The Salience of Reward

Abstract

An important and so far minimally addressed aspect of psychosis research is the manifestation of genetic psychosis susceptibility, as measured with polygenic risk profile scores (RPSs), on human brain function. The study of more than 1500 adolescents by Lancaster et al 1 in this issue of JAMA Psychiatry reveals that the genetic vulnerability to developing psychosis is associated with increased brain activity in the ventral striatum during reward processing. This finding suggests that the genetic risk of psychosis may shape the adolescent response to rewarding stimuli.Aberrant processing of salience is a fundamental factor underlying psychotic disorders.2 Aberrant salience in this respect refers to the inappropriate attribution of incentive salience to environmental cues, which is the process by which a stimulus grabs attention and motivates goal-directed behavior because of associations with reward or punishment. This phenomenon is thought to underlie the formation of psychotic symptoms and is most likely driven by elevated striatal dopamine function, 3 which is 1 of the most robust pathophysiologic features of psychosis. Since the early 2000s, numerous functional magnetic resonance imaging (MRI) studies 4-6 have investigated the effect of incentive cues on human brain activity patterns with a monetary incentive delay task that involves reward anticipation and receipt. In this task, individuals are required to press a button as fast as possible when seeing a target stimulus. The cue that precedes the target stimulus indicates whether a timely button press is rewarding or nonrewarding. The time between cue and target is considered the anticipation time, and reward receipt is assessed when feedback on performance is given at the end of every trial. Results of studies with healthy individuals have unequivocally indicated the ventral striatum as the brain area critically involved in reward processing 4 and have also revealed the heritability of brain activity patterns underlying reward processing. 7 Neuroimaging in patients with a psychotic disorder has consistently revealed significantly attenuated activity in the ventral striatum during reward anticipation, as confirmed by a recent meta-analysis 5 that included 23 functional MRI studies. This pattern of reduced striatal activity during reward anticipation has also been found in unaffected siblings 8 and offspring 9 of patients with a psychotic disorder, which suggests that genetic risk of psychosis contributes to the response to rewarding cues. Recently, the ability to stratify individuals on the basis of polygenic RPSs for psychiatric disorders, such as schizophrenia and bipolar disorder, has offered new opportunities for clinical and epidemiologic research. Risk profile scores are derived from large genome-wide association studies 10,11 that examined individual genetic variants associated with a particular disorder and indicate an individual's genetic susceptibility of developing this disorder. Thereby, RPSs provide the possibility to examine phenotypic manifesta...

Altered activation and connectivity in a hippocampal–basal ganglia–midbrain circuit during salience processing in subjects at ultra high risk for psychosis

“… 43 They may also reflect developmental differences: a recent study of over 1500 adolescents found reward-related responses in the ventral striatum increased with increased polygenic psychosis risk scores. 46 , 47 …”

Impaired cognitive performance under psycho-social stress in cannabis-dependent males is mediated by attenuated precuneus activity

“…26 A similar approach has been employed in previous studies on stress reactivity 27 and in previous studies examining emotional processing in cannabis users. 19,20,28,29 Exclusion criteria included (1) age < 18 or > 40 years, (2) left-handedness, (3) history or current DSM-IV axis I disorders (based on MINI, exception: cannabis abuse or dependence), (4) Beck Depression Inventory (BDI-II) score > 20 30 , (5) current or history of a medical disorder including endocrinological abnormalities (6) current or regular use of medication, (7) usage of other illicit substances > 75 lifetime occasions or during the 28 days prior to the experiment, (8) positive urine screen for cocaine (300 ng/ml), methamphetamine (500 ng/ml), amphetamine (500 ng/m), methadone (300 ng/ml) or opiate (300 ng/ml) (Drug-Screen-Multi 7TF, von minden GmbH, Moers, Germany), (9) breath alcohol >0.00% (analyzed using TM-7500, Trendmedic, Penzberg, Germany). For controls, additional exclusion criteria were applied: (1) cumulative lifetime use of cannabis > 15 g (M = 1.29, SD = 1.02), (2) use of any other illicit substance >10 lifetime occasions.…”

“…3 Cannabis use-associated alterations in the domains of reward processing and cognition have been extensively studied 4,5 and there is growing evidence from functional imaging studies suggesting neuroplastic adaptations in neural systems subserving these functions. 6,7 In the cognitive domain, selective impairments in attention, working and associative memory have been reported most consistently. 4,5,8,9 Long-term stress has detrimental effects on mental health 10 and the acute stress response is an adaptive mechanism to environmental demands that are perceived as potentially threatening.…”

Impaired cognitive performance under psychosocial stress in cannabis-dependent men is associated with attenuated precuneus activity

“…26 A similar approach has been used in previous studies on stress reactivity 27 and in studies examining emotional processing in cannabis users. 19,20,28,29 Exclusion criteria included (1) age younger than 18 or older than 40 years; (2) left-handedness; (3) history or current DSM-IV axis I disorder (based on MINI; exception: cannabis abuse or depend ence); (4) Beck Depression Inventory (BDI-II) score greater than 20; 30 (5) current or history of a medical disorder, including endocrinological abnormalities; (6) current or regular use of medication; (7) use of other illicit substances on more than 75 lifetime occasions or during the 28 days before the experiment; (8) positive urine screen for cocaine (300 ng/mL), methamphetamine (500 ng/mL), amphetamine (500 ng/mL), methadone (300 ng/mL) or opiate (300 ng/mL; Drug-Screen-Multi 7TF, von minden GmbH, Moers, Germany); (9) breath alcohol > 0.00% (analyzed using TM-7500, Trendmedic, Penzberg, Germany). For controls, additional exclusion criteria were applied: cumulative lifetime use of cannabis > 15 g (mean ± standard deviation [SD] 1.29 ± 1.02); use of any other illicit substance on more than 10 lifetime occasions.…”

“…3 Cannabis use-associated alterations in the domains of reward processing and cognition have been extensively studied, 4,5 and there is growing evidence from functional imaging studies suggesting neuroplastic adaptations in neural systems that subserve these functions. 6,7 In the cognitive domain, selective impairments in attention and working and associative memory have been reported most consistently. 4,5,8,9 Long-term stress has detrimental effects on mental health, 10 and the acute stress response is an adaptive mechanism to environmental demands that are perceived as potentially threatening.…”