The topographical features of EEGs in patients with affective disorders

EEG data were obtained in the basic state from 16 scalp sites of 44 patients with affective disorder, diagnosed by DSM-III criteria, and 44 normal controls. The EEG power spectra were computed and the t statistic significance probability mapping (SPM) was applied to visualize regions where the patient group showed differences in the EEG topogram from the controls. The results show: (1) left occipital predominance (P3, O1) of alpha activities in the patients with affective disorders, (2) decreased alpha activities in Fp2 and F8 areas in patients with major depression without melancholia, (3) decreased alpha activities in F7 area in patients with bipolar disorder, manic, and (4) increased beta₂ activity in F4 and C4 areas in patients with major depression with melancholia.These results suggest that inter-hemispheric and intra-hemispheric relationships may be disturbed in patients with affective disorder.     

Sleep EEG in bulimia

To evaluate the sleep electroencephalogram (EEG) characteristics of bulimia, all-night sleep EEGs were performed on 11 women meeting DSM-III criteria for bulimia. Comparison groups consisted of young women outpatients with major depression (n = 44) and young normal women (n = 20). The sleep EEGs of the bulimic patients were largely indistinguishable from those of the normal controls, except for a trend toward increased rapid eye movement (REM) density in the first REM period among the bulimic subjects. No differences in any sleep EEG measure were observed between bulimic patients with major depression and those without affective disorder. By contrast, the outpatients with major depression displayed marked sleep continuity disturbances, as well as significantly increased REM intensity and REM density, as compared to normal controls. Implications of these results with respect to the hypothesis that bulimia is related to major affective disorder are discussed.     

alpha 2-Adrenergic receptor sensitivity in depression. The plasma MHPG, behavioral, and cardiovascular responses to yohimbine

alpha 2-Adrenergic receptors play a major role in the regulation of the noradrenergic system. To assess the function of these receptors relative to possible abnormalities in noradrenergic function in depression, responses to the alpha 2-antagonist yohimbine hydrochloride were investigated in 45 depressed patients and 20 healthy control subjects. Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), blood pressure (BP), pulse, subjective mood, and somatic symptoms were measured before and during yohimbine and placebo administration. The 25% increase in plasma MHPG levels produced by yohimbine did not differ between patients and controls. Mood responses also tended to be similar between groups, with patients reporting only minor improvement in depression following yohimbine. However, yohimbine caused significantly greater increases in somatic symptoms and tended to produce a greater increase in BP in patients than in controls. Evaluation of patient subgroups divided by the presence or absence of melancholia, psychosis, prominent anxiety, or personality disorder did not demonstrate consistent differences. In contrast, comparison of these findings with a prior study showed that patients with panic disorder and agoraphobia who received yohimbine manifested significantly greater increases in MHPG levels and ratings of anxiety, nervousness, and depression than depressed patients. These findings suggest that patients with major depression do not demonstrate marked abnormalities in alpha 2-adrenergic autoreceptor function.     

单双相抑郁患者的情感气质特征及其与抗抑郁治疗反应的关系

目的探索单相抑郁、双相I型和双相II型抑郁患者情感气质特征的差异及其与抗抑郁治疗反应的关系。方法收集广州医科大学附属脑科医院和暨南大学第一附属医院的住院和门诊患者,包括332例单相抑郁患者、116例双相I型患者和152例双相II型患者,所有患者均处于重性抑郁发作期。在为期6周的半自然临床试验中,所有患者均接受抗抑郁药治疗,完成情感气质问卷中文版(TEMPS-A)和汉密尔顿抑郁量表17项版(HAMD-17)评定。比较治疗4、6周末不同气质类型为主导气质患者HAMD-17评分减分率。结果双相I型患者旺盛情感气质评分高于单相抑郁患者和双相II型患者[(9.91±4.53)分vs.(8.20±4.34)分vs.(8.53±4.14),F=6.562,P=0.002];而双相II型患者环性气质评分高于单相抑郁患者[(10.05±5.02)分vs.(7.47±5.22)分,F=12.89,P0.01]。治疗6周后,情感旺盛气质主导组HAMD-17评分减分率高于情感旺盛气质非主导组(F=6.44,P=0.011)。结论单双相抑郁患者的情感旺盛气质和环性气质的特征有所差异,旺盛情感气质可能可以作为处于重性抑郁发作期的情感障碍患者抗抑郁治疗反应的预测因子。     

Computerized EEG frequency analysis in Gilles de la Tourette syndrome

EEG abnormality has been reported in Gilles de la Tourette Syndrome but not confirmed in later studies. We carried out computerized EEG frequency analysis in 30 patients with the disorder, using Nicolet Pathfinder II frequency analysis software, versions 1.2 and 3.1 EEG was recorded from 01-A1+A2, 02-A1+A2, Fz-A1+A2, F7-C3, F8-C4, T5-01, and T6-02 in Tourette Syndrome patients and controls. Controls were taking no medications, and drug therapy for Tourette Syndrome had been stopped or not yet initiated in the patient group. Modal alpha frequency (MAF), maximal alpha frequency (MxAF), and spectral edge frequency (SEF) was measured in occipital and frontal derivations in 24 patients and controls. Left frontal (MOLF) and right frontal (MORF) mobility was calculated in F7-C3 and F8-C4 in 21 patients and controls. No significant differences were found between Tourette Syndrome patients and controls by two-tailed t-test. These findings are in accord with recent evidence of little or no EEG abnormality in Tourette Syndrome patients as compared to normals.     

Character and temperament in major depressive disorder and a highly anxious-retarded subtype derived from melancholia

BACKGROUND: An anxious-retarded subtype of major depressive disorder, defined by high scores for both anxiety and retardation, has been derived from melancholia and appeared to have higher external validity in terms of poor outcome and vasopressinergic stress hormone regulation. A specific personality could enhance the validity of this subtype, and the association with melancholia suggested the absence of a personality disorder. As 2 character dimensions of the Temperament and Character Inventory (TCI), self-directedness (SD) and cooperativeness, parsimoniously predict the presence of a personality disorder, the primary aim was to test whether patients with the highly anxious-retarded subtype of depression have both normal SD and normal cooperativeness. A secondary aim was to optimally account for the general personality characteristics of patients with a major depressive disorder. METHODS: Eighty-six patients with major depressive disorder and matched healthy controls were selected. Seventy patients were eventually recruited for a 2-year follow-up encompassing 5 assessments of personality (TCI) and psychopathology (Comprehensive Psychopathological Rating Scale). Full remission of depression was defined by the presence of less than 3 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition items of depression during 2 weeks. RESULTS: State-dependent changes of SD and harm avoidance (HA) scores were found in all depressed patients. Fully remitted patients had only high HA compared with healthy controls. Unexpectedly, fully remitted patients with the highly anxious-retarded subtype, in addition, had low SD. CONCLUSION: The temperament of high HA may be the predisposing TCI trait for major depressive disorder in general. Low SD may be a specific presumably premorbid character trait for the highly anxious-retarded subtype derived from melancholia.     

Depression in borderline patients: a prospective EEG sleep study

The relationship between borderline personality disorder and primary major depression was studied prospectively using Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) interviews and electroencephalographic (EEG) sleep studies. Ten consecutively admitted borderline patients (a prospective sample), defined by Gunderson's Diagnostic Interview for Borderlines (DIB), underwent EEG sleep studies on two consecutive nights and were compared to previously reported samples of nonborderline depressed patients (defined by Research Diagnostic Criteria; RDC), normal controls, and DIB-defined borderline patients who had been referred "to rule out major depression" (a retrospective sample). EEG sleep data were analyzed visually and by automated techniques. Rapid eye movement (REM) latency values were similar in depressed and both borderline groups but significantly different from controls. Eighty-five percent of REM latency values in RDC major depressives were less than or equal to 65 minutes, compared to similar rates of 75% in the prospective sample of borderline patients and 65% in the retrospective sample, versus 35% for controls (chi 2 = 10.7, p less than 0.005). The REM latency in borderline patients did not vary with the severity of depression as measured by the Hamilton Rating Scale for Depression. In the prospective borderline sample, the major SADS-L diagnoses were chronic intermittent depression (five), current major depression (four) (two unipolar, two bipolar II), and labile personality (one). A convergence of nosologic and EEG sleep data is suggested, and supports the concept of a close relationship between criteria-defined borderline personality disorder and affective illness.     

Personality styles in patients with fibromyalgia,major depression and healthy controls

Background  

The fibromyalgia syndrome (FMS) is suggested to be a manifestation of depression or affective spectrum disorder. We measured the cognitive style of patients with FMS to assess personality styles in 44 patients with fibromyalgia syndrome (FMS) by comparing them with 43 patients with major depressive disorder (MDD) and 41 healthy controls (HC).     

Noradrenergic function and hypothalamic-pituitary-adrenal axis activity in primary unipolar major depressive disorder

Plasma levels of cortisol, norepinephrine (NE), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were found to be significantly higher in 16 drug-free patients with primary, unipolar major depressive disorder than in 20 controls. Plasma free MHPG and basal cortisol levels showed a significant positive correlation in the controls, but not in the patients. There were, however, significant positive correlations between cortisol and NE, as well as between NE and free MHPG levels in the patients. No correlations were observed between patient plasma NE levels and platelet alpha 2-adrenoceptor or lymphocyte beta-adrenoceptor Kd or Bmax values. These peripheral measures of noradrenergic function are proposed as useful markers for patients with primary, unipolar major depressive disorder with melancholia.     

强迫症患者的事件相关脑电位实验研究

背景 强迫症在辅助诊断上目前还缺乏客观的实验室依据。近年来国内外对强迫症的事件相关脑电位进行了研究,结果并不一致。分析其主要原因与所使用仪器、技术性能有关。为此本研究使用国际标准化的美国Nicolet脑电生理仪,并以较成熟的关联性负变、P300及失匹性负波3种事件相关脑电位为手段,并设临床上较多见的抑郁症和广泛性焦虑症为疾病对照,进一步探讨强迫症的脑电生理机制,为临床诊断及治疗提供参考依据。 方法 应用美国Nicolet Spirit 脑诱发电位仪,采用光和声成对刺激以及“听觉靶-非靶刺激序列”技术,对38例强迫症、20例抑郁症和18例广泛性焦虑症及28名正常人的关联性负变(CNV)、P300及失匹性负波(MMN)作了检测。3组疾病组病例均选自2002年5月至2005年12月上海市精神卫生中心,经2名以上的高年资医师确诊并符合中国精神障碍分类方案第三版（CCMD-3）中的强迫症和抑郁症及广泛性焦虑症诊断标准;听力均正常,并无躯体疾病或其他精神疾病,均为右利手。3组对象均未使用过精神科药物。结果 ①CNV：M1波幅抑郁症组[(5±4)μV]和广泛性焦虑症组[(7±4)μV]低于正常组[(14±6)μV]和强迫症组(16±6)μV,指令信号后负变化的出现率抑郁症组(60%)、强迫症组(45%)和广泛性焦虑症组(35%)均高于正常组(4%),上述组间差异均有统计学意义（P<0.05或P<0.01）。②P300：在靶刺激中,N2潜伏期在4组间的差异有统计学差异(P<0.01),其中强迫症组[(276±22)ms]和抑郁症组[(277±22)ms]的潜伏期均长于正常组[(259±14)ms],广泛性焦虑症组短于抑郁症组和强迫症组(P<0.01);P3波幅在4组间的差异亦有统计学差异(P<0.01),其中强迫症组[(3.4士1.6)μV]、抑郁症组[(2.9±1.3)μV]和广泛性焦虑症组[(3.3士1.3)μV]均低于正常组[(5.9土2.1)μV]。在非靶刺激中,广泛性焦虑症组P2波幅低于强迫症组和正常组(P<0.05)。③MMN：强迫症组、抑郁症组及正常组之间潜伏期和波幅的差异有统计学差异(P<0.05或P<0.01)。其中强迫症组和抑郁症组的潜伏期长于正常组(P<0.05);强迫症组的波幅高于正常组(P<0.05),抑郁症组的波幅低于正常组(P<0.05)和强迫症组(P<0.01)。结论 ERPs波幅一高一低变异特点可能对鉴别强迫症和抑郁症有参考意义。     

Ethological assessment of the DSM-III subtyping of unipolar depression

An ethological method was employed to validate the DSM-III subtyping of unipolar, nondelusional depression. The nonverbal behavior of 44 depressed outpatients was video-recorded during psychiatric interview. The DSM-III subtyping was not significantly associated with sex or level of education. Patients with major depression (with or without melancholia) were significantly older than those with dysthymic disorder. The Hamilton Rating Scale for Depression (HRSD) scores of the 3 diagnostic groups indicated a progressive increase in symptom severity across DSM-III subtypes (dysthymic disorder less than major depression without melancholia less than major depression with melancholia). Ethological assessment failed to find any evidence for the validity of the DSM-III subtyping of unipolar depression. Of the 8 behavioral categories analyzed in this study, none showed statistically significant differences between the 3 diagnostic groups. Our interpretation of these results is that, whereas the DSM-III subtyping primarily reflects illness severity, the ethological profile measures a dimension of depression largely independent from severity, as indicated by the lack of correlation between the HRSD score and the categories of nonverbal behavior.     

Detrended fluctuation analysis of resting EEG in depressed outpatients and healthy controls.

OBJECTIVE: Recent findings have demonstrated that the EEG possesses long-range temporal (auto-) correlations (LRTC) in the dynamics of broad band oscillations. The analysis of LRTC provides a quantitative index of statistical dependencies in oscillations on different time scales. We analyzed LRTC in resting EEG signals in depressed outpatients and healthy controls. METHODS: The participants in this study were 11 non-depressed, age-matched controls, and 11 unmedicated unipolar depressed patients. EEG data were obtained from each participant during 5-min resting baseline periods with eyes closed and then analyzed with detrended fluctuation analysis (DFA), a scaling analysis method that quantifies a simple parameter to represent the correlation properties of a time series. The scaling exponent, the result of DFA, provides a quantitative measure of LRTC from the EEG. RESULTS: The present study demonstrates that all the scaling exponents in depressed patients and healthy controls were greater than 0.5 and less than 1.0, regardless of condition. Furthermore, the scaling exponents of depressed patients have relatively higher values in whole brain regions compared to healthy controls, with significant differences at F3, C3, T3, T4 and O1 channels (p<0.05). Finally, a significant linear correlation was observed between the severity of depression and the scaling exponent over most of the channels, except O2. CONCLUSIONS: These results suggest that the brain affected by a major depressive disorder shows slower decay of the LRTC, and that the persistence of the LRTC of EEG in depressed patients was associated with the severity of depression over most of the cortical areas. SIGNIFICANCE: The DFA method may broaden our understanding of the psychophysiological basis of depression.     

Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment

Abnormal signal transduction pathways have been implicated in the pathogenesis of bipolar disorder and major depression. G-proteins are key elements of these pathways in the regulation of cellular responses by transmission of signals from receptors to effector proteins. In recent years several studies have reported altered levels and activities of G-protein alpha subunits in depressive patients. A recently identified polymorphism of a G-protein beta3 subunit (C825T) has been shown to be associated with increased signal transduction and ion transport activity. Therefore, we investigated whether this Gbeta3 polymorphism is associated with affective disorders or with the response to antidepressant treatment in 88 depressive patients (10 bipolar disorder, 78 major depression) compared with 68 schizophrenic patients and 111 healthy controls. We found a significantly higher frequency of the T allele in depressive patients than in healthy controls (genotype: chi2 = 9.571, df = 2, p = 0.008; alleles: p = 0.004, OR = 1.87, 95% CI 1.23-2.84; Fisher's exact test, two sided) and schizophrenic patients (genotype: chi2 = 8.037, df = 2, p = 0.018; alleles: p = 0.009, OR = 1.94, 95% CI 1.99-3.14; Fisher's exact test, two sided). We also found a statistical significant association between TT homozygosity and response to antidepressant treatment after four weeks (p = 0.01). The results of this study suggest that the investigated G-protein beta3 subunit seems to be a susceptibility factor for major depression and maybe even for bipolar disorder, but not for schizophrenia. Further, the presence of the T allele could be an indicator for treatment response.     

Is resting anterior EEG alpha asymmetry a trait marker for depression? Findings for healthy adults and clinically depressed patients

Several lines of evidence suggest that asymmetric anterior brain activation is related to affective style, linking left hemisphere activation to positive affect and right hemisphere activation to negative affect. However, previous reports of left frontal hypoactivation in depressed patients were not confirmed in recent studies. This study evaluated additional characteristics of resting EEG alpha (8-13 Hz) asymmetry in 15 clinically depressed patients and 22 healthy adults by recording EEG activity on two separate occasions, 2-4 weeks apart. Across both sessions, group differences in anterior EEG asymmetry were compatible with the original hypothesis. However, groups differed in temporal stability of anterior EEG asymmetry, which was retest reliable in controls but not depressed patients. In contrast, temporal stability of posterior EEG asymmetry was acceptable in both groups. Increased variability of anterior EEG asymmetry may be a characteristic feature for depression, and, if so, this would challenge the notion that anterior EEG alpha asymmetry is a trait marker for depression.     

Electroencephalographic sleep in psychotic depression. A valid subtype?

Electroencephalographic (EEG) sleep patterns were examined in 27 psychotic and 79 nonpsychotic subjects with major depression to evaluate the validity of the psychotic-nonpsychotic subtype dichotomy. Sleep in psychotic depression was characterized by increased wakefulness, decreased rapid eye movement (REM) sleep percentage, and decreased REM activity even after controlling for clinical differences in age, severity, and agitation. Psychotic depressive subjects also were more likely to have extremely short sleep-onset REM latencies. In psychotic depression EEG sleep varied as a function of total illness duration. Patients with recent-onset syndromes had profiles characterized by marked initial insomnia, increased stage 1 sleep percentage, and long REM latency; patients with illnesses of longer duration had extremely short REM latencies. Demonstration of selected EEG sleep variables discriminating between psychotic and nonpsychotic depression further supports psychotic depression as a distinct subtype of major affective disorder.     

Seasonal affective disorder: spatial organization of EEG power and coherence in the depressive state and in light-induced and summer remission.

The present study analyzed EEG power and coherence in subjects with seasonal affective disorder (SAD) during depressive episodes and during light-induced and summer remission. Baseline EEG activity was recorded during the winter period before light treatment (31 SAD patients, 30 control subjects); after 10 days of 2-h morning light treatment (10 SAD subjects); and during the summer period (14 SAD subjects, 27 control subjects). EEG power and coherence were calculated for the delta, theta-1, theta-2, alpha, beta-1 and beta-2 frequency bands. Compared with control subjects, SAD subjects had lower than normal EEG power in most frequency bands; asymmetrical distribution of delta, theta-1, theta-2 and alpha activity in parietal and temporal regions due to increased EEG power over the left electrode sites; and beta activity in the lateral frontal region due to increased beta power over the right electrode site. The foci of decreased EEG coherence were mainly in the right and left frontal and the right posterior regions. Remitted SAD subjects showed normalization of inter-hemispheric asymmetry in lateral frontal areas; increases of delta, theta-2, and alpha activity compared with control values; theta-1 activity in excess of control values; and disappearance of the foci of decreased coherence in anterior areas of the left hemisphere.     

Seasonal affective disorder: spatial organization of EEG power and coherence in the depressive state and in light-induced and summer remission

The present study analyzed EEG power and coherence in subjects with seasonal affective disorder (SAD) during depressive episodes and during light-induced and summer remission. Baseline EEG activity was recorded during the winter period before light treatment (31 SAD patients, 30 control subjects); after 10 days of 2-h morning light treatment (10 SAD subjects); and during the summer period (14 SAD subjects, 27 control subjects). EEG power and coherence were calculated for the delta, theta-1, theta-2, alpha, beta-1 and beta-2 frequency bands. Compared with control subjects, SAD subjects had lower than normal EEG power in most frequency bands; asymmetrical distribution of delta, theta-1, theta-2 and alpha activity in parietal and temporal regions due to increased EEG power over the left electrode sites; and beta activity in the lateral frontal region due to increased beta power over the right electrode site. The foci of decreased EEG coherence were mainly in the right and left frontal and the right posterior regions. Remitted SAD subjects showed normalization of inter-hemispheric asymmetry in lateral frontal areas; increases of delta, theta-2, and alpha activity compared with control values; theta-1 activity in excess of control values; and disappearance of the foci of decreased coherence in anterior areas of the left hemisphere.     

Elevated plasma homovanillic acid in depressed females with melancholia and psychosis

Plasma free homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured before drug treatment in 29 patients diagnosed as having major depression with melancholia and in 18 control subjects. Plasma HVA was significantly elevated in the total group of female melancholic patients when compared with female controls or male melancholics. Most female patients with psychotic melancholia had elevated HVA levels. These differences were not found in male patients. No significant differences were found for plasma MHPG.     

Prediction of subtype and severity of depression by means of dexamethasone suppression test, L-tryptophan: competing amino acid ratio, and MHPG flow

The score on the Hamilton Depression Rating Scale (HDRS), the L-tryptophan:competing amino acid (valine + leucine) (L-TRP:CAA) ratio, and the 3-methoxy-4-hydroxyphenylglycol (MHPG) flow in 24-hr urine were recorded in 83 depressed patients undergoing a Dexamethasone Suppression Test (DST). The subjects were diagnostically subdivided according to DSM-III into minor depression (296.82, 300.40, 309.00), major depression without melancholia (296.X2), with melancholia (296.X3), or with psychotic features (296.X4). Minor depression, major depression with melancholia, and major depression with psychotic features can be regarded as distinct biological entities. Major depression without melancholia is a heterogeneous group with reference to the biological markers. By combining these biological data with age in a discriminant function analysis, 81.9% of all depressed patients can be correctly classified into minor or major depression groups. The combined biological markers can also be used to predict the severity of the depression; 42.5% of the variance in the HDRS score is accounted for by multiple regression on the biological figures. Multivariate statistical techniques considerably improve prediction for both subtype and severity of depression.     

Alpha-2-adrenoreceptor binding as a possible vulnerability marker for affective disorders

The affinity (1/Kd) and density (Bmax) of alpha 2-adrenoreceptors in platelet membranes were studied in patients with major depressed illness (n = 10), affected first-degree relatives (n = 17), nonaffected first-degree relatives (n = 44) and controls (n = 31). The alpha 2 selective antagonist 3H-yohimbine was used as the radioligand. The mean Bmax values of affected subjects (probands and relatives) were significantly lower than those of controls. There was no difference in Kd values between the controls and affected subjects. There was a positive gradient of the mean Bmax values from the groups of probands to affected relatives, unaffected relatives and control subjects. A familial effect of Bmax values between members of the same families confirms a genetic control of alpha-receptor affinity. These results support the hypothesis that the density of alpha 2-adrenoreceptors, evaluated by 3H-yohimbine binding on human platelets, could be a potential vulnerability marker for affective disorder.