Instant gratification as a way out of addiction?

Impulsivity is often seen as a hallmark of addiction — acting without thinking about the consequences of your actions and valuing the immediate reward of a drug-induced high over the future long-term payout of a healthy lifestyle. This type of delay discounting has been linked to a greater risk for drug addiction, but new research suggests that this type of “myopia for the future” may also improve someone’s chances of staying sober when they’re trying to get clean.

My latest piece for The Fix investigates the research behind this paradox, which suggests that those who are the most impulsive have the most to gain from effective treatment, cognitive training successfully improving their self-control. But is this effect a result of the treatment program itself or just a regression to the mean? Check out the article here to find out.

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Drug use, decision-making and the blunders of Rob Ford

I’ve got a new piece in The Guardian today on the unfolding debacle that is Toronto Mayor Rob Ford.

His consistent pattern of bad decision-making – including death threats, drunken driving and public boasts about his sex life – have all the signs of problem drug and alcohol use. Substance-dependent individuals frequently show impairments in decision-making abilities, with difficulties in impulse control and executive function, as well as corresponding abnormalities in relevant brain regions.

However, as Mayor Ford has vehemently denied any accusations of addiction, it could just be incompetence.

Check out the full piece here.

Do you have an addictive personality?

You’ll have to bear with me if this is a bit of a self-indulgent post, but I have some exciting news, Brain Study-ers: I’ve officially submitted my dissertation for a PhD in psychology!

In light of this – the culmination of three years of blood, sweat, tears and an exorbitant amount of caffeine – I thought I’d write this week on part of my thesis work (I promise to do my best to keep the jargon out of it!)

One of the biggest questions in addiction research is why do some people become dependent on drugs, while others are able to use in moderation? Certainly some of the risk lies in the addictive potential of the substances themselves, but still the vast majority of individuals who have used drugs never become dependent on them. This then leads to the question, is there really such a thing as an “addictive personality”, and what puts someone at a greater risk for addiction if they do choose to try drugs?

We believe that there are three crucial traits that comprise much of the risk of developing a dependency on drugs: sensation-seeking, impulsivity and compulsivity.

Sensation-seeking is the tendency to seek out new experiences, be they traveling to exotic countries, trying new foods or having an adrenaline junkie’s interest in extreme sports. These people are more likely to first try psychoactive drugs, experimenting with different sensations and experiences.

Conversely, impulsivity is acting without considering the consequences of your actions. This is often equated with having poor self-control – eating that slice of chocolate cake in the fridge even though you’re on a diet, or staying out late drinking when you have to be at work the next day.

While impulsivity and sensation-seeking can be similar, and not infrequently overlap, they are not synonymous, and it is possible to have one without the other. For example, in research we conducted on the biological siblings of dependent drug users, the siblings showed elevated levels of impulsivity and poor self-control similar to that of their dependent brothers and sisters, but normal levels of sensation-seeking that were on par with unrelated healthy control individuals. This led us to hypothesize that the siblings shared a similar heightened risk for dependence, and might have succumbed to addiction had they started taking drugs, but that they were crucially protected against ever initiating substance use, perhaps due to their less risk-seeking nature.

The final component in the risk for addiction is compulsivity. This is the tendency to continue performing a behavior even in the face of negative consequences. The most classic example of this is someone with OCD, or obsessive-compulsive disorder, who feels compelled to check that the door is locked over and over again every time they leave the house, even though it makes them late for work. These compulsions can loosely be thought of as bad habits, and some people form these habits more easily than others. In drug users, this compulsive nature is expressed in their continued use of the substance, even though it may have cost them their job, family, friends and health.

People who are high in sensation-seeking may be more likely to try drugs, searching for that new exciting experience, but if they are low in impulsivity they may only use a couple of times, or only when they are fairly certain there is a small risk for negative consequences. Similarly, if you have a low tendency for forming habits then you most likely have a more limited risk for developing compulsive behaviors and continuing an action even if it is no longer pleasurable, or you’ve experienced negative outcomes as a result of it.

Exemplifying this, another participant group we studied were recreational users of cocaine. These are individuals who are able to take drugs occasionally without becoming dependent on them. These recreational users had similarly high levels of sensation-seeking as the dependent users, but did not show any increase in impulsivity, nor did they differ from controls in their self-control abilities. They also had low levels of compulsivity, supporting the fact that they are able to use drugs occasionally but without having it spiral out of control or becoming a habit.

We can test for these traits using standard questionnaires, or with cognitive-behavioral tests, which can also be administered in an fMRI scanner to get an idea of what is going on in the brain during these processes. Behaviorally, sensation-seeing roughly equates to a heightened interest in reward, while impulsivity can be seen as having problems with self-control. As mentioned above, compulsivity is a greater susceptibility to the development of habits.

In the brain, poor self-control is most commonly associated with a decrease in prefrontal cortex control – the “executive” center of the brain. Reflecting this, stimulant-dependent individuals and their non-dependent siblings both showed decreases in prefrontal cortex volume, as well as impairments on a cognitive control task. Conversely, recreational cocaine users actually had an increase in PFC volume and behaved no differently from controls on a similar task. Thus, it appears that there are underlying neural correlates to some of these personality traits.

It is important to remember that we all have flashes of these behaviors in differing amounts, and it is only in extremely high levels that these characteristics put you at a greater risk for dependence. Also, crucially it is not just one trait that does it, but having all three together. Most notably though, neuroscience is not fatalistic, and just because you might have an increased risk for a condition through various personality traits, it does not mean your behavior is out of your control.

Oh, and I’ll be going by Dr. D from now on.

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Ersche, KE et al., Abnormal brain structure implicated in stimulant drug addiction. Science 335(6068): 601-604 (2012).

Ersche, KE et al., Distinctive personality traits and neural correlates associated with stimulant drug use versus familial risk of stimulant dependence. Biological Psychiatry 74(2): 137-144 (2013).

Smith, DG et al., Cognitive control dysfunction and abnormal frontal cortex activation in stimulant drug users and their biological siblings.Translational Psychiatry 3(5): e257 (2013).

Smith DG, et al., Enhanced orbitofrontal cortex function and lack of attentional bias to cocaine cues in recreational stimulant users.Biological Psychiatry Epub ahead of print (2013).

SFN ’12: Vulnerabilities for drug addiction

For anybody who’s in New Orleans for SFN this week, come by room 273 at 1pm today to learn about vulnerabilities for drug addiction. It’s an excellent nanosymposium set up by the fantastic Dr. Jenn Murray covering both human and preclincial studies into risk factors for addiction. The talks will include investigations into the classic predictive traits of impulsivity, anxiety and novelty-seeking, and they’ll also delve into environmental risk factors for addiction, such as maternal care and environmental stimulation.

I’ll be presenting first (so be there at 1pm sharp!) on my work on endophenotypes for addiction. This involves studying both dependent drug users and their non-dependent biological siblings, who share 50% of their genes and the same environment growing up, but who never developed any sort of drug or alcohol abuse. I’ll be looking specifically at cognitive control deficits and frontal cortex abnormalities in both of these groups compared to unrelated healthy control volunteers. There are some surprises in the results, so if you’re at SFN come by at 1pm to find out what they are!

A predisposition for drug addiction? Shared traits between stimulant dependents and their siblings

An exciting new study published in Science this week attempts to answer the chicken-or-egg question pervasive in drug addiction research of, “Which comes first, drug use or brain abnormalities?” Dr. Karen Ersche from the University of Cambridge* approaches this question with a new perspective, investigating the biological siblings of dependent drug users. And as is the case with most seemingly dichotomous questions in science, the answer is: both.

Dr. Ersche’s group studied 50 stimulant-dependent individuals, 50 of their healthy, non-dependent biological siblings, and 50 unrelated control volunteers on a barrage of cognitive tests, personality measures, and brain imaging techniques. Throughout the assessments, there was a striking pattern of similar responding between the drug users and their siblings, significantly differing in their results from the control participants. Specifically, drug users and their siblings were both significantly more impaired on the Stop Signal Reaction Time Task (SSRT), a test of inhibitory control that measures how well an individual can stop an ongoing response when triggered. Impulse control and inhibition are traits known to be impaired in drug-dependent individuals, and poor performance on the SSRT has previously been associated with an increased risk for drug abuse. However, these dysfunctions have long been debated as to whether they can be attributed to accumulated years of drug use and its effects on the brain, or are instead a predisposing factor that places an individual at an increased risk for drug dependence. In the current study, sibling participants performed as poorly on the SSRT as drug-dependent individuals, requiring more time to inhibit their actions. This would suggest that poor impulse control is a shared trait that is present in drug-dependent individuals before the onset of abuse. However, impaired inhibition is clearly not a determining variable, as dysfunction in the siblings did not lead to subsequent drug abuse or dependency.

The brains of stimulant users and their siblings were also structured similarly as compared to control volunteers, with an increase in gray matter in limbic and striatal regions such as the amygdala and putamen, areas important in emotion regulation and habit formation. Drug addiction is often seen as a disorder involving dysfunctional habits, and the putamen is implicated in the acquisition of these compulsive behaviors, targeted by an influx of dopamine and commonly a site of subsequent adaptations in the brains of heavy drug users. Additionally, the postcentral gyrus was significantly smaller in both groups as compared to healthy volunteers, indicating further pre-morbid differences.

Finally, white matter tract integrity, the neuron fibers that travel throughout the brain relaying messages from one region to another, were less intact in both the drug users and their siblings, signifying a decrease in brain connectivity in these groups as compared to the control participants. This was particularly evident in the inferior frontal gyrus, a region implicated in impulse control, supporting the findings of impaired self-regulation characteristic of compulsive drug users. Changes in connectivity in this area were also associated with an increase in impulse control dysfunction on the SSRT, with decreases in this region accounting for 6% of the variability in SSRT scores. Additional damage to white matter tracts and gray matter regions were also seen in the stimulant-dependent group, correlating with years of stimulant abuse and suggesting further damage and dysfunction due to chronic drug use itself.

Taken together, the abnormalities in the limbic and striatal regions, which have projections to the frontal cortex, as well as the decrease in frontal cortical volume and impaired connectivity between these key areas, confirms prior research indicating the importance of the cortico-limbic-striatal circuitry in drug dependence. These differences in the brains and behaviors of drug users and their siblings could potentially serve as endophenotypes for the development of drug dependence, characterized as stable inherited traits that are seen in clinical disorders and that can serve as indicators or predictors of pathology, both in patients and in their biological relatives. As such, these abnormalities in key regions for drug addiction could act as biomarkers for an increased risk of dependence.

However, the key question arises as to what protective factors could exist in the siblings to prevent them from trying or developing dependence on drugs. Sharing 50% of their genetic make-up, as well as familial environments growing up, drug-sibling pairs have highly similar brains and behaviors. However, clearly the differences that do exist between these groups are incredibly important. Early drug experimentation may exacerbate the structural abnormalities seen in these individuals, increasing the risk for later dependency, or even creating an epigenetic effect as has been seen in previous studies investigating early cigarette smoking and its link to later drug dependence. Alternatively, protective factors in the siblings could include greater education, outside interests or hobbies growing up, or even an increase in exercise and physical activity.

The question of the path to drug dependency is still very much open, however this study may take us one step closer to finding the answer.

*Disclaimer: I am a member of the Ersche lab at Cambridge, but was not involved in this study.