The neurobiology of anhedonia and other reward-related deficits

http://brain-stimulation-group.weebly.com/uploads/2/9/9/8/29983261/schlaepfer_2013_rapid_effects_of_deep_brain_stimulation_for_treatment-resistant_major_depression.pdf

Rapid effects of deep brain stimulation for treatment-resistant major depression.

Background: Many studies using diffusion tensor imaging (DTI) have demonstrated impaired white matter integrity in patients with major depressive disorder (MDD), with significant results found in diverse brain regions. We sought to identify whether there are consistent changes of regional white matter integrity in patients with MDD, as shown by decreased fractional anisotropy in DTI. Method: A systematic search strategy was used to identify relevant whole brain voxel-based DTI studies of patients with MDD in relation to comparison groups. Relevant databases were searched for studies published between January 1994 and February 2011 using combinations of the terms "DTI" or "diffusion tensor;" "whole brain" or "voxel-based;" and "depress*." Using the studies that met our inclusion criteria, we performed a meta-analysis of the coordinates of decreased fractional anisotropy using the activation likelihood estimation (ALE) method, which detects 3-dimensional conjunctions of coordinates from multiple studies, weighted by sample size. We then used DTIquery software for fibre tracking to locate the fascicles involved in each region. Results: We included 11 studies with a combined sample of 231 patients with MDD and 261 comparison participants, providing 50 coordinates of decreased fractional anisotropy. Our meta-analysis identified 4 consistent locations of decreased fractional anisotropy in patients with MDD: white matter in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe. Fibre tracking showed that the main fascicles involved were the right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, right posterior thalamic radiation and interhemispheric fibres running through the genu and body of the corpus callosum. Limitations: The number of studies included was relatively small, and the DTI data acquisition and analysis techniques were heterogeneous. The ALE method cannot handle studies with no significant group differences. Conclusion: Voxel-based analysis of DTI studies of patients with MDD consistently identified decreased fractional anisotropy in the white matter fascicles connecting the prefrontal cortex within cortical (frontal, temporal and occipital lobes) and subcortical areas (amygdala and hippocampus). This is strong evidence for the involvement of these neural circuits in the pathology of MDD.

/pdf/is-depression-a-disconnection-syndrome-meta-analysis-of-37r7z8ug60.pdf

Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD.

Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.

https://www.jneurosci.org/content/jneuro/34/16/5529.full.pdf

Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users

Diffusion-tensor imaging (DTI) is a noninvasive medical imaging tool used to investigate the structure of white matter. The signal contrast in DTI is generated by differences in the Brownian motion of the water molecules in brain tissue. Postprocessed DTI scalars can be used to evaluate changes in the brain tissue caused by disease, disease progression, and treatment responses, which has led to an enormous amount of interest in DTI in clinical research. This review article provides insights into DTI scalars and the biological background of DTI as a relatively new neuroimaging modality. Further, it summarizes the clinical role of DTI in various disease processes such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's dementia, epilepsy, ischemic stroke, stroke with motor or language impairment, traumatic brain injury, spinal cord injury, and depression. Valuable DTI postprocessing tools for clinical research are also introduced.

/pdf/current-clinical-applications-of-diffusion-tensor-imaging-in-18p0ewv8sc.pdf

Current Clinical Applications of Diffusion-Tensor Imaging in Neurological Disorders.

Background: Previous studies of major depressive disorder (MDD) have focused on abnormalities in the prefrontal cortex and medial temporal regions. There has been little investigation in MDD of midbrain and subcortical regions central to reward/aversion function, such as the ventral tegmental area/substantia nigra (VTA/SN), and medial forebrain bundle (MFB). Methodology/Principal Findings: We investigated the microstructural integrity of this circuitry using diffusion tensor imaging (DTI) in 22MDD subjects andcompared them with 22 matched healthy control subjects. Fractional anisotropy (FA) values were increased in the right VT and reduced in dorsolateral prefrontal white matter in MDD subjects. Follow-up analysis suggested two distinct subgroups of MDD patients, which exhibited non-overlapping abnormalities in reward/aversion circuitry. The MDD subgroup with abnormal FA values in VT exhibited significantly greater trait anxiety than the subgroup with normal FA values in VT, but the subgroups did not differ in levels of anhedonia, sadness, or overall depression severity. Conclusions/Significance: These findings suggest that MDD may be associated with abnormal microstructure in brain reward/aversion regions, and that there may be at least two subtypes of microstructural abnormalities which each impact core symptoms of depression.

https://psychiatry-training.wiki.otago.ac.nz/images/5/5a/Journal.pone.0013945.pdf

Microstructural Abnormalities in Subcortical Reward Circuitry of Subjects with Major Depressive Disorder

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Microstructural Abnormalities in Subcortical Reward Circuitry of Subjects with Major Depressive Disorder