Abnormalities In Subcortical Glutamate/Glutamine, But Not GABA, In Adults With A

Abnormalities In Subcortical Glutamate/Glutamine, But Not GABA, In Adults With A www.phwiki.com

Abnormalities In Subcortical Glutamate/Glutamine, But Not GABA, In Adults With A

Martin, Doug, General Manager has reference to this Academic Journal, PHwiki organized this Journal Abnormalities In Subcortical Glutamate/Glutamine, But Not GABA, In Adults With An ASD A [1H]MRS Study M. Andreina Mendez, Jamie Horder, Nicola Gillan, Suzanne Coghlan, Declan Murphy Background – General GABA / glutamate balance implicated in ASD Background – General GABA / glutamate balance implicated in ASD Rodent models e.g. reduced GABA-A receptors, increased glutamate mGluR receptors (subtype-specific) (Selby et al 2007)

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Background – General GABA / glutamate balance implicated in ASD Rodent models e.g. reduced GABA-A receptors, increased glutamate mGluR receptors (subtype-specific) (Selby et al 2007) Human Postmortem Studies (Blatt & Fatemi 2011) Background – General GABA / glutamate balance implicated in ASD Rodent models e.g. reduced GABA-A receptors, increased glutamate mGluR receptors (subtype-specific) (Selby et al 2007) Human Postmortem Studies (Blatt & Fatemi 2011) Genetics – ASD CNVs include GABA-A receptors e.g. 15q11-13 (Urraca et al 2013) Background – General GABA / glutamate balance implicated in ASD Rodent models e.g. reduced GABA-A receptors, increased glutamate mGluR receptors (subtype-specific) (Selby et al 2007) Human Postmortem Studies (Blatt & Fatemi 2011) Genetics – ASD CNVs include GABA-A receptors e.g. 15q11-13 (Urraca et al 2013) Comorbidities – epilepsy common in ASD (20% vs 2% in non-ASD) (Kohane et al 2012)

Background – PET Positron Emission Tomography (PET) can measure GABA-A receptor density We showed preliminary evidence of reduced GABA-A alpha5 (Mendez et al 2013) But PET can’t measure neurotransmitters Background – MRS Proton magnetic resonance spectroscopy (MRS) can measure GABA, glutamate in addition to glutamine (Glx) Previous studies have found evidence of glutamate/glutamine (Glx) abnormalities . But how about GABA Methods – GABA/Glx MRS Left striatum 35 x 30 x 25 mm Function: action in addition to movement control Bilateral midline dorsal ACC 25 x 40 x 30 mm Function: cognitive control, error monitoring, executive

Participants n = 22 adult males with a diagnosis of ASD in addition to IQ>70 in addition to 27 control males matched on verbal, per as long as mance in addition to full-scale IQ (t-test, all p>0.4, mean FSIQ 119 vs. 116. Diagnosis by expert clinical judgement using ICD-10-R criteria based on ADOS Module IV + ADI-R (where possible) Exclusion criteria included: Epilepsy Genetic disorder Psychosis Substance dependence. Any psychoactive medication at the time of scanning, within previous six weeks minimum. Results 1 – MRS We found a significant reduction in Glx in the left striatum (p = 0.033 two-tailed). However, no differences were seen in Glx in the DMPFC, or in GABA in either voxel. There as long as e, replicating previous findings using PRESS MRS (Horder et al 2013), we showed reduced Glx in the basal ganglia region in adults with ASD. (Previous Findings

Discussion 1: MRS – fMRI Might a reduction in striatal Glx have functional implications We used resting state fMRI to examine the correlation between [1H]MRS Glx signal in addition to the functional connectivity to/from the basal ganglia region (putamen) as a seed (seed-voxel correlations): Results 2: MRS-fMRI association in all participants (n=42) A significant (p < 0.05, whole-brain cluster corrected) effect of striatal Glx on the pattern of connectivity with the left putamen was found. Areas of significant differences included the anterior cingulate cortex. Inspection of the scatterplot revealed that this effect was not driven by outliers. Results 3: Glx vs. Connectivity: HV vs. ASD The correlation between left basal ganglia Glx in addition to left putamen connectivity was stronger (p<0.05 whole brain corrected) as long as healthy controls than as long as ASD patients in two regions: Medial prefrontal cortex Lateral temporal lobe including STG in addition to MTG. Conclusions Subcortical (striatum) glutamate/glutamine is reduced in adults with ASD However, we found no differences in GABA in either the cortex or the subcortex Contrasts with prior evidence in addition to theory Or underst in addition to able in terms of multiple ‘pools’ of brain GABA, only some of which may be abnormal Detailed Methods fMRI Instructions were to remain awake with eyes open in addition to fixate on a static cross on a dark background 256 volumes, TR = 2000 ms. Analysed in FSL v 4.18. Preprocessing: MCFLIRT motion correction; registration in addition to normalization to MNI 2mm; 5 mm smoothing. EVs of no interest: 6 motion parameters + pulse in addition to breathing (recorded in scan) + mean signal over all grey, white, in addition to CSF voxels. MRS J-edited MEGAPRESS [1H]MRS at 3T was used, TE = 68 ms. Unsuppressed water signal was acquired in addition to used as long as absolute quantitation Voxel grey, white in addition to CSF composition was calculated from T1 structural MRI. Water-scaled metabolite concentrations were corrected as long as CSF. Data analysed in LCModel software. Unedited spectra were used to quantify Glx while J-edited ON/OFF subtraction spectra were analysed to measure “GABA+” (GABA + macromolecules). Acknowledgements Prof Gareth Barker Christine Ecker Richard Edden Grainne McAlonan Ruth O’Gorman Prof Steve Williams Eileen Daly Dave Lythgoe Ellie Wilson Jessica Faulkner EU-AIMS Consortium Medical Research Council (MRC) National Institute as long as Health Research (NIHR) Wellcome Trust For more in as long as mation, please contact: maria.mendez@kcl.ac.uk Martin, Doug KAPR-AM General Manager www.phwiki.com

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