Monoamine polygenic liability in health and cocaine dependence: imaging genetics study of aversive processing and associations with depression symptomatology.
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.
Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America.
Scott J
SJ
Moeller
Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America.
Muhammad A
MA
Parvaz
Department of Biosciences, Brookhaven National Laboratory, Upton, NY 11973, United States of America.
Elena
E
Shumay
Department of Biosciences, Brookhaven National Laboratory, Upton, NY 11973, United States of America.
Salina
S
Wu
Department of Biosciences, Brookhaven National Laboratory, Upton, NY 11973, United States of America.
Nicasia
N
Beebe-Wang
Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America; Department of Psychology, Stony Brook University, Stony Brook, NY 11794, United States of America.
Anna B
AB
Konova
Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America; Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, United States of America.
Michail
M
Misyrlis
Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America.
Nelly
N
Alia-Klein
Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America. Electronic address: rita.goldstein@mssm.edu.
Rita Z
RZ
Goldstein
D000328:Adult; D015306:Biogenic Monoamines / Q000378:metabolism*; D019970:Cocaine-Related Disorders / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D003863:Depression / Q000150:complications / Q000235:genetics* / Q000523:psychology*; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012701:Serotonin / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
D015306:Biogenic Monoamines; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D008995:Monoamine Oxidase
5-HTTLPR; Cocaine addiction; Depression; Event-related potentials; Imaging genetics; MAOA; comorbidity