The Danish PET/depression project: PET findings in patients with major depression.

BACKGROUND: It is hypothesized from previous positron emission tomography (PET) studies of patients with major depression that dysfunction of regions of the limbic system and the frontal lobes in close connection with the basal ganglia is involved in the pathophysiology of major depression. METHODS: By means of PET and 15O labelled radioactive water we determined an index of the neuronal activity by mapping the cerebral blood flow distribution of 42 unselected in-patients suffering from moderate to severe depression and 47 healthy controls controlling for age and gender. The PET maps were co-registered to magnetic resonance images of the anatomy of the brain. RESULTS: The functions-of-interest analysis revealed significant gender differences in cerebral blood flow and changes in the relative distribution of the blood with increasing age. The patients had increased activity of the hippocampus and the cerebellum compared to the healthy controls when corrected for these confounders and the influence of antidepressant medication. Furthermore, data in the Danish Psychiatric Central Register showed that the patients studied were representative of the population of depressed patients admitted to the hospital during the study period. CONCLUSION: Our main finding is increased blood flow to the hippocampus, even when controlling for a number of confounders. This is in accordance with a rapidly expanding literature suggesting an important role for this structure in major depression.     

急性脑血管病外周血小板上CD59的表达

目的探讨脑血管病急性期外周血血小板上攻膜复合体抵制因子(CD59)表达的变化。方法应用流式细胞仪检测急性脑血管病患者外周血血小板上CD59,观察脑梗死、脑出血患者与正常对照组的变化。结果脑梗死患者急性期外周血血小板上CD59表达明显降低,脑出血患者与正常对照无明显变化。结论急性脑梗死时,患者血小板活化,其膜表面糖蛋白CD59表达降低。     

心理干预对脑卒中患者抑郁状态及认知功能的影响

目的:探讨心理干预对脑卒中患者抑郁情绪和认知功能的影响.方法:将70例脑卒中患者随机分成心理干预组和对照组,在心理治疗前后分别对两组患者进行了P300电位测定和SDS量表评分.结果:首次评定两组P300电位结果和SDS量表分值无显著性差异(P>0.05);再次评定时,心理治疗组P300电位各波潜伏期较对照组缩短,P3潜伏期缩短及波幅升高,与对照组存在显著性差异(P<0.05).SDS量表分值心理干预组低于对照组(P<0.01).结论:心理干预对降低脑卒中患者的抑郁情绪、改善认知功能有一定效果.     

脑梗死患者的焦虑、抑郁情绪与A型行为的相关性研究

目的 探讨脑梗死患者的焦虑、抑郁情绪以及与A型行为的关系.方法 采用Zung焦虑自评量表(SAS)、Zung抑郁自评量表(SDS)及A型行为问卷(TABQ)对86例脑梗死患者(脑梗死组)及86名健康人(对照组)进行问卷调查,并将调查结果加以比较.结果 脑梗死组SAS及SDS评分均明显高于对照组(P＜0.01):其TABQ总分及TH、CH因子分亦均明显高于对照组(P＜0.01).脑梗死组SAS及SDS评分与TABQ总分及TH因子分均呈显著性正相关,其SAS评分与CH因子分亦呈显著性正相关.结论 脑梗死患者存在明显的焦虑及抑郁情绪,并与A型行为有关.     

Visual hallucinations in Parkinson's disease are not influenced by polymorphisms of serotonin 5-HT2A receptor and transporter genes

Psychiatric disorders are common in Parkinson's disease (PD) and hallucinations are observed in nearly 40% of PD patients. The involvement of dopaminergic system in the pathogenesis of psychosis has been sustained by most of the authors even if several evidences indicate that multiple neurochemical substrates might underlie psychosis in PD. In PD there is an extensive loss of serotoninergic raphe neurons and serotonin dysfunction had been implicated in the pathogenesis of many psychiatric disorders such as depression, schizophrenia, and in psychosis of patients with Alzheimer disease. The association of a serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the 5-HT2A receptor T102C polymorphism with psychosis in a group of patients with PD was investigated. No significant differences in the distribution of allele and genotype frequencies of the 5-HTTLPR (p>0.01) and 5-HT2A T102C (p>0.05) were found between patients and controls as well as between the patients' subgroups without and with psychosis. These data might suggest that 5-HTTLPR and 5-HT2A polymorphisms are not major susceptibility factors of psychotic symptoms in PD patients.     

Altered cerebral energy utilization in late life depression

Background: Global and regional changes in cerebral energy utilization are reported to characterize late life depression. Methods: Twenty seven subjects with late life depression (9 prior to starting medication, 18 after starting) and 27 matched controls were evaluated with cordance, a quantitative EEG measure that reflects cerebral energy utilization. Results: Global and focal (anterior and centrotemporal) differences were present in theta-band cordance between unmedicated depressed and control subjects. Depressed subjects receiving treatment had cordance patterns similar to controls. Conclusions: The presence of both diffuse and focal disturbances in energy utilization prior to initiating treatment indicates that cordance detects altered cerebral physiology in depressed patients, and that this measure may also be sensitive to treatment interventions.     

Impaired dynamic cerebral autoregulation in young adults with mild depression

The incidence of depression is increasing, especially in the young adult population. Impaired cognitive function is one of the characteristics of depression, which may be related to impaired cerebral autoregulation (CA). We investigated the characteristics of CA in young adults with mild depression, as well as its validity for identifying patients with depression. Patients (aged 18–35 years) with Hamilton Depression Rating Scale (HAMD) scores ranging from 8 to 17 and a first episode of mild depression were enrolled in this study. Healthy volunteers were recruited as controls. Noninvasive continuous arterial blood pressure and bilateral middle cerebral artery blood flow velocity were simultaneously recorded from each subject. Transfer function analysis was applied to derive phase difference, gain, coherence and rate of recovery for the assessment of CA. Forty-three patients and 43 healthy controls were enrolled. Phase difference values were significantly compromised in young adults with mild depression and were negatively correlated with HAMD scores. Rate of recovery values estimated from depressed patients was significantly lower. The validity in identifying patients with depression was favorable for the phase difference. The cutoff phase difference value was 29.66. Our findings suggest that dynamic CA was impaired in young patients with mild depression and negatively correlated with HAMD scores. CA represented by phase difference can be used as an objective auxiliary examination of depression, and has clinical diagnostic value for the early identification of patients with depression.     

Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese

We determined polymorphism in the serotonin (5-HT) transporter gene-linked polymorphic region (5-HTTLPR) in 501 healthy Japanese, individuals, using the polymerase chain reaction of Lesch et al., with minor modifications. The distribution of allele frequencies was determined and found to differ from that in Caucasians. We also investigated the relationship of polymorphism in 5-HTTLPR to anxiety traits, by having 189 of the 501 subjects complete a self-rating questionnaire for anxiety and depression. Subjects with the short/short (s/s) genotype had significantly higher anxiety scores than those with the long/long (l/l) or l/s genotype. It is suggested that populations with the s/s genotype of 5-HTTLPR have stronger anxiety-related personality traits than those with the l allele. Received: July 16, 1998 / Accepted: August 25, 1998     

Morphometric evaluation of the lateral fossa during the pre-gyrus period

During edification of neocortex, the lateral fossa is involved in the process of development of cerebral hemispheres. It changes its shape and, from a shallow depression at the end of the 3rd month, it becomes a triangular surface with marked borders. Finally, in the same time with the appearance of circumvolutions the opercles that limit it come closer and give rise to the lateral sulcus. The evolution of the lateral fossa can be analysed by linear and surface parameters. Morphometric and statistic analyse of these parameters, compared with those of the cerebral hemisphere, allowed us to establish some original criteria for appreciating the growth of the foetal brain.     

S-100B is increased in melancholic but not in non-melancholic major depression

BACKGROUND: Recent evidence suggests that neurodegeneration may be involved in the pathophysiology of major depression. The astroglial peptide S-100B was shown to be increased in many diseases causing neuronal cell damage or degeneration. METHOD: S-100B plasma levels were determined in 28 patients with major depression and 28 matched healthy controls using an immunofluorometric sandwich assay. RESULTS: Patients suffering from melancholic depression showed significantly increased S-100B levels compared to healthy controls while non-melancholic patients demonstrated normal levels. LIMITATIONS: Medication of patients varied. The differentiation between melancholic and non-melancholic patients was performed clinically without using a standardized instrument. CONCLUSIONS: Neurodegeneration or axonal remodeling may be involved in the pathogenesis of melancholic depression.     

Single photon emission tomography with 99m Tc-HMPAO in Arab patients with depression

BACKGROUND: This study investigates the rate of cerebral blood flow (rCBF) in Arab patients wth depression. METHODS: Forty-four patients with DSM-III-R major depressive disorders were studied at rest using single photon emission computerized tomography (SPECT) with 99m Tc-HMPAO in comparison with 20 normal controls. All patients were assessed using the Hamilton Rating Scale for Depression (HRSD). RESULTS: The depressed group showed greater rCBF in left and right posterior frontal and parietal cortical regions than normal controls. Within the depressed group, patients with the least severe illness (HRSD < 20) had significantly lower rCBF than normal controls, whilst those with moderately severe (HRSD 20-29) and severe (HRSD > 30) had significantly greater rCBF in most cortical regions than normal controls. Symptom scores, derived from the HRSD were predicted by rCBF principally increased rCBF in the left frontal cortex. CONCLUSIONS: These results suggest a generalized cerebral activation principally in the frontal cortex which is in contrast to the results of most previous studies but more in line with the results of studies of induced affect and some studies of depression subsyndromes.     

首发抑郁症患者海马容积与磁共振波谱的研究

目的:探讨抑郁症患者海马容积与氢质子波谱(1H-MRS)的相关性。方法:对50例首发抑郁症患者和50例健康志愿者行磁共振海马容积测量和磁共振波谱检查,将采用相除法标准化海马容积与N-乙酰天门冬氨酸(NAA)、胆碱(Cho)和肌酸(Cr)的比值对照分析。结果:抑郁症患者海马容积不同程度缩小,其中31例重度抑郁症者海马容积明显缩小。抑郁症患者NAA峰高度降低、Cho峰增高,NAA/Cr比值不同程度减小、Cho/Cr值增高,31例重度患者NAA/Cr值明显减小;重度抑郁症患者海马容积缩小与NAA/Cr降低幅度呈正相关。结论:重度抑郁症患者海马容积缩小、NAA丢失严重,提示神经递质N-乙酰天门冬氨酸-谷氨酸在抑郁症发展中起重要作用。     

Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains

Genome-wide gene expression analysis using DNA microarray has a great advantage to identify the genes or specific molecular cascades involved in mental diseases, including major depression and suicide. In the present study, we conducted DNA microarray analysis of major depression using postmortem prefrontal cortices. The gene expression patterns were compared between the controls and subjects with major depression. As a result, 99 genes were listed as the differentially expressed genes in major depression, of which several genes such as FGFR1, NCAM1, and CAMK2A were of interest. Gene ontology analysis suggested an overrepresentation of genes implicated in the downregulation or inhibition of cell proliferation. The present results may support the hypothesis that major depression is associated with impaired cellular proliferation and plasticity. Comparison between the controls and suicide victims with major depression, bipolar disorder, or schizophrenia was also conducted in the present study. Two genes, CAD and ATP1A3, were differentially expressed in the three comparisons in the same direction. Interestingly, these two genes were also included in the differentially expressed 99 genes in major depression. It may be worth investigating the genes in relation to suicide or major depression.     

脑梗死急性期抑郁状态对SF-36生存质量的影响

目的探讨脑梗死患者急性期抑郁状态对其亚急性期生存质量的影响。方法符合研究标准的急性期脑梗死病例88例,经“Zung抑郁自评量表（Self-rating depression scale,SDS）”评分后分为轻度抑郁组（36例）和中度抑郁组（52例）。运用“健康状况调查问卷SF-36（以下简称SF-36）”评定患者的生存质量。结果两组患者在SF-36的8个维度中,轻度抑郁患者躯体健康,躯体疼痛,心理健康,情绪角色,精力,总体健康的评分明显高于中度抑郁组（P〈0．05,0．01,0．001）。结论脑梗死患者抑郁程度与其SF-36生存质量密切相关。抑郁程度重者生存质量较差。     

Cortical spreading depression blocks the hyperthermic reaction induced by orexin A

This experiment tested the effect of cortical spreading depression on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before and 5 h after an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle. The same variables were monitored in rats with cortical spreading depression, induced by an application of cotton pellets soaked with 2 M KCl to the frontal cortex. The results show that orexin A increases the sympathetic firing rate, IBAT and colonic temperatures and heart rate. The increases in firing rate, IBAT and colonic temperatures are blocked by cortical spreading depression, while the increase in heart rate is not affected by cortical spreading depression. These findings suggest that the cerebral cortex is involved in the control of the orexin A-induced hyperthermia. Furthermore, we suggested the name "hyperthermine A," as additional denomination of "orexin A."     

Modulation of soleus H-reflexes during gait in children with cerebral palsy

In healthy adults, soleus H-reflexes are rhythmically modulated and generally depressed during gait compared with rest. From ages 6 to 13 yr, there is a progressive increase in the tonic inhibition of H-reflexes during walking, especially during the stance phase of the step cycle. In adults, rhythmic modulation and tonic depression are severely disturbed after bilateral spinal lesions but remain partly preserved after unilateral cerebral lesions. Children with diplegic cerebral palsy (CP) suffer from a bilateral supraspinal lesion of the corticospinal tract that occurs before the maturation of the CNS is complete. If supraspinal structures are involved in the tonic, but not rhythmic, age-dependent reflex depression, it could be hypothesized that the tonic reflex depression with age is disturbed in CP, whereas the rhythmic part of the modulation remains unaffected. To test this hypothesis, soleus H-reflexes were assessed during gait in 16 CP children aged 5-11 and 15-16 and compared with 25 age-matched healthy children walking at similar velocities. Although the rhythmic part of the modulation pattern was present in CP, there was no significant tonic reflex depression with age, thus reflecting a lack of maturation of the corticospinal tract. It is argued the rhythmic part of the modulation may be generated on a spinal or brain stem level and is therefore not affected by the bilateral supraspinal lesion, whereas the tonic depression that occurs with maturation of the CNS is under supraspinal control. In conclusion, the supraspinal structures affected in CP are therefore likely involved in this age-dependent tonic depression.     

神经衰弱的脑电图分析

目的:了解神经衰弱患者脑电图主节律α波。方法:对38例神经衰弱患者与42例健康者的脑电图主节律α波分析。结果:神经衰弱组主节律多分布在11～13c/s,健康组主节律多分布8～11c/s(P<0.01)。结论:脑电图主节律α波增快,出现方式减弱,说明大脑皮层兴奋性增高并存在兴奋与抑制的失调。     

Comparative analysis of anxiety-like behaviors and sensorimotor functions in two rat mutants, ci2 and ci3, with lateralized rotational behavior

There is increasing evidence that developmental anomalies of cerebral asymmetry are involved in the etiology of psychiatric disorders, including schizophrenia, depression and anxiety. Thus, rodents with abnormal cerebral lateralization are interesting tools to study the association between such anomalies and behavioral dysfunction. The most studied indicator of cerebral asymmetry in the rat is that of circling or rotational behavior. We have recently described two rat mutants, ci2 and ci3, in which lateralized rotational behavior occurs either spontaneously or in response to external stimuli, such as new environment or handling. While cochlear and vestibular defects are found in ci2 rats, ci3 rats do not exhibit any inner ear abnormalities. The abnormal motor response to external stimuli raised the possibility that the circling rat mutants may be more likely to express anxiety-related behavior in tests of emotionality. In the present study, we characterized anxiety-related behaviors of ci2 and ci3 rats in the open field, elevated plus-maze and light/dark exploration test. Furthermore, sensorimotor functions of these rats were evaluated by the rotarod, accelerod and wire hang tests. Heterozygous (ci2/+) littermates or rats of the respective background strains (LEW, BH.7A) were used as controls. In contrast to our expectation, both mutants demonstrated less anxiety-related behavior than controls in tests of emotionality. Ci3 rats exhibited normal sensorimotor functions, whereas marked impairment was observed in ci2 rats, which is most likely a consequence of the vestibular dysfunction in these animals. The acoustic startle response (ASR) and prepulse inhibition of ASR did not differ between ci3 rats and controls. The reduced emotionality of the mutant rats indicated by the present experiments may not be specifically linked to anxiety per se, but is maybe more reflective of impulsivity or the inability to normally perceive or process potentially threatening situations. Based on previous findings of dysfunctions of the central dopamine system in ci2 and ci3 mutant rats, we assume that alterations in dopaminergic activity are involved in the maladaptive behavior observed in the present study.