KOZ: Schizophrenia and Homicidal Behaviour

[jachim3926]

Hi Sean & Jeff,
Just a couple points about Tay- Sachs Disease and the diagnosis of schizophrenia. As you noted, in late onset TDS, as this is a genetic organic brain disorder, physical degenerative changes occur in the brain structure, due to the absence of the enzyme hexaminidase;Hex A for cash! Further, from my understanding, it is almost exclusively found in the Ashkenazi Jewish population. I suppose that marriages outside of this sect may have caused some migration of the problem.

Conversely, schizophrenia ,in all its forms, is a 'cognitive'( thought) disorder which may,or not manifest concurrent affective ( mood) variances. The jury is still out as to whether there is any conclusive evidence to establish that physical changes happen in this disorder.

The article in Wiki on TSD states that late onset sufferers 'may experience a schizophrenic like psychosis. However , for that matter this is true of many other degenerative brain disorders. Huntington's disease, Picks , Alzheimer's, and Korsakov's psychosis all share the same propensity for episodic violent outbursts. This is by no mean restricted to this group of illnesses as many of the genetic disorders associated with mental retardation ( developmentally delayed for the politically correct) may manifest similar aggressive traits.

Happy New Year!
Merv

[Jeff Leahy]

Schizophrenia Nature V Nurture

Hi Everyone

Firstly my apologies for not being around much recently...This is likely to be on going over the next few weeks do to family problems.

However I did pick up on this debate via Radio 4 recently. Its great to see that its not just Ripperologists who in fight constantly...

Perhaps we just need to sit back and let the experts and scientists try and figure it out first... Seems as though this Nature V Nurture argument will carry on over the next few years until proper results can be gained..

Yours Jeff

INTRODUCTION

A familial vulnerability to schizophrenia is agreed even though the exact genes involved seem elusive. But despite epidemiological evidence showing different rates of schizophrenia in sociocultural groups that would be considered genetically similar, the causal role of the environment is still hotly contested. Many service users, social scientists and clinicians are convinced that social factors cause schizophrenia and, therefore, that behavioural or environmental change might offer a more tangible route to prevention than gene manipulation. However, a comparison of the monies given to research into the genetics and the social aetiology of schizophrenia would suggest that funders of research are not convinced. For instance, the Medical Research Council, Wellcome Trust and UK Department of Health have launched Biobank, billed as the largest ever study of nature and nurture. The aim is to investigate complex interactions between genes, lifestyle and the environment. Half a million people between the ages of 45 and 69 will be asked to take part. Unfortunately, the generally earlier onset of schizophrenia will mean that it will be difficult to research in this illness. Would we have benefited from a Biobank for 16- to 25-year-olds?

Is there evidence that social factors cause schizophrenia and, if there is, does it negate or complement the theory that schizophrenia is a genetic illness? We asked Professor Jim van Os from Maastricht University, one of Europe's top social psychiatry researchers, and Professor Peter McGuffin, a psychiatrist and geneticist who heads the Social, Genetic and Developmental Psychiatry Research Centre at the Institute of Psychiatry, London, to debate the question: Can the social environment cause schizophrenia?

FOR

Few would contest the fact that mental states are influenced by the individual's social environment. Follow-up research has demonstrated that the post-onset course of ICD, DSM and RDC psychotic disorders is extremely sensitive to variation in the social environment. It is logical to assume that the same social environment could play a causal role in the onset of psychotic mental states. This assumption is now supported by evidence.

The assertion that psychotic states are not somehow generated from ‘ within’, in isolation from environmental experience, is perfectly compatible with the belief that part of the vulnerability to develop mental states diagnosed as schizophrenia is genetic. It is not known whether the genetic effect on schizophrenia liability represents underlying variation in DNA sequence or epigenetic variation in gene expression. Nevertheless, the findings from general and genetic epidemiology suggest that, in the case of psychosis, the relationship between genotype and phenotype is mediated by the environment (gene—environment interaction). In the most extreme case, ‘ genetic’ transmission of schizophrenia may consist entirely of transmission of sensitivity to the psychosis-provoking effects of a ubiquitous factor in the social environment, such as experience of daily life stress. Most geneticists believe that gene—environment interactions play a role in schizophrenia. However, genetic heritability modelling procedures and, in particular, molecular genetics traditionally ignore gene—environment interplay. They rarely include any measure of the social environment. This results in underestimation of the role of the social environment in the causation of schizophrenia and possibly little success in identifying the genes conferring risk.

There are problems with research into the contribution of the social environment. Many of the likely risk-increasing elements, such as experience of stress in daily life, are not only difficult to measure, but also highly prevalent or even ubiquitous. If everybody smoked, it would be impossible to detect an association between smoking and lung cancer because there would be no non-smokers to compare the cancer rates with. The only way to detect the contribution of cigarette smoking would be to compare populations with different mean levels of cigarette smoking and associate these with differences in the population levels of lung cancer.

This latter approach — demonstrating between-population variation — has been among the most successful in suggesting a causal role of the social environment in schizophrenia. Incidence rates of schizophrenia vary widely within the same country, between urban and rural populations and between sociocultural majority and minority populations.

Perhaps more important is the finding that in urban and minority populations there is an increase not only in the rates of schizophrenia, but also in the rates of associated non-clinical psychosis-like experiences.

The findings in urban and minority populations demonstrate four things. First, genes alone cannot account for these findings because minority populations are not at increased risk of developing psychotic disorder in situations where they become majority populations, and people living in urban environments are not at increased risk if they grew up in a rural area.

Second, the traditional way to conceive of schizophrenia is to assume that it is a rare phenotype. The urban/minority findings oppose this view because the underlying environmental factors associated with the proxy variables urbanicity and minority status have been shown to cause whole populations to have higher levels of non-clinical psychosis-like experiences, rather than just causing a few individuals in these populations to develop rare psychotic disorders. In other words, the psychosis phenotype may be a continuous characteristic, the mean level of which varies between populations as a function of the social environment.

Third, the urban/minority findings point to a role of the social environment giving rise to enduring liabilities to later psychosis, rather than the traditional ‘precipitating’ causal role associated with, for example, stressful life events.

Fourth, the findings point to the importance of environment—environment interactions. For example, the effect of minority status appears to be modified by the size of the minority population in the wider social environment.

In conclusion, therefore, not only common sense but also research findings suggest that the mental states associated with schizophrenia algorithms are not an exception to the rule that psychological and environmental experience go hand in hand.

AGAINST

I shall take it as a given that there is an important genetic contribution to the aetiology of schizophrenia ( Gottesman, 1991). However, schizophrenia is a complex disorder that rarely, if ever, shows Mendelian patters of segregation and this is usually attributed to involvement of multiple genes plus environment, including, perhaps, social factors. The hypotheses that can be entertained regarding the environmental component are as follows.

First, there are broadly two forms of schizophrenia — one that is a genetic disorder (or a collection of genetic disorders) and the other that is caused by the environment, including social stressors. Second, a genetic diathesis is necessary but not sufficient to cause schizophrenia with additional relevant environmental stressors, including features in the social environment being required to produce the disorder. Third, the only constant feature in schizophrenia is a genetic component. A small amount of variance needs to be explained by ‘non-genetic’ factors but these are entirely either physical insults or stochastic processes affecting neural development, gene expression or protein structure.

A very small proportion of cases of schizophrenia subsequently turn out to be organic phenocopies (people who show the schizophrenia phenotype but who do not have the genotype), but otherwise the hypothesis that there are common non-genetic forms has been found wanting. Separation of schizophrenia into familial and non-familial types is open to criticism both on theoretical and statistical grounds. More tellingly, studies based on the relatives of twins suggest that people with schizophrenia who are completely lacking in a genetic vulnerability are rare. Luxenburger, as early as the 1920s, pointed out that if non-genetic forms of schizophrenia are common, most, perhaps all, occurrences of discordant monozygotic twins would be explained by such forms. It would then be expected that their relatives would be less-often affected than the relatives of concordant pairs. Luxenburger was unable to show this, as indeed were all subsequent researchers. Furthermore, Gottesman and Bertelsen showed that the morbid risk to the offspring of the unaffected identical co-twin of a person with schizophrenia was not significantly different from that to the offspring of the index cases with schizophrenia themselves. These findings leave no real room for the existence of common forms of schizophrenia caused entirely by the social or any other form of environment.

If social factors on their own cannot cause schizophrenia, can they contribute to the cause in those individuals who have a pre-genetic disposition? If so, what is the size of such contribution and does it originate within the family or are the environmental effects specific to the individual? We can again obtain answers from analysis of twin data. A meta-analysis of all recent twin studies estimated that the total variance in liability to DSM—III—R schizophrenia accounted for by additive genetic effects was 88% (95% CI 83-92%). This leaves 12% (95% CI 9-17%) to be explained by the environment, but this is entirely of the non-shared type. That is, family environment makes no contribution to twin similarity. Thus, the evidence flies in the face of once fashionable theories that social interactions within families are all-important. There is, on the other hand, good evidence that psychosocial factors, such as high expressed emotion at home or life events, can hasten relapses or precipitate onsets but few would argue that such factors are truly causal, rather they appear to affect the timing or frequency of episodes.

The other group of non-genetic factors that have been widely studied can be placed under the broad heading of physical insult.

These include exposure to viruses in utero, obstetric complications and misuse of certain drugs. However, given that the non-genetic component of schizophrenia is estimated to be small and also given that it has been hard to identify unequivocally, my colleagues and I have previously argued that it might consist entirely of chance events that would be impossible to detect by conventional epidemiological methods. These would include stochastic factors operating at a cellular or sub-cellular level during neural development, somatic mutations including trinucleotide repeat DNA expansions which have been indirectly implicated in schizophrenia, and other epigenetic phenomena such as imprinting and X inactivation.

The hypothesis that some cases of schizophrenia are entirely socially determined cannot be supported. Although we cannot exclude the possibility that social factors contribute to the aetiology of schizophrenia in those with a genetic predisposition, the non-genetic proportion of variance in liability is small and is more likely to be explained by physical stressors or even by stochastic processes.

© 2003 Royal College of Psychiatrists
References

Boydell, J., van Os, J., McKenzie, K., et al ( 2001) Incidence of schizophrenia in ethnic minorities in London: ecological study into interactions with environment. BMJ, 323, 1336 .Abstract/FREE Full Text
Cardno, A. G. & Gottesman, I. I. ( 2000) Twin studies of schizophrenia: from bow-and-arrow concordances to Star Wars Mx and functional genomics. American Journal of Medical Genetics, 97, 12 -17.CrossRefMedlineWeb of Science
↵ Gottesman, I. ( 1991) Schizophrenia Genesis. Origins of Madness. San Francisco, CA: Freeman.
Johns, L. C. & van Os, J. ( 2001) The continuity of psychotic experiences in the general population. Clinical Psychology Review, 21, 1125 -1141.CrossRefMedlineWeb of Science
McGuffin, P., Asherson, P., Owen, M., et al ( 1994) The strength of the genetic effect. Is there room for an environmental influence in the aetiology of schizophrenia? British Journal of Psychiatry, 164, 593 -599.Abstract/FREE Full Text
Myin-Germeys, I., van Os, J., Schwartz, J. E., et al ( 2001) Emotional reactivity to daily life stress in psychosis. Archives of General Psychiatry, 58, 1137 -1144.CrossRefMedlineWeb of Science
van Os, J. & Marcelis, M. ( 1998) The ecogenetics of schizophrenia: a review. Schizophrenia Research, 32, 127 -135.CrossRefMedlineWeb of Science

[Anna Morris]

There is some interesting research on Post Traumatic Stress Disorder (PTSD), that identifies a newly discovered neurotransmitter which, in normal people, buffers reactions to traumatic events. People prone to PTSD either lack this neurotransmitter altogether or have weak amounts of it. I will try to find this information again and post a more technical review here.

A number of decades ago schizophrenia was considered in most cases to have an onset in mid to late teen years. I am sure this is overly simplistic. However, anecdotally, I am continually surprised to know of former methamphetamine users who develop "schizophrenia" in their 30s to 40s. We have a great deal of meth use here in the west, to the extent it is possible to have "normal" and nice friends who are using or have used. Sometimes after years of not using, these people have sudden, extraordinary mental breakdowns that lead to temporary institutionalization and diagnoses of schizophrenia.

[Anna Morris]

My perspective is that everything is genetic and I largely discount environment or "nurture". The latter makes an easy out for doctors and scientists who refuse to treat illness they don't understand.

However fairly new research into neurotransmitters that regulate how experiences are perceived is very interesting.

One such neuropeptide is Neuropeptide Y which has several functions including regulating food intake and storing energy as fat, reducing anxiety and stress, reducing pain perception and reducing voluntary alcohol intake. It helps lower blood pressure and controls epileptic seizures. It also affects circadian rhythms.

This is not the neurotransmitter I was thinking of earlier. There is a very recent discovery of another neuropeptide which regulates how severely a human experiences negative experiences. I was researching this subject in relation to my own issues of chronic migraine and an odd form of tachycardia. Very little is yet known about migraine but there is reasonable research pointing to the idea that the terrible pain is a product of the brain, not swollen blood vessels. This other neurotransmitter is scarce or lacking in many who have migraine. Perhaps the pain should be silenced if this neurotransmitter was available. Migraine is very genetic.

Considering neurotransmitters regulating perception I think could apply to schizophrenia. On the other hand, neuro-imaging of schizophrenic brains has shown overgrowth of some areas of the brain.

[Jeff Leahy]

Hi Caz

Most interesting...I'm beginning to change my view point but will allow the experts to battle it out....

But I've been thinking recently about what my expert told me relating to the schizophrenic chases he treated in the 1980's...

He said that just because these were typical of the chases he treated at that time that he was cautious of drawing parallels with Victorian chase for many reasons...Which he went on to list in detail from drugs, alcohol to environment.

To some extent I poah poah'd this...I mean Schizophrenia is schizophrenia right?

But what if it isn't?

What if the illness like other illnesses are in a constant state of FLUX?

Think about flue vaccinations and the constant battle between mutating viruses and the constant changing of the human defence system... Flue germs can mutate over just a few weeks, and the human resistance adapts...

I'm not suggesting that Schizophrenia is like a virus, simply what if human selection and evolution works faster than previously;y thought? This might explain why there are such wide cultural variation around the globe...

What if schizophrenia in 1888 really was different to today for a wide variety of reasons, not just social but also bialogical....from diet to living conditions perhaps it manifested itself in different ways and like the human condition is also constantly evolving?

Not quiet sure where i'm going with this line of thought but the more i look at schizophrenia the less i think I understand about it

Its hard to pin down

Yours Jeff

[Anna Morris]

Nothing in living systems is simple cause and effect. Nothing is simple.

Very little of the damage from flu is actually caused by the virus. The deadly damage comes from our immune systems rooting out the virus. Doctors will say that lung tissue, severely damaged during flu, looks like it has been scalded & that is the work of the immune system.

Women especially are prone to autoimmune diseases like lupus wherein the immune system attacks the body for unknown reasons. I have had Guillan Barre` syndrome which is the body attacking the nervous system in response to flu or pneumonia. MS works similarly.

The original work published here on schizophrenia also accounts for epigenetics which is a fairly new field that accounts for how genes turn on over generations. This was mentioned in the work at the University of Maastricht. Epigenetics takes into account how what happened to grandparents and beyond affects future generations. When this was discovered I wondered if the passages in the Old Testament about the sins of the fathers being visited on the offspring to the seventh generation might be the result of observation by ancient sages. I don't think epigenetics have worked out to seven generations, but I wonder if that is so.

Look at basic history. In the time of Henry VIII people had short lives, even if they escaped plague, execution and warfare. Is there a lesson in epigenetics there? By the time of Elizabeth I, people lived longer in general yet people were no cleaner and diets no better.

The problem with diseases of the nervous system and brain is that there are few if any quantitative tests that can be done for diagnosis. Therefore doctors and even scientists look at the overt signs and symptoms. Traumatic brain injury can cause psychosis, as well as drugs, alcohol and fever delirium. Yet these things are not schizophrenia.

There were things in JtR's time that we no longer have to the extent they existed then. How many "lunatics" in Jack's time had syphilis? Also disease conditions that can now be treated, such as basic endocrine disorders like hypo or hyper-thyroid, Addison's and Cushing's diseases, etc. could not be treated in Jack's day. Some of these conditions, untreated, will lead to psychosis which is not schizophrenia. I have long wondered if something like these conditions affected Druitt's family and that was why there was a tendency to suicide and depression.

Genetically speaking, would the genetic predisposition lead to abnormal neural pathways in the brain, or would it lead to faulty neurotransmitters? Some genetic conditions code for malformed proteins as in connective tissue disorders. Neuropeptides are made of proteins. A very small malformation can have devastating consequences.

In looking at history I think one needs to look at family history to see if there was a tendency toward any specific conditions. If a family was strong and productive, yet one member of the family was mentally ill, in those far off days, perhaps the one who differed had something other than a genetically based mental illness. Also it is useful to look at comorbidities within families. Sometimes comorbidities point the way to other diagnoses.

To the best of my knowledge, there is as yet, no firm diagnosis for schizophrenia and there are wide variations in conditions that share similar symptoms.

[Sean Crundall]

Hi Sean & Jeff,
Just a couple points about Tay- Sachs Disease and the diagnosis of schizophrenia. As you noted, in late onset TDS, as this is a genetic organic brain disorder, physical degenerative changes occur in the brain structure, due to the absence of the enzyme hexaminidase;Hex A for cash! Further, from my understanding, it is almost exclusively found in the Ashkenazi Jewish population. I suppose that marriages outside of this sect may have caused some migration of the problem.

Conversely, schizophrenia ,in all its forms, is a 'cognitive'( thought) disorder which may,or not manifest concurrent affective ( mood) variances. The jury is still out as to whether there is any conclusive evidence to establish that physical changes happen in this disorder.

The article in Wiki on TSD states that late onset sufferers 'may experience a schizophrenic like psychosis. However , for that matter this is true of many other degenerative brain disorders. Huntington's disease, Picks , Alzheimer's, and Korsakov's psychosis all share the same propensity for episodic violent outbursts. This is by no mean restricted to this group of illnesses as many of the genetic disorders associated with mental retardation ( developmentally delayed for the politically correct) may manifest similar aggressive traits.

Happy New Year!
Merv

Hi Merv,

Apologies for not picking up on your post earlier.

While true that many other disorders, as you highlight, can lead to "violent outbursts" none of these disorders, as far as I'm aware, can be confined to the Ashkenazi sect of Jewry, which is highly significant as regards Kozminski.

As mentioned in my previous post I claim no expertise in this field having only read a handful of articles relating to the disease.

As an interesting aside to your post, Waren Tay worked at the Whitechapel Hospital c.1902 and also worked with Thomas Horrocks Openshaw. He also lived at Finsbury Circus in the early 1900s, a few doors from where Dr Gordon Brown lived in 1888.

Best wishes,

Sean.

[jachim3926]

Hi Sean,
This is a little off topic, but will give you and idea of the genetic challenges faced by Ashkenazi Jewry!

http://www.jewishvirtuallibrary.org/jsource/Health/genetics.html

One would have to wonder why this group are so susceptible to such a raft of genetic disorders. There is no suggestion that inbreeding played any part in this. Also the issue in complicated further by the fact that the recessive genes can be carried by both the male and female parents.
Cheers,
Merv

[jachim3926]

'Not quiet sure where i'm going with this line of thought but the more i look at schizophrenia the less i think I understand about it'

Hi Jeff,
Join the club! I think that I have mentioned this before, but as one colleague famously remarked ' There are probably as many schizophrenias as there are schizophrenics'!

One on many difficulties involved with the clinical diagnosis of schizophrenia is the extensive range of symptoms open to individual interpretation. It is rare to find three psychiatrists arriving at the same diagnostic conclusion. This particularly so in medico legal circles.

For the most part, the clinician is reliant upon what information the patient elects to share in terms of discussing symptoms. Delusional ideation may , or may not be a clear indicator of what the subject actually thinks. The same criteria applies to hallucinosis- the most common form of which is auditory. The dreaded 'voices'. Tactile, olfactory, gustatory and visual hallucinations are relatively rarely complained of.

That , of course begs the question as to whether the subject is being entirely truthful when he/she declares that the Devil , God etc. made me act out in a violent manner. Classic manipulation of MacNaughten's Rule (or Durhams's law) to avoid responsibility and punitive outcomes!

Paranoid delusions are a different kettle of fish and under some circumstances understandable ,if not altogether justifiable. Another psychiatrist colleague once opined the view that most Yugoslavs were paranoid-otherwise they would all be dead!

The myths that surround schizophrenia still abound in this day and age. Contrary to popular community beliefs, the vast majority of people so diagnosed do not pose any threat to society. In fact, since the obscene rush to close asylums throughout the western world this vulnerable group has been placed in extreme danger, dwelling among the homeless, or imprisoned for relatively minor offences simply because there was no other facility to accommodate their needs. This is certainly true of the situation in Australia and many other countries that went down this route.At least the Italians were smart enough to reverse the trend.

Don't imagine for one moment that this arose because of any altruistic consideration for the mentally ill. The old asylums that lay around the periphery of Sydney and London had become prime real estate for city commuters and money was there for the taking!

I may be wrong, but I cannot help but think that the whole concept of schizophrenia was based on flawed pseudo science. Apart from changing the original tile from Dementia Praecox ( dementia of the young) ipso dipso little has actually changed. Needless to say, the beneficiaries have been the big pharmaceutical conglomerates with tirelessly produce and market more toxic substances to keep the afflicted suitable sedated.

In effect, the whole kaleidoscope of schizophrenic symptomatology was engineered to slot people into neat little diagnostic boxes and this is why the periodic review of metal illness( DSM) is nothing more than an academic exercise!!!!

For those of you who are sufficiently interested or motivated, do a little research into Phenothiazines and the more recent major tranquilizers . Almost without exception, these noxious compounds cause irreversible conditions - drug induced parkinsonism and a host of other serious disorders. In the past patients were assured that once they stopped taking the drugs , all would return to normal . This was a deliberate lie which psychiatrists saw fit go along with! Not that there was ever likely to be the chance that the drug regimes would be suddenly halted.

Back in the 1980's I made my feeling quite clear about the closure on institutions and suffered persecution for doing so. From a relatively influential position in my State Health Commission I was forced to transfer to another Department on a ' lateral promotion' to escape to calmer waters. Some people blinded by ambition just can't handle the truth!!!!!

[Jeff Leahy]

Hi Guys

Many thanks for your posts which i read with interest..

I would reply in full but in chaos here....house move, painting, father in law in hospital, boat sinking and daughter home from perth...Ah!!!

I'll try and pick up in more detail next week...

But I think the Ashkenazia are not of the jewish blood line but were converted into judaism around 1200 AD

So perhaps it has something to do with the human migration out of africa following tech last ice age....its now known that some inter-breeding happened with declining Neandathal populations

But I must dash so much to do Jeff

PS Just to agree with what your saying Merv....One of the big complaints seems to be that all the research money going into schizophrenic research is for machines that go 'ping' rather than social research....I wonder if that is also driven by the big drug companies who hope the development of another pill might make big bucks?