Prolactin response to fenfluramine administration in patients with unipolar and bipolar depression and healthy controls

The hormonal response to the serotonin releasing agent/uptake inhibitor fenfluramine has been used as an indicator of central serotonin system function. The serotonergic system plays an important role in the etiology and pathogenesis of mood disorders. We compared the prolactin response to fenfluramine administration in unipolar depressed patients (major depressive disorder), depressed patients with bipolar disorder, and healthy controls. We found a trend towards a blunted prolactin response in depressed patients compared to healthy controls, after controlling for sex, family history, family history-by-gender interaction, and baseline levels. There was no significant difference between unipolar and bipolar patients in the baseline prolactin levels or the response to the fenfluramine administration. We also found a negative correlation between aggression and impulsivity scores and prolactin responses in subgroup with unipolar but not bipolar depression. Female patients with unipolar depression who had first-degree relatives with unipolar depression and normal controls had significantly higher prolactin responses than female patients with unipolar depression who did not have first-degree relatives with unipolar depression. The lack of difference in the response to fenfluramine administration between unipolar and bipolar depressed patients may indicate that overall serotonergic function in unipolar and bipolar depressed patients is similarly impaired.     

Hippocampal shape alterations in healthy young women with familial risk for unipolar depression

BackgroundAlthough reduced hippocampal volume (HCV) is a common finding in depression, it is unclear whether the structural alterations leading to reduction of HCV are pre-existing risk factors before the onset of clinical symptoms or a cumulative process that begins with the onset of clinical symptoms. The aim of the present study was to understand the anatomical status of the hippocampus prior to the clinical symptoms in subjects with high familial risk for depression.MethodsTwenty-seven young women (mean age: 22.3 ± 2.1 years) who were at high risk for familial unipolar depression and 26 age- and gender-matched healthy controls (mean age: 22.1 ± 2.1 years) with low familial risk for depression were included in the study. Total hippocampal volumes were measured by manual tracing. For 3D shape differences, the spherical harmonic basis functions (SPHARM) software was used. The segmented images were parameterized, and the point-to-point based group difference was compared by the Hotelling's T-squared test with total brain volume and Beck Depression Scale as covariates.ResultsAlthough there was no difference in overall HCVs, shape analyses revealed a contracted area on the Cornu Ammonis (CA) 1 region of the right hippocampus head in the high-risk group compared to the low-risk group. Cross-sectional design and small sample size, including only females, were the main limitations of this study.ConclusionThis study with shape analyses provided data suggesting that local structural hippocampal alterations in the CA1 region might be associated with depression vulnerability in women at high risk.     

Differentiation of women with premenstrual dysphoric disorder, recurrent brief depression, and healthy controls by daily mood rating dynamics

Enhanced statistical characterization of mood-rating data holds the potential to more precisely classify and sub-classify recurrent mood disorders like premenstrual dysphoric disorder (PMDD) and recurrent brief depressive disorder (RBD). We applied several complementary statistical methods to differentiate mood rating dynamics among women with PMDD, RBD, and normal controls (NC). We compared three subgroups of women: NC (n=8); PMDD (n=15); and RBD (n=9) on the basis of daily self-ratings of sadness, study lengths between 50 and 120 days. We analyzed mean levels; overall variability, SD; sequential irregularity, approximate entropy (ApEn); and a quantification of the extent of brief and staccato dynamics, denoted 'Spikiness'. For each of SD, irregularity (ApEn), and Spikiness, we showed highly significant subgroup differences, ANOVA0.001 for each statistic; additionally, many paired subgroup comparisons showed highly significant differences. In contrast, mean levels were indistinct among the subgroups. For SD, normal controls had much smaller levels than the other subgroups, with RBD intermediate. ApEn showed PMDD to be significantly more regular than the other subgroups. Spikiness showed NC and RBD data sets to be much more staccato than their PMDD counterparts, and appears to suitably characterize the defining feature of RBD dynamics. Compound criteria based on these statistical measures discriminated diagnostic subgroups with high sensitivity and specificity. Taken together, the statistical suite provides well-defined specifications of each subgroup. This can facilitate accurate diagnosis, and augment the prediction and evaluation of response to treatment. The statistical methodologies have broad and direct applicability to behavioral studies for many psychiatric disorders, and indeed to similar analyses of associated biological signals across multiple axes.     

Menstrual dysfunction prior to onset of psychiatric illness is reported more commonly by women with bipolar disorder than by women with unipolar depression and healthy controls

BACKGROUND: Preliminary reports suggest that menstrual cycle irregularities occur more commonly in women with bipolar disorder and unipolar depression than in the general population. However, it is not always clear whether such abnormalities, reflecting disruption of the hypothalamic-pituitary-gonadal (HPG) axis, are caused by psychotropic treatments or associated with the disorder per se. METHOD: The prevalence of early-onset (within the first 5 postmenarchal years) menstrual cycle dysfunction (menstrual cycle length unpredictable within 10 days or menstrual cycle length<25 days or >35 days) occurring before onset of psychiatric illness was compared between subjects with DSM-IV bipolar disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and subjects with DSM-IV unipolar depression or no psychiatric illness participating in the Harvard Study of Moods and Cycles. Data from the Harvard Study of Moods and Cycles were gathered from September 1995 to September 1997, and data from STEP-BD were gathered from November 1999 to May 2001. RESULTS: Early-onset menstrual cycle dysfunction was reported to have occurred in 101/295 women with bipolar disorder (34.2%), 60/245 women with depression (24.5%), and 134/619 healthy controls (21.7%). Women with bipolar disorder were more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi2=16.58, p<.0001) and depressed women (chi2=6.08, p=.01), while depressed women were not more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi2=0.81, p=.37). CONCLUSIONS: Compared with healthy controls and women with unipolar depression, women with bipolar disorder retrospectively report early-onset menstrual dysfunction more commonly prior to onset of bipolar disorder. Future studies should evaluate potential abnormalities in the hypothalamic-pituitary-gonadal axis that are associated with bipolar disorder.     

Prolactin secretion in women with unipolar and bipolar depression

Plasma prolactin levels and prolactin response to thyrotropin releasing hormone (TRH) were studied in 27 unipolar and 24 bipolar depressive female patients before and after tricyclic antidepressant treatment, as well as in 38 normal controls matched for age, sex, and menopausal status. Before antidepressant treatment, basal prolactin levels were significantly lower in both premenopausal and postmenopausal bipolar patients but only in postmenopausal unipolar patients when compared to controls. The prolactin response to TRH was significantly blunted in both unipolar and bipolar postmenopausal subjects but remained normal in all premenopausal (unipolar and bipolar) patients. These data suggest that prolactin pituitary function could be useful in the neuroendocrine study of depressive illness.     

Lymphocyte beta-adrenoreceptor density in patients with unipolar depression and normal controls

Values of binding maximum (Bmax) and dissociation constant (Kd) of (-)3-[125I]iodocyanopindolol (ICYP) were determined in beta-adrenergic receptors of membranes of peripheral lymphocytes in 32 patients with unipolar depression (DSM-III-R) and 31 normal controls. Results were analyzed by a two-way Analysis of Covariance method. A significant difference was noted for group assignment (patient versus control, p less than 0.05). Mean Bmax (fmol ICYP bound/mg lymphocyte membrane fraction total protein) of patients was 31.9 +/- 3.84 (SE) and controls 46.3 +/- 3.92 (SE). A significant interaction was found between group membership and gender (p less than 0.05). In the female patient group (n = 14), mean Bmax was 30.5 +/- 5.79 (SE); in female controls, mean Bmax was 56.0 +/- 5.15 (SE). Differences between male patients and male controls were not significant. Mean values of Kd (pmol/liter) showed a trend for patient values to be lower than control values [69.0 +/- 13.66 (SE) versus 108.5 +/- 14.42 (SE), respectively]. A significant inverse relationship was noted between lymphocyte beta-receptor Bmax and frequency of panic attacks during the depressive episode in 18 patients (p = 0.05). No relationship was found between values of Kd and frequency of panic attacks in these patients. Thus, preliminary evidence is provided for relationships among altered beta-adrenergic receptor binding, gender, and indices of panic-anxiety in unipolar depressed patients.     

Perception of facial emotion in adults with bipolar or unipolar depression and controls

Previous research indicates that patients with depression display deficits in their ability to perceive emotions. However, few studies have used animated facial stimuli or explored sensitivity to facial expressions in depressed individuals. Moreover, limited research is available on facial processing in unipolar versus bipolar depression. In this study, 34 patients with DSM-IV major depressive disorder (MDD), 21 patients with DSM-IV bipolar disorder (BPD) in the depressed phase, and 24 never-depressed controls completed the Emotional Expression Multimorph Task, which presents facial emotions in gradations from neutral to 100% emotional expression (happy, sad, surprised, fearful, angry, and disgusted). Groups were compared in terms of sensitivity and accuracy in identifying emotions. Our preliminary findings suggest that subjects with bipolar depression may have emotional processing abnormalities relative to controls.     

Effects of acute cortisol administration on response inhibition in patients with major depression and healthy controls

Glucocorticoids (GCs) have repeatedly been shown to impair hippocampus-mediated, declarative memory retrieval and prefrontal cortex-based working memory in healthy subjects. However, recent experimental studies indicated that patients with major depressive disorder (MDD) lack these impairing effects. These missing effects have been suggested to result from dysfunctional brain GC receptors. The purpose of the present study was to investigate whether response inhibition, an executive function relying on the integrity of the prefrontal cortex, would be impaired after cortisol administration in patients with MDD. In a placebo-controlled, double blind crossover study, 50 inpatients with MDD and 54 healthy control participants conducted an emotional go/no-go task consisting of human face stimuli (fearful, happy, and neutral) after receiving a dose of 10 mg hydrocortisone and after placebo. GC administration had an enhancing effect on inhibitory performance in healthy control participants, indicated by faster responses, while no GC effect was revealed for the patients group. Moreover, patients showed an overall worse performance than healthy participants. In conclusion, this study further supports the hypothesis of impaired central glucocorticoid receptor function in MDD patients. Regarding the importance of inhibitory functioning for daily living, further studies are needed to examine the impact of glucocorticoids on response inhibition.     

女性单相抑郁症对照研究

目的:了解女性单相抑郁症临床特征,包括共病情况与患病风险。方法:采用复合国际诊断访谈与自评式问卷调查方式,入组100例女性单相抑郁症患者与100例正常女性对照。结果:女性单相抑郁症与广泛性焦虑障碍、惊恐障碍、心境恶劣共病率较高,与对照组相比,抑郁症患者家族史阳性率高,艾森克人格问卷神经质维度评分高,生活应激明显。结论:女性单相抑郁症共病较多。神经质、家族史阳性、生活应激事件可能是患病风险因素。     

Effects of morning bright light on sleep in healthy elderly women

Subjective sleep feeling and polysomnography were measured in 10 elderly women to investigate the effects of 8000 lux morning bright light (BL) exposure. The profile of sleep feeling in the BL condition was better than in the control condition. The proportion of awakening time in the first one-third of night sleep decreased, and the amount of awakening time in the last one-third increased in BL condition. Daytime napping reduced in BL condition. These findings suggested the effectiveness of exposure to bright light on the improvement of sleep quality and daytime vigilance of healthy elderly women.     

Changes in brain metabolism associated with remission in unipolar major depression

OBJECTIVE: Functional brain correlates of remission in patients with major depressive disorder (MDD) are measured with positron emission tomography (PET) and 18F-fluorodeoxyglucose. METHOD: Glucose metabolism was measured in patients (n = 41) with moderate to severe MDD during acute depression and in the remitted state defined as a period of asymptomatic condition over 12 weeks. Data analyses used a region-of-interest (ROI) approach and statistical parametric mapping (SPM). RESULTS: There were significant decreases in metabolism upon remission with respect to the baseline scan in left prefrontal, anterior temporal and anterior cingulate cortex and bilateral thalamus (SPM analysis) and bilateral putamen and cerebellum (SPM and ROI analyses). There was a significant asymmetry in prefrontal and anterior cingulate cortex metabolism with lower metabolism in the left hemisphere that persisted despite clinical remission. CONCLUSION: These findings support the hypothesis that selective monoamine reuptake inhibition leads to an attenuation of a brain circuit that mediates depressive symptomatology.     

Electroencephalographic sleep of adolescents with major depression and normal controls

Forty-nine, mostly outpatient (86%), nonbipolar adolescents, aged Tanner stage III to 18 years, with a current diagnosis of major depressive disorder and 40 adolescents without current presence or history of psychiatric disorder were studied polysomnographically for three consecutive nights. Sleep latency was significantly longer in the depressive groups. The nonendogenous depressive patients exhibited significantly more awake time and lower sleep efficiency during the sleep period. No significant group differences were found for first rapid eye movement (REM) period latency, REM density, or any other REM sleep measures. Age correlated significantly with REM latency and delta sleep time, especially among depressive patients. No significant correlations between sleep measures and severity of illness were found. It appears that the classic REM sleep findings associated with the adult depressive syndrome are not present among depressive adolescents, indicating a later ontogeny for these abnormalities.     

Hippocampal volume changes in healthy subjects at risk of unipolar depression

Unipolar depression is moderately heritable. It is unclear whether structural brain changes associated with unipolar depression are present in healthy persons at risk of the disorder. Here we investigated whether a genetic predisposition to unipolar depression is associated with structural brain changes. A priori, hippocampal volume reductions were hypothesized. Using a high-risk study design, magnetic resonance imaging brain scans were obtained from 59 healthy high-risk subjects having a co-twin with unipolar depression, and 53 healthy low-risk subjects without a first-degree family history of major psychiatric disorder. High-risk twins had smaller hippocampal volumes than low-risk twins (p < 0.04). The finding was most pronounced in DZ twins. Groups did not differ on global brain tissue volumes or regional tissue volumes assessed in exploratory voxel-wise whole cerebrum analyses. In conclusion, hippocampal volume reduction may index a predisposition to develop depression and thus may be predictive of future onset of the disorder. Further studies are needed to elucidate the role of (shared) environmental and genetic factors.