Monoamine polygenic liability in health and cocaine dependence: Imaging genetics study of aversive processing and associations with depression symptomatology

Abstract

Background Gene polymorphisms that affect serotonin signaling modulate reactivity to salient stimuli and risk for emotional disturbances. Here, we hypothesized that these serotonin genes, which have been primarily explored in depressive disorders, could also have important implications for drug addiction, with the potential to reveal important insights into drug symptomatology, severity, and/or possible sequelae such as dysphoria. Methods Using an imaging genetics approach, the current study tested in 62 cocaine abusers and 57 healthy controls the separate and combined effects of variations in the serotonin transporter (5-HTTLPR) and monoamine oxidase A (MAOA) genes on processing of aversive information. Reactivity to standardized unpleasant images was indexed by a psychophysiological marker of stimulus salience (i.e., the late positive potential (LPP) component of the event-related potential) during passive picture viewing. Depressive symptomatology was assessed with the Beck Depression Inventory (BDI). Results Results showed that, independent of diagnosis, the highest unpleasant LPPs emerged in individuals with MAOA-Low and at least one ‘Short’ allele of 5-HTTLPR. Uniquely in the cocaine participants with these two risk variants, higher unpleasant LPPs correlated with higher BDI scores. Conclusions Taken together, these results suggest that a multilocus genetic composite of monoamine signaling relates to depression symptomatology through brain function associated with the experience of negative emotions. This research lays the groundwork for future studies that can investigate clinical outcomes and/or pharmacogenetic therapies in drug addiction and potentially other psychopathologies of emotion dysregulation.

Stress Induced Hormone and Neuromodulator Changes in Menopausal Depressive Rats

“…Major depressive disorder is a leading cause of disability worldwide, and affects more than 17% of the populations, making it one of the most prevalent health-related causes of human suffering ( 1 , 2 ). However, the mechanisms of depression are far from clear ( 3 ), the most widely accepted theory about the mechanism of depression points to the monoamine neurotransmitters, including norepinephrine (NE), serotonin (5-HT), and dopamine (DA) ( 4 – 6 ). The 5-HT and NE reuptake inhibitors and selective 5-HT reuptake inhibitors are considered to be the first choice of treatment for depression ( 2 , 7 – 9 ).…”

A meta‐analysis of electrophysiological biomarkers of reward and error monitoring in substance misuse

“…(2016). 6 Eight studies (Asmaro et al., 2014; Cochran et al., 2018; Kiat & Cheadle, 2018; Littel & Franken, 2011; Moeller et al., 2013, 2014; Stothart et al., 2016; van de Laar et al., 2004) plus 13 studies used in LPP meta‐analysis (for list of studies, see Webber et al., 2022). 7 Lannoy et al.…”

Effects of an opioid (proenkephalin) polymorphism on neural response to errors in health and cocaine use disorder

“…Some of these participants have been included in prior imaging genetics studies in our lab, but these studies have always included different genes and/or different neural probes, and accordingly have reported activations in different brain regions [54–56]. More specifically, we previously reported on polymorphisms of the dopamine transporter ( DAT1 ) [54] and the protein-coding monoamine oxidase A gene ( MAOA ) [55, 56] while participants performed a drug-word inhibitory control task during fMRI [54], viewed unpleasant images during EEG [55], or simply while they underwent structural MRI scans [56]. For these reasons, overlap in variance with the current study is likely minimal.…”