This one suggests that the culprit may be nothing more than the common ‘flu’.
Doctors have known for many years that microbes such as syphilis and Streptococcus can, if left untreated, lead to serious psychiatric problems. Now a growing number of scientists are proposing that microbes are to blame for several mental illnesses once thought to have neurological or psychological defects at their roots. The strongest evidence pertains to schizophrenia, but autism, bipolar disorder and obsessive-compulsive disorder have also been linked to bacterial, viral or parasitic infections in utero, in childhood or in maturity. Some of these infections can directly affect the brain, whereas others might trigger immune reactions that interfere with brain development or perhaps even attack our own brain cells in an autoimmune mistake.
In 1973 E. Fuller Torrey, now a research psychiatrist at the Stanley Medical Research Institute in Chevy Chase, Md., published an article in the British journal Lancet that revived an idea that had been set aside for decades—could microbial infection cause mental illness?
For the next 20 years, a few rogue scientists dominated the field, searching for connections between infections and psychiatric disorders—and the closer they looked, the more they found.
The research indicated a high incidence of peri-natal mothers who developed flu, particularly in the first and second trimester and discusses the immunological activity of the host mother being potentially damaging to the fetus who then goes on to develop anatomical and psychological disparities.
The most compelling evidence is for schizophrenia. More than 200 studies have suggested that schizophrenia occurs between 5 and 8 percent more frequently than average in children born in the winter or spring. Scientists realized that viruses, which are most prevalent in the cold, dry winter months, could be one of the factors influencing this correlation.
No shagging on summer holidays then. Wonder if that’ll make it into the MHA?
Brown had also found in a 2001 study that children born to mothers who were exposed to the viral infection rubella, known as German measles, during the 1964 U.S. epidemic were 10 times more likely than other children to develop schizophrenia. Most people today are vaccinated against rubella during childhood, so the risk from this infection is now negligible. But Brown also showed a link between schizophrenia and Toxoplasma gondii, a single-celled parasite that infects about 40 percent of the human population through contaminated water and uncooked meat. One of his studies suggests that if T. gondii antibodies—the human immune system’s soldier cells that are a sure sign of ongoing or previous infection—are elevated in a mother’s blood, her child is 2.5 times more likely than other children to develop schizophrenia.
In 2004 Alan S. Brown, a psychiatrist at Columbia University, analyzed blood samples collected from 1959 through 1966 from 189 pregnant women, 64 of whom had later given birth to children who became schizophrenic. The women had had their blood drawn multiple times during pregnancy, allowing Brown and his colleagues to compare if and when the women had been exposed to the flu. “We showed that if [flu] infection occurred in the early to middle part of pregnancy, the risk of schizophrenia was increased three times,” Brown explains. “For first-trimester exposure, it was increased seven times.”
This Toxoplasma gondii seems to be a key component…
T. gondii is also one of the few microbes that can cross the blood-brain barrier, a protective membrane separating brain cells from the rest of the body. Once in the brain, T. gondii affects its hosts’ behavior. Infected rats and mice lose their fear of cats, making the rodents more likely to approach and be eaten by a cat, which is in the parasite’s best interest—it can reproduce only in a feline.
Of course, Ted will tell you the rats are just making bad choices.
In people, T. gondii appears to subtly alter personality, making its hosts more neurotic and insecure and making men more cautious and women more kind and openhearted.
The parasite probably instigates these behavioral changes by affecting the levels of certain brain chemicals. One study, for example, found that T. gondii increases the production of dopamine, an important neurotransmitter involved in a variety of brain processes, including motor activity, sleep, attention and reward. In a fetus, changes in dopamine levels can wreak havoc on normal brain development, and scientists have long known that schizophrenia is associated with an overabundance of dopamine in specific parts of the brain.
But a dormant T. gondii infection, which may also be correlated with an increased risk of schizophrenia in the fetus, does not cross the placenta and therefore cannot directly affect the fetal brain. The influenza link is equally difficult to understand, because flu does not usually infect the fetus. Something else, then, may be at play.
The article also points out, since flu vaccines tend to work by encouraging the development of an immunity, flu vaccines could not only be detrimental in pregnancy, but might also be contributory to a fetus developing major mental disorder.
Some studies suggest that infections per se are not responsible for disrupting brain development; rather the body’s immune response to infection affects the nervous system and does the damage. “When the immune system becomes activated, it can influence the functioning of the brain and, in turn, emotional and behavioral responses,” explains Christopher L. Coe, a psychologist at the University of Wisconsin–Madison who studies the effects of psychological and environmental factors on the immune system.
The Centers for Disease Control and Prevention currently recommend that all pregnant women get flu shots—a dangerous proposition if immune response, rather than infection itself, is responsible for harming the fetal brain. “I don’t think they have considered this risk. In fact, I know they haven’t considered this risk,” Patterson says, referring to the CDC. “If you take it seriously and vaccinate everybody, then what’s going to happen?” Researchers cannot yet predict how often a prenatal immune response might lead to fetal brain damage, but even if it happens less than 1 percent of the time, vaccinating an entire population of pregnant women could affect thousands of children
Of course, this does nothing to aid the ongoing treatment but it (yet another) potential cause that can perhaps be easily eradicated.
It would be interesting to see the response of the great Doc Crippen to this contentious hypothesis. As we know, the MMR/Autism debate (debacle) was hugely detrimental to many children. But what if, as suggested in some of the research data, this phenomena does exist?
Having flu when pregnant, which may later lead to the child developing schizophrenia, is an unfortunate event.
Developing flu from a dose of flu vaccine that later develops a child with schizophrenia is iatrogenic.
Someone needs to get the calculator out again and start costing the balance of risk probabilities, I think……
Tags: mental health, microbiology, research, Schizophrenia
12 comments
May 23, 2008 at 10:43 am
Cockroachcatcher
This is straight from the opening of Ch. 49 of my book The Cockroach Catcher”
“It would not be a great surprise to anyone who has any inkling of the history of medicine that sooner or later any medical condition with an alleged aetiology of pure psychological origin will prove to have a non psychological cause. This is particularly true of those conditions classified by non-psychiatrists.”
Has anyone considered how actually did the best medication for Schizophrenia really worked? Why did we have to check the blood?
The Cockroach Catcher
May 23, 2008 at 6:43 pm
anniepema
What about all the research showing that autism and schizophrenia in many non-familial cases is caused by older men having babies. There is much evidence for this cause:
http://www.schizophreniaforum......efault.asp
Schizophrenia Risk and the Paternal Germ Line
By Dolores Malaspina
Dolores Malaspina
Paternal age at conception is a robust risk factor for schizophrenia. Possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The predisposing genetic events appear to occur probabilistically (stochastically) in proportion to advancing paternal age, but might also be induced by toxic exposures, nutritional deficiencies, suboptimal DNA repair enzymes, or other factors that influence the
fidelity of genetic information in the constantly replicating male germ line. We propose that de novo genetic alterations in the paternal germ line cause an independent and common variant of schizophrenia.
Seminal findings
We initially examined the relationship between paternal age and the risk for schizophrenia because it is well established that paternal age is the major source of de novo mutations in the human population, and most schizophrenia cases have no family history of psychosis. In 2001, we demonstrated a monotonic increase in the risk of schizophrenia as paternal age advanced in the rich database of the Jerusalem Perinatal Cohort. Compared with the offspring of fathers aged 20-24 years, in well-controlled analyses, each decade of paternal age multiplied the risk for schizophrenia by 1.4 (95 percent confidence interval: 1.2-1.7), so that the relative risk (RR) for offspring of fathers aged 45+ was 3.0 (1.6-5.5), with 1/46 of these offspring developing schizophrenia. There were no comparable maternal age effects (Malaspina et al., 2001).
Epidemiological evidence
This finding has now been replicated in numerous cohorts from diverse populations (Sipos et al., 2004; El-Saadi et al., 2004; Zammit et al., 2003; Byrne et al., 2003; Dalman and Allenbeck, 2002; Brown et al., 2002; Tsuchiya et al., 2005). By and large, each study shows a tripling of the risk for schizophrenia for the offspring of the oldest group of fathers, in comparison to the risk in a reference group of younger fathers. There is also a “dosage effect” of increasing paternal age; risk is roughly doubled for the offspring of men in their forties and is tripled for paternal age >50 years. These studies are methodologically sound, and most of them have employed prospective exposure data and validated psychiatric diagnoses. Together they demonstrate that the paternal age effect is not explained by other factors, including family history, maternal age, parental education and social ability, family social integration, social class, birth order, birth weight, and birth complications. Furthermore, the paternal age effect is specific for schizophrenia versus other adult onset psychiatric disorders. This is not the case for any other known schizophrenia risk factor, including many of the putative susceptibility genes (Craddock et al., 2006).
There have been no failures to replicate the paternal age effect, nor its approximate magnitude, in any adequately powered study. The data support the hypothesis that paternal age increases schizophrenia risk through a de novo genetic mechanism. The remarkable uniformity of the results across different cultures lends further coherence to the conclusion that this robust relationship is likely to reflect an innate human biological phenomenon that progresses over aging in the male germ line, which is independent of regional environmental, infectious, or other routes.
Indeed, the consistency of these data is unparalleled in schizophrenia research, with the exception of the increase in risk to the relatives of schizophrenia probands (i.e., 10 percent for a sibling). Yet, while having an affected first-degree relative confers a relatively higher risk for illness than having a father >50 years (~10 percent versus ~2 percent), paternal age explains a far greater portion of the population attributable risk for schizophrenia. This is because a family history is infrequent among schizophrenia cases, whereas paternal age explained 26.6 percent of the schizophrenia cases in our Jerusalem cohort. If we had only considered the risk in the cases with paternal age >30 years, our risk would be equivalent to that reported by Sipos et al. (2004) in the Swedish study (15.5 percent). When paternal ages >25 years are considered, the calculated risk is much higher. Although the increment in risk for fathers age 26 through 30 years is small (~14 percent), this group is very large, which accounts for the magnitude of their contribution to the overall risk. The actual percentage of cases with paternal germ line-derived schizophrenia in a given population will depend on the demographics of paternal childbearing age, among other factors. With an upswing in paternal age, these cases would be expected to become more prevalent.
Biological plausibility
We used several approaches to examine the biological plausibility of paternal age as a risk factor for schizophrenia. First, we established a translational animal model using inbred mice. Previously it had been reported that the offspring of aged male rodents had less spontaneous activity and worse learning capacity than those of mature rodents, despite having no noticeable physical anomalies (Auroux et al., 1983). Our model carefully compared behavioral performance between the progeny of 18-24-month-old sires with that of 4-month-old sires. We replicated Auroux’s findings, demonstrating significantly decreased learning in an active avoidance test, less exploration in the open field, and a number of other behavioral decrements in the offspring of older sires (Bradley-Moore et al., 2002).
Next, we examined if parental age was related to intelligence in healthy adolescents. We reasoned that if de novo genetic changes can cause schizophrenia, there might be effects of later paternal age on cognitive function, since cognitive problems are intertwined with core aspects of schizophrenia. For this study, we cross-linked data from the Jerusalem birth cohort with the neuropsychological data from the Israeli draft board (Malaspina et al., 2005a). We found that maternal and paternal age had independent effects on IQ scores, each accounting for ~2 percent of the total variance. Older paternal age was exclusively associated with a decrement in nonverbal (performance) intelligence IQ, without effects on verbal ability, suggestive of a specific effect on cognitive processing. In controlled analyses, maternal age showed an inverted U-shaped association with both verbal and performance IQ, suggestive of a generalized effect.
Finally, we examined if paternal age was related to the risk for autism in our cohort. We found very strong effects of advancing paternal age on the risk for autism and related pervasive developmental disorders (Reichenberg et al., in press). Compared to the offspring of fathers aged 30 years or younger, the risk was tripled for offspring of fathers in their forties and was increased fivefold when paternal age was >50 years. Together, these studies provide strong and convergent support for the hypothesis that later paternal age can influence neural functioning. The translational animal model offers the opportunity to identify candidate genes and epigenetic mechanisms that may explain the association of cognitive functioning with advancing paternal age.
A variant of schizophrenia
A persistent question is whether the association of paternal age and schizophrenia could be explained by psychiatric problems in the parents that could both hinder their childbearing and be inherited by their offspring. If this were so, then cases with affected parents would have older paternal ages. This has not been demonstrated. To the contrary, we found that paternal age was 4.7 years older for sporadic than familial cases from our research unit at New York State Psychiatric Institute (Malaspina et al., 2002). In addition, epidemiological studies show that advancing paternal age is unrelated to the risk for familial schizophrenia (Byrne et al., 2003; Sipos et al., 2004). For example, Sipos found that each subsequent decade of paternal age increased the RR for sporadic schizophrenia by 1.60 (1.32 to 1.92), with no significant effect for familial cases (RR = 0.91, 0.44 to 1.89). The effect of late paternal age in sporadic cases was impressive. The offspring of the oldest fathers had a 5.85-fold risk for sporadic schizophrenia (Sipos et al., 2004); relative risks over 5.0 are very likely to reflect a true causal relationship (Breslow and Day, 1980).
It is possible that the genetic events that occur in the paternal germ line are affecting the same genes that influence the risk in familial cases. However, there is evidence that this is not the case. First, a number of the loci linked to familial schizophrenia are also associated with bipolar disorder (Craddock et al., 2006), whereas advancing paternal age is specific for schizophrenia (Malaspina et al., 2001). Next, a few genetic studies that separately examined familial and sporadic cases found that the “at-risk haplotypes” linked to familial schizophrenia were unassociated with sporadic cases, including dystrobrevin-binding protein (Van Den Bogaert et al., 2003) and neuregulin (Williams et al., 2003). Segregating sporadic cases from the analyses actually strengthened the magnitude of the genetic association in the familial cases, consistent with etiological heterogeneity between familial and sporadic groups.
Finally, the phenotype of cases with no family history and later paternal age are distinct from familial cases in many studies. For example, only sporadic cases showed a significant improvement in negative symptoms between a “medication-free” and an “antipsychotic treatment” condition (Malaspina et al., 2000), and sporadic cases have significantly more disruptions in their smooth pursuit eye movement quality than familial cases (Malaspina et al., 1998). A recent study also showed differences between the groups in resting regional cerebral blood flow (rCBF) patterns, in comparison with healthy subjects. The sporadic group of cases had greater hypofrontality, with increased medial temporal lobe activity (frontotemporal imbalance), while the familial group evidenced left lateralized temperoparietal hypoperfusion along with widespread rCBF changes in cortico-striato-thalamo-cortical regions (Malaspina et al., 2005b). Other data linking paternal age with frontal pathology in schizophrenia include a proton magnetic resonance spectroscopy study that demonstrated a significant association between prefrontal cortex neuronal integrity (NAA) and paternal age in sporadic cases only, with no significant NAA decrement in the familial schizophrenia group (Kegeles et al., 2005). These findings support the hypothesis that schizophrenia subgroups may have distinct neural underpinnings and that the important changes in some sporadic (paternal germ line) cases may particularly impact on prefrontal cortical functioning.
Genetic mechanism
Several genetic mechanisms might explain the relationship between paternal age and the risk for schizophrenia (see Malaspina, 2001). It could be due to de novo point mutations arising in one or several schizophrenia susceptibility loci. Paternal age is known to be the principal source of new mutations in mammals, likely explained by the constant cell replication cycles that occur in spermatogenesis (James Crow, 2000). Following puberty, spermatogonia undergo some 23 divisions per year. At ages 20 and 40, a man’s germ cell precursors will have undergone about 200 and 660 such divisions, respectively. During a man’s life, the spermatogonia are vulnerable to DNA damage, and mutations may accumulate in clones of spermatogonia as men age. In contrast, the numbers of such divisions in female germ cells is usually 24, all but the last occurring during fetal life.
Trinucleotide repeat expansions could also underlie the paternal age effect. Repeat expansions have been demonstrated in several neuropsychiatric disorders, including myotonic dystrophy, fragile X syndrome, spinocerebellar ataxias, and Huntington disease. The sex of the transmitting parent is frequently a major factor influencing anticipation, with many disorders showing greater trinucleotide repeat expansion with paternal inheritance (Lindblad and Schalling, 1999; Schols et al., 2004; Duyao et al., 1993). Larger numbers of repeat expansions could be related to chance molecular events during the many cell divisions that occur during spermatogenesis.
Later paternal age might confer a risk for schizophrenia if it was associated with errors in the “imprinting” patterns of paternally inherited alleles. Imprinting is a form of gene regulation in which gene expression in the offspring depends on whether the allele was inherited from the male or female parent. Imprinted genes that are only expressed if paternally inherited alleles are reciprocally silenced at the maternal allele, and vice versa. Imprinting occurs during gametogenesis after the methylation patterns from the previous generation are “erased” and new parent of origin specific methylation patterns are established. Errors in erasure or reestablishment of these imprint patterns may lead to defective gene expression profiles in the offspring. The enzymes responsible for methylating DNA are the DNA methyltransferases, or DNMTs. These enzymes methylate cytosine residues in CpG dinucleotides, usually in the promoter region of genes, typically to reduce the expression of the mRNA. The methylation may become inefficient for a variety of reasons; one possibility is reduced DNA methylation activity in spermatogenesis, since DNMT levels diminish as paternal age increases (Benoit and Trasler, 1994; La Salle et al., 2004). Another possible mechanism is that this declining DNMT activity could be epigenetically transmitted to the offspring of older fathers. There are a number of different DNMTs that differ in whether they initiate or sustain methylation, and which are active at different ages and in different tissues.
May 23, 2008 at 11:06 pm
oldschoolbaby
I`ve long been fascinated by this. Nursing folklore suggests psychosis subsides in the pyrexial. My, rather limited, observations support this.
It also ties in with the assertion that a dopamine imbalance is a consequence, rather than a cause, of psychosis.
Big Pharma will take some persuasion to research this. If there is an aetiological pathogen and it can be combatted, the golden goose of the anti - psychotic would be in mortal danger. And, of course, a few RMN`s would be surplus to requirements. I may end my working life dry stone walling after all
June 1, 2008 at 6:22 pm
Ted
“Don’t tell Ted… but here’s another theory on mental illness.”
If schizophrenia were actually viral, then it would be a real disease, and not a mental illness. Why would I not be interested in some evidence that yet another real disease had been discovered? One answer is that the evidence presented is laughable, but makes as much sense as the other hundreds of proposed theories. No wonder real medical scientists have nothing to do with psychiatry!
“Of course, Ted will tell you the rats are just making bad choices.”
It is odd that by insisting human beings have free will, you suggest that I think rats do too. Given that you definitely refuted all of my points in the lengthy thread of the other week (http://www.mentalnurse.org.uk/2008/05/16/does-mental-illness-exist/), I am honoured that you care to mention my name on this posting. Despite my initial confusion and rejection of your coercive advice, I am retrospectively glad for your intervention. The lord hath bespoken, and another soul he hath saved!
Ted.
June 1, 2008 at 7:58 pm
dazedandconfused
But if for example Schizophrenia were proved to be a viral illness it would stilled be classed as a mental illness. As it has it’s primary effect in the brain, thought processes etc.
I don’t know why I bother.
June 3, 2008 at 7:05 pm
Ted
@ dazedandconfused
So a real disease with a physical basis is not a physical disease but a mental illness?!
The sad truth is that after a century and $billions spent on research, there is no evidence whatsoever that what are now called mental disorders are attributable to any underlying physical pathology. If and when such discoveries are made, what will have been discovered is a real physical disease, and not a “mental illness” - these exist already on the say-so of psychiatrists. Those competent scientists we call psychiatrists may choose to class it as a mental illness, but that doesn’t mean they wouldn’t be talking nonsense!
June 3, 2008 at 7:19 pm
zarathustra
Erm…I’ve just been reading and re-reading Ted’s comment above. Is it just me or is that a completely circular argument?
June 3, 2008 at 8:46 pm
Ted
@ zarathustra
Circular in what sense? Disease was once defined as bodily pathology. Now behaviours are included too, under the name of mental disorders. Whether you want to properly distinguish between the two is up for discussion, but either way the distinction remains undeniable. We could just give up completely and announce that anything could a disease, but to miss the ethical implications for such an inflation of a well-defined concept is naive, to say the least.
As Thomas Szasz points out, “Obviously, I don’t deny the existence of brain diseases; on the contrary, my point is that if mental illnesses are brain diseases, we ought to call them brain diseases and treat them as brain diseases — and not call them mental illnesses and treat them as such. In the 19th century, madhouses were full of people who were “crazy”; more than half of them, as it turned out, had brain diseases — mainly neurosyphilis, or brain injuries, intoxications, or infections. Once that was understood, neurosyphilis ceased to be a mental illness and became a brain disease. The same thing happened with epilepsy.”
June 3, 2008 at 9:44 pm
zarathustra
It’s a circular argument in the sense of there’s no such thing as mental illness unless they’re shown to have a physical pathology, in which case they’re not mental illness. *That’s* a circular argument.
Disease was once defined as bodily pathology. Now behaviours are included too, under the name of mental disorders.
No, *mental states* are included under the name of mental disorders - hearing of voices, delusions, manic episodes and so on. The behaviours are a product of those mental states.
Do you have any argument that actually addresses these particular frightening and debilitating mental states? I suspect I’m going to regret asking that.
June 5, 2008 at 12:46 am
Ted
“*That’s* a circular argument.”
Like, how? Epilepsy is not a mental illness, because there is now demonstratable physical pathology. In 1926, a discussion entitled “Epilepsy; A Functional Mental Illness; its Treatment” was written by A.T. Mathers, who suggested that “the camps are divided between the more or less vociferous exponents of what Southard aptly called the “brain spot” and “mind twist” theories.” Sounds familiar…
“No, *mental states* are included under the name of mental disorders”
Is drug addiction a mental illness? Unless you fail to see that diagnoses of mental illness are made to rationalise the treatment of bad behaviour, of course you will think that psychiatrists are naming mental states and not behaviours. Many behaviours are now officially mental illnesses - smoking, gambling, drinking, etc.
“Do you have any argument that actually addresses these particular frightening and debilitating mental states?”
How can you use an argument to address a mental state? Arguments address people, and I have no idea what you are asking. Of course people sometimes feel weird, not themselves, frightened, etc, but this doesn’t mean they have an illness. It is odd that people think it polite to force a vulnerable adult to do something they do not want to do, all in the name of helping them.
In other news, I was stopped by a fund-raiser from MIND today, who assured me that schizophrenics have pathological brains. Any ideas? Bored now.
June 5, 2008 at 6:29 pm
beakie
Just when I thought we should all be nice to Ted, along he comes and tops his own record for drivel. Your sheer ignorance of mental illness and its devastating impact on people is astounding and yet still you think you can gob off like some sort of expert. Psychosis isn’t just about people feeling “a bit weird”, it’s a fucking terrifying experience that not only affects the individual but also those around him. You clearly haven’t spent a single second with someone experiencing psychosis; if you had done, you would be in no doubt that it is humane and right to treat them.
And in what bizarre parallel universe is smoking a mental illness?
June 6, 2008 at 5:38 pm
Ted
@ beakie
Well, apologies for not throwing enough of a certain kind of sympathy the way of mental patients. You sound like you have first-hand experience of psychosis? Therefore it must be whatever you say it is, right? I never said that people in mental hospitals aren’t having a very bad time (is that better?). Life can be very very difficult at times. As we established on the thread concerning the existence of mental illness, I in fact have spent more than “a single second with someone experiencing psychosis,” so again you are incorrect. Anyway, why can’t you say what you mean and use the word “coercion” instead of, or in addition to, “treatment”? If you haven’t been following what I’ve said, I’ve no problems with people agreeing to any kind of “treatments” they want. Good luck to them, and I hope they get something out of it all.
“And in what bizarre parallel universe is smoking a mental illness?”
The one we live in.
http://www.psychiatryonline.co.....dependence