Risk for affective disorders is associated with greater prefrontal gray matter volumes: A prospective longitudinal study

Background: Major depression and bipolar disorders aggregates in families and are linked with a wide range of neurobiological abnormalities including cortical gray matter (GM) alterations. Prospective studies of individuals at familial risk may expose the neural mechanisms underlying risk transmission. Methods: We used voxel based morphometry to investigate changes in regional GM brain volume, over a seven-year period, in 37 initially healthy individuals having a mono- or di-zygotic twin diagnosed with major depression or bipolar disorder (high-risk group; mean age 41.6yrs.) as compared to 36 individuals with no history of affective disorders in the index twin and first-degree relatives (low-risk group; mean age 38.5yrs.). Results: Groups did not differ in regional GM volume changes over time. However, independent of time, high-risk twins had significantly greater GM volumes in bilateral dorsal anterior cingulate, inferior frontal gyrus and temporoparietal regions as compared to low-risk twins. Further, individuals who developed an affective disorder at follow-up (n=12), had relatively the largest GM volumes, both at baseline and follow-up, in the right dorsal anterior cingulate cortex and right inferior frontal cortex compared to high- and low-risk twins who remained well at follow-up. Conclusion: This pattern of apparently stable grater regional GM volume may constitute a neural marker of an increased risk for developing an affective disorder in individuals at familial risk. Keywords: Affective disorders, Structural MRI, Anterior cingulate cortex, VB

The Center for Integrated Molecular Brain Imaging (Cimbi) database

AbstractWe here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes.The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies.The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank

Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder

<p>Abstract</p> <p>Background</p> <p>Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission.</p> <p>Methods/design</p> <p>The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU) or saline (NaCl 0.9%) for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17) <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) <abbrgrp><abbr bid="B2">2</abbr><abbr bid="B3">3</abbr></abbrgrp>. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes.</p> <p>Trial registration</p> <p>The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency: 2008-41-2711 and ClinicalTrials.gov: NCT 00916552.</p

Neural mechanisms underlying working memory : computational and neuroimaging studies

The performance on various cognitive tasks, from language to selective attention and guidance of future actions depends on working memory (WM), the ability to hold and manipulate limited items of information for a period of up to a few seconds. During childhood development, WM capacity, the number of items one can maintain in WM, increases. However, the neural correlates of WM capacity, distractibility and maturational processes underlying WM development are still unclear. The present work addresses these issues by the integration of computational modeling, functional magnetic resonance imaging (fMRI) and behavioral methods. In the first study we used distracting visual stimuli in order to identify cellular mechanisms that account for the observed behavioral decrease in mnemonic accuracy as a function of the spatial distance to distractors. The computational model suggests that independently of the cellular and synaptic properties, increased neuronal firing rates accounted for higher mnemonic accuracy and resistance against distractors. In the second study we performed fMRI experiments on adults and children to monitor brain activity during a WM task. We isolated the delay-related activity and analyzed group differences and the distractor influence both behaviorally and in terms of changed brain activity. Accompanying the higher WM capacity and lower distractibility of adults, the fMRI study showed higher brain activity in middle frontal gyrus and intraparietal cortex in adults compared to children during the delay periods of WM tasks. In a subsequent study we addressed the cellular changes during WM development. The study combined a computational analysis with FMRI in order to establish putative maturation processes governing developmental changes in brain activity. We found that the increase in activity together with higher resistance against distractions could be explained by stronger connectivity between network areas. The final study addressed the limited storage capacity of previous WM models. Implementing structural and connectivity changes likely to occur during WM development in a biophysical WM model we have obtained multiple-item storage capacity similar to human WM performance. Furthermore, by using fMRI we found that the informationactivity curve predicted by the model corresponds to that in the human posterior parietal cortex during performance of WM tasks. In conclusion, in the context of neural networks dominated by reverberatory synaptic input, our studies demonstrate the correlation between a higher WM capacity, resistance to distractors, mnemonic accuracy, BOLD response and average firing rate of the neuronal populations responsible for the memory maintenance

Brain Activity Related to Working Memory and Distraction in Children and Adults

In order to retain information in working memory (WM) during a delay, distracting stimuli must be ignored. This important ability improves during childhood, but the neural basis for this development is not known. We measured brain activity with functional magnetic resonance imaging in adults and 13-year-old children. Data were analyzed with an event-related design to isolate activity during cue, delay, distraction, and response selection. Adults were more accurate and less distractible than children. Activity in the middle frontal gyrus and intraparietal cortex was stronger in adults than in children during the delay, when information was maintained in WM. Distraction during the delay evoked activation in parietal and occipital cortices in both adults and children. However, distraction activated frontal cortex only in children. The larger frontal activation in response to distracters presented during the delay may explain why children are more susceptible to interfering stimuli