ADHD, substance abuse and conduct disorder develop from the same neurocognitive deficits
Now that we can reverse engineer behavior deficits to neurocognitive deficits, I wonder how long will it take before we layer in the nutritional deficits and apply the same statistical rigor to that data set. Seems like low hanging fruit to me. Pun intended.
12 August 2014 Université de Montréal
Researchers at the University of Montreal and CHU Sainte-Justine Research Centre have traced the origins of ADHD, substance abuse and conduct disorder, and found that they develop from the same neurocognitive deficits, which in turn explains why they often occur together.
“Psychopathology exists on multiple continua of brain function. Some of these dimensions contribute to a multitude of problems, others contribute to specific problems.
Together, they explain patterns of comorbidity such as why ADHD and conduct problems co-occur with substance misuse at such a high rate,” explained the study’s lead author, Professor Patricia Conrod.
“Our findings suggest that risk for externalizing problems exist on a continuum in the general population, are easily measured and can be targeted before diagnosable problems arise.
The findings also help reduce stigma and address some of the complexities when diagnosing and treating concurrent psychiatric problems.
The implications are that clinicians can manage multiple psychiatric problems by focusing on how a young person is functioning on a few key neurocognitive dimensions. The next step is to develop evidence-based intervention strategies that will target these three areas of brain function”
The findings were established by studying the reward sensitivity and decision making patterns of 1,778 European 14-year-olds of comparable demographic profile.
The teens were asked to undertake several tasks while undergoing an MRI and answer personality questionnaires. Clinicians also profiled the participants, once at the time of the testing, and again two years later..
At age 14, 4.4% of participants were identified as having a diagnosis of conduct disorder, ADHD, or both; by 16, this figure had risen to 6.6%.
Alcohol and substance abuse were also identified, with 3.7% and 10.6% prevalence respectively at age 14, and 18.0% and 27.1% respectively at age 16.
The researchers were able to use statistical modelling to see what risk factors were linked to which psychiatric symptoms. “This is the first study to model ADHD, conduct disorder and substance use problems in adolescence by using a novel statistical approach that identifies the shared variance among these problems as well as the neurocognitive risk factors that are common across these problems.
Three key neurocognitive dimensions were identified as being implicated in most externalizing problems:
- impulsive action, impulsive choice (valuing immediate rewards over delayed rewards) and reward sensitivity. A young person’s performance and brain function on each of these dimensions were shown to be related to externalizing problems.
- Self report impulsivity, impulsive actions on a response inhibition task and the extent to which frontal brain regions are hypoactive when committing an impulsive action differentiated youth who were most at risk for ADHD and conduct problems from youth who are at risk for all externalizing behaviours more generally.
- Thrill or sensation seeking and abnormal activity in frontal brain regions when anticipating rewards differentiated youth who were uniquely at risk for alcohol misuse relative to those at risk for problems generally.” explained Natalie Castellanos-Ryan, first author of the study.
“There has recently been a trend in psychiatry to reformulate diagnostic categories from a dimensional and neuroscience perspective, fueled mainly by the high rates of comorbidity between certain disorders. This is precisely what we do with regards to externalizing disorders/problems. Our findings provide support for this new “dimensional” approach to psychiatric research by showing these disorder/problems share substantial variance as well as common risk factors and that they exist along a continuum in the general population.”
The findings shed light on the cognitive deficits that could be targeted in order to potentially help treat comorbid cases (e.g. adolescents who have been diagnosed with both conduct disorder and substance use problems).
“Comorbid cases are harder to treat and have worse prognosis than non-comorbid cases, and currently there are very few interventions or clinical strategies that are designed to treat comorbidity,” Castellanos-Ryan said.
“Prevention and intervention approaches for externalizing problems – ADHD, conduct disorder and substance use – could benefit from incorporating training components that target the brain functions or deficits related to impulsive action, impulsive choice, and reward sensitivity.
Furthermore, these findings suggest that new intervention and prevention strategies targeting these deficits, either at the personality, cognitive or neural level, have the potential to concurrently impact on a number of clinical outcomes during adolescence and potentially before problems occur.”
Castellanos-Ryan N, Struve M, Whelan R, Banaschewski T, Barker GJ, Bokde AL, Bromberg U, Büchel C, Flor H, Fauth-Bühler M, Frouin V, Gallinat J, Gowland P, Heinz A, Lawrence C, Martinot JL, Nees F, Paus T, Pausova Z, Rietschel M, Robbins TW, Smolka MN, Schumann G, Garavan H, Conrod PJ; The IMAGEN Consortium.
- Notes for editorsNatalie Castellanos-Ryan, PhD, and Professor Patricia Conrod, PhD, are researchers affiliated with the University of Montreal’s Department of Psychiatry and the Research Centre at the CHU Sainte-Justine Mother and Child Hospital Centre. Castellanos-Ryan is also affiliated with the university’s School of Psychoeducation.The research team published “Neural and Cognitive Correlates of the Common and Specific Variance Across Externalizing Problems in Young Adolescence” in the American Journal of Psychiatry on July 30, 2014.The research was supported by the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement- Related Behaviour in Normal Brain Function and Psychopathology; LSHM-CT- 2007-037286), the FP7 project IMAGEMEND (Imaging Genetics for Mental Disorders) and the Innovative Medicine Initiative Project EU-AIMS (115300-2), the Medical Research Council Programme Grant “Developmental Pathways Into Adolescent Substance Abuse” (93558), and the Swedish funding agency FORMAS. Further support was provided by the Bundesministerium für Bildung und Forschung (BMBF grants 01GS08152 and 01EV0711), the Deutsche Forschungsgemeinschaft (DFG) Reinhart-Koselleck Award (SP 383/5-1), and DFG grants SM80/5-2, SM 80/7-1, SFB 940/1. This research was also supported by the German Ministry of Education and Research (grant 01EV0711). Natalie Castellanos-Ryan’s and Patricia Conrod’s salaries are awarded from the Fonds de Recherche du Québec–Santé.
Hello, Steve has uploaded his latest interview with Dr. Hyla Cass. Our topic is how to ‘Reclaim Your Brain‘.
Reclaim Your Brain and Enhance Your Mood, Memory and Energy
Brain chemistry is the vital link between your mind and body. In order to Reclaim Your Brain it is important to understand your brain chemistry, the mind-body connection, and the relationship between mental health and physical well-being.
Depression, anxiety, panic, obsessions, addictions and memory loss are too often considered to be a matter of “mind over matter.” Friends, family, and sadly, even therapists, will tell you that self discipline or extensive psychotherapy are the ways to kick these mindstates. Or they may urge you to take a prescription medication.
The good news is this: Rather that being crazy, neurotic or hopelessly psychologically damaged, you may simply be low in certain nutrients! Most mainstream medical doctors overlook the fact that mood, behavior, and mental performance all depend on your balance of neurotransmitters, the chemical messengers of the brain. It’s not simply mind over matter, but can also be matter over mind, too. (from Reclaim Your Brain, for a free copy of Dr. Cass’ e-book go to our podcast page)
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05 October 2013
European College of Neuropsychopharmacology (ECNP)
BARCELONA, SPAIN (7 October 2013) – Improved understanding of the roles of inflammation and oxidative stress in psychiatric disorders has generated new leads in the search for novel therapies. One such investigative compound currently in clinical trials is an amino acid, N-Acetyl Cysteine (NAC), which appears to reduce the core symptoms of bipolar disorder, schizophrenia, depression, autism and cravings in addictions including cocaine, cannabis abuse and cigarette smoking.
At the start of the decade of the brain, in the early 1990s, there was great hope that a flurry of new treatment discoveries would eventuate. In contrast, today, most pharmaceutical companies have a drying psychiatry and neurology pipeline and many have exited the field entirely. “One of the factors has been an over reliance on typical monoamine pathways as targets for drug discovery,” said Professor Michael Berk, Chair in Psychiatry at Deakin University, Geelong, Australia.
Professor Berk pointed out that the situation regarding new drug development for psychiatric problems was best summarised by former National Institute for Mental Health Director, Steven Hyman:
“drug discovery is at a near standstill for treating psychiatric disorders such as schizophrenia, bipolar disorder, depression and common forms of autism.”
Beyond the monoamine-based drugs, neuroscience has elucidated an array of other important pathways that are involved in most major psychiatric disorders, for example schizophrenia and both unipolar and bipolar depression.
According to Professor Berk, there is now an incontrovertible evidence base that these disorders share inflammation and oxidative stress as part of their disease physiology. In addition, associated pathways including reduction in proteins that stimulate neuronal growth (neurotrophins), and increased cell death (apoptosis), as well as energy generation in organelles called mitochondria are intimately involved. “This understanding provides an entirely new set of treatment targets.”
The amino acid, NAC, seems to have multiple effects on all these pathways: it
- boosts glutathione, which is the body’s major antioxidant defence;
- has anti-inflammatory properties;
- enhances levels of nerve cell growth proteins and the growth of new neurons; and
- reduces cell death pathways.
- It also appears to reduce dysfunction of mitochondria.
These molecular effects of NAC have been investigated in a series of clinical trials, which show that NAC reduces the core symptoms of schizophrenia including negative symptoms such as improved apathy, social interaction and motivation.
It also appears to reduce depression in people with bipolar disorder and at this meeting, new data on its role in unipolar major depression was presented. Furthermore, there is intriguing evidence that it reduces cravings in a number of addictions including cocaine, cannabis and cigarette smoking. “Apart from nausea, it appears to be relatively free of problematic side effects,” said Professor Berk.
In addition to NAC, a range of other compounds that target similar pathways, particularly inflammation, seem to have therapeutic potential. These include aspirin, cyclooxygenase (COX) inhibitors, statins, omega-3 fatty acids and even some anti-diabetic agents such as pioglitazone. “Capitalising on our understanding of inflammation and oxidative stress in major psychiatric disorders appears to give us an entirely new range of potential treatments for these common, severe and disabling conditions,” said Professor Berk.
29 September 2013 Journal of Psychotherapy and Psychosomatics
A paper published in the current issue of Psychotherapy and Psychosomatics provides new findings on the role of psychotherapy in regulating serotonin receptors.
This study was part of a larger project comparing psychotherapy and selective serotonin reuptake inhibitor (SSRI) drug treatment in major depressive disorder ( MDD).
Patients with MDD were randomized to receive either fluoxetine 20-40 mg/day or brief psychodynamic psychotherapy for 4 months. Brain serotonin 5-HT1A receptors were measured before and after treatment with positron emission tomography and the radioligand [carbonyl-11C] WAY-100635.
Of all the patients in the study, 23 participated in the positron emission tomography part of the study: 8 from the psychotherapy group and 15 from the fluoxetine group. Clinical evaluations included (in addition to the main outcome measures HAM-D and Beck Depression Inventory) Social and Occupational Functioning Assessment Scale (SOFAS) and Social Adjustment Scale-Self-Report (SAS-SR) and Brief Symptom Inventory.
In both groups, the SOFAS scores increased in a similar way. In the whole group, increase in 5-HT1A receptor BPND was positively correlated with increase in SOFAS scores after treatment in the orbitofrontal cortex, suggesting that those who had the highest improvements in social and occupational functioning had the largest increases in 5-HT1A receptor BPND.
Further analyses indicated that this association was driven by patients receiving psychotherapy. In this group, increase in 5-HT1A receptor BPND was positively correlated with an increase in SOFAS scores after treatment in the orbitofrontal cortex, ventral anterior cingulate cortex , medial prefrontal cortex , and parietal cortex and lateral temporal cortex. Such correlations were not seen in the fluoxetine group.
This is the first study to show that the increase in the density of the 5-HT1A receptors after psychotherapy is strongly associated with the increase in social and occupational functioning. Thus, among depressed subjects, 5-HT1A may be a marker of social functioning, not of the severity of depression symptoms.
While both treatments improved SOFAS, only psychotherapy was associated with increase in 5-HT1A density. The reason for this may be that the serotonergic neurotransmission is enhanced by SSRI treatment in a different way than by psychotherapy.
Our findings suggest that SSRI medication, although leading to decreased symptoms and increased functioning in the short run, nevertheless is associated with an incomplete recovery of the serotonin system after treatment. This could be related to higher relapse risk.