It seems to me that many roads lead to psychosis.... whether from high fever or rabies, dehydration or hidden sepsis, sleep deprivation or sever allergies, emotional breakdown or heavy metal overload. No matter the cause we are left with an altered state of consciousness which may actually be an unidentified survival mechanism. This state seems to force the person into either an overly expanded and overly sensitive space or into an intense inner focused state. It is no wonder that people who sail close to this state are creative, inventive and have in the past greatly contributed to human endeavor.

Psychosis itself is not terrifying, it can for some be a life changing event and/or a spiritual emergence. It can become terrifying though when mixed with fear, loss of the known status quo and societies judgement of what it means to be 'out of control'. Its funny though that people pay large sums of money and risk legal ramifications to experience temporary psychosis by using illegal drugs and mind altering plants.

In a recent editorial in JAMA Psychiatry, Kahn and Keefe perhaps belatedly acknowledge what many have been thinking - that Schizophrenia/psychosis is much much more than a sum of the parts of its clinical presentation characterized by hallucinations, delusions, cognitive and other symptoms. In fact, they suggest that schizophrenia ought to be conceptualized as a cognitive disorder rather than how it is conceptualized now (Kahn, R. S., & Keefe, R. S. (2013). Schizophrenia Is a Cognitive Illness: Time for a Change in Focus. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2013.155).

Therefore, when does psychosis or schizophrenia really really start is a very good question and Prof Cyndi Weickert, Vibekke Catts and colleagues reviewed this concept recently here quite elegantly: Catts, V. S., Fung, S. J., Long, L. E., Joshi, D., Vercammen, A., Allen, K. M., . . . Shannon Weickert, C. (2013). Rethinking Schizophrenia in the Context of Normal Neurodevelopment. [Review]. Frontiers in Cellular Neuroscience, 7. doi: 10.3389/fncel.2013.00060.

GWAS studies have shown that as yet, we have been unable to pin point a single gene to play a major part in the pathogenesis of psychosis. Indeed, multiple genes confer multiple levels of risk on a person and in the context of adverse gene x environment interactions, some people develop one type of psychosis and other people develop other types of psychosis and some others do not develop an illness at all. They may all have the same clinical feature by way of hallucinations or delusions, but deep within the genetic and neurobiologic underpinnings of each of these disorders is likely to be different.

In 2007, Carol Tamminga and van Os wrote in the Schizophrenia Bulletin about the role of DSM in perpetuating the ideas of schizophrenia that we have now and how we were wrong to bag them for something they did not do. It was important to have a common understanding of the clinical disorder that we see in practice and manuals such as DSM and ICD-10 did help in this regard. But, nowhere did DSM or ICD claim that these disease classifications actually address the neurobiologic correlates of the disorder. Fittingly, DSM 5 (despite other problems) has removed references to 'subtypes' of schizophrenia that drove clinical practice and research over the past 60 years (paranoid, disorganised, hebeprehic and residual schizophrenia et al have all been removed) (van Os, J., & Tamminga, C. (2007). Deconstructing psychosis. [Editorial]. Schizophr Bull, 33(4), 861-862. doi: 10.1093/schbul/sbm066).

Currently, people are looking at subtyping the disorder on cognitive performance amongst other things.

However, there are miles to go before we sleep!

Psychosis is not once disorder. It are a very different syndroma of mental and cerebral dzsfunctions, with different etiology. The altered consiousness is the only stabile szmptoms of psychotic state. Derealisation, depersonalisation, hallucination and delusion are inconsistent symptoms od psychotic disorders. Hallucionation and delusion are frequently organic origin.

Nikola Ilankovic: Real causes of some psychotic disorders

European Psychiatry (impact factor: 2.77). 04/2010;

The hallucinations associated with schizophrenia occur in clear consciousness, by definition (as opposed to hallucinatory experiences associated with delirium, for example). Anyone, with or without a diagnosable mental disorder, can experience hypnagogic or hypnopompic imagery when falling asleep or awakening, and such experiences -- while similar to the auditory and visual hallucinations seen in some psychoses -- are best viewed as a normal variant, in my opinion.

Some psychoses or apparent psychoses can be clearly attributed to neurological issues, such as Korsakoff's, alcohol hallucinosis, and others. Schizophrenia was in the past classified as "functional" (as opposed to "organic") because its etiology was (and is?) unknown.

Hallucinations can often occur in the healthy without any impairment of consciousness, eg Ordronaux J On hallucinations consistent with reason Am J Insan 1861;17:353.

Cases discussed include Swedenborg, Socrates, Dr Johnson, Pascal, Luther, Napoleon, etc.

Auditory hallucinations can also occur in those with ear disease and normally functioning brains and nervous systems.

It is true Anthony. Some new research show that tha hallucinations and delusions are not consistent symptom of schizophrenia. By Eugen Bleuler hallucinations are secondary symptoms, too.

Psychosis, according to Alfred Adler, is often rooted in a profound feeling of inferiority. Despairing of conquering that feeling in reality, the individual merely compensates for that felt insufficiency by escaping into fantasy, delusion, and hallucination, thereby rejecting reality as well as common sense. The deeper the initial feeing of inferiority, the higher the ultimate, compensatory, fictional final goal. The polar gap may range from the depth of total insignificance to the height of godlikeness. Ultimately, the ongoing "cause" of the psychosis is the embracing of an intoxicating illusion of super-human superiority. (Of course, this explanation would probably not apply to organically induced psychosis.) For more information, read "The Collected Clinical Works of Alfred Adler, Volume 1 - The Neurotic Character," available at http://www.adlerian.us/nc-3.htm.

But there is a genetic component... Pyroluria, an inability to excrete blood waste products which binds with B6 and zinc. Without adequate B6 the body is not able to convert many metabolic processes including typtophan to serotonin. Pyroluria is indicated in 50% of autism, 40% of alcoholics, 70% of schizophrenics, 70% of depression and 30% of people with ADD. B6 is the co-enzyme in over 50 enzymatic brain functions including dopamine production. The brain uses at least 60 zinc enzymes. Zinc also regulates insulin activity, is an antioxidant and plays a critical role in immune function. Look to the work done in the 1950's, 60's and 70's... it has all been done before, with good success but to the displeasure of big pharma.

Heather, do you have a reference for the data you cited about pyroluria being found in the conditions you listed? I would be very interested to read more on this topic.

Hi Neil, I took it from half a dozen sites I found while googling pyroluria. Orthmolecular doctors used to be very familiar with it. It was also know as the mauve factor as the urine test changes colour when the waste products were present. I have more information on the question I asked on this topic.... I am having the test myself shortly as I go downhill when I stop taking vitamins, minerals and amino acids.

Hi Heather, you need to produce some up-to-date references. I remember getting excited about the pink spot, but this was over 40y ago, and I haven't heard about it since. I cannot think of any plausible reason why Big Pharma is not inundating us with orthomolecular products, other than the obvious one that BP doesn't think they work.

The Discovery of Kryptopyrrole and its Importance in Diagnosis of Biochemical Imbalances in Schizophrenia and in Criminal Behavior J. Orthomolecular Medicine 10(1):3 1995 (by Abram Hoffer M.D, PhD)

Fatty Acid Profiles of Schizophrenic Phenotypes, 91st AOCS Annual Meeting and Expo San Diego, California 2000 (by William Walsh PhD of the Pfeiffer Treatment Center)

Urinary Pyrrole (Mauve Factor): Metric for Oxidative Stress in Behavioral Disorders, presented to the Linus Pauling Institute, 2003 (by Woody R. McGinnis MD)

Hi Neil,

It seems you are asking two questions?

In answer to the question that titles this discussion, there is an abundance of evidence that suggests the immediate origin of any episode of psychosis is dysregulation of dopamine.

Excellent overview here;

http://www.schizophreniaforum.org/for/curr/AbiDargham/

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In terms of episodes of psychosis induced by dopaminergic drugs, saying "dysregulation of dopamine may induce psychosis" is probably an adequate explanation of aetiology. However in the case of psychotic disorders that are not induced by stimulant use, this "origin" is unsatisfying, as it is clearly a proximate cause of any episode of psychosis, not the ultimate cause of any psychotic disorder.

I'd suggest your second question, (as to whether there are qualitatively different kinds of psychosis) is actually related to your first question, (as to ultimate causes) by way of a continuum model of psychosis in the population.

I's suggest that there is a continuum between simple misperceptions and full blown delusions and hallucinations, and that psychosis is best understood as a phenotypic expression distributed throughout the population, to which specific individuals have a greater or lesser vulnerability.

I am increasingly of the opinion that there is no such thing as "schizophrenia", if by this label we mean a distinct disease entity.

All people have the potential to experience psychosis, (it is a phenotype, not a genotype), and also to experience the negative symptoms of schizophrenia, but that vulnerability to experiencing these sorts of symptoms varies widely across the population.

Some people (due to a combination of co-occurring genetic risk factors, and/or infection, neurological insult, or injury in-utero or in early infancy, and/or certain types of life experiences) are far more prone to psychotic breaks, and some people are far more robust in this regard. Even the least vulnerable humans can experience psychotic states if you stress them enough, (prolonged sleep deprivation, malnutrition, dehydration, extreme fear or anxiety provoking environments, stimulant toxicity, etc).

25% of people who experience a “first episode psychosis” never experience a second episode. They don’t have a disorder. They have just had a bad experience that has triggered this sort of response.

Those people who are most vulnerable typically have a family history of psychotic disorders, and we know that a large part of your risk of being diagnosed is heavily influenced by heritable factors. There are many studies that clearly show an association between certain single nucleotide polymorphisms (SNiPs) and a diagnosis of psychotic disorders.

However studies in different populations identify completely different SNiPs as significant risk factors. There are dozens of them. And none is a sufficient or necessary causal factor in and of itself.

http://snpedia.com/index.php/Schizophrenia

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I am becoming more and more convinced that this means there is no real, single disease entity we can call Schizophrenia. Instead, I am tending towards the opinion that the cluster of acute symptoms that identify stress-related psychotic breaks, drug-induced psychosis, Schizophrenia, Schizophreniform disorders and Bi-Polar Affective Disorder are simply a phenotype that humans may express in response to stressors in their physical and social environment, but that the likelihood of any experience triggering this response in any individual is heavily modulated by genetics and experience in-utero and perinataly.

Those people with many co-occurring risk factors, who experience psychosis chronically, get diagnosed with a form of Schizophrenia or a form of Bi-Polar Disorder.

Studies into the heritability of both disorders identify the same familial risk factors, and the same factors are also associated with Autism.

>

http://www.medscape.com/viewarticle/528669_3

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This is consistent with the idea that these diagnostic labels are not describing distinct disorders, but instead are describing different expressions of a wide spectrum of potential human behaviour.

Sullivan et al, Family History of Schizophrenia and Bipolar Disorder as Risk Factors for Autism;

http://archpsyc.jamanetwork.com/article.aspx?articleid=1206780

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Discussion of the above study;

Study Links Autism, Bipolar, and Schizophrenia;

http://www.medpagetoday.com/Pediatrics/Autism/33589

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Van Os et al, A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness–persistence–impairment model of psychotic disorder;

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=3405404

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Linscott et Van Os, Systematic Reviews of Categorical Versus Continuum Models in Psychosis: Evidence for Discontinuous Subpopulations Underlying a Psychometric Continuum. Implications for DSM-V, DSM-VI, and DSM-VII;

http://www.annualreviews.org/doi/abs/10.1146/annurev.clinpsy.032408.153506?journalCode=clinpsy

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Nuevo et al, The Continuum of Psychotic Symptoms in the General Population: A Cross-national Study;

http://schizophreniabulletin.oxfordjournals.org/content/38/3/475.short

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Is Aberrant Functional Connectivity A Psychosis Endophenotype? A Resting State Functional Magnetic Resonance Imaging Study”

Sabin Khadka et al. (doi:10.1016/j.biopsych.2013.04.024).

>

http://www.elsevier.com/about/press-releases/research-and-journals/what-is-the-brain-telling-us-about-the-diagnoses-of-schizophrenia-and-bipolar-disorder

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Regards,

Paul.

" My naturopath had the test for Pyroluria and organised the same test for her grandmother. Guess what they both had Pyroluria."

I also guess that the naturopath recommended minerals and vitamins which just happened to be on sale in that clinic. Why is it that Big Pharma gets dismissed for selling medicines to patients, when exactly the same business model is universal? For example, the 3 references just provided by Heather derive from persons or organisations with strong financial interests in selling their treatments.

About 50 years ago orthomolecular practitioners published in mainline psychiatric journals, and I still read those papers with interest. As I suspected, the recent references supplied by Heather do not incline me to look them up. One is in the orthomolecular house journal, one is an unpublished (unrefereed?) conference presentation, one is just an in-house seminar.

It is simply not true that journals are prejudiced against unconventional ideas. I have smuggled many bizarre ones into respectable journals. For example, in JAMA I asserted that persons could be revived from apparent drowning after days at the bottom of cold lakes. The reason that orthomolecular papers no longer get published in influential journals is that they are simply not good or thorough enough (they might also fail because conflict of interest is taken much more seriously nowadays).

G'day Anthony,

Long time, no see. Hope you well.

>

Wow. Cool.

Can you provide a link or doi for that article Anthony?

I'd love to add it to my collection.

Regards,

Paul.

Hi Paul. I am well, apart from an intermittently quite painful left elbow. As an Australian, you must be an expert on cricket, so do you think this could be connected with being hit by a full toss on the point of that elbow, since I carried on batting, and had no symptoms till about a month later.

M drowning piece (based on an old book I came across in the RSM library) is in JAMA 1988;260:3438 (see my pub list on RG). I don't think anyone has taken any notice at all of it, but I heard on the BBC World Service a year or two ago an interview with a Japanese man who had survived after immersion for many hours in a cold stream.

Maree,

While I do agree that the side effects of atypical anti-psychotics have negative impacts on the quality of life of many patients, people can be severely disadvantaged by taking unnecessary supplemental B group vitamins.

Treatment advice on the internet leads to a life-threatening adverse reaction: hypotension associated with Niacin overdose.

Mularski et al Clin Tox 2006

http://www.ncbi.nlm.nih.gov/pubmed/16496499

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Paul.

...Subsequently, an American team using an extensive computer search was able to locate 12 studies on B6 and magnesium for autism. Their analysis, published in 1995, concluded:

The majority of studies report a favorable response to vitamin treatment. However, interpretation of these positive findings needs to be tempered because of methodological shortcomings inherent in many of the studies. For example, a number of studies employed imprecise outcome measures, were based on small samples and possible repeat use of the same subjects in more than one study, did not adjust for regression effects in measuring improvement, and omitted collecting long-term follow-up data [6].

All 12 of these studies appear to have been written by researchers who are close associates. (One person, for example, coauthored eleven of the reports.) Each of the studies used at least 600 mg per day of vitamin B6, which is well above the minimum amount reported to cause nerve damage. So even if such doses of B6 are effective, they are probably not safe to use.

A recent randomized double-blind study found no evidence that regulating the vitamin levels of adult schizophrenics influenced the clinical status of 19 adult schizophrenic patients. The experimental group received amounts of megavitamins based on their individual serum vitamin levels plus dietary restriction based on Radioallergosorbent (RAST) tests. The control group received 25 mg vitamin C and were prescribed substances considered allergenic from the RAST test. After five months, there were marked differences in serum levels of vitamins but no consistent symptomatic or behavioral differences between the groups [7].

http://www.quackwatch.org/01QuackeryRelatedTopics/ortho.html

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Paul.

The word psychosis was introduced to the psychiatric literature in 1841 by Karl Friedrich Canstatt in his work Handbuch der Medizinischen Klinik. He used it as a shorthand for 'psychic neurosis'. At that time neurosis meant any disease of the nervous system, and Canstatt was thus referring to what was considered a psychological manifestation of brain disease. Ernst von Feuchtersleben is also widely credited as introducing the term in 1845, as an alternative to insanity and mania.

The term stems from Modern Latin psychosis, "a giving soul or life to, animating, quickening" and that from Ancient Greek ψυχή (psyche), "soul" and the suffix -ωσις (-osis), in this case "abnormal condition".

The word was also used to distinguish a condition considered a disorder of the mind, as opposed to neurosis, which was considered a disorder of the nervous system. The psychoses thus became the modern equivalent of the old notion of madness, and hence there was much debate on whether there was only one (unitary) or many forms of the new disease. One type of broad usage would later be narrowed down by Koch in 1891 to the 'psychopathic inferiorities' - later renamed abnormal personalities by Schneider.

The division of the major psychoses into manic depressive illness (now called bipolar disorder) and dementia praecox (now called schizophrenia) was made by Emil Kraepelin, who attempted to create a synthesis of the various mental disorders identified by 19th century psychiatrists, by grouping diseases together based on classification of common symptoms. Kraepelin used the term 'manic depressive insanity' to describe the whole spectrum of mood disorders, in a far wider sense than it is usually used today.

In Kraepelin's classification this would include 'unipolar' clinical depression, as well as bipolar disorder and other mood disorders such as cyclothymia. These are characterised by problems with mood control and the psychotic episodes appear associated with disturbances in mood, and patients often have periods of normal functioning between psychotic episodes even without medication. Schizophrenia is characterized by psychotic episodes that appear unrelated to disturbances in mood, and most non-medicated patients show signs of disturbance between psychotic episodes.