Despite significant advances in neuroscience and treatment development, no widely accepted biomarkers are available to inform diagnostics or identify preferred treatments for individuals with major ...depressive disorder.
In this critical review, the authors examine the extent to which multimodal neuroimaging techniques can identify biomarkers reflecting key pathophysiologic processes in depression and whether such biomarkers may act as predictors, moderators, and mediators of treatment response that might facilitate development of personalized treatments based on a better understanding of these processes.
The authors first highlight the most consistent findings from neuroimaging studies using different techniques in depression, including structural and functional abnormalities in two parallel neural circuits: serotonergically modulated implicit emotion regulation circuitry, centered on the amygdala and different regions in the medial prefrontal cortex; and dopaminergically modulated reward neural circuitry, centered on the ventral striatum and medial prefrontal cortex. They then describe key findings from the relatively small number of studies indicating that specific measures of regional function and, to a lesser extent, structure in these neural circuits predict treatment response in depression.
Limitations of existing studies include small sample sizes, use of only one neuroimaging modality, and a focus on identifying predictors rather than moderators and mediators of differential treatment response. By addressing these limitations and, most importantly, capitalizing on the benefits of multimodal neuroimaging, future studies can yield moderators and mediators of treatment response in depression to facilitate significant improvements in shorter- and longer-term clinical and functional outcomes.
The structural abnormalities in the brain that accurately differentiate unipolar depression (UD) and bipolar depression (BD) remain unidentified.
First, to investigate and compare morphometric ...changes in UD and BD, and to replicate the findings at 2 independent neuroimaging sites; second, to differentiate UD and BD using multivariate pattern classification techniques.
In a 2-center cross-sectional study, structural gray matter data were obtained at 2 independent sites (Pittsburgh, Pennsylvania, and Münster, Germany) using 3-T magnetic resonance imaging. Voxel-based morphometry was used to compare local gray and white matter volumes, and a novel pattern classification approach was used to discriminate between UD and BD, while training the classifier at one imaging site and testing in an independent sample at the other site. The Pittsburgh sample of participants was recruited from the Western Psychiatric Institute and Clinic at the University of Pittsburgh from 2008 to 2012. The Münster sample was recruited from the Department of Psychiatry at the University of Münster from 2010 to 2012. Equally divided between the 2 sites were 58 currently depressed patients with bipolar I disorder, 58 age- and sex-matched unipolar depressed patients, and 58 matched healthy controls.
Magnetic resonance imaging was used to detect structural differences between groups. Morphometric analyses were applied using voxel-based morphometry. Pattern classification techniques were used for a multivariate approach.
At both sites, individuals with BD showed reduced gray matter volumes in the hippocampal formation and the amygdala relative to individuals with UD (Montreal Neurological Institute coordinates x = -22, y = -1, z = 20; k = 1938 voxels; t = 4.75), whereas individuals with UD showed reduced gray matter volumes in the anterior cingulate gyrus compared with individuals with BD (Montreal Neurological Institute coordinates x = -8, y = 32, z = 3; k = 979 voxels; t = 6.37; all corrected P < .05). Reductions in white matter volume within the cerebellum and hippocampus were found in individuals with BD. Pattern classification yielded up to 79.3% accuracy (P < .001) by differentiating the 2 depressed groups, training and testing the classifier at one site, and up to 69.0% accuracy (P < .001), training the classifier at one imaging site (Pittsburgh) and testing it at the other independent sample (Münster). Medication load did not alter the pattern of results.
Individuals with UD and those with BD are differentiated by structural abnormalities in neural regions supporting emotion processing. Neuroimaging and multivariate pattern classification techniques are promising tools to differentiate UD from BD and show promise as future diagnostic aids.
Background Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals ...being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Methods Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. Results The BDd—relative to HC, BDr, and MDD—showed elevated left amygdala activity to mild and neutral facial expressions in the sad ( p < .009) but not other emotion experiments that was not associated with medication. There were no other significant between-group differences in amygdala activity. Conclusions Abnormally elevated left amygdala activity to mild sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression.
Background Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD). ...Methods Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined. Results The BD versus HC showed significantly greater right amygdala-OFC FC ( p ≤ .001) in the sad experiment and significantly reduced bilateral amygdala-OFC FC ( p = .007) in the happy experiment. Depressed but not remitted female BD versus female HC showed significantly greater left amygdala-OFC FC ( p = .001) to all faces in the sad experiment and reduced bilateral amygdala-OFC FC to intense happy faces ( p = .01). There was a significant nonlinear relationship ( p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces ( p = .001). Conclusions In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC–FA relationships in BD and HC require further study.
The fate of high-redshift massive compact galaxies de la Rosa, Ignacio G; La Barbera, Francesco; Ferreras, Ignacio ...
Monthly notices of the Royal Astronomical Society,
04/2016, Letnik:
457, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Massive high-redshift quiescent compact galaxies (nicknamed red nuggets) have been traditionally connected to present-day elliptical galaxies, often overlooking the relationships that they may have ...with other galaxy types. We use large bulge–disc decomposition catalogues based on the Sloan Digital Sky Survey to check the hypothesis that red nuggets have survived as compact cores embedded inside the haloes or discs of present-day massive galaxies. In this study, we designate a compact core as the bulge component that satisfies a prescribed compactness criterion. Photometric and dynamic mass–size and mass–density relations are used to show that, in the inner regions of galaxies at z ∼ 0.1, there are abundant compact cores matching the peculiar properties of the red nuggets, an abundance comparable to that of red nuggets at z ∼ 1.5. Furthermore, the morphology distribution of the present-day galaxies hosting compact cores is used to demonstrate that, in addition to the standard channel connecting red nuggets with elliptical galaxies, a comparable fraction of red nuggets might have ended up embedded in discs. This result generalizes the inside-out formation scenario; present-day massive galaxies can begin as dense spheroidal cores (red nuggets), around which either a spheroidal halo or a disc is formed later.
Objectives The absence of pathophysiologically relevant diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We aimed to determine whether whole ...brain white matter connectivity differentiated BD from UD depression. Methods We employed a three-way analysis of covariance, covarying for age, to examine whole brain fractional anisotropy (FA), and corresponding longitudinal and radial diffusivity, in currently depressed adults: 15 with BD-type I (mean age 36.3 years, SD 12.0 years), 16 with recurrent UD (mean age 32.3 years, SD 10.0 years), and 24 healthy control adults (HC) (mean age 29.5 years, SD 9.43 years). Depressed groups did not differ in depression severity, age of illness onset, and illness duration. Results There was a main effect of group in left superior and inferior longitudinal fasciculi (SLF and ILF) (all F ≥ 9.8; p ≤ .05, corrected). Whole brain post hoc analyses (all t ≥ 4.2; p ≤ .05, corrected) revealed decreased FA in left SLF in BD, versus UD adults in inferior temporal cortex and, versus HC, in primary sensory cortex (associated with increased radial and decreased longitudinal diffusivity, respectively); and decreased FA in left ILF in UD adults versus HC. A main effect of group in right uncinate fasciculus (in orbitofrontal cortex) just failed to meet significance in all participants but was present in women. Post hoc analyses revealed decreased right uncinate fasciculus FA in all and in women, BD versus HC. Conclusions White matter FA in left occipitotemporal and primary sensory regions supporting visuospatial and sensory processing differentiates BD from UD depression. Abnormally reduced FA in right fronto-temporal regions supporting mood regulation, might underlie predisposition to depression in BD. These measures might help differentiate pathophysiologic processes of BD versus UD depression.
Abstract
The claimed detection of a diffuse galaxy lacking dark matter represents a possible challenge to our understanding of the properties of these galaxies and galaxy formation in general. The ...galaxy, already identified in photographic plates taken in the summer of 1976 at the UK 48-in Schmidt telescope, presents normal distance-independent properties (e.g. colour, velocity dispersion of its globular clusters). However, distance-dependent quantities are at odds with those of other similar galaxies, namely the luminosity function and sizes of its globular clusters, mass-to-light ratio, and dark matter content. Here we carry out a careful analysis of all extant data and show that they consistently indicate a much shorter distance (13 Mpc) than previously indicated (20 Mpc). With this revised distance, the galaxy appears to be a rather ordinary low surface brightness galaxy (Re = 1.4 ± 0.1 kpc; M⋆ = 6.0 ± 3.6 × 107 M⊙) with plenty of room for dark matter (the fraction of dark matter inside the half-mass radius is >75 per cent and Mhalo/M⋆>20) corresponding to a minimum halo mass >109 M⊙. At 13 Mpc, the luminosity and structural properties of the globular clusters around the object are the same as those found in other galaxies.
ABSTRACT
Self-gravitating astronomical objects often show a central plateau in the density profile (core) whose physical origin is hotly debated. Cores are theoretically expected in N-body systems of ...maximum entropy, however, they are not present in the canonical N-body numerical simulations of cold dark matter (CDM). Our work shows that despite this apparent contradiction between theory and numerical simulations, they are fully consistent. Simply put, cores are characteristic of systems in thermodynamic equilibrium, but thermalizing collisions are purposely suppressed in CDM simulations. When collisions are allowed, N-body numerical simulations develop cored density profiles, in perfect agreement with the theoretical expectation. We compare theory and two types of numerical simulations: (1) when DM particles are self-interacting (SIDM) with enough cross-section, then the effective two-body relaxation time-scale becomes shorter than the Hubble time resulting in cored DM haloes. The haloes thus obtained, with masses from dwarf galaxies to galaxy clusters, collapse to a single shape after normalization, and this shape agrees with the polytropic density profile theoretically expected. (2) The inner radii in canonical N-body numerical simulations are always discarded because the use of finite-mass DM particles artificially increases the two-body collision rate. We show that the discarded radii develop cores which are larger than the employed numerical softening and have polytropic shape independently of halo mass. Our work suggests that the presence of cores in simulated (or observed) density profiles can used as evidence for systems in thermodynamic equilibrium.
Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a ...neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.
A recent paper reported the serendipitous discovery of a thin linear object interpreted as the trail of star-forming regions left behind by a runaway supermassive black hole (SMBH) kicked out from ...the center of a galaxy. Despite the undeniable interest in the idea, the actual physical interpretation is not devoid of difficulty. The wake of a SMBH produces only small perturbations in the external medium, which has to be in exceptional physical conditions to collapse gravitationally and form a long (40 kpc) massive (3 × 10
9
M
⊙
) stellar trace in only 39 Myr. Here we offer a more conventional explanation: the stellar trail is a bulgeless galaxy viewed edge-on. This interpretation is supported by the fact that its position–velocity curve resembles a rotation curve, which, together with its stellar mass, puts the object exactly on the Tully–Fisher relation characteristic of disk galaxies. Moreover, the rotation curve (
V
max
∼ 110 km s
−1
), stellar mass, extension, width (
z
0
∼ 1.2 kpc), and surface brightness profile of the object are very much like those of IC 5249, a well-known local bulgeless edge-on galaxy. These observational facts are difficult to interpret within the SMBH wake scenario. We discuss in detail the pros and cons of the two options.
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