Altered Risk-Aversion and Risk-Seeking Behavior in Bipolar Disorder

We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson's disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre-and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky and two conservative) and is designed to promote learning to make advantageous (conservative) choices over time. Thirty-four BPD patients completed both assessments (18 placebo and 16 pramipexole). Baseline performance did not differ by treatment group (F ¼ 0.63; p ¼ 0.64); however, at week 8, BPD patients on pramipexole demonstrated a significantly greater tendency to make increasingly high-risk, high-reward choices across the five blocks, whereas the placebo group's pattern was similar to that reported in healthy individuals (treatment Â time Â block interaction, po0.05). Analyses of choice strategy using the expectancy valence model revealed that after 8 weeks on pramipexole, BPD patients attended more readily to feedback related to gains than to losses, which could explain the impaired learning. There were no significant changes in mood symptoms over the 8 weeks, and no increased propensity toward manic-like behaviors were reported. Our results suggest that the enhancement of dopaminergic activity influences risk-associated decision-making performance in euthymic BPD. The clinical implications remain unknown.

Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Dopaminergic Influences on Emotional Decision Making in Euthymic Bipolar Patients

Burdick

Braga

Gopin

et al. 2013

“…Anxiety and depression are especially common (Chandler et al, 2008). In fact, a number of young people with the BPP already meet DSM-IV-TR criteria for bipolar II or NOS (Rock et al, 2010;Chandler et al, 2009); the symptom profiles and alterations in emotional processing are relatively homogeneous for patients whether or not they meet a syndromal definition of BD.…”

Section: Discussionmentioning

confidence: 99%

“…Such individualsFhereafter referred to as individuals with the bipolar phenotype (BPP)Fare at increased risk for a range of mental health problems including, but not limited to, BD (eg, anxiety, depression;Chandler et al, 2008;Calabrese et al, 2003). Moreover, among individuals with the BPP some already meet DSM-IV-TR criteria for bipolar II or NOS (Rock et al, 2010;Chandler et al, 2009) and their symptoms and alterations in emotional processing are relatively homogeneous. Follow-up of young people with the BPP indicates that intermittent mood elevation in young people is a significant predictor of a variety of subsequent mental health problems even in the short term (Tijssen et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Reduced Subjective Response to Acute Ethanol Administration Among Young Men with a Broad Bipolar Phenotype

Yip

Doherty

Wakeley

et al. 2012

Self Cite

Elevated lifetime prevalence rates of alcohol use disorders (AUDs) are a feature of bipolar disorder (BD). Individuals at-risk for AUDs exhibit blunted subjective responses to alcohol (low levels of response), which may represent a biomarker for AUDs. Thus, individuals atrisk for BD may exhibit low responses to alcohol. Participants were 20 unmedicated adult males who reported high rates of hypomanic experiences (bipolar phenotype participants; BPPs), aged 18 to 21 years, and 20 healthy controls matched on age, gender, IQ, BMI, and weekly alcohol intake. Subjective and pharmacokinetic responses to acute alcohol (0.8 g/kg) vs placebo administration were collected in a randomized, double-blind, cross-over, placebo-controlled, within-subjects design. BPP participants reported significantly lower subjective intoxication effects ('feel high': F ¼ 14.2, p ¼ 0.001; 'feel effects': F ¼ 8.1, p ¼ 0.008) across time, but did not differ in their pharmacokinetic, stimulant, or sedative responses. Paradoxically, however, the BPP participants reported significantly higher expectations of the positive effects of alcohol than controls. Our results suggest that unmedicated young males with previous hypomanic experiences exhibit diminished subjective responses to alcohol. These blunted alcohol responses are not attributable to differences in weekly alcohol intake, pharmacokinetic effects (eg, absorption rates), or familial risk of AUDs. These observations suggest that the dampened intoxication may contribute to the increased rates of alcohol misuse in young people at-risk for BD, and suggest possible shared etiological factors in the development of AUDs and BD.

“…Decision making has been a research target in substance and alcohol misuse disorders (Bechara et al, 2001;Ersche et al, 2008;Rogers et al, 1999b;Rogers and Robbins, 2001), unipolar depression and bipolar disorder (Chandler et al, 2009;Murphy et al, 2001), suicidaility (Dombrovski et al, 2010;Jollant et al, 2005), and impulsive personality disorders (Bazanis et al, 2002;Kirkpatrick et al, 2007). Adjunctive work has explored the idea that impairments in decision making can serve as markers for likely relapse (Adinoff et al, 2007;Bechara et al, 2001) and facilitate the exploration of therapeutic interventions (Rahman et al, 2006;Robbins and Arnsten, 2009).…”

Section: Introductionmentioning

confidence: 99%

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

Rogers

2010

201

130

Neurophysiological experiments in primates, alongside neuropsychological and functional magnetic resonance investigations in humans, have significantly enhanced our understanding of the neural architecture of decision making. In this review, I consider the more limited database of experiments that have investigated how dopamine and serotonin activity influences the choices of human adults. These include those experiments that have involved the administration of drugs to healthy controls, experiments that have tested genotypic influences upon dopamine and serotonin function, and, finally, some of those experiments that have examined the effects of drugs on the decision making of clinical samples. Pharmacological experiments in humans are few in number and face considerable methodological challenges in terms of drug specificity, uncertainties about pre-vs post-synaptic modes of action, and interactions with baseline cognitive performance. However, the available data are broadly consistent with current computational models of dopamine function in decision making and highlight the dissociable roles of dopamine receptor systems in the learning about outcomes that underpins value-based decision making. Moreover, genotypic influences on (interacting) prefrontal and striatal dopamine activity are associated with changes in choice behavior that might be relevant to understanding exploratory behaviors and vulnerability to addictive disorders. Manipulations of serotonin in laboratory tests of decision making in human participants have provided less consistent results, but the information gathered to date indicates a role for serotonin in learning about bad decision outcomes, non-normative aspects of risk-seeking behavior, and social choices involving affiliation and notions of fairness. Finally, I suggest that the role played by serotonin in the regulation of cognitive biases, and representation of context in learning, point toward a role in the cortically mediated cognitive appraisal of reinforcers when selecting between actions, potentially accounting for its influence upon the processing salient aversive outcomes and social choice.