Brain, Immunity and Treatment Failure – Neuroscience Evidence

Psychiatric Drugs: New Science, Better Outcomes
April 25, 2011
Clay Shirky: Think Medical Collaboration
May 10, 2011
Brain Meeting in San Fran

Brain and Body Meet In SF

Neurotransmitters, Endocrine and Immune Imbalances Do Matter

What an outstanding meeting in San Francisco! This brief review will cover some points for those who couldn't make it.  – And BTW, you did miss the excited bicycle crowd shouting their unhappiness with automobiles, and the naked guy in that same fossil fuel protest zooming in a bike-cloud past the palms here >>>

No he wasn't wearing a naked suit, he was truly naked… you had to be there. The inherent lesson: we don't have to get naked to make a difference.

NeuroScience Highlights

– Dr Gottfried Kellerman [PhD Biochemistry]: So many clinically important points it will be difficult to summarize, but suffice it to say at the outset that Dr G is exceedingly serious about pulling the biomedical/psychoneuroimmunology puzzle together. With each next presentation he sharpens the interaction between the Sympathetic Nervous System [SNS], the Parasympathetic System [PNS], and the changes that occur with neurotransmitters in the central nervous system, immune dysfunction and chronic illness. Some brief highlights:

– Neural [Norepinephrine related, A5 nucleus in the brain stem] and Adrenal [Epinephrine related, C1 nucleus in the brain stem] branches of the SNS are in balance under normal healthy conditions.
Locus Ceruleus [LC in the brain stem] is the regulator of that balance – and if stressed by life stressors, or immune dysfunction [from gluten to Lyme Disease, to toxins in the environment], can become so chronically unbalanced that recovery remains impaired by that imbalance.
– The LC balance can be improved by specific identification of the targeted imbalance with “both medications and supplements” as referenced in this piece.
Lechin F, J Appl Res 2008, 8: 151. [Journal of Applied Research]
– Understanding these fundamental imbalances may guide clinicians to more specifically targeted interventions.

– Dr Sirid Kellerman [PhD Cellular Immunology]: The depth of these two presentations are truly beyond the scope of CorePsych Blog, as you can see from my comments on Dr G Kellerman's presentation. And rest assured that Dr S left no stone unturned in her review of the specifics of cytokine aberrations leaving imbalanced communications between endocrine and neurotransmitter pathways. These two neuroscientists are on a serious mission to look at the laboratory evidence, measure it, and then treat. Some brief highlights from Dr S:

– The sensory circuitry is signaled by many different inflammatory triggers: bacteria, parasites, viruses, food proteins [gluten/casein], environmental toxins [lead/mercury], psychosocial stress. Sternberg, EM Nature Reviews 2006, 6: 318-328
– These inflammatory triggers send measurable cytokine messengers to a variety of sites including the SNS, the PNS and the HPA axis creating imbalances in epinephrine and norepinephrine pathways.
– Measuring and specifically addressing these cytokine imbalances can reveal specific underlying medical conditions such as Lyme, candida, and provide improved target recognition, and clinical outcomes for those who, on the surface, appear to be troubled by non-specific psychiatric conditions.

The CorePsych View

My theme in San Francisco, faithful readers, has not changed from these CorePsych Blog comments for 6 years: Far too many remain glib, indeed superficial, with reductionistic views of brain and body conditions found in the oversimplified DSM4 psych diagnoses. I used the now-familiar misunderstandings so prevalent with current ADHD diagnosis and treatment to a encourage review of underlying functional biological data that looks on the surface like ADHD – but turns out to reside downstream from a variety of biomedical issues, not the least of which is measurable immune dysfunction with endocrine and neurotransmitter imbalances. Yes, I did hit Transit Time! 😉

A brief review of my comments:

– The challenging problems that occur with successful treatment for ADHD encourage an improved review of underlying biomedical issues. With that additional laboratory understanding more precise treatment strategies often provide improved outcomes.
– Using ADHD as an example I documented several cases with underlying measurable immune issues that effected neurotransmitter balance and endocrine dysfunction. Correcting the entire picture often provides more predictable outcomes. Evidence matters.
– New treatment strategies must seek to combine the excellent responses witnessed with balanced psychiatric medication management [the “traditional” view] with new science insights from molecular and cellular physiology [the “functional” view] into a more Comprehensive Neuroscientific view of biomedical intervention strategies.

Take a quick listen to this brief summary:

Understanding these new measures does significantly improve patient care – I've seen it in the office. Nothing in medicine is categorically correct, so why guess? Appreciation of the complexity of these matters makes a difference.


  1. […] superficial penetration of the facts has led to considerable confusion, missed diagnosis, failed treatments, unexplained dangerous impulsivity for self and others, and an overall disillusion with both the ADHD diagnosis and the medical […]

  2. Wnd,
    Oh yeah, the science of non-science. Experience is the short answer here – your experience is the only real marker for all of this craziness.

    Said another way: Good show on your awareness of the DOE game, – just make sure you know the generic brand 😉 and simply mark it down. Even the specific generic appears to vary at times for the same person.

    If that happens I then switch back to my other metabolic thinking, every time. Therein often lies the rub.

    Said more simply: the complexity of dosage absolutely requires one’s full attention. If the window is moving, think metabolism.

  3. Sandy,
    Long distance high five for working to become well informed: I don’t think it’s the l-AMP, it’s more likely the Norepinephrine as Adderall inhibits the reuptake of both DA and NE.

    My choice if you can afford it: Vyvanse – better for compliance, purely DA effective with less NE activity and much closer to your original Dex.

    Good job, best in recovery!

  4. 3T,
    A way around that problem with the scripts – an easy single script for 30mg 3 in the AM = 90 and done.

    I have found Effexor to work best in over 80% of folks, like Pristiq for the same reasons, as both work quite well and are clean on 2D6, unlike prozac and paxil.

    Regrettably on the antidepressants only these few guidelines work… the rest is idiosyncratic based upon each person’s specific metabolic challenges.

  5. Andrew,
    Thanks so much for your remarks, and totally agree. My only point is the drive for comprehensive neuroscience rather than the short sighted assumption that a label covers the landscape. Inattention does significantly contribute to the downstream issues… as some just wish to keep going right down the line with whatever food is corrupting the system – hoping to just take meds to turn it around.

    You may be interested in this recent CinchCast as we are on the same path:

  6. Anonymous says:

    Dr. Parker, I was hoping to ask your advice on some questions. I’m 44/F, diagnosed with ADHD 3 years ago. Initially I was started on Ritalin, which did nothing for me, then Dexedrine. The Dexedrine was life changing, as in my life looks NOTHING like it did just a few years ago, and this is good. I was living overseas when DX’d and am now back in the US. My new psychiatrist wanted me to try Adderall XR, which I did, but the side effects were too much; depression, obsessive behavior, irritability and sluggishness, not to mention it didn’t really do much for the ADHD.

    At my last appointment I asked if we could go back to the Dexedrine but she wanted me to try Adderall IR instead, dosing in much the same way as I had been with the Dexedrine, which was 3 X P/D, for a total of 15MG. (I found that a low dose works best for me and tend to be sensitive to meds in general.) I’m currently working my way up to a higher dose but am already feeling the depression and irritability kicking in.

    One of the reasons she stated that she thought Adderall would be a better med for me was that Dexedrine has greater potential for abuse. A bit of back story, I do have a history of addiction, although I’ve been clean for over 15 years and no longer even drink. Heroin was my drug of choice, and although I did sometimes use cocaine it was more of a means to stay awake while drinking, as I didn’t particularly enjoy it.

    But what I’m trying to figure out is if l-Amphetamine is exacerbating something and if d-Amphetamine has the same mechanism as opiates, which might explain why I have a positive reaction to one and negative with the other. Other information which might be useful, I’m gluten intolerant and also react very badly to starches in general. I follow a paleo diet, healthy fats, no grains, which I’ve found to help.

  7. Time to Thrive says:

    I take Vyvanse, 80 mg in the morning. Overall I like it better than Adderall, but it is harder to see when it takes effect and it does take longer than 30 minutes; I think closer to an hour. Before it’s reached 12 hours, I know it’s not effective. I think 90 would be better, but you can’t easily write for that one without doing 2 prescriptions and 2 prescriptions equals twice the $.
    1. My question though is more about antidepressants. SSRIs do not help my ocd/anxiety…they make the anxiety worse and give me insomnia (which is not because of the anxiety). What are your thoughts on effexor (that’s what we’re trying now)? How long of a trial is needed before I give up on this combo?

    2. why do some of the antidepressants make it seem like the stimulant is less effective? I won’t be sure if that’s the case with this one until a few more days in.

    3. What else can I try that won’t take forever to work, won’t make the stimulant ineffective, and won’t give me intolerable side effects (pretty much all I can’t handle is increased anxiety and insomnia)?

    4. I do have seasonal allergies, so my histamine should be high, especially right now because the allergies are full blown and really dragging me down. Lots of trees, weeds, and grass…and I like hiking but won’t stop that! Exercise also aggravates it, but can’t stop that either! I am using the antihistamine nasal spray until this kind of clears up.

    Looking for some encouragement and some pointers…We know what the deal is, we just don’t know what’s going to work!

    3T (Time to Thrive)

  8. Andrew says:

    Hi Charles
    while your post was interesting I do not think that the presence of neuroendocrine or immune problems rule out ADHD.
    In fact I would argue that the neuroendocrine problems arise directly as a result of the consequences of attentional instability- ie they are part of the co-morbidity- not “separate diagnoses that look like ADHD”.

    The bottom line is that living with unstable attention is very stressful When we are stressed- then autonomic dysregulation, and subsequent epigenetic effects contingent upon the alterations in the HPA axis become inevitable.

    Equally I would argue that brain changes will arise.
    I know that when my ADHD was out of control I became so chronically stressed that I became adept at learning to screen out the physiological symptoms of stress. I had to- otherwise I simply could not have functioned. When one is stressed all the time and screens out those symptoms one then becomes chronically dissociated from one’s body. Small wonder that I became clumsier and more impulsive and less intuitive. Small wonder that I felt emotiaonally isolated.

    Equally the research I have seen indicating that the lenticular nuclei in the thalamus are reduced in size. They are sensory relays involved in routing sensory information into the forebrain and hence into consciousness.
    I would argue that this documented change represents disuea atrophy. According to the principals of neuroplasticity the inverse of “neurones that fire together wire together” is “use it or lose it”.

    It is important to realise that it has been known for thousands of years that “all phenomena are preceded by the mind”. When our attention is unstable we suffer a fundamental derangement or the functioning of the mind which affects every aspect of the integration of our mind and body and our mind-body with the greater environment. ADHD affects everything- and manifests in all aspects of our being.

    You might be interested to know that when I was being treated for ADHD with stimulants I learned to meditate and was trained to be a provider of a technique called Mindfulness Ingtegrated CBT. When I was completing that training- my need for stimulants simply withered away, ad I am now approaching 10 months medication free. I am only going from strength to strength- with no apparent end in sight to the accelerating improvements in my functioning.

    Dr. Andrew Kinsella

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