The endosomes thus formed are eventually converted into the lysosomes and ultimately result in the drug release [102]. Liu et al. developed SWCNT conjugated with paclitaxel (PTX) and reported the nonreceptor mediated endocytosis mechanism for the cellular uptake in murine 4T1 breast carcinoma cells [110]. Islam et al. investigated the cellular uptake of pluronic copolymer-stabilized, purified ~145nm long single walled carbon nanotubes (SWCNTs) through a series of complementary cellular, cell-mimetic, and in vitro model membrane experiments. The Raman intensity LDK378 mouse distribution, obtained from the G-band (1590cm−1), shows SWCNT concentration Inhibitors,research,lifescience,medical localized to the midplane of a fixed, hematoxylin-labelled

cell. SWCNTs were preferentially Inhibitors,research,lifescience,medical located within cells versus the extracellular regions, and most SWCNTs were localized in the perinuclear region. SWCNTs localized within fluorescently labelled endosomes and confocal Raman spectroscopy showed a dramatic reduction in SWCNT uptake into the hematoxylin-labeled HeLa cell at 4°C compared with 37°C, after being incubated for 2 days. These data suggested energy-dependent

endocytosis. Inhibitors,research,lifescience,medical To confirm this, a direct measurement to check the endocytosis was conducted in which endocytosis in HeLa cells was visualized using a Green Fluorescent Protein, GFP-tagged RhoB-GTPase, which labels endosomes in mammalian cells. On confocal imaging it was confirmed that the internalization of SWCNTs was occurring through the endocyte formation as there was a slight increase

in Inhibitors,research,lifescience,medical endosome numbers per cell with increased time of exposure to SWCNTs, with a statistically significant increase in endosome number at 20 and 25 minutes [111]. In endocytosis independent pathway there is a direct translocation of CNT through the plasma membrane into the cytoplasm which has been termed by some researchers as the “nanoneedle” mechanism [100]. This pathway includes processes such as diffusion, membrane fusion, and direct pore transport Inhibitors,research,lifescience,medical (Figure 5(c)). Individually dispersed CNTs in aqueous solutions have been experimentally demonstrated to be able to enter the cytoplasm of cells by directly crossing the cell membrane. Such cellular uptake of CNT, which is not influenced by the presence of endocytosis inhibitor (such as sodium azide), suggests the endocytosis second independent pathway of internalization [112]. The mechanism of how CNT enters cells via the insertion and diffusion is poorly understood. Some theoretical studies suggest a two-step process in which, first, the tubes accommodate onto the lipid cell membrane and then orient to adopt the transmembrane configuration. In this model, the internalization of nanotubes into the cells was spontaneous and was mediated by the lipid membrane and that the hydrophilic interactions and/or static charge interactions between the tubes and the lipid membrane which drove the translocation of the nanotubes [113].

11). Under basal metabolic conditions, portions of the cytoplasm, which contain the entire cohort of cellular proteins, are segregated within a membrane-bound compartment and are then fused to a primary nascent lysosome and their contents digested. This process was called microautophagy. Under more extreme conditions, starvation for example, mitochondria, endoplasmic reticulum membranes, glycogen bodies, and other cytoplasmic entities can also be engulfed by a process called macroautophagy (see, for Inhibitors,research,lifescience,medical example, Ashford et al.12; the different modes of action of the lysosome in digesting extra- and intracellular proteins are shown in Figure 2). However, over a period

of more than two decades, between the mid-1950s and the late 1970s, it has become gradually more and more difficult to explain several aspects of intracellular protein degradation based on the known mechanisms of lysosomal activity: accumulating lines of independent experimental evidence Inhibitors,research,lifescience,medical indicated that the degradation of at least certain classes of cellular proteins must be non-lysosomal. Yet, in the absence of any “alternative,” researchers came up with different explanations, some more substantiated and others less, to Inhibitors,research,lifescience,medical defend the “lysosomal” hypothesis. First was the gradual discovery, from different laboratories, that different proteins vary in their stabilities and their half-life times can span three orders of magnitude, from a few minutes to many

days. Thus, the t1/2 of ornithine decarboxylase Inhibitors,research,lifescience,medical (ODC) is ~10 min, while that of glucose-6-phosphate dehydrogenase (G6PD) is 15 hours (for review articles, see, for example, Schimke et al.13 and Goldberg et al.14). Also, rates of degradation of many proteins were shown to change with changing physiological conditions, such as availability of nutrients or hormones. It was conceptually

difficult to reconcile the findings of Inhibitors,research,lifescience,medical distinct and changing half-lives of different proteins with the mechanism of action of the lysosome, where the microautophagic vesicle contains the entire cohort of cellular (cytosolic) proteins that are therefore expected to degrade at the same rate. Similarly, changing pathophysiological conditions, such as starvation or resupplementation of nutrients, were next expected to affect the stability of all cellular proteins to the same extent. Clearly, this was not the case. Another source of concern about the lysosome as the organelle in which intracellular proteins are degraded was the finding that Selleck Autophagy Compound Library specific and general inhibitors of lysosomal proteases have different effects on different populations of proteins, making it clear that distinct classes of proteins are targeted by different proteolytic machineries. Thus, the degradation of endocytosed/pinocytosed extracellular proteins was significantly inhibited, a partial effect was observed on the degradation of long-lived cellular proteins, and almost no effect was detected on the degradation of short-lived and abnormal/mutated proteins.

Beyond the actual presence of the relevant symptoms, the sixth criterion for clinical diagnosis of PTSD is clinically significant distress or impairment of functioning, which is a common denominator for all anxiety disorders. Figure 1. Time course and post-traumatic stress disorder (PTSD) subtypes.

In the minds of many, PTSD is related to mega-events such as 9/11, tsunami, war, etc. However, the major contributors to PTSD are actually daily civilian events, such as car accidents, work-related accidents, violence, and armed robbery, to name a few PTSD can also occur after Inhibitors,research,lifescience,medical exposure to a serious illness (for example myocardial infarction). In modern civilian life, exposure to traumatic events (that might lead to PTSD) is prevalent. In fact, about 50% of the (Western) population Inhibitors,research,lifescience,medical would have been exposed to a traumatic event that might later on lead to PTSD during their lifetime.2 What is unique about PTSD is that the vast majority (80% to 90%) of those exposed

to this type of trauma will eventually adapt. Only 10% to 20% become fixated on the event, and develop PTSD.3 If 50% of the population are exposed at some point of their life to traumatic events, and if on average 15% of them will develop PTSD, then the expected prevalence of PTSD in the population would be 7.5%. Indeed, in the National Comorbidity Survey,2 the prevalence was found to be 6.8%, Inhibitors,research,lifescience,medical while in earlier studies the prevalence ranged from 7.8% to 8.7%3-5 (Figure 2). Figure 2. Lifetime prevalence of post-traumatic stress disorder in the community. What are the risk factors for PTSD? Pretraumatic risk factors A meta-analysis of risk factors6 proposed trauma intensity as an important factor, along with previous traumatic Inhibitors,research,lifescience,medical history,7 family history of psychiatric disorders,8,9 personal history of emotional or psychiatric disorders prior to the trauma, history of substance abuse, and poorer intellectual abilities.10 In a semiprospective study conducted by our group,11 we compared 2362 war veterans who developed PTSD with an equal number of war veterans who did not Inhibitors,research,lifescience,medical develop PTSD. Comparisons were made on predrafting

personal factors and pretrauma army characteristics. The Selleck GSK126 intention was to find mafosfamide out whether careful predrafting cognitive and behavioral screening would help to predict who will develop PTSD. It turned out that neither behavioral assessment, including measures such as socioeconomic background and motivation to serve, nor training were found to predict PTSD. Hence, predraft screening done at age 17 failed to predict who would develop PTSD either during their mandatory service (age 18 to 21), or during reserve duties (age 21 to 49). The only exception was a borderline significance related to intelligence, which in any case measures the ability of individuals to adapt, and is therefore believed to be a nonspecific mediator.

The right hemisphere, by contrast, is actively watching for discrepancies, more like a devil’s advocate.140 Both approaches are needed, but are mutually contradictory. These differences operate across all realms and apply equally to the verbal as to the visuospatial. For example, the left hemisphere operates focally, suppressing verbal meanings that are not currently relevant, whereas the right Inhibitors,research,lifescience,medical hemisphere recruits

wider semantic associations,141-145 and the right posterior superior temporal sulcus may be selectively involved in verbal creativity146 In the “close” situation, by contrast, the left hemisphere actively suppresses the right, to exclude associations which are semantically only distantly related.147,148 Integration versus division In general the left hemisphere is more closely interconnected within itself, and within regions of itself, than the right hemisphere.14,17 By contrast, the right hemisphere Inhibitors,research,lifescience,medical has a greater degree of myelination, facilitating swift transfer of information between the cortex and centers below the cortex,17 and greater connectivity in general.149 Functionally, its superior integration is evidenced by EEG measures150 and by

the more diffuse but overlapping somatosensory Inhibitors,research,lifescience,medical projections and auditory inputs in the right hemisphere.151 At the experiential level it is also better able to integrate perceptual processes, particularly bringing together different kinds of information from different senses.109,154,155 By contrast, the left hemisphere may be ‘inadequate for

Inhibitors,research,lifescience,medical the more rapid complex syntheses achieved by the [right] hemisphere.’156 As mentioned, new stimuli lead to release of noradrenalin in the right hemisphere. Its neurons are relatively resistant to fatigue, so that exploratory attention is held Inhibitors,research,lifescience,medical open across a greater expanse of both space and time.21 The range of the right hemisphere is R788 cell line further increased by the fact that it has a longer working memory, and so is able both to access more information and hold it together at any one time for longer.157 It is capable of bearing more information in mind and doing so over longer periods, with greater specificity (which also means less susceptibility to degradation over time by memory).128,157-159 This broader field of attention, open to whatever may be, and coupled with greater integration over time and space, however is what makes possible the recognition of broad or complex patterns, the perception of the “thing as a whole,” seeing the wood for the trees.160-163 In short, the left hemisphere takes a local short-term view, where the right hemisphere sees the bigger picture. The whole versus the part The link between the right hemisphere and holistic or Gestalt perception is one of the most reliable and durable of the generalizations about hemisphere differences, which follows from the differences in the nature of attention.

The ability to differentiate between gray and white matter tissue had to await the introduction of magnetic find more resonance imaging (Figure 2). Parenthetically, and of historical interest here, following the introduction of CT, nuclear magnetic resonance (NMR), as it was called then, was developed in the early 1970s based on the work of Peter Mansfield14 and Paul Lauterbur.15 These individuals went on to share the Nobel Prize in Medicine in

2003 for their independent contributions to the seminal ideas that led to MRI and its application, in vivo, to humans. Importantly, MRI has no known adverse effects (ie, no radiation as in X-rays and CT), and it is a far more Inhibitors,research,lifescience,medical powerful tool than CT for visualizing soft tissue contrast in the brain and body. Figure 1. This CT scan shows separation of brain from fluid, including CSF and blood. This is a CT scan, post-contrast, Inhibitors,research,lifescience,medical of a patient with a bleed from an aneurysm (black color is blood and CSF). CT, computed tomography; CSF, cerebrospinal

fluid Figure 2. This MR scan shows one coronal slice Inhibitors,research,lifescience,medical through the superior aspects of the lateral ventricles. Note the clear differentiation between gray and white matter. Gray matter appears gray and can be seen in the ribbon around the cortex, as well as in subcortical … The first MR scanners were built in the 1980s, with, as noted above, the first MRI of a patient with schizophrenia performed in 1984. These early MR images of the brain were quite poor in resolution, with slices as thick as 1 cm, and they did not cover the entire brain. This is in contrast to major advances in technology today, where 1-mm slice thickness is common, Inhibitors,research,lifescience,medical and it is relatively easy to image the entire brain in a relatively short period of time. Today, in fact, MR scanners Inhibitors,research,lifescience,medical are used routinely to measure tissue properties in the brain and body at submillimeter spatial resolution, based on the NMR of

hydrogen in the magnetic field. Put even more into perspective, the ability to examine the inner workings of the human body was limited, historically, to the study of cadavers. Advances in medical imaging technology, however, have provided researchers with a new window into the living human body. Such advances have revolutionized nearly every Methisazone area of medicine, with psychiatry in the forefront of this revolution. These advances include both dramatic improvements in image resolution and the development of novel imaging techniques, from CT to positron emission tomography (PET), to single-photon emission computed tomography (SPECT), to MRI, including functional MRI (fMRI) and diffusion tensor imaging (DTI), to magnetic resonance spectroscopy (MRS), and ultrasound – all of which provide an unprecedented view, in exquisite detail, of anatomical structures and/or functions in the living human.

Network and gene ontology (GO) analyses were performed in order to determine relationships between the

functionally linked pathways from the microarray dataset. The network analysis revealed a lower degree of modularity of DNA methylation “nodes” in the major psychosis samples, indicating that there is some degree of systemic signaling pathway epigenetic dysregulation involved Inhibitors,research,lifescience,medical in the disorder. From the GO analysis, several categories were highlighted, including those involved in epigenetic processes, transcription, and development, as well as brain development in female BD and SZ samples, and in those related to stress response in male BD samples.46 To date, this is the largest and most comprehensive epigenomic study of major psychosis – the data presented supports epigenetic mechanisms underlying broader hypotheses of major psychosis and uncovers some new avenues for future exploration. Both SZ and BD have also been examined using the candidate gene approach,

Inhibitors,research,lifescience,medical as epigenetic downregulation of genes is emerging as a possible underlying mechanism of the GABAergic neuronal dysfunction in SZ. One of the more intensively investigated SZ-related genes is RELN, which is involved in neuronal Inhibitors,research,lifescience,medical development and cell signaling, and has been found to be hypermethylated in cases of SZ.47 However, no differences were observed Inhibitors,research,lifescience,medical at this locus in a replication attempt,46,48 and the

focus seems to be shifting to other candidate genes, namely the 67 kDa glutamate decarboxylase (GAD67, aka GAD1) and DNMT1. GAD67 catalyzes the conversion of glutamic acid to GABA. In cases of SZ, the levels of this enzyme and several others involved in GABAergic neurotransmission, such as GAD65 and GABA plasma membrane transporter-1 (GAT-1), display decreased mRNA levels, as determined by real-time quantitative polymerase chain reaction (qPCR) and in situ hybridization.49-52 In Inhibitors,research,lifescience,medical addition to aberrant methylation at this locus, an analysis of the microarray Vasopressin Receptor collection of the National Brain Databank (USA) has shown that decreased GAD67 mRNA levels strongly correlated with upregulated HDAC1 in the prefrontal cortices of SZ subjects.53 Oddly enough, at the GAD67 promoter, SZ patients have been shown to display an ~8-fold deficit in repressive chromatin-associated DNA methylation.54 In the prefrontal cortex of 41 SZ patients, another histone modification, H3-(methyl)arginine 17 (H3meR17) was found to exceed control levels by 30%, and this was associated with downregulated metabolic gene expression.55 So, while it is apparent that histone modifications are involved in the development of SZ, their exact mechanism is not entirely clear.

The fluorescent reagents www.selleckchem.com/products/pfi-2.html included: a mixture of two phycoerythrin (PE) conjugated anti-CK monoclonal antibodies that bind to CTCs intracellular cytokeratins 8, 18, 19 and nucleic acid dye 4′, 6-diamidino-2-phenylindole (DAPI) to fluorescently label the cells nuclei and anti-CD45-Allophycocyanin (APC) conjugated monoclonal antibodies specific

for leukocytes. Peripheral blood (7.5 mL) was collected into CellSave Preservative Tubes (Veridex LLC, Raritan, NJ), which are evacuated Inhibitors,research,lifescience,medical blood draw tubes containing EDTA as anticoagulant and a cellular preservative. Blood samples were maintained at room temperature for different time intervals and processed within a maximum of 96 h after blood drawing (2,26). One representative sample result is shown in Figure 1. Figure 1 Selected frames represent CTC isolated from peripheral Inhibitors,research,lifescience,medical blood by immunomagnetic capture and analyzed by a fluorescent microscope. CTC are positive for cytokeratin and DAPI and negative

for CD45 markers. A positive CTC was defined at two cells per 7.5 mL of blood based on the expected frequency of EpCAM detection in patients with biliary cancer. No spiking experiments were done in biliary cancer cells. The CellSearch positive Inhibitors,research,lifescience,medical control kit is used to maintain quality control for reagents, instruments and operator techniques and is performed for each patient’s sample. The control kit includes 24 single use control bottles containing two populations of a fixed breast cancer cell line at high and low concentrations. Different fluorescent dyes specific to each populations permit simultaneous enumeration of high and low Inhibitors,research,lifescience,medical controls in one assay. Each of the high and low CTC control values obtained has to fit within two standard deviation of the relevant reference range mean. Results Patients’ baseline characteristics are shown in Table 1. Sixteen patients were identified and included; mean age at the time of diagnosis was 62 (31-78) years. Twelve patients (75%) were females, 13 (81%) had intrahepatic cholangiocarcinoma, Inhibitors,research,lifescience,medical three patients had gallbladder

cancer. Stages at assessment of CTC were: Stage I (n=1), stage II (n=1), stage III (n=5) and stage IV (n=9). Fifteen patients (94%) died during the time of follow up. Mean followup time was twenty months. Patients’ therapies Carnitine palmitoyltransferase II and outcome details are shown in Tables 2 and ​and33. Table 1 Patients’ baseline characteristics. Table 2 Clinical information of patients with intrahepatic cholangiocarcinoma. Table 3 Clinical information of patients with gallbladder cancer. Using 2 CTC/7.5 mL as a cutoff; 3/13 patients with cholangiocarcinoma and 1/3 with gallbladder cancer were positive. All patients with positive CTC had stage III or IV when the assay was conducted as shown in figure 2 . Figure 2 Patients with positive CTC by stage of disease.

8).92 One of the most interesting candidate genes for schizophrenia and psychosis came from the multistage GWAS analyzing over 20 000 cases and CPI-613 cell line controls.93 In the initial GWAS (479 cases, 2937 controls), O’Donovan et al93 observed 12 loci to be moderately associated with schizophrenia (P<10-5). In the first replication sample (1664 cases, 3541 controls) association of 6 of the 12 SNPs was replicated. These six SNPs were genotyped in the second

replication sample (4143 cases, 6515 controls). In the complete replication sample set (stage one + two), three loci namely: Zinc finger protein 804A (ZNF804A, rs1344706, 2q32.1, P=9.25×10-5), intergenic regions on 11p14.1 (rs1602565, Inhibitors,research,lifescience,medical P=3. 22×10-4) and 16p13.12 (rs7192086, P=5.10×10-4) were modestly associated with schizophrenia.

In the combined sample from the initial stage plus the two replication sets, ZNF804A showed strong evidence of association (OR=1.12; P=1.6×10-7). Furthermore, when patients with bipolar disorder Inhibitors,research,lifescience,medical were included, the obser-vation became more significant, suggesting that ZNF804A might be a susceptibility gene for the broader psychosisphenotype. ZNF804A is a putative transcription factorand the risk allele of the rs1344706 polymorphism (intron2, C>A) has been recently shown to be associated withdisturbed connectivity between the dorsolateral Inhibitors,research,lifescience,medical pre-frontal cortex (DLPFC) and the hippocampus, as well asbetween left and right hemispheres. Also there wasaltered coupling of DLPFC with the amygdala.94 The former may lead to disturbed executive function and the latter can affect the interaction between prefrontal and limbic structures. The association of ZNF804A markerrs1344706 with schizophrenia was recently replicated inpatients Inhibitors,research,lifescience,medical from Ireland (n=1021 cases, 626 controls; P=0.01).95 Increased expression of the A allele comparedwith the C allele was observed in the dorsolateral pre-frontal

cortex of postmortem control brain samples. However, there was Inhibitors,research,lifescience,medical no difference between the two alleles in overall mRNA expression between postmortem schizophrenia cases and controls.94 The SNP rs1344706 was also significant in the GWAS conducted by theInternational Schizophrenia Consortium (P=0.029, OR (A-allele) =1.08).96 Additionally, Chlormezanone in a large multicenterstudy, association of rs1344706 with schizophrenia (5164 cases and 20 709 controls; OR=1.08, P=0.0029) and psy-chosis (OR=1.09, P=0.00065) has been replicated.97 Based on this replication by three other independent groups, andthe demonstration of functional effect on brain connec-tivity, ZNF804A is a promising candidate gene for schiz-ophrenia and psychosis in general. The small effect sizes (OR 1.08-1.12) account for only 1% to 2% of the variancein risk for the disease. In general these replicating smalleffects are consistent with the common disease commonvariant hypothesis.

Further, due to

movement restrictions, tasks are typically covert and often involve Bosutinib molecular weight considerable meta-cognitive skill, which are challenging for young children to perform and add extra assumptions when interpreting results. This makes it hard to establish to what extent it is the ability to comply with complex task instructions rather than the process of interest itself that drives developmental changes in cerebral lateralization. A viable alternative method has presented itself in recent years in the form of functional transcranial Doppler ultrasonography (fTCD). This noninvasive and relatively inexpensive technique has been shown to be a reliable Inhibitors,research,lifescience,medical method for determining cerebral lateralization of function (Deppe et al. 2004).

Because Inhibitors,research,lifescience,medical fTCD is quick to set up and can be carried out in a quiet and comfortable environment, it has great potential for assessing cerebral lateralization in children. Furthermore, fTCD is relatively insensitive to movement which makes it possible for participants to speak while lateralization of function is assessed, making complex task instructions unnecessary. To date studies using fTCD with children have mainly focused on documenting feasibility, validity, and reliability of child-friendly tasks Inhibitors,research,lifescience,medical (Lohmann et al. 2005; Bishop et al. 2009; Haag et al. 2010; Groen et al. 2011; Stroobant et al. 2011). Studies of lateralization of language function in children using fTCD report left-lateralized activation in the majority of children (Lohmann et al. 2005; Bishop et al. 2009; Haag et al. 2010; Stroobant et al. 2011), even in toddlers (Lohmann et al. 2005; Bishop et al. 2009). Studies that did include Inhibitors,research,lifescience,medical children of different ages did not report changes in the direction lateralization with age (Lohmann et al. 2005; Haag et al. 2010; Stroobant et al. 2011). The first aim of the present study was therefore to assess the direction and strength of lateralization across age for language production Inhibitors,research,lifescience,medical and for visuospatial memory in a large

group of typically developing children. Additionally, we considered the effect of gender on functional lateralization as the idea of gender before differences in brain anatomy and function remains popular (Wallentin 2009), typically suggesting more bilateral activation on language tasks in women, but little evidence has been reported to support these claims (Sommer et al. 2004, 2008; Wallentin 2009). The second aim of the current study was to consider whether individual differences in cerebral lateralization were related to cognitive function. In particular, we aimed to test the functional crowding hypothesis by reliably assessing lateralization of multiple functions and cognitive abilities in the same individuals. To achieve these aims we used fTCD to assess simultaneously the cerebral blood flow velocity to the left and right hemisphere during a language production and a visuospatial memory task in a large group of school-aged children.

However, as noted earlier we contend that a population such as this should show a yearly average decline in MMSE of 1.8–4.2 points, and over a 4–5 months period one would therefore expect to observe a partial decline in cognition and not general improvements, as was observed in this research. In addition, evidence indicates that practice effects are rare particularly in populations experiencing cognitive impairment. Research has shown that retesting at 1 week showed no effect on tasks such as verbal fluency; thus, at 4–5 months we Inhibitors,research,lifescience,medical can feel fairly secure that what is seen

is not a practice effect, particularly on these types of tasks (Cooper et al. 2010). As well, evidence suggests that individuals with cognitive impairments given only one follow-up test should be safe from practice effects (Abner et al. 2012). Inhibitors,research,lifescience,medical Thus, we believe these points should adequately address any concerns related to the issue of practice effects. Conclusion The proposed next program phase will be undertaken in a larger center to help facilitate greater number of participants Inhibitors,research,lifescience,medical and to ensure an ease in access to the program. The end goal, however, is to demonstrate the success of this program and to develop an in-home system for those individuals who may suffer from lack of access to additional care, such as for individuals even in this pilot

program that showed difficulty completing all Inhibitors,research,lifescience,medical elements. Providing proper

tools and greater access to care in the most efficient and effective manner is our ultimate goal. Acknowledgments Funding for the research was provided by W. J. T.’s initial research allowance and also through a seed grant competition hosted by University of Northern British Columbia. The authors would also like to thank Charity Gillett for assistance editing this work. Conflict of Interest None declared. Funding Information This work was supported by University of Northern British Columbia.
Alcohol is the most readily available and commonly abused drug Inhibitors,research,lifescience,medical across all age groups in the United States (Substance Abuse and Mental Health Services Administration 2010), making alcohol-related brain damage a pressing public health Indoximod concern. In particular, next white matter damage is a signature injury of alcohol use disorders (AUDs; Harper and Kril 1990; Kril and Halliday 1999). Evidence suggests that chronic alcohol abuse damages white matter on the cellular level by increasing oxidative stress (Crews and Nixon 2009; Fernandez-Lizarbe et al. 2009; Pascual et al. 2011) and downregulating genes critical to myelination (Lewohl et al. 2000; Liu et al. 2007). A recent meta-analysis of magnetic resonance imaging (MRI) studies comparing white matter volume in AUD and healthy control groups found a significant effect size of g = 0.304 for the white matter volume deficit associated with AUD diagnosis (Monnig et al. 2012b).