Addiction & mental illness research: the latest, a summary

Here's a summary of some of the latest research presented at a 3-days international conference I was at (some of these findings have yet to publish, and I'm too sleepy at the moment to find existing links for the rest but I'll be sure to add them at a later time):

1. Sensitizing the brain to drug effects with prolonged use: Exposure to Amphetamine over time increases dopamine's readiness response (up-regulating) in the nucleus accumbens region, which is important for motivation. Furthermore, in the presence of drug-related cues in the environment, there's an increase of dopamine release in the amphetamine-overexposed brain, thereby increasing motivation which gets directed to seeking drugs for use. This would explain some of the "triggers" that come with being in the same environment in which drugs (e.g. amphetamine) were involved - the same triggers that could lead to relapse. However, in the absence of these cues, there's actually a depression of motivation due to a decrease in dopamine being released in the nucleus accumbens region. This may explain why it's hard to feel motivated or up to doing anything when in a drug-free environment.


2. Emotional abuse / neglect: most important predisposition for mental illness development


3. Trauma and substance use disorders (SUDs): It's more effective to improve PTSD (Post traumatic stress disorder) in people with SUDs first, then address their substance use. Some researchers argued that the underlying "cause" of SUDs was trauma. While trauma was likely to present in people with SUDs' personal history, it may not necessarily be PTSD (people who experience relived trauma as if it was happening right now).


4. Trauma, SUDs, stress and the brain: A young person's trauma correlated with a smaller prefrontal cortex (imaging studies). Total cumulative adversity was found to associate with decrease in brain volume, especially areas associated with decision making process (prefrontal cortex) and emotional regulation (amygdala). Higher traumatic events experienced by the person with SUDs --> nucleus accumbens (N.A.) activity increases with stress. N.A. activity is up-regulated when presented with a neutral relaxing stimuli. In short, persons with SUDs and a history of trauma were found to have a heightened motivational system, one that also responds to stress, and decreased resources for strategic long term decisions and regulation of emotions.
   
   There may be a place for mindfulness therapy in SUDs treatment. Engaging in meaningful relationship and activities could help increase stress resilience and help with SUDs. Other ways to deal with SUDs by addressing stress: time management, problem solving, relaxation, behavioural modification, cognitive restructuring, biofeedback, medication, etc. It was found that early trauma changed sensitivity of cortisol receptors in the brain. It would be interesting to research how the brain is affected through the developmental stages. We know, for one, that the brain doesn't reach its full developmental potential until the late 20s. How would trauma as experienced by people with SUDs at an early age affect them later in life? Is there a window within which the effect would be more pronounced?


5. Epigenetics: for the uninitiated, the basis for your blueprint is in your genes (and your jeans). It is your genotype. The expressed characteristics of your genes are called phenotypes. The regulation of gene expression without actually changing the DNA is what epigenetics focus on. They call it the "dimmer" of DNAs, akin to dimming or brightening (?) the DNA light. Various factors can act as dimmers for DNA expression, including, surprise surprise, maternal diet and maternal stress. Your mother's experience and intake during pregnancy can predispose you to substance use disorders, by affecting how your genes for certain brain regions get expressed. Interestingly, according to the latest study done in Wisconsin, paternal stress in pre-school posed a notable effect on sensitivity to dopamine release in the brain, especially for girls. Basically, daddy's little girl could go on to abuse cocaine if exposed to daddy's stress in pre-school. "Could" is the functional key word here. Nevertheless, who knew that would have a secondary chemical basis at all?


6. Social Economic Status (SES) and SUDs: lower SES earlier in life was associated with cells resisting signals and blocking cortisol's feedback pathway. Interestingly, care giving quality (e.g. maternal warmth) earlier in life was found to offset this lower SES problem. Family emotional climate played a role in stress sensitivity. However, they didn't find this to be true with higher SES group. Possibility of higher SES mothers hiring others to be the surrogate mothers, thereby changing what the results might have looked like?


7. Personality traits & SUDs: Impulsivity and sensation seeking are two traits that can predict the externalizing behaviour specific to SUDs (Castellanos-Ryan, Rubia, & Conrod, ACER, 2010). Impulsivity is defined as behaviour that is poorly conceived, prematurely expressed, unduly risky / inappropriate to situations and often results in undesirable consequences. 20% of experimenters go on to develop SUDs. They were found to display: behavioural disinhibition, intolerance to delay gratification, lack of long-term/consequence consideration when making decisions, and poor attention. Addiction is often considered in the context of: compulsion (motivation to use), control (inability to refrain), and consequences (maintaining drug use despite consequences). The latter two relate to impulsivity. It was found that if you decreased motor impulsivity in cocaine users, you'd be able to decrease rate of relapse. As an aside, gambling addiction has no direct relationship to impulsiveness. It's more about making risky decisions and novelty seeking than anything else.


8. NAOMI project / SALOME project: The Canadian Institutes of Health Research (CIHR) funded a clinical project that tested the benefits of heroin maintenance therapy. This was NAOMI (North American Opiate Medication Initiative), conducted in Vancouver and Montreal (starting in 2005). The pharmaceutical graded heroin was imported from Europe. The idea was that giving hard core users controlled heroin over a period of time and introducing them to associated therapy would help stabilize this group long enough for them to improve other aspects of their life, which in turn would hopefully help them get off heroin or move on to other (oral) treatment methods that previously failed with them. The researchers reported success in the retention of these folks in treatment and decrease illicit drug use and associated activities. More remarkably, the double blind substance used, hydromorphone (Dilaudid), was also an effective treatment. It's remarkable because Dilaudid is legal (it's used for pain management).
   
   They considered the project a success, but they failed to persuade the government to consider allowing prescription of diacetylmorphine, the active ingredient in heroin, under a compassionate use. So now they're moving on to SALOME (Study to Assess Long-term Opioid Maintenance Effectiveness), which would be conducted in Vancouver (the Montreal site fell through). They want to compare the effectiveness of diacetylmorphine against Dilaudid. My biggest concern for the implement of heroin assisted therapy is security - there's been a rash of robberies in the States of pharmacies stocking narcotics recently in the news. Heroin has such a great street value that it'd be hard to operate pharmacies dispensing it without strict security (like the one employed by NAOMI). How many pharmacies can afford such security? The researchers cited European's report on safety to ease such concerns, but North America is a bit different in culture and size. I'm cautious about the reality of implementing this therapy. Maybe we should look into using injectable Dilaudid as an alternative instead?


9. Stats on people seeking treatment: People suffering from SUDs for 10 years --> 25% would enter treatment. Of those people suffering for 30 years or more, only 50% would enter treatment. People who abused legal drugs were more likely to enter treatment than those who abused illegal ones. 40% of people entering treatment were more likely to have other psychological disorders as well.


10. DSM: has no official status in Canada. ICD is the official guideline for us, but most clinicians use the DSM. For the coming DSM V, changes may include assessment for the level of disability, need for treatment, and changes in diagnoses (e.g. merging of substance use and substance dependence, creating a new category for gambling addiction, etc.). It was suggested that we should consider re-arranging the DSM in a hierarchical fashion, rather than in lists of symptoms under discrete categories like it is now. Similar pathways and shared effective medication were cited as possible arguments for the continuum of disorders. I suspect, however, that our meds are still too crude to be affecting a single vital part of the brain specific to a disorder, so the argument about shared medication may not hold water. It's also more likely that pathways maybe shared, but patterns of distribution for various disorders may differ. Disorders may have their own pathway profile - that's how things work in the brain, anyway. Behaviours are complex and involve many parts of the brain. It's a matter of associating certain pattern profiles with certain behaviours, I would think.

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