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Thursday, April 19, 2018

OCD : A Matter of "Low-Activation Syndrome" In Many Patients... (Low CNS Stimulation State and OCD/Obsessions Explored)

Although OCD is classified as an "Anxiety Disorder", it is atypical in that, findings regarding norepinephrine levels in *most* Anxiety Disorders have shown they are typically high [1] (consistent with a High Stress:High-Anxiety Paradigm [2])...whereas OCD may be the sole exception and Norepinephrine-enhancing agents such as Reboxetine [3] and Clomipramine (Anafranil) (approved for OCD) [4] are often VERY effective at treating "Resistant OCD"...

In addition, Adderall (mixed amphetamine) can treat OCD in a subgroup of Patients who fail to respond to other treatments [5] [6]. Amphetamines are well-known Norepinephine-enhancers (though they also raise Serotonin & Dopamine). Ritalin/Concerta (Methylphenidate) can in some cases improve Obsessive-Compulsive disorder, although, Dextroamphetamine (D-Amphetamine) is generally better for this purpose.

Finally, Deep Brain Stimulation and other "stimulation" therapies are often the last resort for severe, treatment-resistant OCD [7] [8] [9].

This all proves a theory of mine as well as other Doctors such as Ray Peat who state that both Depression & Obsessive-Compulsive-Disorder are the result of an "Energy Imbalance" [10]...often marked by negative-thoughts which can actually be a result of a "tired brain" rather than an Active Brain. David Healy, another well-known Doctor in the field of Psychiatric and Neurological Medicine - has also published many articles which suggest similar concepts.

Also moving in that direction, another "Energy-Imbalance" disorder; ADHD, is often diagnosed in those with a Family History of OCD and often is the first (pediatric) diagnosis which is then followed by OCD in years following the initial  diagnosis...this trend is not 100% and surely varies [11]. However, since similar Genes can create the "neurobiological environment" for both ADHD and OCD - and since there is *often* cross-over - it stands to reason that in many Patients there is a similar etiology for both disorders...

Obsessive-Compulsive Disorder (OCD) affected individuals often also have other Health Complaints; even if hypochondriasis is completely ruled out. One of the main complaints is a feeling of mental "Fatigue" [12] [13], high-motivation followed by a period of "burn-out" or low motivation [14] - a pattern often recognized since Childhood [15] and often, Pain disorders or Chronic Muscle Pain [16].

While it can be argued that these can be a RESULT of the disorder itself causing significant mental stress, there are studies to suggest that they may be as well, precursor factors, which are then reinforced, hastened, or made worse by the OCD-disorder [17]


Meaning the following...
  1. Chronic Fatigue type-Syndromes may lead to changes in the Brain, if untreated, which can lead to particularly, Pure "O" OCD or Obsession-predominant OCD [18].
  2. OCD can then Worsen Fatigue/Stress [19].
  3. The Cycle continues.

***NEUROTRANSMITTER RESEARCH***

  • OCD can be a result of elevated Serotonin levels [20] or deficient levels [21]. Obsession-Predominant OCD trends toward higher-monoamine levels but poor usage [22].
  • It appears that despite this - the reason SSRI's are "effective" for OCD though, is because of their effects on "neuropeptides" like Oxytocin, Beta-Endorphin and Vasopressin [23].
  • Low NMDA/Glycine-receptor activity; a type of Glutamate-receptor - has been found in OCD-patients [24], often a result of an altered NMDA-related gene passed down [25] and NMDA-agonists such as D-Cycloserine can prove helpful in ridding the Patient of Obsessions and Compulsions *Psychologically* [26]. Something called "Fear Extinction" used in an aspect  of Cognitive Behavioral Therapy (CBT). Called "Response Prevention Therapy" tailored specifically to OCD-Behaviors.
  • In addition to Human evidence, Animals with low NMDA activation seem to show more compulsions.
  • High-Dose Glycine can treat refractory/treatment-resistant OCD in many cases [27].


CONTRADICTIONS THAT JUSTIFY THE LOW-STIMULATION STATE OF OCD


  • OCD Patients seem to have higher Brain-dopamine levels in some Brain regions [28] whereas in others the level is Low [29] - but a high-dopamine level does not explain the high-rates of Anhedonia (lack of pleasure/enjoyment) in treatment-naive OCD patients [30], who also seem to experience the symptom more than the Average person, untreated
  • Anhedonia, typically a "low-dopamine" symptom - seems to indicate that, at BEST, the Dopamine levels fluctuate and often become low in Patients with OCD - suggested in this study - and at WORST, we have it all wrong...and its just a 'coincidence' that Dopamine is elevated in *some*, but not all OCD-Patient studies. 
  • If OCD is primarily a Low-Dopamine state - at least in a subgroup of Patients, then SSRI's may very well make the Patients worse...if not the OCD, then AT LEAST the Anhedonia symptoms (if present) and Depression symptoms (if present).
  • Dopamine D2-Receptors are substantially LOWER in the Brains of OCD-Patients [31] [32]. The Endocrine Responses (Growth Hormone Release) are lower in OCD-Patients treated with a dopamine stimulating drug (Apomorphine) [33]. This would indicate low Dopamine 'D2S' or "AutoReceptor" activity [34] - which would, in theory, mean enhanced 'firing' rate of Dopamine and enhanced Dopamine (DA) release in OCD.
  • Problem is that theory can quickly go to shit when you consider that Dopamine D2 'autoreceptors' also "regulate" GABA-ergic neurons [35] so *technically* activating Dopamine D2-autoreceptors; which decrease Dopamine, can also really INCREASE Dopamine in discreet areas of the Brain by decreasing Brain GABA-concentrations.
  • This was proven in Animals and Humans lacking Dopamine D2-autoreceptors who seem to have reduced, even eliminated responses to Cocaine and Amphetamine [36] [37].
  • So Dopamine D2 Receptors, 'autoreceptors' or not - seem to be a very LARGE contradiction that does not seem to be a good base point to work from as it can lead down two seemingly opposite roads.
  • On one hand, an OCD-Patient may have LESS Dopamine floating around because of more inhibitory GABA activity due to less Dopaminergic "control" of GABA (D2S-Autoreceptor Mediated) - on the other hand, they  may have MORE Dopamine firing and release due to less autoreceptor influence on basal (resting) dopamine release.
  • In either case, it does NOT justify a CONSISTENTLY high Dopamine level, rather, a fluctuating one with a higher probability of being Low.
  • If certain Brain Regions are 'dysfunctional' due to Elevated GABA levels in Obsessive-Compulsive Patients - whereas in others the extracellular  Glutamate is high - this creates what we call a 'confused' communication system where one Brain region is abnormally calm and the Basal Ganglia, for example, is practically haywire in OCD [38].
  • Interestingly, 'stimulating' neurotransmitters such as Norepinephrine can actually 'stabilize' the projecting nerve terminals and forward, eventually the Basal Ganglia activity by modulating other neurotransmitters such as Serotonin and GABA [39].
  • A 'defect' in Norepinephrine-transmission was found in OCD-patients compared to 'healthy controls' [40].
  • Streptococcus (strep throat) and Herpes Simplex; both of which cause Fatigue and are capable of causing nervous system changes - have been strongly implicated in the development of OCD in Children and Adults [see Strep study here] [see Herpes study here].

***MAIN CONCLUSIONS***

When carefully screening for biases, both in my own Writing and in Published Research - it appears that not only does research truly justify the existence of a Low-Activation or "Low-Stimulation" syndrome in many people with OCD - but also that it is an important aetiological factor and sustained fatigue may pave the way for 'negativistic' thought patterns versus 'optimistic' thought patterns associated with a healthy degree of CNS-stimulation.

The Frontal hypoactivity consistent with abnormally increased inhibitory nerve activity/tone in OCD also indicates a dysfunctional nervous system...this could indeed be the true link between Norepinephrine and OCD - since Norepinephrine is the main 'driving' input and ITS transporters take precedent in regulating excitatory Dopamine function in the Prefrontal Cortex [41]...suggesting again, a Norepinephine-deficiency, especially in the Frontal Regions of the Brain in OCD.

Role of radiology in central nervous system stimulation - a report also dived into the important role in absolute stimulation of the CNS and its specific correlation to Mental Disorders, including OCD.

  One of the conclusions, besides far-reaching therapeutic value in treating Basal Ganglia-related disorders (such as OCD) is that the stimulation helped to improve and stabilize nerve communication in these Regions...

Again, consistent with my Theory, and upon talking to OCD-sufferers, describing similar phenomenons and trends (such as the elimination of OCD with hard stimulants). 

Of course, NOT ALL OCD-affected persons exist on this spectrum. Many will have a worsening of OCD from Stimulants...its  just that there is another fairly large portion (maybe 35-40%) who by nature of functional Brain Imaging (fMRI etc) [42] and other neuroimaging studies clearly fall into the 'low-stimulation' category and thus, may benefit from Stimulants versus SSRI's. 


LOGICAL EVIDENCE OF LOW-STIMUATION IN OCD

This may be the greatest argument out of all for the "low-stimulation" subtype of OCD.

When our Brains are tired and fatigued, ANY task tends to feel EXHAUSTING. As a result, many of us get into the habit of dwelling on negative or pessimistic thoughts. 

...For many OCD-sufferers, this 'tired' phenomenon is directly related to their Obsessions [43] - and for many OCD-affected individuals, their OCD-simply vanishes when something shifts their focus, a high-priority, a loved one, danger, basically any activating circumstance which forces the persons Mind to focus on the environment and the people in it versus on the thoughts in their own head.

THINK: What is the central reason why Stimulants help both ADHD and Motivational deficits; its clear-sharp FOCUS. Its not just about the desire for something, but actually the will and more specifically, the consistent ATTENTION to that Task.

...Perhaps, that is why Stimulants help some people with OCD...they shift people 'out of their head' and into the real-world...the environment, logical things, common-sense things associated with the Norepinephine system of the Brain.

Stimulants are thus - a force to Ground a subset of OCD-Patients back into Reality by breaking the cycle of 'tired brain syndrome' and thus eliciting true focus on things that actually matter.

Its also of course possible, that others issues (hormones) influencing Brain stimulation are going on in OCD-Patients; of both sexes. Particularly, a deficiency in Progesterone, Estrogen or too much or too little of both could be a driving factor [see study].

Still, if taken at face value, any deficiency of say Thyroid hormones [44] or even Testosterone [45] could probably set the ground work for this specific subtype of OCD: characterized by "low-stimulation" and related syndromes [46].


As a Final Note: Vitamin B12 Deficiency - B12 of which which stimulates Norepinephrine, CNS activity and is *necessary* for all monoamine activities in the Brain - was found to be a "causative" factor in low-stimulation OCD-types.

***FINAL CONCLUSIONS AND SUMMARY***


  1. In this article we have explored functional deficits in neurotransmitters, rather than excesses, apparent in ALL OCD-subjects, a low Frontal EEG-report, possibly reduced Dopamine levels and almost certainly reduced Norepinephine activity in the frontal lobe.
  2. Fatigue Syndromes/CFS, Chronic Pain, and many other Physical illnesses often precipitate OCD - many of which themselves cause Fatigue, and where CNS pathogens such as Streptococcus (strep throat) and Herpes Simplex can easily cause a form of mild neurodegeneration; primarily in Brain Regions that are *known* to be dysfunctional in OCD.
  3. That "FOCUS" and "LOGIC" often go hand-in-hand, and Intrusive Thoughts often aren't rational or logical - thus, this reflects a Central "under-stimulation" as stimulating neurotransmitters like Norepinephrine and Histamine tend to get us to focus on our environment and logical tasks rather than things inside our head, or meaningless compulsions which have no real momentary nor financial value etc.
  4. These conclusions of course, exclude hand-washing and organizing of Work-Desk, or school-materials etc - as those are environment related tasks and thus those with those EXTERNAL forms of OCD rather than "racing thought" or "intrusive thought/obsessional" types probably have more than Enough CNS-activity.
  5. It is only the Intrusive Thought type - or "Pure O" OCD which is (generally) characterized by Low CNS Activity.
***CAUTIONS IN INTERPRETING THE INFORMATION WITHIN THIS ARTICLE***

It should be noted that we at Area-1255 do not universally recommend stimulants to OCD-sufferers. Even if you believe firmly that you fall into one of these "low-stimulation" groups, you should still speak to a Psychiatrist or Physician regarding the proper treatment option - and if you'd like, you can bring up the information in this article as a Starting Point for Discussion. 

Kindly point out that Our Work is fully referenced at each point, and encourage the Physician/Psychiatrist to read into the References.

In regards to research, a final point should be made that not all stimulants are built equally; that is, some have an utter propensity to worsen OCD regardless of which 'type' you have...even the Low-Energy types often find that certain stimulants, like Yohimbine, worsen their OCD. The same can be said about Beta-Adrenergic Agonists such as Albuterol or the bodybuilding/fat loss drug Clenbuterol.


  • Modafanil; a "wakefulness" drug also classified as a "smart drug" or Nootropic - has not really produced any Positive studies proving one way or another with regard to OCD symptoms, in fact, the only true unbiased study with Modafanil in regards to OCD - is that it exacerbated the Obsessional Component of OCD-Patients already being medicated.
  • This seems to indicate that 1.) Modafanil's Norepinephrine properties aren't strong enough to positively impact OCD and 2.) That Modafanils complex effects on the Glutamate-system [47] or its inhibition of GABA-currents [48] worsen the cortical dysfunction seen in OCD, of all types. 3.) Lastly, that Modafanil seems to *somehow* activate the Serotonin 5-HT3-Receptor [49] and this Serotonin Receptor, when activated, worsens OCD-symptoms [50].

***OTHER SOURCES***





Current Chemical Genomics and Translational Medicine (ISSN: 2213-9885 ― Volume 12, 2018)
Jonathan T Ting, Guoping Feng*
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA









Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei. (NIH/PubMed)

Modafinil elicits sympathomedullary activation. (Taneja I, et al. Hypertension. 2005.) (NIH/PubMed)

Modafinil as a Catecholaminergic Agent: Empirical Evidence and Unanswered Questions (NIH/PubMed)

Comparative Effects of Methylphenidate, Modafinil, and MDMA on Response Inhibition Neural Networks in Healthy Subjects (NIH/PubMed)

The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade. (NIH/PubMed)

Clinical and neurocognitive changes with modafinil in obsessive-compulsive disorder: a case report. (NIH/PubMed)

Exacerbation of Obsessions With Modafinil in 2 Patients With Medication-Responsive Obsessive-Compulsive Disorder. (NIH/PubMed)



In/Tags: ocd low activation, ocd and low norepinephrine, ocd and stress hormones, ocd low stress hormones, ocd high norepinephrine, obsessive compulsive disorder and tired brain, ocd caused by fatigue

2 comments:

  1. As evidenced by Daniel Turner of the Department of psychiatry, University of Cambridge, "the use of modafinil (https://modafinilxl.com/buy/modafinil-200-mg-x-100-pills/) could make a revolution in the understanding of the mechanism of occurrence and preservation of memories. Apparently, this drug has a very special point of influence on the processes taking place in the human brain."

    ReplyDelete
  2. How about pramipexole usagefor the obsession dominant OCD type?

    ReplyDelete

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