoms in patients with complex partial seizures are associated with a bilateral reduction in inferior frontal glucose metabolism, compared with patients without depressive symptoms and normal control subjects. The frontal lobe hypometabolism observed in patients with depressions associated with epilepsy, Parkinson's disease, and primary affective disorder suggests that similar frontal lobe metabolic disturbances could underlie these conditions.     

Differential response to combined treatment in patients with psychotic versus nonpsychotic major depression

Research has demonstrated that depressed patients with psychotic features show poorer outcomes when treated with pharmacotherapy alone compared with those without psychotic features. However, research has not investigated whether this differential response also applies to combined treatment that includes pharmacotherapy and psychotherapy. In the current study, data were pooled from two clinical trials in which patients diagnosed with major depressive disorder with or without psychotic features were treated with combined treatment. Although similar in severity at pretreatment, results indicated that patients with psychotic depression showed a poorer response in terms of depression severity at postoutpatient treatment and at 6-month follow-up compared with those with nonpsychotic depression. Following treatment, patients with psychotic depression were over four times as likely to exhibit high levels of depression and suicidal ideation. Current state-of-the-art combined treatments have poorer efficacy in depressed patients with psychotic symptoms, and adapted treatment approaches are needed.     

State and trait influences on mood regulation in bipolar disorder: blood flow differences with an acute mood challenge.

BACKGROUND: Even in remission, patients with bipolar disorder (BD) remain sensitive to external stressors that can trigger new episodes. Imitating such stressors by the controlled transient exposure to an emotional stimulus may help to identify brain regions modulating this sensitivity. METHODS: Transient sadness was induced in 9 euthymic and in 11 depressed subjects with BD. Regional blood flow (rCBF) changes were measured using (15)O-water positron emission tomography. RESULTS: Common changes in both groups were increased rCBF in anterior insula and cerebellum and decreased rCBF in dorsal-ventral-medial frontal cortex, posterior cingulate, inferior parietal, and temporal cortices. Decreases in dorsal ventral medial frontal cortices occurred in both groups, but subjects in remission showed a greater magnitude of change. Unique to remitted subjects with BD were rCBF increases in dorsal anterior cingulate and in premotor cortex. Lateral prefrontal rCBF decreases were unique to depressed subjects with BD. At baseline, remitted subjects showed a unique increase in dorsal anterior cingulate and orbitofrontal cortex. CONCLUSIONS: Common rCBF changes in remitted and depressed subjects identifies potential sites of disease vulnerability. Unique cingulate and orbitofrontal changes both at baseline and with induced sadness seen in the absence of prefrontal rCBF decreases may identify regional interactions important to the euthymic state in this population.     

Attentional disturbances in patients with unipolar psychotic depression: a selective and sustained attention study

Psychotic depression is a clinical subtype of major depressive disorder in the recent editions of the psychiatric diagnostic systems ICD-10 (1992) and DSM-IV (1994). Recent evidence suggests that psychotic depressed patients are more impaired on neuropsychologic tests measuring attention as compared to nonpsychotic depressed patients. However, information on this issue between psychotic and nonpsychotic depression is limited. It has become clear that attention is not a single concept; thus we studied both selective and sustained attention using the theoretic model of automatic and controlled information processing. Thirty-two patients with major depressive disorder, 16 psychotics and 16 nonpsychotics, were investigated and compared with 20 patients with schizophrenic disorder and 20 healthy volunteers who comprised the control groups, using Ruff's 2 and 7 selective attention tests. Compared to the healthy controls, both depressed groups were impaired; however, the psychotic depressed group was more severely impaired on both measures. Attentional performance speed and accuracy scores, on both effortless and effortful conditions, were significantly lower in the psychotic depressed group than in the nonpsychotic depressed group. No significant differences were found on attentional performance between the psychotic depressed patients and those with schizophrenic disorder. Attention deficits are thus more prominent in psychotic than in nonpsychotic depression. Furthermore, taking attention as a criterion, psychotic depression, although of mood congruent subtype, lies closer to schizophrenia than to nonpsychotic depression.     

Auditory hallucinations elicit similar brain activation in psychotic and nonpsychotic individuals

While auditory verbal hallucinations (AVH) are most characteristic for schizophrenia, they also occur in nonpsychotic individuals in the absence of a psychiatric or neurological disorder and in the absence of substance abuse. At present, it is unclear if AVH in these nonpsychotic individuals constitute the same phenomenon as AVH in psychotic patients. Comparing brain activation during AVH between nonpsychotic and psychotic individuals could provide important clues regarding this question. 21 nonpsychotic subjects with AVH and 21 matched psychotic patients indicated the presence of AVH during 3T functional magnetic resonance imaging (fMRI) scanning. To identify common areas of activation during the experience of AVH in both groups, a conjunction analysis was performed. In addition, a 2-sample t-test was employed to discover possible differences in AVH-related activation between the groups. Several common areas of activation were observed for the psychotic and nonpsychotic subjects during the experience of AVH, consisting of the bilateral inferior frontal gyri, insula, superior temporal gyri, supramarginal gyri and postcentral gyri, left precentral gyrus, inferior parietal lobule, superior temporal pole, and right cerebellum. No significant differences in AVH-related brain activation were present between the groups. The presence of multiple common areas of AVH-related activation in psychotic and nonpsychotic individuals, in the absence of significant differences, implicates the involvement of the same cortical network in the experience of AVH in both groups.     

Regional cerebral blood flow in depressed patients with white matter magnetic resonance hyperintensity.

BACKGROUND: Functional neuroimaging studies have consistently demonstrated decreased regional cerebral blood flow (rCBF) or metabolism in the frontal lobe, temporal lobe, or anterior cingulate gyrus of depressed patients. On the other hand, white matter hyperintensity as defined by magnetic resonance imaging (MRI) has been the most consistently replicated finding in structural neuroimaging studies on depression; however, these functional and structural neuroimaging findings of depression have not been well integrated. We aimed to clarify the possible associations of MRI-defined subcortical hyperintensities with rCBF changes in depressed patients. METHODS: Twelve depressed patients with subcortical hyperintensities defined by MRI, 11 depressed patients without MRI hyperintensities, and 25 healthy volunteers underwent 99mTc ECD SPECT. Group comparisons of their rCBF and correlation analysis between MRI hyperintensity and rCBF in patients were performed with a voxel-based analysis using statistical parametric mapping (SPM) software. RESULTS: Depressed patients showed decreased rCBF compared with control subjects in the frontal lobe, temporal lobe, and anterior cingulate gyrus whether subcortical hyperintensity existed or not; however, the patients with MRI hyperintensity showed decreased rCBF in the thalamus, basal ganglia, and brainstem in addition to cortical areas. Further, the score for white matter hyperintensity correlated negatively with rCBF in subcortical brain structures, including the thalamus and right basal ganglia. CONCLUSION: Our study indicates that depressed patients with MRI hyperintensities may have dysfunction in subcortical brain structures in addition to dysfunction in the fronto-temporal cortical structures.     

抑郁症患者局部脑血流的研究

目的：了解抑郁症患者局部脑血流灌注的特点：方法：应用单光子发射计算机断层扫描对20例抑郁症患者及18例正常对照者局部脑血流灌注进行对比分析。结果：抑郁症组双侧基底核、双侧额叶、左颞叶及左枕叶局部血流低灌注；抑郁症组与对照组左右大脑半球局部血流灌注无显著性差异：结论：抑郁症患者局部脑血流存在低灌注，但未发现局部脑血流低灌注有侧化现象。     

SPECT检测利培酮对精神分裂症患者脑血流灌注的影响

目的探讨利培酮对局部脑血流灌注(rCBF)的影响及疗效与rCBF之间的关系。方法研究组为24例未用过药的精神分裂症患者。男10例,女14例。正常对照组26例,男12例,女14例。用利培酮(3～6mg/d)治疗8周。患者在治疗前后进行基础状态及认知激活状态脑SPECT显像。结果与正常对照组相比,治疗前基础状态时,24例患者左右颞叶后下部血流灌注增加;激活状态时,左额叶外侧中部血流灌注显著下降。治疗后与治疗前相比,右颞叶外侧部、左右颞叶后上部基础状态的血流灌注显著下降;左右额叶中下部、左额叶外侧下部、左额颞上部及左额外侧上部认知激活状态的血流灌注显著增加。PANSS减分率与脑血流灌注的变化有关。结论利培酮治疗精神分裂症后,右颞外侧部、左右颞叶后上部、左右额叶中下部及左额叶外侧上下部的血流灌注变化显著。疗效与血流灌注变化有关。提示脑血流灌注对预测药物疗效具有重要意义。     

Dysfunctional cognitions in hospitalized patients with psychotic versus nonpsychotic major depression

Previous research suggests that psychotic major depression (PMD) is associated with greater illness severity and functional impairment as well as poorer treatment response to antidepressants and psychotherapies compared with nonpsychotic major depression. Although patients with PMD exhibit a number of neurobiological abnormalities, little research has been conducted to date on possible psychological factors that are related to illness in this depression subtype. In the current study, baseline data were pooled from 2 clinical trials in which depressed patients (n = 235) were recruited during a psychiatric hospitalization for an acute episode. Twelve percent (n = 28) of this treatment-seeking sample met criteria for PMD and showed elevated levels of depression severity and dysfunctional beliefs compared with individuals with nonpsychotic major depression. However, even after controlling for depression severity and other relevant baseline variables, only a measure of common dysfunctional beliefs differentiated those with vs those without psychotic features. Furthermore, higher levels of depressive cognitions were related to poorer psychosocial functioning and suicidality in PMD patients. Results suggest that elevated levels of common negative cognitions in depressed patients may be associated with the presence of more severe psychotic symptoms. Adapted cognitive-behavioral treatments may be useful for treating patients with PMD specifically.     

Elevated thalamic and prefrontal regional cerebral blood flow in obsessive-compulsive disorder: a SPECT study

Functional neuroimaging studies have pointed to a possible role of cerebral circuits involving the prefrontal and anterior cingulate cortices, the striatum, and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Regional cerebral blood flow (rCBF) of 16 drug-free Brazilian patients with OCD and 17 healthy subjects matched for age, gender, handedness and level of education was measured with [99m-Tc] HMPAO single photon emission computed tomography. Analysis of covariance identified four regions of interest with significantly higher rCBF: the right superior and inferior frontal cortex and the right and left thalamus. Positive correlations between symptom severity measured by Clinical Global Impression scores and rCBF were found in the right and left inferior frontal lobes and in the right basal ganglia. Compulsive behavior was inversely correlated with rCBF in the right thalamus, and duration of illness correlated positively with rCBF in the right and left superior frontal lobes and with the right thalamus. The findings of this SPECT study conducted in Brazil are in agreement with prior studies and provide additional support for the involvement of prefrontal-subcortical circuits in the pathophysiology of OCD. Furthermore, the study suggests that similar brain mechanisms appear to be involved cross-culturally.     

强迫症与抑郁症的脑单光子发射计算机断层扫描对照研究

目的探讨强迫症、抑郁症局部脑血流量(rCBF)特点。方法应用单光子发射计算机断层扫描(SPECT)技术,对首发且未经治疗的39例强迫症患者、36例抑郁症患者和39名正常人于静息状态下行脑血流显像。以小脑皮质的放射性计数值为参考,对局部脑血流进行半定量分析。结果强迫症组两侧前额叶、前颞叶rCBF高于正常组(P<0.01);抑郁症组两侧前额叶、枕叶、扣带回及右前颞叶、右顶叶rCBF低于正常组(P<0.05);在两侧前额叶、前颞叶、顶叶、枕叶及右后额叶、扣带回,强迫症组rCBF高于抑郁症组(P<0.05)。结论强迫症组的前额叶及前颞叶呈高灌注改变,抑郁症组脑血流普遍低灌注,SPECT技术可望作为二者鉴别诊断的客观依据之一。     

Cerebral blood flow in corticobasal degeneration and progressive supranuclear palsy

To compare brain perfusion between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), we investigated regional cerebral blood flow (rCBF) semiquantitatively with single-photon emission computed tomography and [123I]iodoamphetamine in six patients with CBD and five with PSP. Compared with 12 age-matched control subjects, the average of the left and right rCBF values for the CBD patients was significantly reduced in the inferior prefrontal, anterior cingulate, medial premotor, sensorimotor, posterior parietal, and superior temporal cortices as well as in the basal ganglia and thalamus, whereas only the medial premotor cortex was significantly hypoperfused in the PSP patients. Compared with the PSP patients, the CBD patients showed significantly decreased rCBF in the inferior prefrontal, sensorimotor, and posterior parietal cortices, but not in the subcortical regions. Compared with the controls, interhemispheric differences of rCBF were significant in the inferior prefrontal, sensorimotor, and posterior parietal cortices of the CBD patients but in only the medial prefrontal cortex of the PSP patients. These results indicate that rCBF reductions are more extensive and asymmetric in CBD than in PSP, although the two diseases share medial frontal involvement.     

Relationships between brain CT scan findings and cortisol in psychotic and nonpsychotic depressed patients

In this report, data are presented on pre- and postdexamethasone cortisol levels, neuropsychological testing, and computed tomography (CT) scan findings in 30 depressed patients (15 psychotic and 15 nonpsychotic). Particularly significant findings were observed when data from the unipolar subgroup (n = 22) were analyzed separately. Unipolar psychotic depressed patients had significantly larger (p less than 0.05) anterior pole and cella media ventricle-to-brain ratios (VBRs) and significantly greater (p less than 0.05) left and right inferior parietal brain "atrophy" than nonpsychotic depressed patients. Higher rates of Dexamethasone Suppression Test (DST) nonsuppression were observed in psychotic depressed patients and in patients with larger cella VBRs. Inferior parietal brain atrophy and large VBRs were also associated with greater cognitive impairment on psychometric testing. Implications of these findings are discussed.     

抑郁症首次发病患者静息态脑功能局部一致性的研究

目的 利用功能磁共振(fMRI)和局部一致性(regional homogeneity,ReHo)探讨抑郁症首次发病(以下简称首发)患者在静息态脑功能是否存在异常及异常部位.方法 对34例符合美国精神疾病诊断与统计手册第4版诊断标准的首发抑郁症患者(抑郁症组)和34名性别、年龄、文化程度匹配的健康志愿者(对照组)进行静息态fMRI扫描.结果 抑郁症组静息态脑血氧水平依赖信号的ReHo高于对照组的脑区有左侧额叶眶回、顶下小叶、颞上回,右侧额内侧回、顶下小叶、小脑后叶;低于对照组的脑区有左颞下回、右颞上同和胼胝体、双侧后扣带回(P＜0.005,K≥10).结论首发抑郁症患者在静息态存在多个腩区功能活动的异常,并可能和抑郁症的病理机制有关.     

One-year outcome of psychotic depression after successful electroconvulsive therapy

BACKGROUND: Psychotic depression is thought to have a higher relapse frequency after electroconvulsive therapy (ECT) compared with nonpsychotic depression, although this observation is contradicted by previous studies that have found the opposite. In this study, the 1-year risk of relapse after successful ECT was determined prospectively in patients with psychotic depression and compared with the risk of relapse observed for depressed patients without psychotic features. METHOD: Fifty-nine responders to ECT (a decrease in Hamilton Rating Scale for Depression [HAM-D] score > or = 50%) were followed for 1 year: 29 with and 30 without psychotic features. Relapse was defined as meeting DSM-IV criteria for major depressive disorder and a HAM-D score > or = 16. The frequency of relapse after 4 and 12 months was compared between both samples, adjusted for the co-variables duration of the index episode and type of post-ECT pharmacotherapy. RESULTS:: At both 4 and 12 months after ECT, instances of relapse were significantly lower in patients with psychotic depression compared with nonpsychotic patients: 3/28 (11%) versus 16/27 (59%) and 4/27 (15%) versus 19/28 (68%), respectively. CONCLUSIONS: The main finding of the present study is the favorable 1-year outcome for patients with psychotic depression after response to ECT with a trend toward the same result at 4 months. The 1-year outcome of the total sample is also more favorable than expected.     

Visual priming within and across symbolic format using a tachistoscopic picture identification task: a PET study

The present work was aimed at characterizing picture priming effects from two complementary behavioral and functional neuroimaging (positron emission tomography, PET) studies. In two experiments, we used the same line drawings of common living/nonliving objects in a tachistoscopic identification task to contrast two forms of priming. In the within-format priming condition (picture-picture), subjects were instructed to perform a perceptual encoding task in the study phase, whereas in the cross-format priming condition (word-picture), they were instructed to perform a semantic encoding task. In Experiment 1, we showed significant priming effects in both priming conditions. However, the magnitude of priming effects in the same-format/perceptual encoding condition was higher than that in the different-format/semantic encoding condition, while the recognition performance did not differ between the two conditions. This finding supports the existence of two forms of priming that may be subserved by different systems. Consistent with these behavioral findings, the PET data for Experiment 2 revealed distinct priming-related patterns of regional cerebral blood flow (rCBF) decreases for the two priming conditions when primed items were compared to unprimed items. The same-format priming condition involved reductions in cerebral activity particularly in the right extrastriate cortex and left cerebellum, while the different-format priming condition was associated with rCBF decreases in the left inferior temporo-occipital cortex, left frontal regions, and the right cerebellum. These results suggest that the extrastriate cortex may subserve general aspects of perceptual priming, independent of the kind of stimuli, and that the right part of this cortex could underlie the same-format-specific system for pictures. These data also support the idea that the cross-format/semantic encoding priming for pictures represents a form of lexico-semantic priming subserved by a semantic neural network extending from left temporo-occipital cortex to left frontal regions. These results reinforce the distinction between perceptual and conceptual priming for pictures, indicating that different cerebral processes and systems are implicated in these two forms of picture priming.     

Psychoses in drug-resistant temporal lobe epilepsy.

In the survey of 74 Danish patients with temporal lobe epilepsy who underwent temporal lobectomy, a total of 20 patients were psychotic. Nine of these became psychotic during the follow-up period, six of them after cessation of their epileptic seizures. There were 13 schizophrenia-like psychoses, six paranoid delusional and depressive psychoses, and one childhood psychosis. Operation was on the right side in 39 and on the left side in 35 patients. When the various psychotic groups were compared with each other or with the nonpsychotic patients, the side of operation was not found to be statistically important. The patients with psychoses were older at operation and showed a higher rate of focal lesions in the resected specimens. Although more psychotic patients were bright or normally gifted, and had achieved a higher standard of schooling than nonpsychotic patients, their social status after operation was inferior. Surgery had no effect on psychosis present preoperatively nor on its possible postoperative onset. The diagnosis of psychosis was not considered to be contraindication to temporal lobectomy.     

Alterations of rCBF and mitochondrial dysfunction in major depressive disorder: a case report

OBJECTIVE: 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. METHOD: 99mTc-HMPAO rCBF SPECT and muscle biopsy to assess mitochondrial functions were performed in the patient. RESULTS: 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). CONCLUSION: The MAPRs decreases support the suspicion of mitochondrial dysfunction in the patient. A subgroup of depressed patients may have mitochondrial dysfunctions.     

Changes in prefrontal cortex and paralimbic activity in depression following two weeks of daily left prefrontal TMS

Twenty-two depressed adults were scanned with perfusion single-photon computed emission tomography before and after 2 weeks of left perfrontal transcranial magnetic stimulation (TMS) in a parallel design, double-blind treatment study. At medication-free baseline, across all subjects, blood flow in the bilateral medial temporal lobes, left prefrontal cortex, and caudate significantly declined with increased depression severity. Also at baseline, depressed adults who responded to TMS, compared with nonresponders, showed increased inferior frontal lobe activity. Following treatment, there was an even greater difference in inferior frontal blood flow in responders compared with nonresponders, and the negative baseline correlations between depression severity and limbic and prefrontal blood flow disappeared. These results suggest that in depressed adults, 10 days of prefrontal TMS affects prefrontal and paralimbic activity, which may explain its antidepressant effects.     

Recovery from wernicke's aphasia: A positron emission tomographic study

Changes in the organization of the brain after recovery from aphasia were investigated by measuring increases in regional cerebral blood flow (rCBF) during repetition of pseudowords and during verb generation. Six right-handed patients who had recovered from Wernicke's aphasia caused by an infarction destroying the left posterior perisylvian language zone were compared with 6 healthy, right-handed volunteers. In the control subjects, strong rCBF increases were found in the left hemisphere in the posterior part of the superior and middle temporal gyrus (Wernicke's area), and during the generation task in lateral prefrontal cortex (LPFC) and in inferior frontal gyrus (Broca's area). There were some weak right hemisphere increases in superior temporal gyrus and inferior premotor cortex. In the patients, rCBF increases were preserved in the frontal areas. There was clear right hemisphere activation in superior temporal gyrus and inferior premotor and lateral prefrontal cortices, homotopic to the left hemisphere language zones. Increased left frontal and right perisylvian activity in patients with persisting destruction of Wernicke's area emphasizes redistribution of activity within the framework of a preexisting, parallel processing and bilateral network as the central mechanism in functional reorganization of the language system after stroke.