Clinical Patterns and Treatment Outcome in Patients with Melancholic,Atypical and Non-Melancholic Depressions

Objective

To assess sociodemographic, clinical and treatment factors as well as depression outcome in a large representative clinical sample of psychiatric depressive outpatients and to determine if melancholic and atypical depression can be differentiated from residual non-melancholic depressive conditions.

Subjects/Materials and Method

A prospective, naturalistic, multicentre, nationwide epidemiological study of 1455 depressive outpatients was undertaken. Severity of depressive symptoms was assessed by the Hamilton Depression Rating Scale (HDRS) and the Self Rated Inventory of Depressive Symptomatology (IDS-SR₃₀). IDS-SR₃₀ defines melancholic and atypical depression according to DSM-IV criteria. Assessments were carried out after 6–8 weeks of antidepressant treatment and after 14–20 weeks of continuation treatment.

Results

Melancholic patients (16.2%) were more severely depressed, had more depressive episodes and shorter episode duration than atypical (24.7%) and non-melancholic patients. Atypical depressive patients showed higher rates of co-morbid anxiety disorders and substance abuse. Melancholic patients showed lower rates of remission.

Conclusion

Our study supports a different clinical pattern and treatment outcome for melancholic and atypical depression subtypes.     

Advanced computer graphics technology reveals cortical asymmetry in endocasts of rhesus monkeys

Lengths of cortical sulci were measured on ten endocranial casts (endocasts) from skulls of rhesus monkeys, using advanced computer technology that permits analysis and imaging of surface morphology in three dimensions. Sulcal lengths were compared in left and right hemispheres and, contrary to earlier reports, the length of the left Sylvian fissure was found to be significantly longer than its right counterpart, as is the case for chimpanzees and humans. This asymmetry in humans is thought to be associated with asymmetrical representation of language functions in the left hemisphere and, although this report is the first to demonstrate a significantly longer left Sylvian fissure in rhesus monkeys, our results are in keeping with psychophysical evidence that suggests that Macaca is left hemisphere dominant for perception of meaningful vocalizations. We attribute the difference between our findings and previous reports to the sensitivity of the new computer technology used to collect data from endocasts.     

Anatomical brain asymmetries in New World and Old World monkeys: stages of temporal lobe development in primate evolution

Relatively large (n = 20-30) samples of formalin-fixed brain specimens from five Old and New World monkey species were examined in a study measuring anatomical temporal-lobe asymmetries. Linear measurements of the length of the Sylvian fissure were taken on each cerebral hemisphere to evaluate lateral differences related to development of auditory association cortex. The results indicate significantly greater Sylvian fissure length on the left hemisphere than on the right hemisphere in four of these species. Measurements of a different parameter on Saimiri sciureus brain specimens (length of anterior portion of the Sylvian fissure) also suggested temporal-lobe asymmetry favoring the left hemisphere. Other measurements (length of the Sylvian fissure lying posterior to the central sulcus, and dorso-ventral position of the Sylvian point) in Macaca mulatta and M. fascicularis did not reveal significant right/left-hemisphere differences. Sylvian-fissure length determined from photographs of M. mulatta hemispheres in contrast to results of direct measurements did not yield significant right/left-hemisphere asymmetry. We mention possible reasons why previous anatomical studies of brains from monkeys did not discern temporal-lobe asymmetry, and we also discuss whether or not certain of these asymmetries in monkeys foreshadowed the evolution of language-processing areas of the cerebral cortex in hominids.     

Hippocampus shape analysis and late-life depression

Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F(1,103) = 5.26; p = 0.0240) but not right hippocampus volume (F(1,103) = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms.     

Cerebral asymmetry in Old World monkeys.

A photogrammetric computer analysis of 88 endocasts, representing 8 genera of Old World monkeys, reveals cortical asymmetry in lengths of the Sylvian fissure, superior temporal sulcus, lateral edge of the orbit and distance separating rectus and arcuate sulci. Hypothetical expansion of left prefrontal and parietal integration cortices explains these asymmetries.     

Disentangling depression and distress networks in the tinnitus brain

Tinnitus is the continuous perception of an internal auditory stimulus. This permanent sound often affects a person's emotional state inducing distress and depressive feelings changes in 6-25% of the affected population. Distress and depression are two distinct emotional states. Whereas distress describes a transient aversive state, interfering with a person's ability to adequately adapt to stressors, depressive feelings should rather be considered as a more constant emotional state. Based on previous observations in chronic pain, posttraumatic stress disorder and depression, we assume that both states are related to separate neural circuits. We used the Dutch version of the Tinnitus Questionnaire to assess the global index of distress together with the Beck Depression Inventory to evaluate the depressive symptoms accompanying tinnitus. Furthermore sLORETA analysis was performed to correlate current density distribution with distress and depression scores, revealing a lateralization effect of depression versus distress. Distress is mainly correlated with alpha 2, beta 1 and beta 2 activity of the right frontopolar cortex and orbitofrontal cortex in combination with beta 2 activation of the anterior cingulate cortex. In contrast, the more permanent depressive alterations induced by tinnitus are associated with activity of alpha 2 activity in the left frontopolar and orbitofrontal cortex. These specific neural circuits are embedded in a greater neural network, with the parahippocampal region functioning as a crucial linkage between both tinnitus related pathways.     

Altered Spontaneous Brain Activity in Patients with Parkinson’s Disease Accompanied by Depressive Symptoms,as Revealed by Regional Homogeneity and Functional Connectivity in the Prefrontal-Limbic System

As patients with Parkinson’s disease (PD) are at high risk for comorbid depression, it is hypothesized that these two diseases are sharing common pathogenic pathways. Using regional homogeneity (ReHo) and functional connectivity approaches, we characterized human regional brain activity at resting state to examine specific brain networks in patients with PD and those with PD and depression (PDD). This study comprised 41 PD human patients and 25 normal human subjects. The patients completed the Hamilton Depression Rating Scale and were further divided into two groups: patients with depressive symptoms and non-depressed PD patients (nD-PD). Compared with the non-depressed patients, those with depressive symptoms exhibited significantly increased regional activity in the left middle frontal gyrus and right inferior frontal gyrus, and decreased ReHo in the left amygdala and bilateral lingual gyrus. Brain network connectivity analysis revealed decreased functional connectivity within the prefrontal-limbic system and increased functional connectivity in the prefrontal cortex and lingual gyrus in PDD compared with the nD-PD group. In summary, the findings showed regional brain activity alterations and disruption of the mood regulation network in PDD patients. The pathogenesis of PDD may be attributed to abnormal neural activity in multiple brain regions.     

Corticotropin-releasing hormone in depression and post-traumatic stress disorder

Corticotropin-releasing hormone (CRH) has been implicated in the regulation of a wide range of behaviors including arousal, motor function, feeding, and reproduction. Because depressed patients are often hypercortisolemic and intracerebroventricular administration of CRH to experimental animals produces a syndrome reminiscent of depression, dysregulation of this compound has been suggested to be involved in the pathogenesis of depressive and anxiety disorders. Studies of cerebrospinal fluid CRH levels and clinical neuroendocrine tests in patients with anxiety and affective disorders have supported this hypothesis. This review discusses these neuroendocrine findings in melancholic and atypical depression as well as post-traumatic stress disorder (PTSD). Overall, the data suggest that melancholic depression is characterized by hyperactive central CRH systems with overactivity of the pituitary-adrenal (HPA) axis. On the other hand, atypical depression is characterized by hypoactive central CRH systems and accompanying underactivity of the hypothalamic-pituitary-adrenal axis. Furthermore, the neuroendocrinology of PTSD appears to be unique, in that patients have hyperactive central CRH systems with underactivity of the pituitary-adrenal axis.     

Cortical thinning in patients with recent onset post-traumatic stress disorder after a single prolonged trauma exposure

Most of magnetic resonance imaging (MRI) studies about post-traumatic stress disorder (PTSD) focused primarily on measuring of small brain structure volume or regional brain volume changes. There were rare reports investigating cortical thickness alterations in recent onset PTSD. Recent advances in computational analysis made it possible to measure cortical thickness in a fully automatic way, along with voxel-based morphometry (VBM) that enables an exploration of global structural changes throughout the brain by applying statistical parametric mapping (SPM) to high-resolution MRI. In this paper, Laplacian method was utilized to estimate cortical thickness after automatic segmentation of gray matter from MR images under SPM. Then thickness maps were analyzed by SPM8. Comparison between 10 survivors from a mining disaster with recent onset PTSD and 10 survivors without PTSD from the same trauma indicates cortical thinning in the left parietal lobe, right inferior frontal gyrus, and right parahippocampal gyrus. The regional cortical thickness of the right inferior frontal gyrus showed a significant negative correlation with the CAPS score in the patients with PTSD. Our study suggests that shape-related cortical thickness analysis may be more sensitive than volumetric analysis to subtle alteration at early stage of PTSD.     

Insular and Hippocampal Gray Matter Volume Reductions in Patients with Major Depressive Disorder

Background

Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder.

Methods

For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes.

Results

Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala.

Conclusions

The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy.     

Reduced lumbar CSF somatostatin levels in Alzheimer's disease

The lumbar CSF of control, demented (Alzheimer's and Korsakoff's) and schizophrenic patients was examined for markers of cholinergic, monoaminergic and peptidergic systems. In all groups, no alteration in CSF acetylcholinesterase was observed, with the monoamine metabolites homovanillic acid, monohydroxyphenylglycol, and 5-hydroxy-indole acetic acid expressing only minor alterations. In contrast, somatostatin (SRIH) was dramatically (50%) reduced in the CSF of Alzheimer's dementia (AD) and mixed dementia patients. These decreases in CSF SRIH correlate with previous reports of reductions in cortical SRIH in AD suggesting that such measurements may be useful markers of AD.     

Le soi vulnérable: Identité, ipséité et depersonnalisation dans la mélancolie et dans la schizophrénie

Schizophrenic and melancholie abnormal experiences reveal—an statu-detrahendi—different levels of the self Schizophrenic depersonalization shows the most profound level of self awarness the pre-reflective one—the self as the tacit dimension of what is given the non reflexsive first-person In schizophrenia, this involves the experiencing of a dualistic Cartesian form of existence in which embodied self-awarness. Melancholic depersonalization highlights narrative identity—the self as the product of concerving oneself in a certain way An abnormal of the melanchoic-type existense, a manner of exiting in accordance with a finite perspective of arise when melancholic people cannot escape the demands of identity as a diatective process, by festricting themselves to being the-same and avoiding otherness in themselves.     

Hippocampal and Left Subcallosal Anterior Cingulate Atrophy in Psychotic Depression

Background

Psychotic depression is arguably the most diagnostically stable subtype of major depressive disorder, and an attractive target of study in a famously heterogeneous mental illness. Previous imaging studies have identified abnormal volumes of the hippocampus, amygdala, and subcallosal region of the anterior cingulate cortex (scACC) in psychotic depression, though studies have not yet examined the role of family history of depression in these relationships.

Methods

20 participants with psychotic depression preparing to undergo electroconvulsive therapy and 20 healthy comparison participants (13 women and 7 men in each group) underwent structural brain imaging in a 1.5 T MRI scanner. 15 of the psychotic depression group had a first-degree relative with diagnosed affective disorders, while the healthy control group had no first-degree relatives with affective disorders. Depression severity was assessed with the Hamilton Depression Rating Scale and duration of illness was assessed in all patients. Automated neural nets were used to isolate the hippocampi and amygdalae in each scan, and an established manual method was used to parcellate the anterior cingulate cortex into dorsal, rostral, subcallosal, and subgenual regions. The volumes of these regions were compared between groups. Effects of laterality and family history of affective disorders were examined as well.

Results

Patients with psychotic depression had significantly smaller left scACC and bilateral hippocampal volumes, while no group differences in other anterior cingulate cortex subregions or amygdala volumes were present. Hippocampal atrophy was found in all patients with psychotic depression, but reduced left scACC volume was found only in the patients with a family history of depression.

Conclusions

Patients with psychotic depression showed significant reduction in hippocampal volume bilaterally, perhaps due to high cortisol states associated with this illness. Reduced left scACC volume may be a vulnerability factor related to family history of depression.     

Antidepressant treatment normalizes white matter volume in patients with major depression

Objective

To investigate white matter volume abnormalities in patients with major depression and the effects of antidepressant treatment on white matter volume.

Method

Magnetic resonance imaging (MRI) was performed on 32 treatment-naïve depressed patients, 17 recovered patients who had received antidepressant treatment and subsequently achieved clinical recovery and 34 matched controls.

Results

Relative to the healthy controls, the treatment-naïve depressed patients showed increased white matter volumes in the left dorsolateral prefrontal cortex (DLPFC) and left putamen and reduced white matter volumes in the left cerebellum posterior lobe and left inferior parietal lobule. For the treatment-naïve patients, the length in months of the current depressive episode was positively correlated with the white matter volumes in both the left DLPFC and left putamen. In the recovered patients, the differences in white matter volume were no longer statistically significant relative to healthy controls. No significant difference was found in the total white matter volume among the three groups.

Conclusions

This study demonstrates that there were alterations in the white matter volumes of depressed patients, which might disrupt the neural circuits that are involved in emotional and cognitive function and thus contribute to the pathophysiology of depression. The finding of the significant correlations between refractoriness and the white matter volumes in the left DLPFC and left putamen combined with the finding that antidepressant treatment normalized the white matter volume of recovered patients, suggests that a quantitative, structural MRI measurement could act as a potential biomarker in depression therapy for individual subjects.     

Robust Volume Assessment of Brain Tissues for 3-Dimensional Fourier Transformation MRI via a Novel Multispectral Technique

A new TRIO algorithm method integrating three different algorithms is proposed to perform brain MRI segmentation in the native coordinate space, with no need of transformation to a standard coordinate space or the probability maps for segmentation. The method is a simple voxel-based algorithm, derived from multispectral remote sensing techniques, and only requires minimal operator input to depict GM, WM, and CSF tissue clusters to complete classification of a 3D high-resolution multislice-multispectral MRI data. Results showed very high accuracy and reproducibility in classification of GM, WM, and CSF in multislice-multispectral synthetic MRI data. The similarity indexes, expressing overlap between classification results and the ground truth, were 0.951, 0.962, and 0.956 for GM, WM, and CSF classifications in the image data with 3% noise level and 0% non-uniformity intensity. The method particularly allows for classification of CSF with 0.994, 0.961 and 0.996 of accuracy, sensitivity and specificity in images data with 3% noise level and 0% non-uniformity intensity, which had seldom performed well in previous studies. As for clinical MRI data, the quantitative data of brain tissue volumes aligned closely with the brain morphometrics in three different study groups of young adults, elderly volunteers, and dementia patients. The results also showed very low rates of the intra- and extra-operator variability in measurements of the absolute volumes and volume fractions of cerebral GM, WM, and CSF in three different study groups. The mean coefficients of variation of GM, WM, and CSF volume measurements were in the range of 0.03% to 0.30% of intra-operator measurements and 0.06% to 0.45% of inter-operator measurements. In conclusion, the TRIO algorithm exhibits a remarkable ability in robust classification of multislice-multispectral brain MR images, which would be potentially applicable for clinical brain volumetric analysis and explicitly promising in cross-sectional and longitudinal studies of different subject groups.     

Increased Neural Cell Adhesion Molecule in the CSF of Patients with Mood Disorder

Abstract: Neural cell adhesion molecule (N-CAM) is involved in cell-cell interactions during synaptogenesis, morphogenesis, and plasticity of the nervous system. Disturbances in synaptic restructuring and neural plasticity may be related to the pathogenesis of several neuropsychiatric diseases, including mood disorders and schizophrenia. Disturbances in brain cellular function may alter concentrations of N-CAM in the CSF. Soluble human N-CAM proteins are detectable in the CSF but are minor constituents of serum. We have recently found an increase in N-CAM content in the CSF of patients with schizophrenia. Although the pathogenesis of both schizophrenia and mood disorders is unknown, ventriculomegaly, decreased temporal lobe volume, and subcortical structural abnormalities have been reported for both disorders. We have therefore measured N-CAM concentrations in the CSF of patients with mood disorder. There were significant increases in amounts of N-CAM immunoreactive proteins, primarily the 120-kDa band, in the CSF of psychiatric inpatients with bipolar mood disorder type I and recurrent unipolar major depression. There were no differences in bipolar mood disorder type II patients as compared with normals. There were no significant effects of medication treatment on N-CAM concentrations. It is possible that the 120-kDa N-CAM band present in the CSF is derived from CNS cells as a secreted soluble N-CAM isoform. Our results suggest the possibility of latent state-related disturbances in N-CAM cellular function, i.e., residue from a previous episode, or abnormal N-CAM turnover in the CNS of patients with mood disorder.     

La dépression et le traitement antidépresseur: de la neurotoxicité à la neurogenèse

Major depressive disorder is characterized by structural and neurochemical changes in limbic structures, including the hippocampus that regulates mood and cognitive functions. Hippocampal atrophy is observed in patients with depression: structural changes in the hippocampus associated with depression include dendritic atrophy, decreased adult neurogenesis and reduced volume. Impairment of neuroplasticity in the hippocampus, amygdala and cortex is hypothesized to be the mechanism by which cognitive function, episodic verbal memory and emotions are altered in depression. Chronic stress exposure and depression leads to hippocampal atrophy and cell loss as well as to decreased expression of neurotrophic growth factors. All types of antidepressant drugs reverse or block the effects of stress. Chronic antidepressant administration upregulates neurogenesis and neuroplasticity in the adult hippocampus and these cellular responses are required for the effects of antidepressants in animal models of depression.     

EEG of the interstimulus intervals during habituation of auditory evoked potentials in depressive moods

Averaging of EEG of interstimulus intervals in the process of study of habituation of auditory evoked potentials (EPs) in healthy subjects and patients with endogenous depression, revealed a rhythmic wave process (RWP) especially expressed in patients. RWP appeared and became stronger in successive averaging of 10 realizations completing each of four series of 30 clicks; often (especially in depressive patients) it was manifest in averaging of all 120 realizations with an amplitude comparable with that of main EPs components and even greater. A significant correlation was found of RWP parameters with characteristics of melancholic mood in both subgroups. It is suggested that RWP appears as a result of regular changes of EEG background during multiple stimuli repetition in connection with increased "slow" habituation and in a special manifestation of perceptive defence during depression including mechanisms of active isolation from external world.     

Antepartum Depression Severity is Increased During Seasonally Longer Nights: Relationship to Melatonin and Cortisol Timing and Quantity

Current research suggests that mood varies from season to season in some individuals, in conjunction with light-modulated alterations in chronobiologic indices such as melatonin and cortisol. The primary aim of this study was to evaluate the effects of seasonal variations in darkness on mood in depressed antepartum women, and to determine the relationship of seasonal mood variations to contemporaneous blood melatonin and cortisol measures; a secondary aim was to evaluate the influence of seasonal factors on measures of melancholic versus atypical depressive symptoms. We obtained measures of mood and overnight concentrations of plasma melatonin and serum cortisol in 19 depressed patients (DP) and 12 healthy control (HC) antepartum women, during on-going seasonal variations in daylight/darkness, in a cross-sectional design. Analyses of variance showed that in DP, but not HC, Hamilton Depression Rating Scale (HRSD) scores were significantly higher in women tested during seasonally longer versus shorter nights. This exacerbation of depressive symptoms occurred when the dim light melatonin onset, the melatonin synthesis offset, and the time of maximum cortisol secretion (acrophase) were phase-advanced (temporally shifted earlier), and melatonin quantity was reduced, in DP but not HC. Serum cortisol increased across gestational weeks in both the HC and DP groups, which did not differ significantly in cortisol concentration. Nevertheless, serum cortisol concentration correlated positively with HRSD score in DP but not HC; notably, HC showed neither significant mood changes nor altered melatonin and cortisol timing or quantity in association with seasonal variations. These findings suggest that depression severity during pregnancy may become elevated in association with seasonally related phase advances in melatonin and cortisol timing and reduced melatonin quantity that occur in DP, but not HC. Thus, women who experience antepartum depression may be more susceptible than their nondepressed counterparts to phase alterations in melatonin and cortisol timing during seasonally longer nights. Interventions that phase delay melatonin and/or cortisol timing—for example, increased exposure to bright evening light—might serve as an effective intervention for antepartum depressions whose severity is increased during seasonally longer nights.     

Increased Cortical-Limbic Anatomical Network Connectivity in Major Depression Revealed by Diffusion Tensor Imaging

Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients = 86.4%, controls = 96.2%; permutation test, p<0.0001) of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease.