Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

Cerebral Balance, Recognition Accuracy, and Confidence when Task Performance Requires the Use of Preconsciously Acquired Information

a. This TP is an attempt to identify brain mechanisms associated with the finding that mere exposure to words, patterns, and other stimuli often leads to liking, even when the exposure is too brief to produce conscious awareness. The authors investigate recognition accuracy of very brief (subliminal) exposure to stimuli following instructions to report either which stimulus they thought was familiar (left brain) or which the liked better (right brain). Results showed that participants instructed to process stimuli using right brain were more accurate. The authors interpreted the data as showing that right brain processing, which occurs outside of conscious awareness, is responsible for the subliminal “familiarity leads to liking” phenomenon.This work was supported, in part, by The Office of Naval Research (SRO-OOl: N00014-79-C00796)

Indices of Hemispheric Lateralization: A Methodological Analysis

The authors describe and evaluate several indices of brain hemisphere lateralization. The methods use different data, including response accuracy, reaction times, and EEG asymmetry. They describe an index- free ranking procedure that uses two or more kinds of data and that makes few assumptions and does not impose a numerical scale. EEG asymmetry data entails measurement decisions and scaling assumptions, which the authors discuss in some detail

Interaction of opiate peptide and noradrenalin systems: Light microscopic studies

In this light microscopic immunocyto-chemical study [beta]-Endorphin ([beta]-END), leu-enkephalin and dopamine-[beta]hydroxylase (DBH) antisera are used to obtain an overview of the interaction of the noradrenergic and opiate peptide systems in brain. Serial brain areas were analyzed for DBH and then for [beta]-END or leu-enkephalin. Several areas were evaluated for cell and fiber interactions between these systems. The areas of richest possible contact between [beta]-END and DBH positive systems include the rostral locus coeruleus region, the periaqueductal grey, possibly the dorsal thalamus, the paraventricular hypothalamus and the arcuate nucleus. Enkephalin cells and fibers were seen surrounding the locus coeruleus throughout its length with a few fibers in the nucleus itself.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23268/1/0000205.pd

The Impact of Selected Social Environmental and Individual Factors on Stress Responses

a. The authors attempt to clarify some factors in the relationships between high levels of stress and poor physical and mental health. They review many possible sources of individual variation in responses to stress, including different living environments, interrelated social and individual factors, and differences across gender groups. Physiological and behavioral data collected from college students at a blood bank assessed multiple social and individual factors, self-reported stress, and levels of norepinephrine, a physiological indicator of stress. Results showed a fairly complex pattern of results, although social support was generally helpful in reducing stress, and gender differences in both social and physiological responses were found.This research was supported in part by the Office of Navel Research and in part by the gracious contributions of Edward and Marjorie Grey

An Individual-Oriented Model on the Emergence of Support in Fights, Its Reciprocation and Exchange

Complex social behaviour of primates has usually been attributed to the operation of complex cognition. Recently, models have shown that constraints imposed by the socio-spatial structuring of individuals in a group may result in an unexpectedly high number of patterns of complex social behaviour, resembling the dominance styles of egalitarian and despotic species of macaques and the differences between them. This includes affiliative patterns, such as reciprocation of grooming, grooming up the hierarchy, and reconciliation. In the present study, we show that the distribution of support in fights, which is the social behaviour that is potentially most sophisticated in terms of cognitive processes, may emerge in the same way. The model represents the spatial grouping of individuals and their social behaviour, such as their avoidance of risks during attacks, the self-reinforcing effects of winning and losing their fights, their tendency to join in fights of others that are close by (social facilitation), their tendency to groom when they are anxious, the reduction of their anxiety by grooming, and the increase of anxiety when involved in aggression. Further, we represent the difference in intensity of aggression apparent in egalitarian and despotic macaques. The model reproduces many aspects of support in fights, such as its different types, namely, conservative, bridging and revolutionary, patterns of choice of coalition partners attributed to triadic awareness, those of reciprocation of support and ‘spiteful acts’ and of exchange between support and grooming. This work is important because it suggests that behaviour that seems to result from sophisticated cognition may be a side-effect of spatial structure and dominance interactions and it shows that partial correlations fail to completely omit these effects of spatial structure. Further, the model is falsifiable, since it results in many patterns that can easily be tested in real primates by means of existing data

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, PPeer reviewe

Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder

Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n similar to 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders