Impulsivity and Aggression in Female BPD and ADHD Patients: Association with ACC Glutamate and GABA Concentrations

Abstract

Borderline personality disorder (BPD) and attention-deficit-hyperactivity disorder (ADHD) are both characterized by high impulsivity and difficulties in controlling anger and aggression. In BPD, comorbid ADHD may further increase impulsivity. For both disorders, altered MR spectroscopy levels of the neurotransmitters glutamate and GABA as well as some correlations with impulsivity were previously reported. The objective of this study was to investigate the neurotransmitters glutamate and GABA in relation to impulsivity and aggression as expressed in the anterior cingulate cortex (ACC) in groups of female patients with BPD and ADHD, respectively. Associations of glutamate and GABA levels with further BPD (symptom severity) and ADHD aspects (hyperactivity and inattention) were exploratively evaluated. 1H MR spectra were acquired at 3T to determine glutamate to total creatine ratios (Glu/tCr) and GABA levels from the ACC in a BPD group (n = 26), an ADHD group (n = 22), and a healthy control (HC) group (n = 30); all participants were females. Both patient groups showed higher scores on self-reported impulsivity, anger, and aggression compared with HCs. ACC GABA levels were significantly lower in ADHD than HC. Although measures of impulsivity were positively related to glutamate and negatively to GABA, for aggression only a negative correlation with GABA could be demonstrated. These data provide human in vivo evidence for the role of ACC Glu/tCr and GABA in impulsivity and aggression. If distinct associations of Glu/tCr and GABA for BPD and ADHD can be confirmed in future studies, this might yield implications for more specific pharmacological treatments.

Large-scale functional network overlap is a general property of brain functional organization: Reconciling inconsistent fMRI findings from general-linear-model-based analyses

“…There is strong evidence that glutamatergic excitation, GABAergic inhibition and balanced E/I are altered in older adults and psychiatric patients relative to younger adults and healthy controls (HCs), respectively, and that unbalanced E/I contributes to impaired cognitive functioning (Brady et al, 2013; Caspary et al, 2008; Edden et al, 2012; El Idrissi et al, 2013; Ende et al, 2016; Gonzalez-Burgos et al, 2015; Legon et al, 2015; Luscher and Fuchs, 2015; Murray et al, 2014; Nelson and Valakh, 2015; Pehrson and Sanchez, 2015; Purkayastha et al, 2015; Riese et al, 2015; Robertson et al, 2016; Roux and Buzsaki, 2015; Schmidt and Mirnics, 2015; Stebbings et al, 2016; Tse et al, 2015). This pathophysiological mechanism may contribute importantly to inconsistent GLM findings because they may lead to BOLD signal decrease, increase, or no change in different brain regions in older adults and patients, depending on the relative extent of changes in excitation and inhibition in each region.…”

Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: An 18F-FPEB PET Study

“…Subsequently, genetic determinants of receptor expression and neuronal function in the normal variation of human behavior have been validated (2). Several temperament and personality traits, including novelty seeking (NS), harm avoidance, and impulsivity, have been associated with the vulnerability to mental illnesses (3,4) and have been directly related to receptors and neurotransmission using functional imaging (5)(6)(7). In parallel, dysregulation or disequilibrium of brain neurotransmitters have repeatedly been linked to mental diseases.…”

“…Glutamate is the main excitatory neurotransmitter in the brain and is involved in numerous aspects of behavior and cognition. Glutamate concentrations in the anterior cingulate cortex (ACC) have been associated with personality and behavior including sensation seeking (8), harm avoidance (9), reward processing (10), anxiety (11), impulsivity, and aggression (7). On release, glutamate can bind to metabotropic glutamate receptors (mGluR) located pre-, post-and perisynaptically, which are in turn responsible for modulating the synaptic transmission of glutamate and other neurotransmitters.…”

Quantifying absolute glutamate concentrations in nucleus accumbens of prescription opioid addicts by using 1H MRS

“…Based on MRS studies, glutamate concentrations in the ACC correlated with impulsivity in borderline personality disorder (Hoerst et al, 2010) and attention-deficit hyperactivity disorder (Ende et al, 2016). In addition, Bauer et al (2013) reported increasing glutamate levels in the NAc in alcoholdependent patients, with glutamate levels in the NAc and the ACC both strongly correlated with the level of the Obsessive Compulsive Drinking Scale.…”