Theory of Addiction - Hypoism (1) Hypothesis- A global medical neurobiological addiction (2) paradigm.
Abstract for Hypoism Hypothesis
The correct theory of addiction causation is paramount to finding effective solutions to addictions. The current theories on the cause of addictionsare incorrect. Because of this prevention, treatment, recovery, and public policies are ineffective and maintain the addiction epidemic. Using updated interpretations of past and current valid research findings in addiction epidemiology, behavioral genetics, evolutionary psychology, genetic diversity, and animal genetics, a new perspective on the cause of addictions is presented. This hypothesis, the disease of Hypoism, is a general and overriding genetic neurobiological theory of the cause of all addictions, to drugs, behaviors, instincts, and even beliefs. It presents for the first time a testable and practical hypothesis that: 1. Answers all questions about the meaning and origins of addictions, and 2. Provides a framework for early diagnosis of this disease and the means for prevention of addictions and recovery from the disease itself rather than having to wait for addictions to appear and be dealt with as if they were separate and unique entities. Hypoism has massive research, social, and policy implications.
Currently there is no paradigm of addictions that answers all the questions any addiction paradigm must answer to be considered a complete paradigm. A few of these questions are: (3)
·What is an addiction?
·What are the criteria and characteristics of an addictor (4)?
·What is the biological difference between different addictors?
·What is the difference between the people (and animals) who get addicted and those who do not, never, even on experiencing the same addictors? Or, asked in a different way, why can most people use addictors without ever getting addicted while others do get addicted?
·What role does genetics, the predominant etiological factor in addictions, have in this system and in the differences between addicts-to-be and non-addicts-to-be?
·Why do different people get addicted to different specific addictors rather than to all of them, and moreover, not the same one(s), even in the same families?
·How do behavioral addictors relate to chemical addictors, and why are they both similarly addicting and their addictions identical to one another?
·What is the brain module (5) present in everyone that is genetically broken that causes addictions in only addicts-to-be?
·How does the reward system fit into and participate in the normal and abnormal function of this module?
·How well does the paradigm fit the science and empiricisms of addictions, all addictions?
·Does the paradigm produce valid scientific experimentation delineating the actual cause, prevention, treatment, and policies of addictions?
Pre-paradigm times are always full of multiple, contradictory, confusing, and superstitious (believed without an iota of proof) ideas. We are now living in such a time concerning addictions.In Chapter 8, Psychodynamics, from Substance Abuse - A Comprehensive Textbook (6), the bible of the present addiction paradigm, are the following statements by the authors in the opening paragraph: “Unraveling the etiology of substance abuse continues to be a challenge. There have been many technological advances in understanding the chemistry of human behavior, including the highly significant discovery of opiate receptor sites and endorphins, as well as other neurotransmitter systems. However, the substance abuse field continues to be in a preparadigm stage of development, suggesting a lack of agreement between theory and treatment.”
When I first read the Hijacked Brain hypothesis (7), one of two major current addiction hypotheses, several years ago I had already developed the major conceptual foundation for Hypoism and was honestly attempting to answer the above questions. I was shocked when Alan Leshner from NIDA, although admitting addiction had something to do with the brain and genetic “predisposition,” would sum up his concept with, “The initial use of the drug is voluntary. The brain is hijacked by the drug. The drug changes the user’s brain to an addicted brain.” These statements basically say that there are two villains in drug addiction, the drug and the drug user’s willful and voluntary decision to use the drug. It also implies that anyone can become addicted through this mechanism. I don’t have time to detail the mountains of real science [See REFERENCES: 46-70] disputing this (I will discuss this again later in the article), but four well documented phenomena make this theory untenable: 1) experimental spontaneous addictions in only genetically capable and inbred animals to drugs including alcohol, 2) the non-random occurrence of addictions in humans - the high heritability of spontaneous human addictions (60-83%) and the fact that the closer the people are to each other genetically the higher the heritability, 3) The existence of numerous and just as powerful human behavioral addictions (sex, gambling, eating, etc.) that have no drug associated with them, and 4) That most people who experience addicting drugs never get addicted. [See REFERENCES: 71-76] Hiroi (cited below) states, "Among a sample of people in the US between the ages of 15 and 54 years who tried a substance at least once in their lifetimes, the probability of becoming dependent is estimated to be 32% for tobacco, 23% for heroin, 17% for cocaine, 15% for alcohol, 11% for stimulants other than cocaine, 9% for cannabis, 9% for anxiolytic, sedative and hypnotic drugs, 8% for analgesics, 5% for psychedelics, and 4% for inhalants. A more recent survey including 500 persons aged 12 years old or older yielded similar estimates. For example, among the 120 million current drinkers in the US, 15.9 million aged 12 or older are heavy alcohol drinkers (13%). These estimates are based on individuals who ‘tried a substance at least once in their lifetime' or at least once in the past 30 days. A series of studies on the rate of addiction/behavioral dependence in chronic users of nicotine, alcohol, and opioids elegantly demonstrated that only a subpopulation of chronic substance users become dependent, as discussed below."Thus, the hijacked brain hypothesis is incorrect and everything based on it is wrong. That nothing beneficial has ever come out of this hypothesis is additional proof of its invalidity. Moreover, a recent addiction causation theory review article (79), Genetic susceptibility to substance dependence, Molecular Psychiatry (2005) 10, 336–344, by N Hiroi and S Agatsuma, [view and read the paper by clicking HiroiMPFeatureReview.pdf , or at: http://www.nvo.com/hypoism/nss-folder/publicfolder/ ] the most important theory article in the addiction literature to date other than mine, dispels the Hijacked Brain Hypothesis (model 1. in the article, the plasticity model) and supports Hypoism (model 2. in the article, the genetic model) and says exactly what I’m saying here: “A majority of substance users do not develop addiction to nicotine, alcohol, or opiates. Currently available plasticity-based models (model 1.) of addiction do not adequately account for the limited prevalence of addiction among chronic substance users and the presence of pre-existing, comorbid traits. The genetic model (Model 2) of addiction predicts that addiction is more likely to develop after initial substance use in individuals with genetic susceptibility, which is also associated with comorbid traits in some (Gdc), but not all cases (Gd). Model 2 [Hypoism] highlights the need for a new direction in addiction research as well as new treatment strategies.”Similarly, Nestler emphatically states in his review article on addiction causation (88), “The current challenges are to translate this increasingly impressive knowledge of the basic neurobiology of addiction to human addicts, and to identify the specific genes that make some individuals either particularly vulnerable or resistant to addiction,” - genes, not environment. And lastly, Ahmed (91) states, "Interestingly, the postulation of an early hedonic deficit[hypo]as the basis for initial drug use in both vulnerable humans and laboratory animals provides a unitary framework for conceptualizing the transition from drug use to drug addiction as a continuum of increased negative reinforcement. Individuals would first engage in repeated drug use to ameliorate acquired and/or inherited hedonic deficits. Then, due to their powerful pharmacological actions, drugs would exacerbate the initial deficit by further decreasing reward system responsivity (through an allostatic decrease in reward function). Decreased reward system responsivity will, in turn, reduce the impact of natural rewards on brain reward systems and thus increase the motivation to take drugs as an attempt to recover initial reward system responsivity." This, of course, is Hypoism exactly. Further support for Hypoism, genetically mediated low dopamine activity, is the study by Volkow et al. which showed low dopamine activity in adults with ADHD, a large group of people known to have high levels of addictions; people with Hypoism, and in another study of people with ADHD. Quoted in a telephone interview about this study (http://www.reuters.com/article/latestCrisis/idUSN03330661) she said, “If you take a drug of abuse, whether it’s alcohol, nicotine or cocaine or methamphetamine — it doesn’t matter — what you’re going to be doing is temporarily increasing the concentration of dopamine in the brain. So a person then has a greater risk (of substance abuse) because it’s not just that they are taking the drug because they want to get high, but by taking the drug, they may actually feel better and temporarily perform better.” Another way of looking at the same phenomenon was done by Soderpalm and Soderpalm. 
These four above listed phenomena demand only one possible explanation: There is a genetically diverse and inborn brain mechanism present in all people that essentially inexorably causes both drug and behavioral addictions in only those who have the prerequisite genetic alleles or combinations of alleles. Moreover, the particular alleles will specifically dictate the future addictions. The following paper discusses my hypothesis about this mechanism.
In the last few years several genetic and neurobiological reviews discuss the concept of "underlying vulnerability," for both substance and behavioral addictions caused by the same pathophysiology, what I have named Hypoism, as a means of connecting drug and behavioral addictions into a single paradigm for the sake of improving prevention, treatment, and public policies. (112, 113, 114, 115) This next study shows we can pick up kids as young as 3 y.o. who will predictably get addicted when they grow up - a prospective study .
Figure 1. Court
The evolution vs. creationism debate continues to this day in general society as well as in addictionology. I hope you're on the side of evolution.
Let me translate. The Genetics/Environmentalism debate as it relates to addictions and other human behaviors is the evolution/creationism debate all over again. Behavioral Genetics is evolution, and environmentalism is creationism. There is no debate, however, because you can't debate an intellectual idea against a superstitious belief.
Real medicine, like evolution and genetics, is intellectual and testable, not based on belief or invalid pseudoscience. Contrarily, witchcraft is based on belief and superstition, the current state of addictionology. A second major addiction etiologic hypothesis, as put forth by Henri Begleiter (8),the so-called temperamental/environmental vector model of addiction etiology, is an example of this.
Figure 2. Vector Diagram
As illustrated, the vectors are unproven environmental forces that in conjunction with genetic “temperament” cause addictions or not depending on how strong the vectors are during different periods in the subject’s life. I call it the celestial spheres model because it reminds me in its complex absurdity of Aristotle's view of the geocentric universe. This model is still witchcraft even though it concedes addiction etiology as partly neurobiological and genetic. It's better than pure environmentalism, but it is not quite enough. Until we transform addictionology from witchcraft and superstition into modern medicine backed by real science we will perpetuate exactly what we all say we want to terminate, the misunderstanding and mistreatment of addictions and addicts.
Around 1992, I became motivated to understand and explore the basis of addictions for personal reasons. I began looking into the realities of addiction etiology rather than relying on the superstitious beliefs I blindly accepted in the past as part of my own recovery, be they psychological or supernatural. Clearly, because of the paradigmatic vacuum in addictionology (9), neither of them offered any obvious etiological insight, although Alcoholics Anonymous' recovery program, the only barely successful addiction recovery program, did present some hints. I was fortunate to be an addictionology outsider with no deeply held preconceived notions about the disease of addictions except those concerning the general disease concept on which all medical diseases are based as I had been taught in medical school: modern medicine and all medical disease are based on pathophysiology. One pathophysiology - one disease. I began looking for the pathophysiology of addictions, something that did not exist in 1992. [Reference 78 discusses this issue.]
View or perspective is always a problem in interpreting, discovering, and perceiving reality. I would like to put addictionology into perspective. Compared to the rest of medicine, addictionology is in the dark ages. The reason is simple: Superstition, bias, and ignorance.
But mostly ---- the wrong perspective.
Three wrong perspectives are: 1) The "psychological" and "environmental" basis of human nature, behavior, and thus, addictions, an unproven bias, 2) That the addictor is seen as the cause of the addiction, 3) That the addiction is the disease (for example, that alcohol addiction equals alcoholism, a disease).
First, evolutionary psychology has buried number one. Human nature and behavior is primarily founded on genetics, behavioral genetics. Absent this principle, evolution and natural selection would have been and are impossible. Environment selects from already existing genetic entities, it doesn't cause them. "Psychology" and "environment" are merely fine tuners and have superficial influences on behavioral genetics, but they are not the primary etiological determinants. Thus, psychology and environment cannot provide a pathophysiology. They cannot provide a primary mechanism on which a disease, any disease for that matter, can be based. The psychological and environmental basis of disease is a wrong and impossible perspective on which to base a disease. Addictionology has been wasting its time and resources traveling this road to reality and thereby has misled the populous as well. Supporting this, Dr. T. J. Bouchard, Jr., a prolific twin genetic epidemiological researcher wrote in Genes, Evolution, and Personality, Behav Genet. 2001 May;31(3):243-73, "There is abundant evidence, some of it reviewed in this paper, that personality traits are substantially influenced by the genes. Much remains to be understood about how and why this is the case. We argue that placing the behavior genetics of personality in the context of epidemiology, evolutionary psychology, and neighboring psychological domains such as interests and attitudes should help lead to new insights. We suggest that important methodological advances, such as measuring traits from multiple viewpoints, using large samples, and analyzing data by modern multivariate techniques, have already led to major changes in our view of such perennial puzzles as the role of "unshared environment" in personality. In the long run, but not yet, approaches via molecular genetics and brain physiology may also make decisive contributions to understanding the heritability of personality traits. We conclude that the behavior genetics of personality is alive and flourishing but that there remains ample scope for new growth and that much social science research is seriously compromised if it does not incorporate genetic variation in its explanatory models." One such mechanism, Hypoism (genetic variation working in the instinct regulation apparatus as the cause of addictions), is discussed in this paper. A recent review of the genetics of personality [Genetics of personality: are we making progress?, by S Van Gestel and C Van Broeckhoven, Molecular Psychiatry (2003) 8, 840–852] reinforces all this.
Second, if the addictors themselves (drugs, including alcohol, and certain behaviors) cause addictions by hijacking brains there would be countless more addicts than there actually are. The reality is that if one hundred people spontaneously use an addictor such as alcohol, opiate, gambling or sex, only or so will end up addicted. This is the case with all addictors. There is something special about the people who get addicted, not something special about the addictor. This misperception of addiction etiology promulgated by current addiction paradigms, and especially Dr. Leshner's Hijacked Brain Hypothesis, which happens to remain NIDA's current theory, wrongly places the emphasis on the addictors and perpetuates the drug war and stigmatizing prevention efforts. Leshner's and other current addiction hypotheses are ideology, not science, based. Moreover, the gateway hypothesis, as well as the roles of drug availability and attitudes about drugs, mainstays of the Hijacked Brain Hypothesis and the drug war, have been shown to be untenable “environmental” causes of addictions by Kendler (10, 80).
Lastly, we've been looking at addictions as if they were "the diseases" ---- that's wrong! A recent article discusses this necessary concept. [See REFERENCE 77, which states, “we suggest that evidence of multiple and interacting biopsychosocial antecedents, manifestations, and consequents—within and among behavioral and substance-related patterns of excess—reflects an underlying addiction syndrome.] Addictions are symptoms of the actual disease, a word defined as: Any perturbation of a normal physiology that results in negative consequences to the organism. A disease must be a pathophysiology, not a symptom, not a behavior. An excellent example of this distinction is the Prader-Willi syndrome, where symptoms of obesity and incessant eating behavior (and other “compulsions”) are recognized as symptoms not diseases themselves. This disease, whose experts call it a “purely genetic” disease, is known to be caused by genetic defects. [Mihaela Stefan, PhD, and Robert D. Nicholls, PhD., What have rare genetic syndromes taught us about the pathophysiology of the common forms of obesity? Curr Diab Rep. 2004 Apr;4(2):143-50.]
Why have we made these three mistakes? Because we are misinformed, and because we have been following the psychology/environmentalism road to nowhere. Behaviors can't be and are not diseases. Behaviors are not primary mechanisms. Cognitive mechanisms are primary. Behaviors result from and are determined by cognitive mechanisms, neurological machines, if you like, as all human behavior is. Diseases of behavior can only be based on cognitive mechanisms which underlie the behaviors. Moreover, behavior can't be genetic, the major determiner of addictions, only cognitive mechanisms can be genetic. Hypoism is a cognitive mechanism. In fact, it is the only complete addiction etiologic hypothesis that is based on a genetic cognitive mechanism.
Some of these wrong perspectives and unfounded beliefs are:
--Traditional and rigid belief of psychological/environmental basis of human behavior.
--That the addiction is the disease.
--That the addictors cause the disease and the addiction.
--Psychobabble explanations of addicts’ motivations.
--Traditional bias towards using antiquated and functionally obsolete words like “alcoholism” as if it were a distinct entity.
--The moralistic/religious bias against addiction as willful “bad behavior” and the need to punish this behavior. [In fact, unconscious bias against addicts, disgust, what I call addictophobia, has been studied and confirmed in a study with brain scanning in Princeton undergraduates.]
--Haven’t looked at the whole picture of addiction from afar - no perspective, no overview - only looked at one addiction or compulsive behavior at a time.
--Old biases concerning psychology, environmentalism, addictions, and traditional, non-critical thinking.
--Don’t rock the boat mind set--the authorities, old timers, know best. Go with the flow.
--Lack of rational imagination.
--Excess of irrational imagination.
Thus, we have missed the forest (the underlying mechanism) for the trees (addictions)----the perspective has been wrong. We all know in our hearts that what we have been calling the disease just has never made any sense. Addictionology has been unwittingly stuck in the wrong perspective leading to biases which have maintained the wrong perception of addictions.
Moreover, non-addict scientists just can't identify with what is an addict's inner experience. They can't relate to it, can't conceptualize it. Addiction is alien to non-addicts; non-addicts have no feel for the reality of addiction much like a eunuch wondering what all the commotion is about sex and can't translate it into a realistic hypothesis. Thus, the perpetuation of the conundrum and current conceptual addictionology vacuum. What we see is not what we have; no different from believing the sun goes around the earth because we see it do that every day, because it appears that way. The same king of thinking, the assumption that addictions “obviously” appear voluntary, anti-social, and willful and therefore must so be, has led to convoluted and invalid explanations of addiction causation that support this initial incorrect assumption. This is superstition, not science.
The history of medicine is laden with superstitious, psychobabble, and pseudoscientific explanations of diseases especially for those above the neck. These are later replaced by valid pathophysiology with extinction of the psychobabble and superstition. An old example is the miasma etiology of infections. Recent examples are epilepsy, schizophrenia, manic-depression, depression, ADD, OCD (11), Tourette's syndrome, autism spectrum, and even sleep disorders. Differing personalities are now known to be derived from permutations and combinations of a handful of genetically based biological temperaments (12). Even our baseline level of "happiness" or well-being is neurobiologically derived.(13)Mental and emotional phenomena are being explained by neurobiological physiology and pathophysiology, more each day, yet addictionology desperately holds on to psychobabble/environmentalism explanation of addictions for dear life. In fact, most importantly, ADHD has been proven to be caused by the Hypoism pathophysiology as I've been writing about for many years:
Evaluating Dopamine Reward Pathway in ADHD, by Volkow and Wang, et al., JAMA. 2009; 302(10):1084-1091. Quoting the lead authors from this interview (http://www.sciencedaily.com/releases/2009/09/090908193432.htm): "These deficits in the brain's reward system may help explain clinical symptoms of ADHD, including inattention and reduced motivation, as well as the propensity for complications such as drug abuse and obesity among ADHD patients," said lead author Nora Volkow, Director of the National Institute on Drug Abuse and a long-time collaborator on neuroimaging research at Brookhaven Lab. Said Wang: "Other studies from our group suggest that patients who abuse drugs or overeat may be unconsciously attempting to compensate for a deficient reward system by boosting their dopamine levels. Understanding how deficits in the dopamine system contribute to ADHD and finding ways to improve the functioning of the reward system could help mitigate these troubling consequences in the ADHD patient population." This study proves both the Hypoism (genetic low reward activity) pathophysiology and that ADHD is pediatric Hypoism, not a separate disease.
There hadn’t been a new idea in addictionology in years until Ken Blum's reward deficiency syndrome(14) appeared, [and now Hiroi’s (79 ), and Schaefer’s (77)], but that concept, a pathophysiological concept, the first in addictionology, fell on mostly deaf ears and besides was wrong, not reproducible. Good concept, good idea, bad follow-through. Something as diverse as addictions can not possibly be due to one gene, the A1 allele of the dopamine D2 receptor. Moreover, genes don’t work in a vacuum. They work within mechanisms. Blum provided us with none, however. That idea is narrow-minded and shortsighted, but overall, the reward deficiency syndrome is at least moving us in the right conceptual/mechanistic direction. [I want to add an important footnote here to list some of Ken Blum's and others' papers on the Reward Deficiency Syndrome [99, 100, 101, 102, 103], a concept quite similar to Hypoism though absent my brain mechanism which makes it useless, discussed in greater depth in my book, so readers can experience some of the scientific basis of Hypoism from people other than me. I want to warn readers, however, that Blum's claims of treatment efficacy from his company's "neutraceuticals" and other theoretical outgrowths of this theory are unsubstantiated and unproved, and are merely his attempt, absent FDA regulation in this area of "nutritional supplements," to cash in on this theory, a behavior I am deeply opposed to. My referencing of his work here is for their conceptual value supportive of Hypoism, not their therapeutic claims.] Quoted from the abstract of reference 99, written in 2008, is exactly what I wrote in 1992 in my first paper on Hypoism – A Real Disease which evolved into the Hypoism Hypothesis paper: “Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the “brain reward cascade,” especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD2 A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other “reward genes” are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype.” This paper is such a good scientific backing of Hypoism I have placed a link to it here so everyone can read it: adhd and reward deficiency syndrome - hypoism.pdf
A recent study by Eric Stice, et al, not yet published, Dopamine-related activity of food reward circuits in the brain and weight gain: A prospective fMRI study, http://www.ssib.org/web/index.php?page=press&release=2009-4 shows a real example of this concept in obesity, food addiction: "Research to be presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, finds that women who possess genetic modifications associated with low activity of the reward neurotransmitter dopamine in the brain when they imagine eating appetizing foods are more prone to weight gain. Functional Magnetic Resonance Imaging (fMRI) scans of brain activity revealed that women who had lower activity in food reward regions of the brain and who had genetic modifications associated with lower dopamine activity showed the greatest weight gain after one year. Eric Stice from the Oregon Research Institute says, “These findings provide some of the first prospective evidence that people who experience blunted reward from food may compensate by overeating, increasing risk for unhealthy weight gain.” Overconsumption of appetizing foods may occur in an attempt to increase brain reward in less responsive systems." The value of this being prospective vs. retrospective (as in previous studies) is that it rules out that the obesity is the cause of the low dopamine activity as was believed in the past. This clarifies that it's the low dopamine activity that is the actual cause of the weight gain, not that the weight gain causes the low reward activity. Similar previous papers by Stice are (110, 111).
We need a real paradigm of addictions that fits real addicts and addictions based on real pathophysiology of a real brain mechanism.
A real medical disease paradigm works like this.
The equation of a real medical entity is first, the normal:
Understanding of the Normal Physiology of the specific system involved in any disease leads to 2. Understanding of the Normal function of that system leads to 3. Testable and predictable understanding, insight and accurate policy on that system.
And, for the abnormal, the disease equation is:
1. Understanding of the pathophysiology (abnormal or altered physiology) of the system involved in the disease leads to 2. Understanding of the disease leads to 3. Testable and predictable understanding of the symptomsleads to4. Rational and effective policy which includes treatment, recovery, and public and political policies for the disease).
When the left side (blue) of the equation is wrong, the right side (red) is definitely wrong. This is the case today in addictionology.
There is an undiscovered and unconceived disease causing addictions. The emphasis must be on discovering this, the left side of the equation. This is where I want to begin this reorientation to the disease of addictions.
Thus, addiction is not a choice and is not invented by the patient. Addiction must necessarily resonate with some brain mechanism (15) that already exists in the susceptible person whom I call the hypoic. Addiction doesn’t resonate in the non-hypoic. It doesn’t happen in the non-hypoic. It doesn’t relate to non-hypoics in any way. It can’t. The pathophysiology is just not present in them.
In medicine, for there to be a “disease,” there must be an existing, “normal,” mechanism behind it: its substrate. There must be something in the organ involved with the “disease entity” that resonates with it. Diseases in medicine don’t come out of a vacuum or psychobabble or superstition. Diseases are real and involve real physiologic mechanisms.
There is a disease, an addiction mechanism, an addiction machine if you will, already in place and only in hypoics, the ones with the disease that inexorably causes addictions. The normal mechanism exists in all humans doing something non-addictive (regulating instincts) but is altered in hypoics by a pathophysiology acting within that system to produce radically different effects, the inexorable capability to be an addict. This pathophysiology turns out to be genetic.
That this is the most complex disease in all of medicine and is confounded by the most superstition, pseudoscience and misconceptions is the cause of past perspective problems. Let's, then, bring addictions into the realm of modern medicine and perceive them as part of and caused by a real disease, which, of course, they are.
A List of Several Common Addictions
Drugs, drug addiction, "substance abuse"Cigarettes, nicotinePeople addiction (so-called co-dependency).Compulsive overeating,
These are just some of the addictions (symptoms) seen in humans. There are many more. What a mess. These are the trees, the symptoms. Stand back and see it as the forest it truly is. Can you see the disease, or at least the cognitive mechanism in there? There is a disease that causes all of these symptoms, they are not individual diseases. What you will readily notice when I point it out is that there is a clue to the disease mechanism right up there on that list. Can you see the common denominator?
Every addiction is either related to a known human instinct (behavioral addictions and their endogenous neurotransmitters) or is a neurotransmitter substitute (drugs) for or stimulator of the endogenous neurotransmitters used to reward the use of the instincts.
A short list of some human instincts includes: Attachment, Revenge, Gluttony/Eating, Pride, Approval/Ostracism, Superstition, Lust/Sex, Greed, Xenophobia, Authority/Agonic, Altruistic/Hedonic, Envy, Falling in love, Sloth, Risk Taking/Exploration, Jealousy. Yes, the seven deadly sins are instincts and there are many more. To show how instincts are related to addictions I put together the "instinct - addiction table." http://www.nvo.com/hypoism/graphicsforepperspective/#Addiction%20Table (to come back here after looking at this table hit your browser's back button, not the word "back" at the end of the table). This table lists many known instincts and shows their corresponding addictions in hypoics. The Hypoism paradigm shows them to be just as real as any drug addictions for one good reason, their pathophysiology is exactly the same as for drug addictions - the genetic alteration of the decision-making apparatus by the low activity genetic alleles of regulatory genes. As an example, go down the left hand of the addiction list and find violence and gangs. The middle column shows the instincts associated with them. Recently  it was shown that a low activity allele of the MAOA gene (a hypoic gene) is associated with gang membership and violence of the gang member having this allele. This is how behavioral addictions work and an example of some of their genetic pathophysiology.
Figure. 3 Normal Decision-Making Apparatus
This clue, that instincts and their regulatory brain mechanism lead to all addictions, directed me to the presence and location of the disease mechanism, the genetically altered normal cognitive mechanism: The Instinct Regulating and Reward Mechanism, The Decision-Making Apparatus (16,17), present in all humans and bequeathed to us via evolution and natural selection. One of the best worked out example of this principle in animals is the work on the prairie vole in regards to the attachment instinct and vasopressin (86). This principle, connecting the particular instinct to the reward system, has been documented in gambling addiction (82) and anorexia (83), and in the regulation of human behaviors associated with attachment and trust, falling in love and pair bonding (84), eating regulation (85), and money and social approval (the approval/ostracism instinct) – reputation (97).
Figure 4. Normal Instinct Regulating “Windmill”
Also, like all symptoms in medicine, addictions only happen in certain "susceptible" people and not in others, never: Only in those with the pathophysiology. Besides, patients (addicts) don't cause their own diseases; therefore, they don't cause their own symptoms, addictions. Three recent papers (104, 105, 106) help delineate this principle. ADHD is a symptom complex that includes impulsivity. ADHD is actually pediatric Hypoism. Impulsivity is a symptom of Hypoism (and ADHD) and this symptom has been associated with addictions in humans and rats. It is well known that ADHD has a very high heritability, 76%, (107) and is associated with all kinds of future addictions. The first paper associates childhood impulsivity (and other ADHD symptoms) with future gambling. The second paper associates impulsivity in rats with alcoholism. The third associates single nucleotides polymorphisms (simple mutations) of genes regulating monoamine neurotransmitters such as dopamine. Thus, we have here a demonstration of various symptoms of Hypoism being associated with addictions and mutations of dopamine regulating genes. Similarly for obesity (109).
Like all diseases, only if one has the pathophysiology will one have its symptoms. Addictions are thus inexorable symptoms in hypoics and only in hypoics; not necessarily specific addictions, however, like alcohol addiction, so-called "alcoholism," but some addictions. The mechanism and its pathophysiology are what is genetically transmitted and determined, not necessarily specific symptoms and not specific addictions.
Again, like all medical diseases, there is an organ involved, in this case, the brain. There is a normal brain mechanism, the Decision-Making Apparatus/Instinct Regulating Mechanism, present in all humans for an evolutionarily designed purpose unrelated to addictions but altered by the genetic pathophysiology causing its manifest symptoms, addictions. There is an etiology. There is a pathophysiology. There is a course, a prognosis, treatment, outcome, complications, etc. Just like all other medical diseases. We just don't recognize what these are, specifically because we haven't yet acknowledged there is even a unifying disease, no less what that disease is. We need to identify the mechanism and acknowledge its etiologic role in causing addictions.
Just like any other disease in medicine the principles involving a disease, the perspectives, must be, and are:
1. What's the normal brain mechanism involved?
2. What does this normal brain mechanism do normally for the normal person?
3. How does it work?
4. What causes its perversion?
5. How does this perversion change the function of this normal mechanism?
6. What are all the signs and symptoms of this perverted physiology, pathophysiology?
7. What is the course?
8. What are the complications?
9. What can we do to help someone with this disease ONCE WE KNOW THE ABOVE; just like any other disease?
Let’s use this scheme to define the disease causing addictions.
Many years ago addictionology began looking at addictions starting at number 9. Treating the symptoms and working backwards towards number 1. BACKWARDS - Wrong perspective. That's not always necessarily bad or wrong. Many diseases get discovered and worked out this way. It just hasn't happened with this one. We can change that. During this backwards journey we lost perspective and were waylaid by what we call in medicine, "THE WHITE BEAR SYNDROME." The big, scary, white bear, the major manifestation, is just so formidable and obvious it monopolized our perspective. We called it alcoholism. We called it drug abuse. We called it compulsive gambling, co-dependency, sex addiction, religious fanaticism, compulsive overeating, anorexia, etc. We had fifty or so white bears, but no disease. Others looked solely at the molecular and subcellular levels for the molecular biological problems they could readily fix with drugs. This view was too close and narrow. No one looked at the whole picture from the molecular level to the functional organizational level to the clinical level. It's time to return to real medical concepts, the real disease concept, the whole disease, principles 1 through 9 above, and in the correct order.
When we do this we discover a single disease that puts the jigsaw puzzle of addictions and the rest of those goofy hypoic behaviors into a single, although quite diverse, pathophysiology; diverse because there are many different ways to genetically alter the same physiology of the normal brain mechanism. These diverse ways of altering the pathophysiology lead to different addictions, different combinations of addictions, and combinations of other goofy behaviors; ALL COMING OUT OF VARIOUS GENETIC PERVERSIONS OF THE SAME SINGLE NORMAL BRAIN MECHANISM CAUSING HYPOISM.
Let's start with #1.
1. What's the normal brain mechanism involved?
Figure 3. Normal DMA
I call this brain mechanism THE DECISION-MAKING APPARATUS or (FOKS/DMA), the instinct regulating mechanism. This hypothesized mechanism controls and regulates instinctive behaviors in animals as primitive as fish, amphibians, and early reptiles right up to humans. This neurobiological mechanism is the evolutionary crowning glory that has directed unconscious animal behavior on earth for 100's of millions of years. It is so significant yet subtle that no one has yet thought of or discovered it. It is the Rosetta Stone of human behavior that has gone unrecognized and for which psychobabble has been substituted since man first tried to explain human behavior. This is the mechanism, once researched, delineated, and whose function relative to the cerebral cortex is understood that will finally result in man's understanding of himself as the evolved animal he truly is. I have hypothesized this working model mechanism in very rudimentary form because I have no anatomical neurobiological data on it. It is a geographically diffuse neurobiologic organ extending from the hypothalamus to the cingulate cortex and parts of the frontal lobes that will eventually reveal, I predict, most of the hows and whys of normal as well as diseased human behaviors and emotions. Conceptually, it includes the reward cascade, evaluator, believer, and decision maker at the base of an inverted pyramid of all the built-in instincts bequeathed to humans via evolution and its connection to other neurological organs such as memory, cortical analyzers, and the conscious will. I will leave its delineation to other people but have hypothesized it and its rudimentary functions as a prototype for understanding the most likely neurological basis of addictions that I could arrive at considering our limited understanding of its actual neurobiological reality. This model is the basis for the Hypoism paradigm of human nature of which addictions is but a small but important and illuminative part.
Definition of the Feel O.K. System (FOKS) - This is the key instinct evaluative organ, thermostat if you will, that determines Hypoism and inexorably produces addictions in hypoics while working within the decision-making apparatus (DMA) of the brain. The FOKS exists in all people and has the same function in all people, but works very differently in hypoics. This is the physical location where diverse genetic alleles produce their effects in Hypoism.It is this hard-wired evaluation mechanism and its connections to the common pathway of reward which basically gives us our genetic level of how well we like ourselves (self-esteem), how we respond emotionally to our own internal and external needs (instincts), and, finally, how we place emotional content onto decisions and emotional conceptualization of past events and future outcomes. Its role in our brains lies in its key position in the decision-making apparatus. In hypoics, the FOKS is stuck in the ON or YES position concerning certain FOKS-raising stimuli. These stimuli, in general, all consist of mood-raising chemicals (drugs, alcohol, substances), ideas and beliefs (instincts), certain people (via instincts), and behaviors related to the instincts which internally raise FOKS activity (gambling, falling in love, violence, racism, work, etc.). This state of being stuck on YES is what an addiction is. The cause of this stuck position is the critically low-activity level of the FOKS, defined by the genetically transmitted diverse (different from normal, the most common) alleles of the genes making up the physiology of the FOKS. It is the basic feedback mechanism that tells us (via emotional feelings) internally how we are doing, evaluates our thinking, feelings, behavior, and experiences and provides motivation and direction for fulfilling our survival needs. It gives emotional context to every experience, both internal and external, and is included in our memories. Obviously, it is quite important to the continuity of our lives, survival, and quality of our existence. Another more romantic way to look at the FOKS is that it is the soul or spirit of the individual. This is the irrational, emotional, and individualistic face of each person. It is the person's uniqueness. There is no FOKS just like your own unless you have an identical twin. As nebulous as it may seem, it still is a physical and substantial organ, not ghostly or phantasmagoric.
2. What does this normal brain mechanism do normally for the person?
The DMA has evolved to unconsciously (18) handle the use of instincts in the organism, decisions, and to evaluate external and internal stimuli to produce survival behaviors (19). Until very recently, evolutionarily, this was the predominant way animal behavior was modulated. (20)
3. How does it work?
Look at the FOKS/DMA diagram (Figure 3.) again. It's manufactured and regulated by and from genes and gene products. It is, for the most part, located in an unconscious part of the brain, the limbic system. The FOKS is a neurobiological decision-making switch or thermostat whose settings are determined at conception by a myriad of genetic alleles (21). The conscious mind is aware of its activity only through feelings and urges to act in certain ways. These urges are OK'd by the ATB, the autonomous thinking belief, the believer of one's instinctive thinking, and become decisions unless there is higher cortical intervention (frontal lobe) and if that intervention is strong enough to overcome what occurs in the DMA. Functions of this mechanism?
1.instinctive behavioral decisions
2.emotional evaluations of situations
3.emotional interpretations of events
4.What causes its alteration and powerful influence?
Two things: 1. the physical location of this mechanism, the limbic system. 2. Genetic diversity of the mechanism.
Figure 5. Hypoic DMA
First - The mechanism is located in the limbic system which at this point in human evolution has many limbic-cortical neuronal fibers but few cortico-limbic fibers (22). The neuroanatomy of the mechanism makes the decision-making apparatus particularly unconscious and unamenable to conscious influences.
Second - Genetic diversity making up the FOKS and other regulating/evaluating parts of this system and the existence of multiple low activity alleles of these regulatory genes acting in this system. This major issue is just beginning to be explored but, I predict, will be quite revealing and rewarding when accomplished. For example, a recent monumental study (98) which looked at low activity ADHD-associated genetic alleles of the DRD2 and DRD4 dopamine receptors in a particular African clan confirmed and validated this entire Hypoism concept (17) and its behavioral consequences. [ADHD is a subgroup of people with Hypoism] An excellent example also confirming the above prediction is the study by Zion et al (89) which showed, “The current results are consistent with animal studies that show a role for dopamine and specifically the DRD4 receptor in sexual behavior and suggest that one pathway by which individual variation in human desire, arousal and function are mediated is based on allelic variants coding for differences in DRD4 receptor gene expression and protein concentrations in key brain areas.” Clinically this is recognized as low levels of various neurotransmitters in various drug and behavioral addicts, (23-28) or as predictors of the enjoyment of psychostimulants (29). In extensive animal studies, as documented in the addiction literature, and reviewed in "Substance Abuse - A Comprehensive Textbook," ('97) chapter 6 by Eliot Gardner, and by Crabbe and Li in "Psychopharmacology: The Fourth Generation of Progress (30)," Chapter 69, and Uhl et al. Chapter 153, multiple neurotransmitter deficiencies have been discovered in, or bred into, rodents, associating multiple drug addictions in these animals with their specific neurotransmitter system deficiencies. I will summarize here a massive amount of supportive experimental work accomplished using rats and other rodents whose brains, at least the parts we're talking about, are quite similar to the same parts of the human brain. In these animal studies:
· 1. Certain specific strains (genetically identical animals), and not other strains, voluntarily and spontaneously get addicted to certain drugs and not to others, and do so predictably over and over again according to their genetics (breeding). These behaviors were established through inbreeding. Thus, there is delineation, similar to my delineation between hypoic and non-hypoic humans,between genetically similar strains of rats who get addicted and those who don't get addicted even when exposed to the same drugs. The word voluntary here only means that the addictors weren't forced on them, not that the behavior was willful or volitional or conscious, just the opposite. In lower animals all behavior is unconscious and involuntary.
· 2. These specific strains are found to have specific genetically transmitted defects (deficiencies) of specific gene products located in specific places in the reward system.(93) Commenting on this reference, Volkow said, “the results are not surprising, since scientists have long known that low levels of dopamine receptors in the nucleus accumbens are linked to addiction and not just for cocaine. "In animal models, when you bring down the dopamine D2 receptors, those animals then have a vulnerability for taking a wide variety of drugs.” Healthday, 3/1/07 – “Some Brains May Be Predisposed to Substance Abuse. Less dopamine encourages impulsivity and addiction, rat study suggests.”
· 3. The drugs to which these animals voluntarily get addicted are specifically the same ones to which humans get addicted. (31)
· 4. These drugs all exert their actions specifically in the reward system pathways as well as in the specific locations where these defective genes (alleles with deficient activity) are located.
An example of the validity and utility of these principles is a recently published demonstration (32) that alcohol preferring rats, genetically deficient in DRD2 receptors, will significantly decrease their alcohol intake when the deficient receptors are increased in their nucleus accumbens via gene transfer.
The totality of the animal work is critical in that it provides a much more likely mechanism for addictions having nothing to do with the environment on causing drug addictions. Drug addictions act similarly in humans as suggested by recent valid studies of addictions in twins at VirginiaCommonwealthUniversity by Kendler et al. A review of the high heritabilities of many human addictions can be found on my web site (33). One of these articles by Sullivan and Kendler (34) definitively showed both initiation of addictor use, in this case smoking, and the ultimate addiction to cigarettes were primarily and mostly genetic. Initiation of cigarette smoking was found to be 60% heritable while subsequent addiction was found to be 70% heritable. If the hijacked brain hypothesis were correct, that initiation were a voluntary free-will choice and that addiction is caused by the drug itself, then the heritability of initiation of smoking and ultimate addiction would have been 0%. It was 60% and 70%, not very close to 0%. No current paradigm other than Hypoism both reconciles and predicts this study’s outcome. Eventually, all addictions will be shown to be genetic in both initiation of addictors use and ultimate addiction.
An important heritability caveat is discussed in that article and I will repeat it here briefly: Because the individual addictions are not what is being inherited, their heritability numbers are high (60-83%), depending on the addiction studied and who studies it, but lower than 100% and do not represent the actual heritability of the disease, Hypoism, whose genetics have, of course, never been studied. Absence of 100% heritability for an addiction, therefore, in no way implies environmental etiology for that addiction as is currently and wrongly inferred. Moreover, heritability is not equivalent to genetic causation. Heritability can be less than 100% and genetics can still be the cause of the trait. Thus, heritability underestimates the role of genetics. These are just two of the major mistakes made by the current addictionologists using their misperception of addiction etiology and what they call the disease, the addictions, which are symptoms, not diseases. The genetics of symptoms are actually irrelevant to understanding the genetics of the disease causing them. I predict that when studied correctly, heritability of addictability, a study not yet done by anyone, the genetics of Hypoism will be 100% heritable. Recently (81), it’s been shown that the assumption used to calculate gene vs. environmental heritabilities, that identical twins have identical DNA, is not actually correct due to epigenetic changes in DNA and its regulators in the nucleus, thus necessitating a complete revision in heritability calculations with an obvious resultant increase in genetic influence and decrease in environmental influences of traits. Quoting from a recent (2007) review on the epigenetics of depression [J Mill and A Petronis, Molecular studies of major depressive disorder (MDD): the epigenetic perspective, Molecular Psychiatry (2007) 12, 799–814]: “Twin studies have strongly implicated genetic factors in the aetiology of MDD, but as is the case for all complex psychiatric conditions, MZ twin concordances are observed to be considerably less than 100%. In the classical twin-study approach, in which MZ twins are assumed to be genetically identical, any discordance between MZ twins is attributed solely to 'non-shared' environmental factors. An alternative explanation, however, is that some of the observed phenotypic differences between MZ twins may be the result of epigenetic factors. A recent study by Fraga et al. has demonstrated that fairly profound epigenetic differences across the genome do arise during the lifetime of MZ twins, highlighting the dynamic nature of epigenetic processes. Interestingly, MZ twin methylation differences have been reported for CpG sites in a number of specific genes that have been associated with psychiatric illness including the dopamine D2 receptor (DRD2) gene and the catechol-O-methyltransferase (COMT) gene. Similarly, genetically identical inbred animals have been shown to demonstrate considerable epigenetic differences that may be linked to gene expression differences resulting in marked phenotypic variation. It is becoming increasingly apparent that many of the observed epigenetic differences between MZ twins and inbred animals may be the result of random stochastic events. It can be envisaged that such stochastic epigenetic 'mutations' may accumulate over the millions of mitotic divisions occurring during the lifetime of two MZ twins, and could lead to profound gene expression alterations if present in regulatory regions of the genome. It has been proposed that such stochastic epigenetic variation may be more important in complex psychiatric disorders than is currently recognized, perhaps accounting for some of the risk currently attributed to environmental factors.”
Three more reasons for the heritabilities calculated to be less than 100% are: 1) denial of addictions by individual participants of the epidemiological studies used to calculate heritability, and 2) the recently documented phenomenon (94) of variation of gene expression unrelated to any changes in gene sequencing. Thus, because “environmental” causation is calculated as the difference between the genetic heritability (a number less than 100) and 100%, and we have at least four major reasons why the number 100% is actually less than 100%, it is evident that the environmental percentage may well be way overestimated, possibly zero depending on the effects of these four phenomena. The third reason for falsely low heritabilities is the recently discovered phenomenon of “half-identical twins” where the egg splits in half and the two halves are fertilized by different paternal sperms. This yields twins that may look like identical twins but only share 75% of their DNA.
[More information on why identical twins are not identical and how this can falsely lower heritabilities for genetic diseases such as [addictions] Hypoism. "Monozygotic (MZ) twins represent an important resource in genetic studies related to normal development and disease. Numerous twin registries exist, often specializing in collection of phenotypically discordant MZ twins. Consequently, twin research has become a powerful tool for studying various diseases and endophenotypes, evaluating quantitative-trait loci, estimating heritability, studying differences in gene expression, and testing hypotheses regarding gene-environment interactions. It is generally presumed that MZ twins are genetically identical and that phenotypic differences between twins are mainly due to environmental factors. Examples of genetic and, more recently, epigenetic differences between MZ twins have, however, been described., ,  and  The former are mainly related to aneuploidies. Somatic mosaicism is usually defined by the presence of genetically distinct populations of somatic cells in a single organism. Any genetic difference between MZ twins represents an extreme example of somatic mosaicism. Earlier reports have shown somatic mosaicism for mutations in specific disease-related genes or chromosomal aberrations that are connected with a disease and can, for instance, result in a milder disease phenotype. This steadily growing body of data indicates that somatic mosaicism for pathogenic mutations affecting known disease genes might be seen as a rule rather than as an exception. In addition, it was recently demonstrated that the frequency of inversions is altered between different populations of normal somatic cells in a healthy subject. However, the frequency of in vivo somatic mosaicism for copy-number variations (CNVs) in populations of apparently normal cells is so far unexplored." References are: Reference for above quote comes from this one---1. Phenotypically Concordant and Discordant Monozygotic Twins Display Different DNA Copy-Number-Variation Profiles The American Journal of Human Genetics, In Press, Corrected Proof, Available online 14 February 2008 Carl E.G. Bruder, Arkadiusz Piotrowski, Antoinet A.C.J. Gijsbers, Robin Andersson, Stephen Erickson, Teresita Diaz de Ståhl, Uwe Menzel, Johanna Sandgren, Desiree von Tell, Andrzej Poplawski, Michael Crowley, Chiquito Crasto, E. Christopher Partridge, Hemant Tiwari, David B. Allison, Jan Komorowski, Gert-Jan B. van Ommen, Dorret I. Boomsma, Nancy L. Pedersen, Johan T. den Dunnen, et al.2 G.A. Machin, Some causes of genotypic and phenotypic discordance in monozygotic twin pairs, Am. J. Med. Genet.61 (1996), pp. 216–228. 3 P. Gringras and W. Chen, Mechanisms for differences in monozygous twins, Early Hum. Dev.64 (2001), pp. 105–117. 4 M.F. Fraga, E. Ballestar, M.F. Paz, S. Ropero, F. Setien, M.L. Ballestar, D. Heine-Suner, J.C. Cigudosa, M. Urioste and J. Benitez et al., Epigenetic differences arise during the lifetime of monozygotic twins, Proc. Natl. Acad. Sci. USA102 (2005), pp. 10604–10609. 5 A. Petronis, Epigenetics and twins: Three variations on the theme, Trends Genet.22 (2006), pp. 347–350.]
Figure 6. Population Distribution Bell Curve of FOKS Activity
This bell curve graphically illustrates and defines the hypoic population by its hypothetical FOKS activity level if measuring it were possible. The hypoic FOKS unconsciously causes the hypoic to incessantly prowl for a FOKS raising experience or neurotransmitter substitute, and it is never satisfied even when it finds one (35). The neurophysiological adaptation mechanism makes sure of that.
Figure 7. Neurophysiological Adaptation
This mechanism is also responsible for craving, progression (worsening severity of the disease symptoms and increased addictors use over time), tolerance, withdrawal, and relapses due to the low FOKS activity lasting for prolonged periods of time after detox. It is basically caused by downregulation of the system; the baseline FOKS activity is lowered. Downregulation is when the genes for receptors and neurotransmitter system component production are turned down or off by the presence of an excess of neurotransmitter substitutes (drugs) or endogenous neurotransmitters produced by excessive use of instinctive behaviors that raise endogenous neurotransmitter levels in the regulatory neurons.
5. 5. How does this genetic alteration change the function of this normal mechanism?
Figure 8. Hypoic Windmill
Only a critically low (HYPO) genetically transmitted level of activity of this system can lead to addictions and manifestations of the disease. Thus, Hypoism.
Definition of the word addictor - Hypoics get addicted to anything that raises their genetically determined critically low FOKS activity level. These FOKS elevators are called addictors. Addictors come in two varieties, neurotransmitter substitutes (drugs) (36)and the FOKS-raising built-in instincts (37). These addictors all work by stimulating the reward cascade or final common pathway (Figure 9. below) of all addictions either directly such as with neurotransmitter substitutes, the actual drugs, or indirectly by stimulating the endogenous neurotransmitters via the FOKS activity raising instincts, the precursors of behavioral addictions. They specifically raise the activity of the genetically determined deficient neurotransmitter within the FOKS. This is explained in more detail in Aiming at an Understanding of Addictions (38). Non-hypoics enjoy addictors, but hypoics get addicted to them.
The Reward Cascade - Reproduced from Gardner’s chapter in Substance Abuse-A Comprehensive Textbook
The Reward System
Schematic diagram of the brain-reward circuitry of the mammalian (laboratory rat) brain, with sites at which various abusable substances appear to act to enhance brain-reward and thus to induce drug-taking behavior and possibly drug-craving, ICSS, descending, myelinated, moderately-fast-conducting component of the brain-reward circuitry that is preferentially activated by electrical intracranial self-stimulation; DA, subcomponent of the ascending mesolimbic dopaminergic system that appears preferentially activated by abusable substances; Raphe, brain stem serotonergic raphe nuclei; LC, locus coeruleus; VTA, ventral tegmental area; Acc, nucleus accumbens; VP, ventral pallidum; ABN, anterior bed nuclei of the medial forebrain bundle; AMYG, amygdala; FCX, frontal cortex; 5HT,serotonergic (5-Hydroxytryptomine) fibers, which originate in the anterior raphe nuclei and project to both the cell body region (ventral tegmental area) and terminal projection field (nucleus accumbens) of the DA reward neurons; NE, noradrenergic fibers, which originate in the locus coeruleus and synapse into the general vicinity of the ventral mesencephalic DA cell fields of the ventral tegmental area; GABA, GABAergic inhibitory fiber systems synapsing upon the locus coeruleus noradrenergic fibers, the ventral tegmental area, and the nucleus accumbens, as well as the GABAergic outflow from the nucleus accumbens; Opioid, endogenous opioid peptide neural systems synapsing into both the ventral tegmental DA cell fields and the nucleus accumbens DA terminal projection loci; ENK, enkephalinergic outflow from the nucleus accumbens; DYN, dynorphinergic outflow from the nucleus accumbens; GLU, glutamatergic neural systems originating in frontal cortex and synapsing in both the ventral tegmental area and the nucleus accumbens.
We can now define Hypoism - The name of the disease I hypothesize for the purpose of developing the global concept of addictions as a real disease. A chronic, progressive, and frequently fatal (albeit recoverable) thinking and decision-making disorder due to the effects of genetically transmitted [unless caused by physical damage to the FOKS by encephalitis, trauma, intracerebral hemorrhage, brain tumor (39), etc.] critically low activity of the FOKS resulting from various physiologic deficiencies of the limbic neurotransmitter systems working within the instinct regulating decision-making apparatus. The hypoic FOKS turns the decision-making apparatus into an addiction machine. Hypoism has at least three inevitable manifestations based on the functional roles of the DMA: 1) addictions to substances, ideas, people, and behaviors, 2) decision-making difficulties leading to disasters, and 3) situation and self-evaluations mistakes having damaging repercussions in the hypoic's life.
Corollary 1. Addictability: Low activity of any neurotransmitter system activity for any particular instinct stimulates motivation to use that instinct, another instinct which can raise the activity of the same system, or the use of a neurotransmitter substitute drug that raises the activity of that system, all at a level below consciousness, allowed by the ATB and rationalized and ensured by the conscious cerebral cortex.
Corollary 2. Specific Addictions - Instinct Diversity: Different people have genetically different levels of strength of instinct rewards and will, therefore, prefer the use of higher strength instincts to perform the FOKS raising job depending on the neurotransmitter system affected by the deficiencies. This corollary encompasses the tendency of specific deficient activity alleles to cause predilection for specific addictors including specific drugs of addiction among hypoics. (40-45, 92)
Both of these corollaries must be fulfilled in the hypoic for any addiction to exist and this is why the disease must be Hypoism rather than the diseases being the individual addictions. Although I’ve been asking the field of addictions to study the trait of addictability, it has refused to the detriment of our understanding of addictions in general. However, the work done on addiction combinations, that people with one addiction have a high likelihood of having multiple addictions, has proved both of these corollaries unintentionally. The reason for multiple addictions in each hypoic is that each individual neurotransmitter system reinforces more than one instinct and one drug (neurotransmitter substitute). Thus, as the hypoic experiences the specific addictors [associated with his particular genetic deficiencies] he’s susceptible to, he gets addicted sequentially, and they occur in groups. If the hypoic has more than one genetic deficiency he will get addicted to more than one group of these addictors. I’ve observed this in my 25 years in AA, but most importantly this phenomenon has been documented repeatedly by the field of addictions. See: http://www.nvo.com/hypoism/1371addictioncombos/ This phenomenon proves conclusively that there is an underlying disease causing addictions rather than each addiction being an individual disease. Thus, Hypoism is the disease and addictions are symptoms of that disease. Otherwise, each individual addiction would be unrelated to any other addiction, and this is just not the case, clearly.
Finally, the definition of the word addiction - A hypoic's use, including the first use, of an addictor, a substance, person, thought, feeling or behavior, for the purpose of changing how they feel, irrespective of the consequences to themselves, their family, their job, their loved ones, or their country against their own conscious will.Aside from the massive evidence above from the human genetics and animal inbreeding experiments that show addictions are caused unconsciously and against the will of the addict-to-be there is the recent documentation of a dopamine agonist drug, Pramipexoledihydrochloride, used to treat Parkinson’s Disease, that out of the blue caused gambling addiction in a small number of people on this drug.(87) Once the drug was stopped the addiction completely disappeared. This experience is an excellent example of the exception proving the rule, where an extraneous drug unexpectedly produced the same neurobiological conditions in certain people taking it that the genetics of Hypoism naturally produces and a de novo addiction appeared where there was none before and disappeared when the drug was withdrawn. What was even more interesting was that in addition to the gambling addiction, many of these patients also were observed to overeat, drink alcohol excessively, and act like sex addicts. Hypoism was reproduced by a pill against the will of the people who had this side effect. Now, does this clear up how something that can appear so conscious and willful is actually unconscious and against one’s will? I think so.
Hypoism produces the capability of being an addict and other manifestations caused by these genes altering the "normal" function of this system. Ordinary decisions in non-hypoics frequently become addictions in hypoics. Because of the way the DMA is organized the critically low FOKS activity unconsciously demands constant use of FOKS activity raisers, drugs and instinct use that specifically raise the levels of the genetically deficient neurotransmitters.
Addictors are turned into addictions only in hypoics by the hypoic FOKS/DMA addiction machine, the neural machine that evolved to deal with and reinforce instinctive decisions. These instincts and their neurotransmitter reinforcers are the clues I mentioned earlier at the time I produced the list of addictions that led me to the brain mechanism responsible for all addictions.
The above discussion is a hypothesis and needs to be worked out experimentally. But, it's a rational beginning based on actual brain mechanisms.
6. What are all the signs and symptoms of this perverted physiology?
Addictions plus the rest of the natural history of the disease Hypoism needs to be studied all over again from scratch because it has never been studied correctly to date.
7. What is the course?
The natural history of the disease Hypoism which needs to be studied from scratch.
8. What are the complications?
The natural history of the disease Hypoism which, again, needs to be studied all over again from scratch.
9. What can we do to help someone with this disease ONCE WE KNOW THE ABOVE, just like in any other disease? Voluntary and destigmatized recovery.
When we look at just the addictions and the outdated addiction model of today, psychobabble plus isolated neurotransmitter deficiencies, then it seems as though the treatment ought to be to raise neurotransmitter levels with either medications or neurotransmitter precursors such as nutritional supplements, and psychotherapy to change addict's thinking. When we look at the new pathophysiology, however, we notice right away that the addictions originate from anything, drugs, medications, or behaviors, that raise FOKS activity.
Figure 10. ATB Intervention
Raising FOKS activity causes addictions in hypoics. Thus, raising FOKS activity with medications can't be therapeutic, and, of course, it's not and never has been. It actually causes new addictions as well as preventing real recovery from Hypoism because it prevents the critical surrender discussed below. Secondly, using psychotherapy to change the decision-making process also seems to make sense except when it is realized that the decision-making apparatus is in an unconscious and unamenable part of the brain and thus, the FOKS/DMA is not listening or participating in the psychotherapeutic process and can't be changed. This is why these two approaches - medication and psychotherapy - have never worked for full and real recovery. A third possible way to stop addiction, by blocking the reward system, is cruel and unconscionable because it prevents even healthy rewards, yet is still being considered as a way to stop addictions. I am against this technique unless the informed addict chooses it instead of recovery.
Remember, recovery needs to be from the disease, not just getting rid of a particular addiction. FOKS raisers and psychotherapy may have occasionally been found to stop the initial addiction, but they frequently lead to substitute addictions and relapses, and don't take into account the other (unrealized) and clinically quite significant manifestations of the disease such as decision-making disasters and evaluation mistakes. JFK, Jr.'s (strong family history of Hypoism) death was an example of one of these despite no obvious addictions. From the pathophysiological disease concept of medicine, one needs to intervene on the whole disease to assure full recovery, our goal, not just interventions on the addictions. Hypoism is the target of recovery, not the addiction. Remember the perspective? The forest and the trees?
What we do notice in figure 10. is that the Autonomous Thinking Belief (ATB) is available for intervention. Intervention here allows for recovery from the disease without needing to change the person into someone else or changing his brain in any way, or by the production of new addictions from FOKS raising medications, and thus can allow full acceptance of the hypoic's self, a necessity for any full recovery. The hypoic can remain himself and also be safe from his disease. The ATB was the clue from A.A. I mentioned at the beginning of this paper; the process of surrender of control of the DMA to an A.A. sponsor. This process bypasses the pathophysiology of the hypoic DMA without necessitating changing the hypoic in any way. AA fortuitously developed this modality without knowing why it is useful or necessary. Thus, they are incapable, absent knowing about Hypoism, of using this modality successfully. Once they do acknowledge Hypoism as their disease rather than alcoholism they can improve their efficacy infinitely. A recent study that differentiates the neural mechanisms underlying the way we assess the consequences of choices depending on whether we are told what to do or are able to exercise our volition adds credence to this recovery methodology. [Mark E Walton, Joseph T Devlin & Matthew F S Rushworth, Interactions between decision making and performance monitoring within prefrontal cortex, Nature Neuroscience 7, 1259 - 1265 (2004)]
What is the ATB? It's the brain's believer of the thoughts and feelings produced by the previous few steps in the DMA. The ATB unconsciously permits the thought to become a decision. You can also call it self-sufficiency, pride, and arrogance if you like. I call it unconscious thinking belief or autonomous thinking belief because it usually occurs below the level of consciousness, and is thus autonomous. When asked, "Why did you do that?" the hypoic responds, "I don't know. It seemed like a good idea at the time," a common occurrence in hypoic decision-making. Hypoism recovery allows the hypoic to surrender control of the ATB and use another person to be a decision consultant without having to change his thinking, feelings, or biochemistry. This is the major essence of real recovery in A.A. even though A.A. itself doesn't realize this. No need to change how one feels, how one thinks or how and why one acts. The recovering hypoic chooses another recovering hypoic to help with counter- instinctive, counter-disease decisions. Remember, Hypoism is instinctive. Also, there is no need for medications and psychotherapy. The recovering hypoic needs to know he has the disease, realize its effects on himself, his decisions and life, surrender control of the ATB, and accept the feelings and the recovery process as directed by his sponsor as OK. Surrendering of self-sufficiency for a hypoic is the recovery process in a nut shell and is OK. The process of surrender also reduces the urgency of the communication from the unconscious part of the brain (FOKS/DMA) to the cortex and relieves the compulsivity and neediness of the hypoic. This process can only work, however, when the brain mechanism is known, understood, and accepted by the hypoic. Thus the need for teaching the workings of this normal brain mechanism among the populous which, by necessity, includes all hypoics as well. Once this disease is understood and accepted by the general population, it will be immediately destigmatized and amenable to rational policy decisions by politicians and regulators just like any other disease. Massive recovery and prevention now becomes a reality. Prevention (of addictions), something that is impossible today, is accomplished by making the genetic diagnosis of Hypoism at birth and beginning recovery from it in childhood long before addictions occur. Much research needs to be done to allow this to eventually happen. But, if we persist in the current addiction paradigm, we will never have this occur.
Because of the physiology and neurological geography of the disease of addictions, Hypoism, it is an instinctive, unconscious, and irrational disease. Its recovery can't therefore be rational, but rather must be anti- or counter-instinctive, and completely voluntary, a totally new concept for addiction intervention. Only the voluntary surrender of the ATB in the informed (informed about the pathophysiology of the disease) hypoic is available for that approach. Hypoic’s Not-Anonymous, the Hypoism recovery program, uses this information and modality to allow real and complete recovery as well as prevention.
That's a brief overview of our problems with addictions today and a summary of a possible pathophysiological mechanism to conceive of the disease that causes addictions.
So, to summarize the Hypoism paradigm of addictions:
·The Decision-Making Apparatus is derived from 100's of millions of years of evolution and exists in all animals including humans. Its function is the unconscious regulation of instincts and direction of survival behaviors little influenced by cortical control because of the paucity of cortico-limbic inhibitory neurons.
·These instinctive decisions are rewarded and reinforced by the reward system involving numerous neurotransmitter systems resulting in dopamine release in the nucleus accumbens.
·Natural selection has allowed to exist numerous alleles of genes making up this reward system including low activity alleles useful to survival. These low activity alleles developed in periods of scarce commodities and were important for stimulation of instinctive survival behaviors producing the most rewards.
·In the presence of widely available commodities (goals of instincts) and neurotransmitter substitutes (drugs) a subset of humans with critical reward system (FOKS) deficiencies (hypoics) inexorably seek out and get addicted to these addictors unconsciously and against their will and cortical inhibitions. Instead of inhibiting this behavior, the cortex consciously justifies and rationalizes this behavior in the presence of an intact Autonomous Thinking Belief.
·Attempts to control and change this hypoic system from without and from within result in perpetuation of addictions and other symptoms.
·Because this behavior is caused by perturbations (genetically transmitted) of "normal" non-hypoic physiology and results in negative consequences to the hypoic, Hypoism can be called a Disease. Addictions, decision-making disasters, and evaluation mistakes, three of the majors manifestations of Hypoism, are but the symptoms of this disease.
·Only surrender of control over the hypoic Decision-Making Apparatus and the ATB result in prevention and recovery of addictions and allow for recovery from the disease of Hypoism and all its manifestations. This recovery can only occur with the complete cooperation of the hypoic in the face of his/her understanding of the disease process.
·Only surrender of the ATB relieves the obsessions, compulsions, and cravings characteristic of Hypoism.
·Changes in public attitudes and policies concerning addictions and addicts can only occur with their complete understanding of the Hypoism paradigm of addictions as well.
·The Hypoism Hypothesis can be used productively, I believe, to stimulate and direct future addiction research.
It is all summarized diagrammatically and graphically in the next two figures,
11 Hypoism chart and 12 The Hypoism Windmill.
Addictionology and society are currently Don Quixote and Sancho Panza.
The base of the windmill is the genetics and pathophysiology, the hub is the instincts involved in this system and the windmill's vanes are the addictions resulting from this functioning system.
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