A neuroendocrine study of serotonin function in depressed stroke patients compared to non depressed stroke patients and healthy controls.

OBJECTIVES: We employed a neuroendocrine challenge paradigm to study serotonergic abnormalities associated with poststroke depression. METHOD: Twelve depressed stroke patients (major depression N= 5, minor depression N = 7), 8 nondepressed stroke patients and 12 healthy volunteers completed a single-blind, placebo-controlled, challenge tests. Baseline cortisol (CORT) and prolactin (PRL) values, and these hormonal responses to 30 mg of oral d-FEN and placebo over a 4 hour period were measured in the three groups. RESULTS: There were intergroup differences for baseline adjusted PRL responses (change scores from baseline) to d-FEN (group effect F = 4.38, df = 2,29, p = 0.02) while these responses to placebo were comparable between groups (group effect F = 1.82, df = 2,29, p = 0.18). Peak PRL responses (post d-FEN maximal PRL change from baseline scores) in depressed stroke patients were significantly greater than in nondepressed patients (p = 0.005) but comparable to healthy normals (p = 0.47). However, these responses between major and minor depression were not significant (p = 0.34). There was a trend suggesting a negative correlation between peak PRL response and severity of depression (p = 0.056). Depressed patients were younger than the controls (p = 0.054). Also, the depressed group was more functionally impaired (p = 0.04) and more likely to have right-sided lesions (p = 0.009) compared with the nondepressed group. Differences in baseline adjusted PRL changes between depressed and nondepressed groups became non significant when the influence of laterality of lesions was covaried, whereas covariation of functional scores and age did not alter the significance. CORT responses did not show intergroup differences. LIMITATIONS: The study group was small and was heterogenous in lesion characteristics, time since stroke and type of depression. A fixed-order design was used in the challenge test paradigm. CONCLUSIONS: When laterality of stroke lesion was taken into account, depressed and nondepressed stroke patients did not differ in PRL responses to d-FEN.     

Oral d-fenfluramine test in treatment-refractory depression. Plasma prolactin response compared in patients with and without suicide attempts and in a healthy reference group

BACKGROUND: Fenfluramine (d-FEN) has been used as a serotonin challenge agent to assess central serotonin availability. Blunted serum prolactin (PRL) response to d-FEN has been reported in depressed patients, in suicide-prone patients, and in patients with aggression and personality disorders. We have analyzed suicidality in relation to central serotonergic events by comparing the PRL response to d-FEN in chronically depressed patients with and without suicide attempts and in healthy volunteers. METHODS: In 56 inpatients (10 patients with and 46 without suicide attempts) with at least 2 years of treatment-refractory depression (TRD) (DSM-IV) and a reference group of 30 healthy adults, the PRL response after an oral dose of 30 mg d-FEN was followed for 5 h. RESULTS: Controlling for group differences in age, sex, and weight, the PRL response to d-FEN did not differ significantly between the three groups. Far from confirming the hypothesis of a blunted PRL response in depressed patients, our results suggest: (1) that duration and treatment resistance of depression may affect the PRL secretion, and (2) that TRD and major depression may differ in biological relationship to suicidal behavior. LIMITATIONS: The findings require corroboration in larger and more closely matched study populations. The fenfluramine concentration was not analyzed in blood. CONCLUSIONS: PRL responses to d-FEN challenge did not differ between TRD patients with and without suicidality and the healthy reference group. Chronicity/treatment refractoriness per se may be related to a serotonergic mechanism.     

Age may affect response to antidepressants with serotonergic and noradrenergic actions

BACKGROUND: Multiple lines of evidence suggest continuity from adolescent to adult depression, but treatment response is different in the two groups. There is some consensus that noradrenergic drugs are ineffective in adolescent depression. The aim of this study was to see whether this poor response extended to young adults. METHODS: Patients from two randomised studies on prediction of antidepressant response were used. The subjects were divided into a youth sample (ages 18-24) and an older sample (ages 25 and over). The 6-week percentage response, based on HDRS scores, and the number of patients in remission (i.e., HDRS < or =7) at 6 weeks were compared in subjects who received a serotonergic (clomipramine (mean dose 145 mg) and fluoxetine (mean dose 27 mg)) or a noradrenergic (desipramine (mean dose 200 mg) and nortriptyline (mean dose 100 mg)) antidepressant. RESULTS: There were no significant differences between the two studies, except for a small variation in baseline Hamilton scores. Young adults had a poorer response to noradrenergic antidepressants than they did to serotonergic antidepressants, whereas there was no differential response in the older age group. Young adults had a lower rate of remission on a noradrenergic antidepressant (38% noradrenergic versus 72% serotonergic) but there was no significant difference in remission rates in older adults (65% noradrenergic versus 57% serotonergic) or the sample as a whole (54% noradrenergic versus 62% serotonergic). LIMITATIONS: The age cut-off at 24 is somewhat arbitrary. One study was double-blind while the other was open. There was no placebo control. DISCUSSION: While the response rate to noradrenergic antidepressants in young adults is lower, it is not clear whether this is comparable to adolescents. The reasons for a reduced response may be related to maturation of the noradrenergic system in the brain. Our results suggest that age may be one factor to consider when choosing antidepressants for patients.     

Serotonergic-1a activity and contingent negative variation

While cholinergic, dopaminergic, noradrenergic, and gabaergic effects on contingent negative variation (CNV) have been largely described, little is known about serotonergic influence. Therefore, the relationship between CNV and serotonergic activity as reflected by prolactin (PRL) response to flesinoxan, a 5-HT(1A) full agonist, has been investigated in 28 healthy volunteers. To investigate the clinical implications of the relationship between CNV and serotonergic-1a activity, a group of 43 depressed patients was included in the study. Results among healthy volunteers showed a significant negative relationship between PRL response to flesinoxan and CNV amplitude at Fz, but no relationship for the other electrodes (Cz and Pz). In depressed patients, the relationships were not significant. Overall, this study does not support serotonergic effects on CNV. However, this information is indirect (correlations) and is limited to 5-HT(1A) activity.     

Alpha-1-acid glycoprotein in major depressive disorder. Relationships to severity, response to treatment and imipramine plasma levels

BACKGROUND: Increased plasma levels of alpha-1-acid glycoprotein (AGP) were reported in major depressive disorder. However, the relationship between AGP levels, severity of depression, treatment response and antidepressant levels are still unclear. METHODS: Plasma AGP levels were measured in 36 subjects with major depressive disorder before and after a 6-week treatment with imipramine and in 30 controls. Free imipramine plasma levels of depressed patients were measured at 6 weeks. Comparative analysis between depressed patients and controls, between non-responders (N = 12) and responders (N = 24), and between severely depressed patients (N = 14) and moderately depressed patients (N = 22) were made. RESULTS: Depressed patients had significantly higher mean values of AGP than control subjects. Imipramine non-responders and specially severely depressed patients had significantly greater increases of AGP levels during treatment than other depressed subgroups. There was no correlation between baseline AGP levels and severity of depression or free imipramine levels. LIMITATIONS: The most significant limitations of this study are the small sample size and the fact that all the subjects were out-patients. Results should not be generalized to in-patient populations. CONCLUSIONS: Depressed patients showed high baseline concentrations of AGP. AGP levels did not predict either free imipramine plasma levels or differential response after 6 weeks of treatment with imipramine. A greater increase of AGP during treatment was associated with severity of depression and treatment non-response. Clinical implications: The relationship between high plasma levels of AGP, severity of depression and lack of treatment response is clarified. The influence of imipramine levels is minimized.     

Subsyndromal depression: an impact on quality of life?

OBJECTIVE: The objective of this study was to demonstrate the association between quality of life and subsyndromal depression in a primary care clinic in a Brazilian sample. METHODS: This was a cross-sectional study. The cases were divided into three groups according to the severity of depressive symptoms: 1) subjects with major depressive disorder; 2) subjects with subsyndromal depression; 3) subjects without depressive symptoms--controls. The participants completed the World Health Organization Instrument to Assess Quality of Life (WHOQOL-BREF), the Quality of Life--Depression (QLDS), the Centers for Epidemiologic Studies--Depression instrument (CES-D), and the Composite International Diagnostic Interview (CIDI). RESULTS: The sample consisted of 438 primary care users (35.2% of them had subsyndromal depression). The subjects with major depression presented the worst impairment of quality of life, which was measured by the WHOQOL-BREF and the QLDS. The patients with subsyndromal depression had a smaller impact on their quality of life and the subjects without depression presented an even lower impact. The hierarchical linear regression involving demographic variables and the severity of depressive symptoms showed that the severity of depression was the variable with higher correlation with quality of life dimensions, presenting increased variation in the domains (from 9% to 24%). CONCLUSIONS: The results suggest that subsyndromal depression causes impairment of the quality of life in primary care patients of a Brazilian sample.     

帕罗西汀并心理干预治疗卒中后抑郁和焦虑共病者81例临床观察

目的：探讨脑卒中后抑郁和焦虑共病对患者生活能力和神经功能康复的影响，及帕罗西汀合并心理干预临床疗效。方法：将脑卒中伴抑郁和焦虑障碍共病者81名随机分成3组，分别接受单用帕罗西汀治疗（A组）、帕岁西汀并心理治疗（B组）以及单用脑血管药物治疗（C组）。采用斯堪的那维亚脑卒中量表、Barthel指数、汉密尔顿抑郁量表、汉密尔顿焦虑量表评估疗效。结果：脑卒中患者中，抑郁和焦虑的共病率为65．9％，A组、B组各项评分与C组比较，差异均有统计学意义。结论：卒中后抑郁和焦虑病人单用帕罗西汀或合并心理治疗均能促进患者神经功能康复和提高生活质量，且帕罗西汀并心理干预的疗效更好。     

A revised interpretation of the TRH test results in female depressed patients. Part II: Prolactin responses. Relationships with sex hormones, corticosteroid state, age, monoamines and amino acid levels

Prolactin (PRL) levels were recorded in baseline conditions and 20 and 60 min after thyrotropin releasing hormone (TRH) administration (200 micrograms i.v.) in 60 depressed females categorized according to DSM-III. Peak PRL responses were significantly (r = 0.727, P less than 0.001) correlated with their baseline levels. Consequently, the PRL responses to TRH were largely predicted by baseline PRL levels. It was suggested that the PRL responses to TRH consisted of two parts. The first component was a relative exaggeration of basal PRL, reflecting the basal activity of the hormone. The second component was the residual response. This part was estimated by partialling out the relative effects of basal PRL on peak PRL responses by means of regression analysis. Basal PRL and residual PRL responses were uninformative for major depression. Post-menopausal females showed significantly reduced basal PRL levels. There was a significant negative correlation between basal PRL and follicle stimulating hormone levels, age and post-dexamethasone cortisol values. The residual PRL responses were negatively correlated with free triiodothyronine levels and positively with serotonergic variables, i.e., 5-hydroxyindoleacetic acid in 24-h urine and the ratio L-tryptophan/competing amino acids.     

Blunted prolactin response to D-fenfluramine in post-stroke major depression

BACKGROUND: This study investigated whether patients suffering from post-stroke depressive disorder had a similar disturbance in central serotonergic function to that described in non-brain injured depressed patients. METHODS: Twenty-three depressed patients (nine major, 14 minor) and 38 non-depressed patients were examined 4-8 weeks post-stroke with a structured interview, rating scales and MRI brain scans. Patients were administered 30 mg D-fenfluramine orally and plasma prolactin and D-fenfluramine concentrations were measured for 6 h post-dose. RESULTS: The prolactin response was significantly blunted in major depression compared to minor depression and non-depressed patients as measured by both delta prolactin and area under the prolactin versus time curve. There was no significant relationship between prolactin response and lesion lateralization or any of the measured clinical characteristics. LIMITATIONS: The major limitation of the study is the relatively small number in each depressive group. CONCLUSIONS: Patients suffering from major depression in the post-stroke period have a blunted prolactin response to D-fenfluramine. This indicates a serotonergic abnormality consistent with that found in major depression where neurological disease is not present.     

Brain volume alteration and the correlations with the clinical characteristics in drug-naïve first-episode MDD patients: A voxel-based morphometry study

Structural brain abnormalities have been widely reported in major depressive disorder (MDD). However, many previous results cannot exclude the interferences of medication or multiple recurrent episodes. In this study, we examined structural brain abnormalities by comparing 68 drug-naïve first-episode adult-onset MDD and 68 healthy controls (HCs). Structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) methods were used. The mean values of grey matter volume/white matter volume (GMV/WMV) were calculated, then the differences between MDD and HCs were analyzed, and the associations of the differences with clinical characteristics of depression were discussed. The whole brain GMV/WMV did not differ between MDD patients and HCs; however, the regional GMV of the right pre-supplementary motor area (pre-SMA) was smaller in MDD patients. The GMV of both hippocampi was positively correlated with symptom severity and lower in patients with long durations. These results indicate the GMV reduction of the pre-SMA at an early stage of depression, whereas the GMV of the hippocampus is associated with depressive characteristics. Moreover, the whole brain GMV/WMV was negatively related to the duration of depression, supporting that volume loss could become progressive during the development of disease. These results may suggest the importance of identifying and intervening depression at an early stage, especially the first year after onset, to prevent volume loss in the brain.     

Neuropsychological functioning in major depression and responsiveness to selective serotonin reuptake inhibitors antidepressants

BACKGROUND: Only two thirds of patients with major depression (MD) respond to antidepressants. Thus, far applicable predictors of responsiveness to selective serotonergic reuptake inhibitors (SSRIs) have not been found. Cumulative evidence linking serotonergic depletion and cognition led us to hypothesize that the neuropsychological functioning of major depression patients may predict their responsiveness to SSRI antidepressants. METHODS: Fifty-five patients meeting DSM-IV criteria for major depression and strict inclusion and exclusion criteria underwent an extensive clinical and neuropsychological assessment prior to the initiation of selective serotonergic treatment. Following 6 weeks of treatment, severity of depression was reassessed, yielding a responsiveness score by which classification of each subject as a responder or nonresponder was made. The study was double blind. RESULTS: Logistic regression yielded neuropsychological indices, which significantly predicted the probability of depressed patients to respond favorably to SSRIs. Responders were characterized by better functioning in "simple" tasks and by worse functioning in "complex" tasks compared to nonresponders. No differences were found for more lateralized right or left hemisphere functions between responders and nonresponders. LIMITATIONS: Drug treatment comprised of SSRIs but was not standardized. Responsiveness was assessed following 6 weeks of treatment providing for initial amelioration rather than full remission. Placebo response was not controlled for. These limitations may influence the interpretation of the findings. CONCLUSIONS: The present findings suggest that responders and nonresponders to SSRIs might be distinguished by their neuropsychological functioning before treatment. If our findings are replicated, more efficient treatment might be practiced.     

Growth hormone and prolactin response to apomorphine in bipolar and unipolar depression

BACKGROUND: It has been suggested that patients with bipolar disorder may have an increased sensitivity to dopaminergic (DA) compounds. This was investigated by measuring growth hormone (GH) or prolactin (PRL) response to apomorphine (APO), a dopamine receptor agonist, in patients with bipolar depression, unipolar depression and control subjects. METHODS: Fourteen patients in an episode of bipolar depression (BP), 15 in an episode of unipolar depression (UP) and 19 age- and gender-matched control subjects (C) participated. The growth hormone (GH) and prolactin (PRL) responses to subcutaneous administration of 0.005 or 0.008 mg/kg APO were measured over 2 h. RESULTS: The rise in GH was greater with the higher APO dose. Both the GH rise and the PRL fall following APO were similar in BP, UP and C. Neither the GH or PRL responses in BP and UP were affected by successful treatment of the depressive episode. CONCLUSION: Our findings do not indicate an altered sensitivity of DA neurones in the hypothalamic-pituitary system in either bipolar or unipolar depression.     

The role of spatial store and executive strategy in spatial working memory: a comparison between patients with obsessive–compulsive disorder and controls

Introduction: Patients with obsessive–compulsive disorder (OCD) showed impaired spatial working memory (SWM). We evaluated whether patients and healthy controls (HCs) differed in spatial store capacity, and whether they differed in the relative weight of spatial store capacity and/or executive strategy in SWM.

Methods: Thirty inpatients with OCD and 31 age- and education-matched HCs underwent the CANTAB SWM, SRM (a measure of spatial store). The severity of OC symptoms was assessed using the Y-BOCS. Statistical significance: α?=?0.05.

Results: Patients showed poorer performance than HCs in all neuropsychological outcomes. Both poorer SRM and SWM strategy were significantly associated with poorer SWM in the entire sample. No significant interaction between SRM and Group was found, while a significant interaction between SWM strategy and Group emerged; in patients the magnitude of this association was approximately twofold larger than in HCs. OC symptom severity did not correlate with neuropsychological performance.

Conclusions: Patients with OCD had poorer spatial store capacity than HCs. However, the weight of poorer executive strategy in SWM was greater in patients than HCs, whereas the weight of spatial store was similar. We provided a direct evidence that an impairment in the executive component might be the crucial factor influencing the poorer SWM of these patients.     

SNCA variants rs2736990 and rs356220 as risk factors for Parkinson’s disease but not for amyotrophic lateral sclerosis and multiple system atrophy in a Chinese population

Previous studies found that polymorphisms rs2736990 and rs356220 in the alpha-synuclein (SNCA) gene increase the risk for Parkinson's disease (PD) in a Caucasian population. In consideration of the overlapping of clinical manifestations and pathologic characteristics among PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA), the possible associations of these 2 polymorphisms and 3 neurodegenerative diseases were studied in the Chinese population. A total of 1011 PD, 778 sporadic ALS (SALS), 264 MSA patients, and 721 healthy controls (HCs) were studied. All subjects were genotyped for the 2 polymorphisms using polymerase chain reaction and direct sequencing. Significant differences in the genotype frequencies (p = 0.0188 and 0.0064, respectively) and minor allele frequencies (MAFs) (p = 0.0065 and 0.0095, respectively) of rs2736990 and rs356220 were observed between the PD patients and HCs. Moreover, significant differences were found between the early-onset PD patients (<50 years) and matched controls but not in the late-onset PD patients (≥50 years). However, no differences were observed between subgroups with regard to clinical features, such as sex, onset symptoms (tremor or rigidity), cognition (normal or abnormal), and anxiety and depression (presence or absence). No significant differences were found in the genotype frequencies and MAFs of these 2 single-nucleotide polymorphisms between SALS patients and HCs and between MSA patients and HCs. No significant differences were found between subgroups with regard to the clinical presentation of SALS and MSA. Our results show that rs2736990 and rs356220 in SNCA decreased the risk for PD in a Chinese population. These candidate polymorphisms were unlikely to be the causes of SALS and MSA in this population.     

男性类风湿关节炎患者血浆催乳素水平的变化及其临床意义

目的：为探讨男性类风湿关节炎（ＲＡ）患者血浆催乳素（ＰＲＬ）水平的变化有临床意义。方法：用放射免疫法对６２例男性ＲＡ患者进行了血浆ＰＲＬ、雄激素睾酮（Ｔ）Ｔ、去氢表雄固酮（ＤＨＥＡ－Ｓ）水平测定及其多聚酶链反应（ＰＣＲ）作了ＨＬＡ＿ＤＲ４筛选,并与相庆的临床和实验室指标作对比分析。结果：ＲＡ患者血冰ＰＲＬ水平与正常人比较无显著差异,但在中度以上活动性的患者或ＨＬＡ＿ＤＲ４阳性患者中的血浆ＰＲＬ水平     

Prediction of the three-year course of recurrent depression in primary care patients: different risk factors for different outcomes

BACKGROUND: The objectives of this study are: (1) identification of predictors for the three-year course of recurrent depression in the rarely studied, but relevant sample of primary care patients, and (2) investigation whether different outcome indicators, time to recurrence, proportion depression-free time and mean severity of depressive symptoms during follow-up, are associated with different risk factors. METHODS: Depression course was established by assessing 110 patients three-monthly with the Composite International Diagnostic Interview and the BDI, during a three-year period. Eight (groups of) predictors, assessed at baseline, were examined: socio-demographics, parental depression, history and severity of depression, anxiety, coping potential, social dysfunctioning and physical functioning. RESULTS: Time to recurrence was predicted by number of previous episodes (OR=1.91). Both proportion depressive disorder-free time and mean depression severity during follow-up were predicted by: severity of depression (B=-.19 and .21 respectively), anxiety (B=-.32 and .33), social dysfunctioning (B=-.21 and .22) and physical functioning (B=.24 and -.39). Mean severity was additionally predicted by: educational level (B=-.21), duration of the longest prior episode (B=.32), and coping potential (B=-.40). Coping potential and number of previous episodes were marginally significant predictors for all three outcomes. LIMITATIONS: Although substantial, sample size was restricted. CONCLUSION: Different outcome variables are predicted by different risk factors. Restriction to one outcome may lead to missing important determinants of the depression course. Number of prior episodes and coping potential seem to warrant special attention from the GP.     

Clinical significance of sirtuin 1 level in sepsis: correlation with disease risk,severity, and mortality risk

This study aimed to investigate the value of sirtuin 1 (SIRT1) in differentiating sepsis patients from healthy controls (HCs), and its correlation with inflammation, disease severity, as well as prognosis in sepsis patients. Serum samples were collected from 180 sepsis patients and 180 age- and gender-matched HCs. The SIRT1 level in the serum samples was detected by enzyme-linked immunoassay. The clinical data of the sepsis patients were documented, and their disease severity scores and 28-day mortality rate were assessed. SIRT1 was decreased in sepsis patients compared with HCs, and the receiver operating characteristic curve (ROC) showed that SIRT1 distinguished sepsis patients from HCs (area under the curve (AUC): 0.901; 95% confidence interval (CI): 0.868-0.934). In sepsis patients, SIRT1 negatively correlated with serum creatinine (Scr), white blood cells (WBC), C-reactive protein (CRP), acute physiology, and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score, while it positively correlated with albumin. No correlation of SIRT1 with primary infection site or primary organism was observed. Furthermore, SIRT1 was reduced in 28-day non-survivors compared with 28-day survivors, and subsequent ROC showed that SIRT1 predicted 28-day mortality of sepsis patients (AUC: 0.725; 95% CI: 0.651-0.800), and its prognostic value was not inferior to Scr, albumin, WBC, and CRP, but was less than SOFA score and APACHE II score. In conclusion, measurement of serum SIRT1 might assist with the optimization of disease assessment, management strategies, and survival surveillance in sepsis patients.     

Depression with atypical features in a sample of primary care outpatients: prevalence, specific characteristics and consequences

BACKGROUND: In the context of the current debate on the clinical relevance of atypical depression, the present study investigated the prevalence and specific characteristics of the disorder in depressed primary care outpatients and compared patients with atypical and with the prototypical form of depression ("non-atypical" depression). METHODS: 403 patients were examined using the Composite International Diagnostic Interview, Inventory of Depressive Symptomatology, Hamilton Depression Scale and DSM-IV criteria. Configurational frequency analyses (CFA) were conducted to identify non-random configurations of symptoms. Moreover, tests for independent sample comparisons were applied. RESULTS: The prevalence of atypical depression in our sample of depressed patients was 26.3%. CFA revealed one significant symptom pattern: mood reactivity without additional atypical features (p<0.000001). A significant difference emerged between patients suffering from atypical versus non-atypical depression in terms of severity (p< or =0.001). LIMITATIONS: The sample size was modest. CONCLUSIONS: A considerable proportion of depressed primary care outpatients may suffer from atypical depression which may contribute to under-recognition of depression in primary care. Results of CFA indicated the significance of mood reactivity which may also occur in depressed patients without additional atypical symptoms. Patients with atypical depression may suffer from less severe depression as compared to patients with non-atypical depression.     

Examining differential effects of psychological treatment of depressive disorder: an application of trajectory analyses

BACKGROUND: Although different psychological treatments of depression seem equally effective, studies in this area have not taken sufficient account of the heterogeneity among patients. Modern techniques for longitudinal data analysis can be helpful in examining differential effects of psychological interventions on specific subpopulations of patients. METHODS: Outpatients in mental health care, diagnosed with DSM-IV major depressive disorder, were randomly assigned to cognitive behavior therapy (N=199) or treatment as usual (N=226). Every 3 months for a total of 1.5 years, depressive symptomatology was measured using the SCL-90. Growth mixture modeling techniques were used to identify different trajectory classes of patients. The impact of type of treatment (treatment as usual vs. cognitive behavior therapy) was examined for each identified trajectory. RESULTS: On average, patients in both test conditions improved significantly from baseline to posttest, and no significant difference was found between the conditions. However, four different trajectory classes could be distinguished within the sample. Most patients were classified into the two classes with the lowest depression scores at baseline (31% and 33% of the total sample). For these two classes, no significant differences in the course of depressive symptoms were found between the two conditions. In the two classes with the more severe depression scores (10% and 26% of the sample), however, cognitive behavior therapy was significantly more effective than treatment as usual. CONCLUSIONS: Although different treatments may seem to be equally effective, this does not have to be true for all classes of patients. Longitudinal research on the treatment of mental disorders should take heterogeneity among patients into account.