A new meta-analysis reveals increased impulsivity is associated with numerous psychiatric disorders

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Individuals with many different psychiatric disorders have a higher tendency to choose smaller, immediate rewards over larger, delayed rewards, a study led by Hamilton researchers has found..

The findings of a meta-analysis by researchers of McMaster University and St. Joseph’s Healthcare Hamilton, which combined data from more than 40 studies, was published in JAMA Psychiatry today.

That this type of decision-making tied to impulsivity, called delay discounting, is heightened in those with certain psychiatric disorders compared to others, is expected to have an important impact on future research and treatment across an array of disorders.

“The revelation that delay discounting is one of these ‘trans-diagnostic’ processes will have a significant effect on the future of psychiatric diagnosis and treatment,” said Michael Amlung, lead author of the study. He is an assistant professor of psychiatry and behavioural neurosciences at McMaster University and researcher for the Peter Boris Centre for Addictions Research at St. Joseph’s Healthcare Hamilton.

The study analyzed data from studies across eight different psychiatric disorders, including major depressive disorder, bipolar disorder, borderline personality disorder, schizophrenia, eating disorders, and others. The largest delay discounting effects were found to be associated with bipolar disorder, borderline personality disorder, and schizophrenia.

Previous research has linked a greater preference for immediate rewards and impulsivity to negative health outcomes, such as addiction, obesity, and ADHD. This study reinforced that negative association, finding that impulsive preferences are consistently observed across an even broader range of psychiatric disorders.

Interestingly, the study also found the opposite pattern in those with anorexia nervosa. The researchers explained that the greater preference for delayed over immediate rewards seen in people with anorexia is consistent with excessive self-control of their eating habits.

The study authors say this pattern suggests that delay discounting preferences are best thought of as being on a continuum, with some disorders exhibiting excessively impulsive decisions and other disorders exhibiting excessively self-controlled decisions.

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The largest delay discounting effects were found to be associated with bipolar disorder, borderline personality disorder, and schizophrenia. The image is in the public domain.

“Examining factors that cut across psychiatric disorders, such as delay discounting, helps to illuminate commonalities and distinguishing characteristics amongst disorders that then guide further research on treatment and prevention,” said Randi McCabe, co-author of the paper, psychologist-in-chief at St. Joseph’s Healthcare Hamilton and professor of psychiatry and behavioural neurosciences at McMaster.

“The more we understand the nature of psychiatric illness, the better we are equipped to provide effective treatment strategies,” she said.

The authors say the study findings support the inclusion of delay discounting in the Research Domain Criteria (RDoC) framework proposed by the National Institute of Mental Health, as a potent indicator of psychiatric illness. RDoC is a biologically-valid framework for understanding mental disorders, and includes research approaches in genetics, neuroscience, and behavioural science.

“Our results provide strong evidence for delay discounting as a core behavioural process within the RDoC framework,” Amlung said. “On a broader level, this study underscores the need for future research examining common neurobiological and genetic underpinnings of this type of decision making in order to inform evidence-based treatments across psychiatric disorders.”

Funding: The Peter Boris Centre for Addictions Research, a partnership of St. Joseph’s Healthcare Hamilton and McMaster University, partially funded this study.


Impulsivity is a common and core feature associated with numerous psychiatric disorders, including attention deficit hyperactivity disorder, substance use disorder, and pathological gambling.

It has become increasingly evident that impulsivity is a multi-faceted, rather than a unitary, trait (13).

In the behavioral approach, the two broadly defined major components of impulsivity are impulsive action and impulsive choice (15).

Impulsive action is behaviorally manifested as the failure to inhibit an inappropriate response, and consequently, showing premature response.

By contrast, impulsive choice is manifested as impulsive decision-making by choosing small immediate rewards over more beneficial delayed rewards.

In addition to their behaviorally distinct features, the brain areas mediating impulsive action and impulsive choice are known to be distinct as well (13), and they are also differentially influenced by pharmacological manipulation (46), further suggesting that the two components are well-segregated.

In animal studies, impulsive action, expressed as premature response, is widely measured using the 5-Choice Serial Reaction Time Task (5-CSRTT).

In contrast, impulsive choice, which involves decision-making, often expressed as devaluing temporally delayed gratification, is frequently measured using delay-discounting task (346).

In humans, however, the deficit of decision-making is widely measured using the Iowa Gambling Task (IGT), which simulates real-life decision-making by adding the features of reward, punishment, and uncertainty (3).

Similarly, adopting the basic principle of IGT, the rodent version of the gambling task (rGT), which shares many of the features of the human gambling tasks (7), has been developed by a few research groups (810).

Recently, we adopted one of the previously developed rGT models (10), with a modification of the touch-screen chamber (11), and successfully trained rats to demonstrate decision-making toward risk-preference (12).

In rGT, for rats to be trained to perform decision-making behaviors with gambling features, they require pre-training steps with multiple stages, one of which is very similar to the 5-CSRTT. Thus, rGT provides experimenters the advantage of measuring impulsive action and impulsive choice simultaneously in a within-subjects frame.

Adolescence is an extremely important period in development, during which the brain matures and higher order cognitive functions develop to shape adjustable normal behaviors.

This period is also vulnerable to the development of many neuropsychiatric disorders and remarkably more prone to risk-taking behavior and impulsiveness (1315).

These behavioral characteristics of adolescence further interact with environmental factors (e.g., stress and drugs of abuse) to determine the onset of neuropsychiatric disorders (13).

When considering the laboratory rat, however, it is difficult to precisely compare rat and human age across the different stages of life.

Albeit based on a limited number of studies, it is generally considered that approximately postnatal day (PND) 28, after weaning, is the beginning of adolescence, and PND 63–70 is the period when male rats enter into adulthood (1316).

Although the two major components of impulsivity are known to exist in segregation, there have been relatively few studies examining their relationship with each other and their differential expression when rats are placed under stressful situations, such as extinction and re-acquisition of a pre-established task; in particular, there is a lack of studies comparing these parameters across different developmental transition periods. To address these issues, in the present study, we exposed rats to rGT at two different ages (i.e., late adolescent/young adult vs. mature adult), and assessed how impulsive action and impulsive choice are expressed under different situations. In addition, as there is ample evidence that maladaptive decision-making is associated with an increase in cocaine usage in both humans and animals (1720), we also examined how acute cocaine administration influences the expression of impulsivity.

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Impulsive personality traits are complex heritable traits that are governed by frontal-subcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse and attention-deficit/hyperactivity disorder (ADHD).

In collaboration with the genetics company 23andMe, we performed 10 genome-wide association studies on measures of impulsive personality traits [the short version of the UPPS-P Impulsive Behavior Scale, and the Barratt Impulsiveness Scale (BIS-11)] and drug experimentation (the number of drug classes an individual had tried in their lifetime) in up to 22,861 male and female adult human research participants of European ancestry.

Impulsive personality traits and drug experimentation showed single nucleotide polymorphism heritabilities that ranged from 5 to 11%. Genetic variants in the CADM2 locus were significantly associated with UPPS-P Sensation Seeking (p = 8.3 × 10−9, rs139528938) and showed a suggestive association with Drug Experimentation (p = 3.0 × 10−7, rs2163971; r2 = 0.68 with rs139528938). Furthermore, genetic variants in the CACNA1I locus were significantly associated with UPPS-P Negative Urgency (p = 3.8 × 10−8; rs199694726).

The role of these genes was supported by single variant, gene- and transcriptome-based analyses. Multiple subscales from both UPPS-P and BIS showed strong genetic correlations (>0.5) with Drug Experimentation and other substance use traits measured in independent cohorts, including smoking initiation, and lifetime cannabis use. Several UPPS-P and BIS subscales were genetically correlated with ADHD (rg = 0.30–0.51), supporting their validity as endophenotypes. Our findings demonstrate a role for common genetic contributions to individual differences in impulsivity. Furthermore, our study is the first to provide a genetic dissection of the relationship between different types of impulsive personality traits and various psychiatric disorders.

SIGNIFICANCE STATEMENT Impulsive personality traits (IPTs) are heritable traits that are governed by frontal-subcortical circuits and are associated with neuropsychiatric disorders, particularly substance use disorders. We have performed genome-wide association studies of IPTs to identify regions and genes that account for this heritable variation.

IPTs and drug experimentation were modestly heritable (5–11%). We identified an association between single nucleotide polymorphisms in CADM2 and both sensation seeking and drug experimentation; and between variants in CACNA1I and negative urgency. The role of these genes was supported by single variant, gene- and transcriptome-based analyses.

This study provides evidence that impulsivity can be genetically separated into distinct components. We showed that IPT are genetically associated with substance use and ADHD, suggesting impulsivity is an endophenotype contributing to these psychiatric conditions.

PMID: 30718321 PMCID: PMC6435820 [Available on 2019-09-27] DOI: 10.1523/JNEUROSCI.2662-18.2019


Source:
McMaster University
Media Contacts: 
Veronica McGuire – McMaster University
Image Source:
The image is in the public domain.

Original Research: Closed access
“Delay Discounting as a Transdiagnostic Process in Psychiatric Disorders: A Meta-analysis”. Michael Amlung, PhD; Emma Marsden, BA; Katherine Holshausen, PhD; Vanessa Morris, BA; Herry Patel, BSc; Lana Vedelago, BA; Katherine R. Naish, PhD; Derek D. Reed, PhD; Randi E. McCabe, PhD.
JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.2102

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