Breaking News! The Cause of Schizophrenia Finally Discovered!(?)

Noel Hunter, Psy.D.
36
798

On January 27, 2016, a study1 was published online in the prestigious journal Nature that touted the possibility of discovering some potential biological origins of an “illness” called “schizophrenia” (See note at the end). Subsequently, headlines across the world beamed excited proclamations of the latest breakthrough to occur in psychiatric research. Here is just a small sample of what the major media outlets were purporting:

“New study helps explain cause of schizophrenia” – CNN

“Researchers say they’re now closer than ever to understanding the science behind schizophrenia” – The New York Times

“Scientists open the ‘black box’ of schizophrenia with dramatic genetic finding” – The Washington Post

“Genetic study provides first-ever insight into biological origin of schizophrenia” – The Broad Institute of MIT and Harvard

“Schizophrenia breakthrough as genetic study reveals link to brain changes” – The Guardian

Clearly some amazing discoveries must have emerged from this groundbreaking study! The sound bites have certainly led a very large population to come to believe so. The problem is, there is nothing profound about this study at all and, in fact, it is one of the least profound studies to emerge in the last few years on the topic of “schizophrenia.” The information that has been disseminated to audiences across the globe, no doubt with the assistance of a rhetorically biased news release and included highlights, is distorted, it asserts exaggerated claims based on reductionistic conclusions, and it ignores the robust support that has accumulated that undermines the genetic disease model of “mental illness” and the categorical understanding of experiences falling under the umbrella term “schizophrenia.”

While these news reports discuss the “dramatic” “first-ever insights” and the assumed fact that scientists do not have a clue what causes “schizophrenia,” the accumulating evidence indicating an almost irrefutable causal relationship between childhood adversity and most experiences labelled psychotic gets completely disregarded. This is despite the fact that childhood adversity can actually explain the very biological “discoveries” being promoted in the first place. Additionally, many of the biological correlates associated with the category of schizophrenia are also found in persons not diagnosed as such, whether they meet criteria for another disorder or none at all, and are more generally associated with chronic stress and trauma than any discovered disease process. How can this “breakthrough” study go viral across the globe without any consideration of context or the broader literature base explaining the causal pathways of “schizophrenia”? How does this study actually fit in to greater research base?

What Are the Study Findings?

Genetic associations with “schizophrenia”

The authors’ premise for conducting the study was an association previously found between variations of the genes of the major histocompatibility complex (MHC) locus and a diagnosis of schizophrenia at the population level. What does this mean in English? It means that there was a very tiny statistical likelihood that variations of genes associated with the immune system were more prevalent in a group of individuals determined to fall into a category called schizophrenia as compared to another group not diagnosed as such. In this particular study, Sekar et al. discovered that, specifically, part of this association was explained by an increased expression of the C4 protein. This particular protein in humans is involved in a process called synaptic pruning. As stated in the New York Times article, an increase in the C4 protein is estimated to be associated with a .25 (one quarter) percent increase in the risk of meeting criteria for a diagnosis of schizophrenia in the general population.

Reduced synapses and synaptic pruning as possible causal mechanisms for schizophrenia

The theory that synaptic pruning may be defective in individuals diagnosed with schizophrenia, and therefore may explain why it tends to emerge in late adolescence, was first purported over 30 years ago by Feinberg2. Synaptic pruning refers to a process that occurs in early childhood (around ages two to four) and again in late adolescence (around the ages of 15 to 18) wherein “excess” neural synapses, or connections, are eliminated in the brain. There is some evidence that individuals who are diagnosed with schizophrenia tend to have reduced neural connections in the brain. The Feinberg hypothesis asserts that this may be explained by a faulty process that occurs during this synaptic pruning in adolescence that is likely genetic in origin.

Due to lack of evidence at that time, this hypothesis was largely ignored, until it was revisited3 10 years later during the “decade of the brain.” It was believed that a specific errant process of synaptic pruning may underlie schizophrenia wherein there is an excessive elimination of neural connections, specifically in the prefrontal cortex. This means that there is less activity in the area of the brain associated with decision making, problem-solving, rational thought, and attention. The prefrontal cortex has been shown fairly frequently to have decreased activity and decreased neural connections in individuals experiencing so-called psychotic phenomena.

The Feinberg hypothesis of excessive synaptic pruning emerging from some illness process is still an unproven hypothesis, but is indirectly supported by the evidence demonstrating the deceased connections and activities in the prefrontal cortex of some individuals diagnosed with schizophrenia. The Sekar et al. study was based upon trying to help explain how, if this hypothesis is true, the process might be explained. The study did not prove this hypothesis, nor did it develop the hypothesis; it simply gave some evidence of how this process might be explained at a biological level if it is, in actuality, true. The study also did not “help explain [the] cause of schizophrenia,” as purported by CNN; it simply provided some possible evidence of a biological correlate that exists in a small number of individuals diagnosed with schizophrenia that may underlie a hypothesized process that may exist in some individuals diagnosed with schizophrenia. This is breaking “dramatic” news?

The Bigger Picture

Taken at face value, if there is, in fact, a greater number of C4 protein and variations of the genes in the MHC locus in some individuals diagnosed with schizophrenia than in the general population, and this explains a hypothesized excessive pruning process that occurs in adolescence, then what might really be going on? Remember, this study (and most others like it) have found a biological correlate associated with a small number of individuals fitting into a particular category called schizophrenia. This does not necessarily mean that there is a causal relationship or that an actual illness process is occurring. As I write this, my brain is demonstrating many biological correlates in activity, including an increased stress response. As you read this, your brain is demonstrating a very different biological correlate that may or may not also have an associated stress response. Just because there is a difference in brain biology, and just because there is an associated stress response, this does not mean that an illness is in place, nor does it prove that either of us is “mentally ill.”

Looking at the broader scientific literature, it is clear that there are certain biological correlates associated with a diagnosis of schizophrenia at the group level. But, this does not tell us much of anything beyond the fact that the brain and body are demonstrating a different physiology than those who are not in such extreme distress. This is to be expected. However, these associations are also evident in other major DSM-defined diagnostic categories, including posttraumatic stress disorder. Most problems that get labelled as mental illness emerge in adolescence as well, and synaptic pruning has been suggested as one major reason for this across diagnostic categories6. In other words, what we seem to be looking at are physiological and neurological responses to difficult life experiences that are correlated with varying manifestations of distress, emotional pain, and socially unacceptable behaviors.

How does all of this relate to the Sekar et al. study?

The Immune System

The immune system, inflammation, and schizophrenia

Recall that the genetic variations found in this study, and previous studies, to be minutely associated with schizophrenia are those genes that are also associated with the immune system. C4 proteins, those found to be increased for those with “schizophrenia” in the Sekar et al. study, work within the immune system, in part, by responding with inflammation in order to protect the body. In general, when the immune system responds to a perceived injury or infection, inflammation is the result. Abnormalities in C4 are associated with various autoimmune diseases, such as lupus, kidney diseases, and even alcoholic liver disease (they did not, as far as I can tell, account for the potential confound of alcoholism, by the way).

Interestingly, an unbalanced immune response and a slight inflammatory process of the central nervous system have been associated with individuals diagnosed with schizophrenia4. Because of the discovery of a higher than normal immune cell activity in the brains of those diagnosed with, or considered at risk of, schizophrenia, it has been suggested that early anti-inflammatory treatments might prove an invaluable treatment intervention5. So, the idea that the immune system may be faulty in some individuals diagnosed with schizophrenia is not surprising. Nor is it surprising that genes associated with immune system may demonstrate some variation in individuals diagnosed with schizophrenia. However, this does not mean that C4 abnormalities or inflammatory responses cause some disease called schizophrenia. It may be that some individuals experiencing a psychotic reaction are suffering the direct results of an autoimmune reaction targeting the neuronal structure of the brain. This is the case with encephalitis. Of course, we call this disease of inflammation in the brain encephalitis not schizophrenia. It is understood that they are at least two entirely different problems.

It is also entirely possible (and not even considered in these studies) that behaviors and experiences associated with the diagnosis of schizophrenia are interconnected with an immune response that are all, or partially, resulting from some other source. In fact, the increased response of the C4 genetic proteins and other variations found may be entirely the result of emotional breakdown rather than the cause. Genes are not determinants of most human behavior or experience. Genes are affected by the environment and may get “turned on” by events within the environment, such as pollution, viruses, psychological trauma, and other acquired experiences. The statement by Sekar et al. that “schizophrenia is a heritable brain illness” is a rhetorical declaration that has not been proven, and there are numerous refutations of the research upon which such assertions have been made7, 8. This is an important point to make because genetic variation does NOT equate with genetic (or inherited) disease. And, brain differences do NOT equate with brain disease. Genetic and brain variations can easily arise from environmental events; first, however, one needs to set aside the assumption that “schizophrenia” is a genetic disease and examine the evidence as a whole.

The immune system, trauma, and autoimmune problems

When the immune system becomes faulty, especially over time, tissue damage may ensue. Autoimmune diseases, such as rheumatoid arthritis, are actually inflammatory disorders that occur when an organ, tissue, or internal system is damaged by the immune response. C-reactive protein (CRP) is a biomarker of inflammation that is also involved in the regulation of the complement system9, which includes the C4 protein measured by Sekar et al. In 2007, Danese et al.10 published a study demonstrating that childhood adversity is associated with increased CRP levels in adults 20 years after the experience of trauma. In fact, childhood trauma has been found to be independently associated with autoimmune diseases (including rheumatoid arthritis11 and chronic fatigue syndrome12) later in life, in part through the process of inflammatory and neuroendocrine responses.

There may be some value in considering the Sekar et al. findings in terms of some forms of psychosis being the result of an autoimmune disorder resulting from childhood trauma. The relationships of childhood adversity and “schizophrenia,” and the problems in ignoring this relationship, will be discussed shortly, but the point to be made here is that no such possibilities were raised. Rather, there was some discussion about “schizophrenia” being an autoimmune disorder caused by a genetic abnormality, despite the fact that not ALL people diagnosed with this disorder demonstrate an inflammatory response, not ALL demonstrate predictable physiological differences of any kind, and that genetics (or more correctly, epigenetics) may simply be a mediating factor wherein something in the environment (i.e., childhood adversity) may actually be the cause.

Synaptic Pruning

Synaptic pruning, as stated previously, is a normal process that occurs in all humans during two different periods of life: early childhood and adolescence. There is large variation in the amount of pruning that occurs, particularly across genders6. The process basically consists of eliminating connections in the brain that are redundant or unused. So, if one is isolated, depressed, and uncared for, areas of the brain associated with empathy, socialization, and executive functioning are likely to be eliminated. Although surely there is some function of genetic determinism in the selection of synapses to eliminate, this is not proven and the environment and one’s lifestyle appear to be much more prudent factors in this regard.

The Feinberg hypothesis, which is the basis upon which the Sekar et al. study and their conclusions are based, purports that “schizophrenia” results from an excess of synaptic pruning in the prefrontal cortex. Yet, it has been found that stress and trauma, especially when experienced during adolescence, can result in decreased synaptic density in the prefrontal cortex and these changes can endure into adulthood13. In other words, one cannot differentiate if decreased synapses in the prefrontal cortex are the result of trauma and childhood adversity or if they are the result of some theoretical disease process called “schizophrenia.”

Trauma and Psychosis

Recently, another study was published regarding “schizophrenia” that did not go viral through the media, but, some (i.e., me) might argue, should have. Anjnakina et al.14 built on several other recent studies to demonstrate specificity of childhood adversity and psychotic experiences as an adult. A robust association was found between childhood adversity, most notably childhood sexual abuse, and delusions and hallucinations. In a previous study, Bentall et al.15 found that bullying had a specific relationship with paranoia. Perhaps most importantly to the Sekar et al. study is the finding that being taken into custody (i.e., foster care, juvenile justice) as a child was associated directly and robustly with an “excited” dimension of psychosis, characterized by hostility, lack of impulse control and uncooperativeness. This builds on previous research demonstrating that children who experience abuse that comes to the attention of social services are more likely to behave in antisocial and impulsive ways.16 These traits are often associated with decreased activity in the prefrontal cortex.

In a very different tone than that of “schizophrenia is a destructive, inherited brain disease,” Anjnakina et al. state at the top of their article “The relationship between childhood adversity and psychotic disorder is well documented.” Indeed, this is true. There is not enough room here to begin to do the vast amount of literature justice, but I will provide just a few key resources. Read et al.17 concluded in 2005 that child abuse is a causal factor in “schizophrenia.” Read et al.18, after identifying similarities in the brains of traumatized children and adults who were diagnosed with schizophrenia, demonstrated the neurodevelopmental pathways through which childhood adversity may cause psychosis. In 2004, Janssen et al.19 established a strong dose-response relationship between childhood abuse and psychosis after following 4045 individuals from the general population for two years. Bentall et al.15 also found a dose-response relationship between childhood abuse and psychosis (meaning that the greater number of adverse experiences and/or the higher the severity, the greater the risk), wherein those who had a high-severity of childhood abuse were 48.4 times more likely to develop psychosis as an adult.  When specificity and dose-response relationships are demonstrated, a causal relationship is strongly probable. In fact, Bentall et al.15 stated that “experiencing multiple childhood traumas appears to give approximately the same risk of developing psychosis as smoking does for developing lung cancer.” And, lastly, in the same month as the Sekar study was released (January 2016), so too was a nationwide cohort study out of Denmark and Sweden20 which found that experiencing the death of a first-degree relative before 18 years of age, especially from suicide or accident, resulted in a 39% increased risk of being diagnosed with schizophrenia.

Yet, the media screams from the proverbial rooftops the “dramatic” findings that a genetic variant has shown there to be an estimated increase of .25% in the risk of “schizophrenia”? How does this happen? I can surmise many reasons, including corporate and guild interests and financial resources, but at the end of the day no one likes to hear about the bad things that exist in the world. Sadly, as a result, those who are unfortunate enough to live with oppression, social isolation, poverty, institutionalization, and/or child abuse find that when they turn for help, their traumatic experiences are rendered meaningless, their response to the trauma is reduced to a “brain disease” that was probably risen from some defective genes in the first place, and “help” consists of further traumatization and isolation and promises of a better life through a pill. This is, at this point, unjustifiable.

To Sum Up

It may seem after reading this that the Sekar et al. study has, indeed, given us some useful findings in understanding the pathophysiological mechanisms behind the psychotic experience for some people. This would be correct as far as academic gratification is concerned. Inflammation is at the root of most modern diseases, and dietary changes, exercise, and psychotherapy have proven invaluable in treating such conditions. It is a positive step forward to consider the healing effects of anti-inflammatory changes in diet and lifestyle.

The conclusions and recommended possible clinical responses suggested by Sekar et al, however,  are dangerously reminiscent of some Orwellian terror. Shall we really entertain the idea that it might be useful to mess around with the brain as it develops and changes over time through invasive chemical or other biological interventions? Does anybody have a clue what Frankenstein result may come out of such actions? Are we supposed to start genetically manipulating people because of a barely noticeable increased risk of a category of disease that is not even valid or reliable in the first place? There is a strong association of “mental illness” and creativity; are we to rid the world of innovation and creation? This may reek of hyperbole, but if there is even a small chance of such outcomes is it worth it? Have we not learned from previous experience that just because those in power say something is so, or even that it is helpful, that this means it’s true?

We keep hearing about how wonderful modern Western mental healthcare is…if that were the case why did the World Health Organization find that countries who did not adopt our paradigm of “care” (i.e., “undeveloped” countries) had better outcomes21, 22 only to find that 30 years later, after adoption of that very paradigm, outcomes are no better than they are here? If our treatment paradigm was so “advanced,” then why have disability rates and rates of illness continued to climb year after year, even as non-mental illnesses have decreased?23

What if, instead, we tried to decrease poverty, inequality, racism, and child abuse? What if that? What if we paid heed to more humane interventions that allow for the variety of human experience (for instance, the Hearing Voices Network, Soteria, Open Dialogue, etc. ) and helped people to feel less isolated, more secure, and empowered to find meaning in life, as those who have personal experience with such experiences have asked for? What if we listened to those who have been there instead of telling them what they should or should not find helpful? What if we considered the whole person instead of reducing them to cells in a brain? These would be silly suggestions for someone facing a genetic brain disease. But, for someone experiencing the natural result of overwhelming life experiences, perhaps they are not. Will the media pay attention to this before it’s too late?

Note: The category of “schizophrenia” has been determined to lack validity and reliability as a diagnostic category and does not have any predictive value, and this is agreed upon even by the most preeminent experts in mental health research. In order to argue the points as they have been put forth in the media, and as they exist in the research, this subject was not argued here for purposes of brevity. 

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References:

1. Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N.,…& McCarroll, S. A. (2016). Schizophrenia risk from complex variation of complement component 4. Nature. doi:10.1038/nature16549

2. Feinberg, I. (1983). Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence? Journal of Psychiatric Research, 17(4), 319-334.

3. Keshavan, M. S., Anderson, S., Pettergrew, J. W. (1994). Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? The Feinberg hypothesis revisited. Journal of Psychiatric Research, 28(3), 239-265.

4. Muller, N., Myint, A. M., Schwarz, M. J. (2012). Inflammation in schizophrenia. Advances in Protein Chemistry and Structural Biology, 88, 49-68.

5. Bloomfield, P. S., Selvaraj, S., Veronese, M., Rizzo, G., Bertoldo, A., Owen, D. R.,…& Howes, O. D. (2015). Microglial activity in people at ultra high risk of psychosis and in schizophrenia: An [11C]PBR28 PET brain imaging study. The American Journal of Psychiatry, 173(1), 44-52.

6. Paus, T., Keshavan, M., Giedd, J. N. (2008). Why do many psychiatric disorders emerge during adolescence? Nature Reviews: Neuroscience, 9, 947-957.

7. Joseph, J. (2015). The trouble with twin studies: A reassessment of twin research in the social and behavioral sciences. New York: Routledge.

8. Ross, C. A., & Pam, A. (1995). Pseudoscience in biological psychiatry: Blaming the body. New York: John Wiley & Sons.

9. Pepys, M. B., & Hirschfield, G. M. (2003). C-reactive protein: A critical update. Journal of Clinical Investigation,111, 1805-1812.

10. Danese, A., Pariante, C. M., Caspie, A., Taylor, A., & Poulton, R. (2007). Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences, 104, 1319-1324.

11. Dube, S. R., Fairweather, D., Pearson, W. S., Felitti, V. J., Anda, R. F., & Croft, J. B. (2009). Cumulative childhood stress and autoimmune diseases in adults. Psychosomatic Medicine, 71(2), 243-250.

12. Heim, C., Nater, U. M., Maloney, E., Boneva R., Jones, J. F., & Reeves, W. C. (2009). Childhood trauma and risk for chronic fatigue syndrome. Archives of General Psychiatry, 66(1), 72-80.

13. Leussis, M. P., Lawson, K., Stone, K., & Andersen, S. L. (2007). The enduring effects of an adolescent social stressor on synaptic density, Part II: Poststress reversal of synaptic loss in the cortex by Adinazolam and MK-801. Synapse, 62, 185-192.

14. Ajnakina, O., Trotta, A., Oakley-Hannibal, E., Di Forti, M., Stilo, S. A., Kolliakou, A.,…& Pariante, C. (2016). Impact of childhood adversities on specific symptom dimensions in first-episode psychosis. Psychological Medicine, 46(2), 317-326.

15. Bentall, R., Wickham, S., Shevlin, M., & Varese, F. (2012). Do specific early-life adversities lead to specific symptoms of psychosis? A study. Schizophrenia Bulletin, 38, 734-740.

16. Cohen, P., Brown, J., & Smaile, E. (2001). Child abuse and neglect and the development of mental disorders in the general population. Development and Psychopathology, 13, 981-999.

17. Read, J., van Os, J., Morrison, A. P., & Ross, C. A. (2005). Childhood trauma, psychosis, and schizophrenia: A literature review with theoretical and clinical implications. Acta Psychiatrica Scandinavica, 112, 330-350.

18. Read, J., Fosse, R., Moskowitz, A., & Perry, B. (2014). The traumagenic neurodevelopmental model of psychosis revisited. Neuropsychiatry, 4(1), 65-79.

19. Janssen, I., Krabbendam, L., Bak, M., Hanssen, M., Vollebergh, W., de Graaf, R., & van Os, J. (2004). Childhood abuse as a risk factor for psychotic experiences. Acta Psychiatrica Scandinavica, 109, 38-45.

20. Liang, H., Olsen, J., Yuan, W., Cnattingus, S., Vestergaard, M., Obel, C., Gissler, M., & Li, J. (2016). Early life bereavement and schizophrenia: A nationwide cohort study in Denmark and Sweden. Medicine, 3. Doi: 10.1097/MD. 0000000000002434.

21. de Girolamo, G. (1996). WHO studies on schizophrenia. The Psychotherapy Patient, 9, 213-231.

22. Jablensky, A., & Sartorius, N. (2008). What did the WHO studies really find? Schizophrenia Bulletin, 34(2), 253-255.

23. Viola, S., & Moncrieff, J. (2016). Claims for sickness and disability benefits owing to mental disorders in the UK: Trends from 1995 to 2014. BJPsych Open, 2, 18-24. Doi: 10.1192/bjpo.bp.115.002246.

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(A version of this article was originally posted on the website for the International Society for Ethical Psychology & Psychiatry.
It has been reprinted here with the author’s permission)

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36 COMMENTS

  1. Here are adapted excerpts from a letter I sent to four of the principal authors behind this research:
    ————–

    Dear Professors Stevens, McCarroll, Barondes, and Lander,

    I’m a member of the organization ISPS (the International Society for Psychological and Social Approaches to Schizophrenia, http://www.isps.org) and also a person who was once diagnosed with schizophrenia but fully recovered.

    I am emailing you because I wanted to give you a window into our group’s discussion of this research. I thought you would find it interesting and perhaps useful. Below, I have put a long comment from our listserv that I placed there today. I expect you may find it disturbing and challenging to read (and I apologize, do not take my critique personally; it is possible that Benedict Carey oversimplified or miscommunicated some of your findings) – but I encourage you to read through it because it may broaden your perspective about schizophrenia in an eye-opening way.

    Lastly, I’d like to also share with you some of our research into psychosocial approaches for psychotic states and schizophrenia. Some of the best psychosocial approaches to “schizophrenia” have been able to return about 80% of first episode-psychotic schizophrenic youth to full engagement with work and relationships, usually with no or minimal remaining psychotic symptoms. The recent RAISE, EASA, and PREP trials actually adopted significant aspects of the models we pioneered. However, this work, particularly the Open Dialogue approach and the 388 program, is little known in the United States due to the dominance of the biological model. Here’s a look:

    The Open Dialogue Approach to Schizophrenia:

    http://www.taosinstitute.net/Websites/taos/Images/ResourcesManuscripts/seikkula-OpenDialoguesWithGoodAndPoorOutcomes.pdf

    http://psychrights.org/Research/Digest/Effective/fiveyarocpsychotherapyresearch.pdf

    The 388 Program, A New Perspective for Treating Schizophrenics

    https://www.youtube.com/watch?v=mmqT-4W4Cvg
    Individual Psychotherapy for Schizophrenia, Lewis Madrona’s Approach

    http://www.transpersonalstudies.org/ImagesRepository/ijts/Downloads/IJTS_33-1-07_pp_57-76_Mehl-Madrona_et_al_2014_Results_of_a_Transpersonal_Narrative_and_Phenomenological_Psychotherapy_for_Psychosis.pdf

    Gottdiener’s Meta-analysis of Psychotherapy for Schizophrenia

    http://psychrights.org/Research/Digest/Effective/BGSchizophreniaMeta-Analysis.htm
    ————————————
    (My own comment on ISPS listserv)

    I would like to offer a detailed critique of the Benedict Carey article reporting progress in discovering the “Cause of Schizophrenia” of January 27

    (http://mobile.nytimes.com/2016/01/28/health/schizophrenia-cause-synaptic-pruning-brain-psychiatry.html?hp&action=click&pgtype=Homepage&clickSource=story-heading&module=second-column-region%c2%aeion=top-news&WT.nav=top-news&referer=&_r=0)

    I took some time this morning to cut out quotes from the article and offer my responses. These are my opinions:

    “(Scientists have) taken a significant step toward understanding the cause of schizophrenia”

    Response: I cannot say it better than Brian K: “There is no entity called “schizophrenia.” It is a syndrome and heterogeneous. The New York Times article “Scientists Home in on Cause of Schizophrenia,” is misleading in its title. It is not a single category (nature is not “carved at her joints” and our genomes did not evolve to reify DSM categories), nor is there one “cause.” The research is correlational not causal.”

    “insight into the biology behind any common psychiatric disorders”

    This phrase presumes that psychiatric disorders are valid, reliable medical classifications. This is false: Mary Boyle, Richard Bentall, Jeffrey Poland, Paula Caplan, Stuart Kirk, and others have argued convincingly that these labels do not represent discrete entities that can be reliably identified by different outside observers. Therefore the “scientific” research on them is not truly scientific.

    “drugs… blunt some of (schizophrenia’s) symptoms but do not touch the underlying cause.”

    This mistakenly assumes there is one” cause of “schizophrenia” or psychotic states. But the research from the Adverse Childhood Experiences study, from John Read, etc. strongly implies that there are many complex causes that can lead to psychotic states (“schizophrenia”) in different combinations. For example, incest, child abuse, social isolation, illicit drug use, lack of sleep, all could lead to psychotic states of different kinds that get labeled “schizophrenia.”

    “why the disorder often begins in adolescence of young adulthood” – This is because psychosis is probably not primarily an illness caused by biology, but primarily a social-psychological-experiential reaction to the world that is expressed in biology. The biggest risk period for vulnerable people is when they are in their teens or 20s when their parenting/social support is not adequate for the task of moving into adulthood and becoming independent. If they are overwhelmed by this transition, psychosis may result.

    “provided researchers with their first handle on schizophrenia”

    Again this mistakenly assumes that there is one reliable discrete entity called schizophrenia, that can be caught, like a fly in amber. But this is an illusion…

    “That risk (of developing “schizophrenia”, another misleading description) is tied to a natural process called synaptic pruning, in which the brain sheds weak or redundant neurons as it matures…People who carry genes that accelerate or intensify that pruning are at higher risk of developing schizophrenia than those who do not, the new study suggests.”

    I will quote Brian K’s wise words at length again:

    “The increased expression of the complement C4A gene may be associated with other processes. First, it is important to rule out confounds like antipsychotic use. APs have effects on our immune system. There are dopamine receptors on immune cells. The MHC (major histocompatibility complex), referred to in the article is involved in cell-mediated immunity-MHC proteins bind viral or bacterial coat proteins, take the peptides to the cell surface where they can be killed by cytotoxic lymphocytes (which stops the cell from being a host to viral replication). There is a great deal of research being done on the role of neuroinflammatory processes (e.g., microglia) in psychosis, depression, etc.

    Second, one must search for other correlations. In regard to the latter, Bronikowski et al (2002) found that inflammatory and stress response genes were most affected by physical inactivity and age. Twenty one inflammatory response genes were upregulated (increased) by age in a sedentary group, including complement C4 (which is invloved in immune function). I wonder if loneliness (and other chronic stressors) also can play a role, since it has significant effects on immune function. The NY Times article neglected to refer to the myriad of social factors demonstrated to play a role in the diagnosis, onset, course and outcome of “schizophrenia,” e.g., urban birth/living, migration, social defeat/social isolation, expressed emotion and communication deviance, childhood maltreatment, etc.”

    I think it is particularly important to note that this article said absolutely nothing about childhood abuse and social isolation as causes of receiving a schizophrenia diagnosis. The ACE Research and John Read’s research implies that these factors are often much more important than any genetic contribution. Understanding these factors does not have to mean blaming the parents or the individual. Further, I wonder whether these researchers are using a model that is truly epigenetic and interactional, i.e. appreciating how much genes are modified by environment/experience after birth. Again, in this context the monolithic construct of schizophrenia is outdated and due for abolition.

    “any step forward is not only rare and unusual, it’s just one step in a journey of a thousand miles” to improved treatments.”

    This implies a narrative of gradual progress at improving treatments (and presumably outcomes) for people labeled schizophrenia. But that is a false narrative. The latest meta-analysis from Jaaskelainen (2013) clearly shows that outcomes for people labeled schizophrenic have been gradually worsening in recent decades, for both symptomatic and functional outcomes. Thus the continued biological and genetic research is not enabling a gradual movement forward to improved treatments. The narrative of psychiatry and schizophrenia is not one of progress and improvement, but one of increasing failure and chronicity.

    “Some researchers had suspected that the pruning must somehow go awry in people with schizophrenia, because previous studies showed that their prefrontal areas tended to have a diminished number of neural connections, compared with those of unaffected people.”

    Again, this research is only correlational, not causal, and suffers severely from the lack of validity of the concept schizophrenia. The researchers also neglect the possibility that adverse environmental experience (e.g. loneliness, abuse) could be the primary (epigenetic) influence driving the process of accelerated pruning.

    “(this research) identifies the genes responsible (for accelerated pruning)”

    This research appears to be reductionistically viewing genes, in a pre-epigenetic way, as isolated actors which “do things” to people’s development. But genes do nothing without environmental input and interaction. So the possibility remains that the real link could be to the environmental experiences and interactions that are driving those genes to prune the neurons faster.

    “provides a showcase of biomedical investigation at its highest level.”

    Perhaps it would be more accurate to say that they are investigating a disease which has not been proven to exist as a discrete entity, and which may well have no one clear biomedical cause, in one way of understanding.

    “speculation that schizophrenia might be a kind of autoimmune condition, in which the body attacked its own cells.”

    It is incredible that this type of possibility is still seriously considered, in light of, 1) The lack of validity and reliability for labels such as schizophrenia, 2) The strong research that John Read has catalogued linking trauma to being diagnosed with schizophrenia. It speaks to the strong distorting influence that the drug companies’ money have on research and inadvertently on the minds of researchers.

    “C4-A could mean too much pruning — which would explain not only the thinner prefrontal layers in schizophrenia, but also the reason that the disorder most often shows itself in people’s teenage years or early twenties.”

    Like Brian, I am not purely or irrationally against genetic research. I think it’s possible that the overactive C4-A gene could confer a slightly increased risk for being overwhelmed by the stresses of life, all other factors being equal (in the statistical, aggregate sense). But that is very different from saying “this gene drives risk for schizophrenia.” Someone having an overactive version of this gene might never become psychotic due to other ameliorating factors. If I understand it right genes do not operate autonomously, but in concert with environmental influences which in turn can modify them throughout life. Further, it’s quite likely that this gene (and genes in general) might confer only a tiny percentage of the risk of “getting labeled with schizophrenia” (which is all it is, schizophrenia is not an illness someone has, but a label someone is given). Environmental-experiential factors may make up a far larger proportion of the risk of being so labeled, given the limitations of twin studies that Jay Joseph and Jonathan Leo have exposed (i.e. the notion that schizophrenia is 70 or 80% genetic is a myth; Brian Koehler is also working on a new model of this research).

    “Having such a variant, Dr. McCarroll estimates, would increase a person’s risk by about 25 percent over the 1 percent base rate of schizophrenia — that is, to 1.25 percent.”

    This is an admission of how small the influence of any one gene or group of genes is likely to be, and why genetic research into “schizophrenia” is unlikely to ever yield significantly improved outcomes, given the complexity involved in genetic-environmental interaction. Further, this sentence mistakenly assumes that there is a “1 percent base rate of schizophrenia”. But that is not a reliable average – “schizophrenia” is more common among poor people, certain ethnic groups, in inner cities, in certain developed countries, etc.

    “That is not nearly enough to justify testing in the general population,”

    Again, there would be little point to such testing because schizophrenia is not one coherent entity that can be reliably identified.

    “The researchers hope that the at-risk genetic profile, once it has been fleshed out more completely, will lead to the discovery of biomarkers that could help clarify a prognosis in these people.”

    This appears to me to be similar to the hopes of developing cold fusion or gold alchemy. The genetic environmental interaction that leads to individual psychotic states of greater or lesser severity is too complex to be reduced reliably to biomarkers, I think.

    “Developing a drug to slow or modulate pruning poses another kind of challenge.”

    Such a drug would probably not work because pruning must be subject to myriad internal and external genetic and environmental factors; I cannot imagine a pill that could precisely influence such a process, effectively reversing human pathological mind-body development from a biological level. Such a pill would almost have to be a “reverse time travel” pill or an “entire environment influence” pill that would do what human/environmental/biological curative influences together can do. Mind boggling.

    “But I’m not ready to call it a victory until we have something that can help patients.”

    I do not feel very optimistic about this, and would note that very effective social-psychological approaches that work such as Open Dialogue, 388, and intensive psychodynamic psychotherapy for schizophrenia already exist.

    As Noel said, it is sad to see that strong research on trauma, abuse, and social influences contributing to “schizophrenia” (below) is totally ignored while this research, which is actually very weak in its effect size and embryonic in its stage of development (if it ever progresses further), gets highlighted.

    https://www.researchgate.net/publication/282043036_Impact_of_childhood_adversities_on_specific_symptom_dimensions_in_first-episode_psychosis

    Furthermore, biological-genetic research continues to correlate with increasing rates of psychiatric disability:

    https://www.madinamerica.com/2016/01/what-disability-benefit-trends-tell-us-about-psychiatric-treatments-and-the-economy/

    Feel free to comment on any of these opinions.
    ——————–

    • So far three out of the four authors ignored my email, with a fourth answering, to his credit, in a polite way, but saying simply that he felt and hoped that this research would eventually yield “Measurable improvement in outcomes”. To which I say, good luck with that.

      It is telling that these researchers who are lauded so highly in the media cannot answer or logically engage with well-informed critics who questiontheir research. This speaks to something I have repeatedly observed with research psychiatrists: when it comes to their “research” they are extremely vulnerable, fragile, and britle to the point of almost immediately using the defenses of avoidance, denial, and sometimes projection. These non-responses occur when the validity of their diagnoses, the efficacy of neuroleptics, and the potential value of genetic-biological approaches are questioned.

      It can’t feel good to be a “professional” in a field like psychiatry where one is so insecure, so vulnerable, and so unable to answer criticisms, that one has to hide from critics in this way. It actually gives us as critics a lot of power and the ability to tell the public a different story.

      Because people like me know that their diagnoses are fraudulent, their researchis based on egregious distortions about how human emotional development works, and their treatments mostly ineffective and harmful for vulnerable psychotic people. It is only by misleading the public and the press that research psychiatrists are able to hold onto their jobs and stay in a position of power. It is time to begin to undermine and expose them in a more rigorous way, something for which I have specific plans over the next couple of years.

  2. Noel, I have to say, that was impressive! Your grasp of both the issues and the research is obvious, and your writing style allows the lay reader to understand the research without being bogged down in technicalities. And you make SO much sense! Thanks for sharing this – I hope it can be published elsewhere as well, as it is a remarkable review of the data as well as an overdue critique of the media habit of trumpeting almost trivial results as if they were earth-shattering.

    Well done!

    —- Steve

  3. Noel,

    Thank you for your thoughtful and scholarly article. I am unclear about what point you were trying to make in the paragraph below and was surprised that you described the behaviors as being suggestive of traits.

    Recently, another study was published regarding “schizophrenia” that did not go viral through the media, but, some (i.e., me) might argue, should have. Anjnakina et al.14 built on several other recent studies to demonstrate specificity of childhood adversity and psychotic experiences as an adult. A robust association was found between childhood adversity, most notably childhood sexual abuse, and delusions and hallucinations. In a previous study, Bentall et al.15 found that bullying had a specific relationship with paranoia. Perhaps most importantly to the Sekar et al. study is the finding that being taken into custody (i.e., foster care, juvenile justice) as a child was associated directly and robustly with an “excited” dimension of psychosis, characterized by hostility, lack of impulse control and uncooperativeness. This builds on previous research demonstrating that children who experience abuse that comes to the attention of social services are more likely to behave in antisocial and impulsive ways.16 These traits are often associated with decreased activity in the prefrontal cortex.

  4. Mr. McCrea is right. You could show those hacks at the NY Times a thing or two about how to examine and summarize research. Science is not my forte, but you’ve given me some new talking points to use when I speak out against psychiatry’s “bio-bio-bio” model. This article was fantastic! Thanks a million, Ms. Hunter!

  5. Noel,

    Thank you for your skilled assessment, and your exposure of media insight.

    I know I asked for psychotherapy when I went into hospital and not drug treatments. Eventually I came off the drugs and got well through psychotherapy. As far as I’m concerned recovery can start at any time; and I don’t at all believe in “schizophrenia” .

  6. Thanks for the blog, Noel, I always enjoy your blogs, very insightful. I, too, hope you try to at least get part of this, or a synopsized version, published in the opinion page of the NYT, since the “other side” was so prominently displayed.

    And I’d like to point out that it is not only child abuse, or ACEs, that can result in a “psychosis” diagnosis, but also denial, and concerns of the abuse, of one’s child. And that goes for a person who’d previously led a “semi-charmed life.”

    And the reason this is so, is because today’s “gold standard” treatment for “psychosis,” the neuroleptics can, in fact, create both the negative and positive symptoms of “schizophrenia.” And these are almost always misdiagnosed by doctors. Since neither neuroleptic induced deficit syndrome, which causes the negative symptoms of “schizophrenia.” Nor the central symptoms of neuroleptic induced anticholinergic intoxication syndrome, which mimics the positive symptoms of “schizophrenia,” is included in the DSM as possible causes of “psychosis” or the other symptoms of “schizophrenia.”

    Not to mention, the current drug cocktail treatment recommendations for “bipolar,” are, in fact, a recipe for how to make a person “mad as a hatter,” via anticholinergic toxidrome.

    I’m quite certain the reason that 2/3’s of all so called “schizophrenics” today are child abuse or ACEs survivors. Is because these child abuse victims likely had their symptoms of distress misdiagnosed as “psychosis.” And then psychiatrists created either, or both, the negative symptoms of “schizophrenia” in these patients, via neuroleptic induced deficit syndrome, or the positive symptoms of “schizophrenia,” via neuroleptic or poly pharmacy induced anticholinergic toxidrome.

    No doubt, the last thing in the world the psychiatric community wants to confess, is that psychiatrists do cover up child abuse, for profit. But this reality was confessed to me by an ethical pastor to be “the dirty little secret of the two original educated professions.” The psychiatrists have been covering up child abuse for the religions for likely centuries, since witch hunting, went out of fashion. And they also cover up easily recognized iatrogenesis for the incompetent and paranoid of a malpractice doctors, too. This likely comprises at least a part of the remaining 1/3 of all “schizophrenics.”

    Which means it is possible almost all “schizophrenia” is a completely iatrogenic illness. Although, no doubt, “psychosis” can be created in lots of ways, so I do believe “psychosis” does exist. But today, claims of “psychosis,” merely represent a psychiatrist claiming a patient’s real life concerns are “psychosis,” with zero proof the patient’s concerns are invalid, whatsoever. Absolutely, this needs to end. Thanks again for speaking the truth.

    • I agree completely, “Someone Else”, and I’m living proof of the TRUTH you speak.
      You just do a better job writing the TRUTH in more clinical-sounding words than I do!
      I still like to say that “schizophrenia” is exactly as “real” as a present from Santa Claus – but
      not more real…..Think about it! And THANK-YOU!

  7. My question is could the synaptic over-pruning be related to neuroleptic drugs given for people with schizophrenic diagnoses? In order to rule out such a possibility they would need the brains of people with “schizophrenic” symptoms who were not medicated or given ECT to compare with the other brains. Maybe they did such a thing, but psychiatry is notorious for proving only what they want to prove–at the expense of scientific inquiry and openness and honesty.

  8. This is the sort of thing that happens when you try to treat a syndrome like it was an independent disease. I’d be surprised if you did get coherent results. There are biological correlates to some of the schizophrenias, such as- resistance to viruses, resistance to shock, partial immunity to some cancers (if not on antipsychotic medications) and strong immunity to lung cancer (a population of 90%+ heavy smokers, 1 in 3000 or so who’ll get lung cancer). I’ve never noticed the orthodox experimental psychiatric community come up with explanations for this, though Hoffer and Osmond mentioned it 50 years ago in their first psychiatric self-help book, How to Live With Schizophrenia.

  9. Thank you Noel!
    I read the “breakthrough” headlines on the front page of the Toronto Star, and was wondering if (when?) someone from MadinAmerica might shed some light on the subject. I’ve been reading MIA weekly since it’s launch, and yours might be the best article ever.
    Tremendous work!
    Sean

  10. This is a great, articulate article; thank you for your community service.

    I have read about biological breakthroughs for understanding schizophrenia for forty years; none have been replicated over time. It is frustrating that science writers have no memory of the history of past failed promises to temper enthusiasm for pills to correct natural mental distress.

    I thought that heredity theory proves that schizophrenia cannot be an inherited problem because it does not “breed true.” With the low reproductive rate of people diagnosed with “schizophrenia” (20%), I understood that any heredity component would breed out of existence after a few generations.

    Thanks again for this article, Steve

  11. Thanks Noel, for your excellent response to the hype around that study. Your thinking seems very clear, and it’s so sad to say that this sort of thinking is still rare!

    I had been working on a post about this same subject, I won’t post it to MIA because I think it mostly just covers the same ground in a less thorough fashion, but some of you might want to check it out, it’s “”Schizophrenia Breakthrough” – Or a Case of Ignoring the Most Important Evidence?” at
    http://isps-us.org/blog/

    One thing I touch on in that article is to point out that the NIMH is still pretending it is “unknown” what kind of psychosocial events might contribute to a later schizophrenia diagnosis – despite everything we know about childhood adversity and psychosis! It’s a scandal on the scale of the Catholic church hiding the facts about sexual abuse by priests!

    • Ron, you & your group might be well-positioned to do some research here….
      I’ll bet, that to the extent the data exists, those persons who were abused by priests have a rate of “psychiatric diagnosis” that is FAR above what would be expected…..
      And, even in my small town, I know three women, who were later “diagnosed”, and *DRUGGED*, after they were sexually molested / abused by their Fathers…. Yes, they’re all 3 Catholic families. Just sayin’ what’s the REALITY I’ve seen. So, yes, psychiatry IS USED to cover up sexual abuse. These “dirty little secrets” NEED TO BE EXPOSED to Sunlight.
      Your group could do something profoundly healing here. The cover-up is worse than the crime.

  12. Noel,
    A very interesting piece – I agree with just about all of it.
    A couple questions:

    If I understand correctly, the C4 variant is associated with a 0.25% increase in the chances of “schizophrenia” in the general population. The usual (probably wrong) estimate of “schizophrenia” in the general population is 1%.

    As near as my non-statistician mind can make out, a 0.25% increased risk in the general population, when the “known” general population risk is 1%, would mean that this variant is associated with 25% of the overall risk of “schizophrenia” in the general population. Do I have that right? If so, it’s at least a hefty correlation, setting aside the question of causality.

    Next question: what percentage of the general population has this variant? If it is a small number, that would mean most or almost all of those with the variant become “schizophrenic.” While not proving causality, this would indeed be an interesting finding. But if a large percentage of the general population has the variant, it would mean the vast majority of those with the variant never become “schizophrenic,” and the potential impact of this study would be greatly diminished.

    Thanks for any help you can give me.

  13. I am not an academic but I was shocked when the doctor asked me if my son was abused as a child when he had the first psychotic break. My son was born after 5 years of us trying to get conceived. He is our only child with 2 loving parents and given the best of everything. The only trauma I can recall was when his pediatrician placed him on potocen for 3 days during the birthing process and was finally given a cesarean. He also had a fall when about 3 years old.
    Almost all the parents I know with mentally ill children are all middle class with normal families. Childhood abuse cannot be as significant as the author would lead us to believe in my opinion unless I misunderstood.

    • Josh,

      You might want to look into John Read’s research on child abuse / ACEs / schizophrenia. Here’s a quick read on a 2006 theory of his:

      http://psychcentral.com/news/2006/06/13/child-abuse-can-cause-schizophrenia/18.html

      2/3’s of so called “schizophrenics” today were initially child abuse victims, people dealing with an appalling crime, not people with a “chemical imbalance” in their brain.

      And, as a healthy woman who dealt with “the dirty little secret of the two original educated professions” / a cover up of the abuse of my child by my ex-religion and doctors. Who gas lighted me, then created “the classic symptoms of schizophrenia,” via drug induced anticholinergic intoxication syndrome, to cover up the sexual abuse of my child, and a “bad fix” on a broken bone.

      I will tell you that when a healthy person, including a non brain diseased child abuse victim, is put on the “bipolar” or “schizophrenia” drugs, the drugs can and do create both the negative and positive symptoms of “schizophrenia” via neuroleptic induced deficit syndrome and neuroleptic or poly pharmacy induced anticholinergic toxidrome.

      An ethical pastor of mine was later moved to confess to this historic “dirty little secret” way that the religions, their hospitals, and the doctors profiteer off of covering up child abuse. And I absolutely agree with Ron, “It’s a scandal on the scale of the Catholic church hiding the facts about sexual abuse by priests!” And my ex-religion is filled with “psychopathic” child abuse covering up pastors and bishops, too, according to me, and this former insider.

      https://books.google.com/books?id=xI01AlxH1uAC&printsec=frontcover#v=onepage&q&f=false

      Best of luck in your family’s healing journey.

    • “josh” – if I may butt in here: What first jumps right out at me, is when you say “first psychotic break”. I don’t know exactly what you mean by that, in terms of whatever “symptoms” there might have been. It’s possible, that *SOMEBODY* claimed, or mis-identified that “psychotic break”. Children can be very imaginative, and all kinds of other things. And, even college-educated parents can fall victim to bogus “diagnosis”. I have seen teachers LIE about a childs’ behavior in the classroom, so the kid could get labelled, and drugged, so the school district could get more money for that “Special Ed” kid. Yes, it DOES happen. And, it’s possible, that a baby sitter, even a trusted family member or friend, *could**have* abused or molested your child.
      I’m trying to get you to think of ALL the possibilities, to rule them out, if nothing else.
      And, I want to stress that you and your child’s mother, and others need to “TRUST YOUR GUT FEELINGS”, if that’s the case. You’ve come to a very good website to get some support.
      Thank-you, and I hope this helps. Especially with those “2 loving parents”, your childs’ future remains very bright….