Posts tagged schizophrenia
There is an article in press in Neuropsyhcologia by Lackner et al that related Dopamine (DA) levels as measured by Eye Blink Rate (EBR) to preschoolers (3-5 yrs old) Representational theory of Mind (RTM).
The authors hypothesized that as one of the neural correlates of RTM is dMPFC, and as dMPFC has dopamine receptors and is innervated by dopmainergic projections along the dopamine mesocortical pathways , hence perhaps it is the dopamine’s tonic and phasic levels that may be correlated with and have a causal role in the preschoolers’ developing RTM abilities.
3-5 years is a critical period in which the RTM abilities are developing in a normal kid and are first found to be deficient in autistic kids. another linkage the authors seem relevant, but which I don’t agree to much, is the error -prediction theory of dopamine. They believe that ToM/RTM abilities develop when one takes into account the behavior of others and finds discrepancies in ones own knowledge and why they act based on certain different assumptions and by realizing this error of prediction modifies ones understanding of others and starts attributing a mind to them. The authors believe that phasic dopamine which has error prediction functions may be affecting RTM via this pathway too; I find that not very convincing.
However, their basic premise that tonic or baseline dopamine affects RTM abilite seems to be on firm ground and they found support for this hypothesis. They did not measure DA levels directly , but instead relied on Eye Bink Rate (EBR) which is a robuts predictor of overall dopamine in the mesolimbic pathways via the caudate nucleus dopamine levels. They also did not measure EBR directly but measured it using EEG waveforms of relevant brain regions above the eyes.
The RTM tasks they used and the Response -conflict executive function (RC-EF) tasks they used are very simple and intuitive and I refer the reader to methods section to pursue them in detail. For our purpose it is sufficient to mention that RTM did not include the famous anne-sally false belief task but had other variants like false belief location task etc.
Their findings were unequivocal. They found that DA levels as gauged from EBR were a significant predictors of RTM abilities and the effect was not mediated by a possible confound- that of RTM and RC-EF linkages and correlations.
For our purposes what is most important is the direction of the effect . More DA levels were associated with better RTM ; while lower DA was associated with lower RTM performance. This is consistent with the DA relation of Schizophrenia/Autism one of which has higher DA levels and better ToM; while the other both poorer ToM and lower baseline DA. To quote:
These findings dovetail with other research connecting dopamine and representational theory of mind in autistic and schizophrenic populations. Both autism and schizophrenia have been associated with RTM impairment (Pickup, 2008; Sabbagh,2004; Savina & Beninger, 2007) and dysregulation of DA (Braver, Barch, & Cohen, 1999; Lam, Aman, & Arnold, 2006). For instance, in the case of schizophrenia there is some evidence that increased levels of frontal dopamine, as a consequence of the pharmacological activity of some atypical antipsychotics, leads to increased performance on RTM tasks (Savina & Beninger, 2007). The present study added to this body of literature by demonstrating associations between RTM and DA in typically developing children. Considered together, this further supports the hypothesis that dopaminergic functioning plays a role in RTM development.
As always, I am excited by more support for Autism and Psychosis as opposites theory and belive this further cements the case and shows possible neurochemichal mechanisms underlying the difference.
Lackner, C., Bowman, L., & Sabbagh, M. (2010). Dopaminergic functioning and preschoolers’ theory of mind Neuropsychologia DOI: 10.1016/j.neuropsychologia.2010.02.027
I have blogged extensively about the Autism and Schizophrenia as opposites on a continuum theory. I remember first putting this theory in words in an article 3 yrs back on the mouse trap titled Autism and Schizophrenia: the two cultures. That 2006 article, in turn, was inspired by Daniel Nettle’s 2005 article in Journal of Research in Personality where Nettle had also proposed the dichotomy and that paper helped crystallize my thoughts on the subject, a theory which I had been building on my own and now supported by someone like Nettle who I respect a lot. Important to note that at that time I was blissfully unaware of Badcock or Crespi and their work. It is to the credit of Badcock that he had published in 2006 his own theory of Autism and Schizophrenia as opposites on a continuum based on parental imprinting of genes and proposed a mechanism. Crespi I guess got involved in Badcocks’s efforts later on and gave it more experimental and theoretic grounding. I firts became aware of Badcock and Crespi’s work in early 2008.
The wider world became aware of the Autism/Schizophrenia dichotomy sometime in late 2008 (November 2008) . at that time too, I was a little disappointed because most of the coverage did not mention Daniel Nettle, who I think should be credited for this work and line of reasoning too. As a consolation, some reports did mention Chris Frith who has also been partly supporting the thesis.
I wanted to give a historical perspective, because I am sure the recent Crespi article would be grabbed on by mainstream media and the pioneers Chris Frith/Nettle perhaps overlooked- but to me they too are heroes for having come up with such profound early insights. this is not to discredit teh work of Badcock and Crespi- they are doing a thorough job of convincing the skeptics and delineating the exact mechanism and genetics involved.
While we are on the topic of historical perspective , let me also pat myself on the back. In May 2008, a study came out that de novo Copy Number Variations’s (CNVs) were quite high in schizophrenics and they are in the same region as that for autistics who also have high CNVs in the same region. While some took that result to imply that Schizophrenia and Autism are same and are not different, I persisted and proposed a mechanism, whereby they could still be opposites : To quote:
Now as it happens previous research has also found that CNVs are also found to a higher extent in autistics. Moreover, research has indicated that the same chromosomal regions have CNVs in both Autism and Schizophrenia. To me this is exciting news. Probably the chromosomal region (neurexin related is one such region) commonly involved in both schizophrenia and autism is related to cognitive style, creativity and social thinking. Qualitatively (deletions as opposed to duplications) and quantitatively (more duplications) different type of CNVs may lead to differential eruption of either Schizophrenia or Autism as the same underlying neural circuit gets affected due to CNVs, though in a different qualitative and quantitative way.
Now one and half year later Crespi et al report the results of their study which has found exactly the same- that is, if deletions in some locus lead to autism, duplications lead to schizophrenia and vice versa. That to me is clinching evidence of my thesis. Who says Science does not happen on blogs- I proposed something to flow as a consequence of theory and exactly the same thing is found as per the hypothesis. I feel vindicated and emotional to some extent. Loves labor has not been lost to deaf ears.
Let us then return to the new and latest study that has sort of proven that Autism and Schizophrenia are opposites, genetically. Crespi et al, report in the latest PNAS edition that comparative genomics leads to that conclusion. What Crespi et al did was look at theCNV s and the locus whee CNV in both Autism and Schizophrenia are involved and sure enough they found the pattern I had proposed. I’ll now quote from the abstract and the article extensively:
We used data from studies of copy-number variants (CNVs), singlegene associations, growth-signaling pathways, and intermediate phenotypes associated with brain growth to evaluate four alternative hypotheses for the genomic and developmental relationships between autism and schizophrenia: (i) autism subsumed in schizophrenia, (ii) independence, (iii) diametric, and (iv) partialoverlap. Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other. Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance. However, differentiation between the partial overlap and diametric hypotheses using these data is precluded by limited overlap in the specific genetic markers analyzed in both autism and schizophrenia. Evidence from the effects of risk variants on growth-signaling pathways shows that autism-spectrum conditions tend to be associated with upregulation of pathways due to loss of function mutations in negative regulators, whereas schizophrenia is associated with reduced pathway activation. Finally, data from studies of head and brain size phenotypes indicate that autism is commonly associated with developmentally-enhanced brain growth, whereas schizophrenia is characterized, on average, by reduced brain growth.These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurodevelopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain.
Copy Number Data. Rare copy-number variants (CNVs) at seven loci, 1q21.1, 15q13.3, 16p11.2, 16p13.1, 17p12, 22q11.21, and 22q13.3 (Tables S1 and S2), have been independently ascertained and associated with autism and schizophrenia in a sufficient number of microarray-based comparative genomic hybridization (aCGH) and SNP-based studies to allow statistical analysis of the frequencies of deletions versus duplications in these two conditions (Table 1, Tables S3–S9). For five of the loci (1q21.1, 16p11.2, 16p13.1, 22q11.21, and 22q13.3), specific risk variants have been statistically supported for both autism and schizophrenia using case-control comparisons, which allows direct evaluation of the alternative hypotheses in Fig. 1. One locus (16p13.1) supports a model of overlap, and four loci support the reciprocal model, such that deletions are associated with increased risk of autism and duplications with increased risk of schizophrenia (16p11.2, 22q13.3), or deletions are associated with increased risk of schizophrenia and duplications with increased risk of autism (1q21.1, 22q11.21). For 1q21.1 and 22q11.21, contingency table analyses also indicate highly significant differences in the frequencies of deletions compared with duplications for the two disorders, such that schizophrenia is differentially associated with deletions and autism with duplications. By contrast, for 16p11.2 and 22q13.3 such analyses show that autism is differentially associated with deletions and schizophrenia with duplications.
I cannot cut n paste the table, but a look at the table clears all doubts. They also look at gene association data and come to a similar conclusion ruling out model A (autism, subsumed in schizophrenia) or model B (autism and schizophrenia are independent of each other).
Models 1C (diametric) and 1D (overlapping) both predict broad overlap in risk genes between autism and schizophrenia, and do not necessarily predict an absence or paucity of genes affecting one condition but not the other. In theory, these models can be differentiated by using data on specific risk alleles for specific loci (such as single-nucleotide polymorphisms, haplotypes, or genotypes), which should be partially shared under the overlapping model but different under the diametric model. For the genes DAO, DISC1, GRIK2, GSTM1, and MTHFR, the same allele, genotype, or haplotype was associated with both autism and schizophrenia, and for the genes AHI1, APOE, DRD1, FOXP2, HLA-DRB1, and SHANK3, alternative alleles, genotypes, or haplotypes at the same loci appear to mediate risk of these two conditions (SI Text). For the other genes that have been associated with both conditions, heterogeneity in the genetic markers used, heterogeneity among results from multiple studies of the same genes, and the general lack of functional information preclude interpretation in terms of shared or alternative risk factors.
Models of autism as a subset of schizophrenia (Fig. 1A), and autism and schizophrenia as independent or separate (model 1B), can be rejected with some degree of confidence, but models involving diametric etiology (model 1C) or partial overlap (model 1D) cannot be clearly rejected. Taken together, most of the data and analyses described here appear to support the hypothesis of autism and schizophrenia as diametric conditions, based primarily on the findings that reciprocal variants at 1q21.1, 16p11.2, 22q11.21, and 22q13.3 represent statistically-supported, highly-penetrant risk factors for the two conditions (Table 1), and that for a number of genes, alternative alleles or haplotypes appear to mediate risk of autism versus schizophrenia.
Additional lines of evidence supporting the diametric hypothesis, from previous studies of autism and schizophrenia, include:
- 1. Data showing notable rarity of familial coaggregation of autism with schizophrenia (38), in contrast, for example, to strong patterns of co-occurance within pedigrees of schizophrenia, schizoaffective disorder, and bipolar disorder (39).
- 2. Psychiatric contrasts of Smith-Magenis syndrome with Potocki-Lupski syndrome (due to the reciprocal duplication at the Smith-Magenis locus), Williams syndrome with cases of Williams-syndrome region duplication, and Klinefelter syndrome with Turner syndrome, each of which tends to involve psychotic-affective spectrum phenotypes in the former syndrome, and autistic spectrum conditions in the latter (5, 40).
- 3. Effects of autism and schizophrenia risk alleles on common growth-signaling pathways, such that autism has been associated with loss of function in genes, such as FMR1, NF1, PTEN, TSC1, and TSC2 that act as negative regulators of the PI3K, Akt, mTOR, or other growth-signaling pathways (41–45), whereas schizophrenia tends to be associated with reduced function or activity of genes that up-regulate the PI3K, Akt, and other growth-related pathways (46–49).
- 4. Increased average head size, childhood brain volume, or cortical thickness in individuals with: (i) idiopathic autism (50–53), (ii) the autism-associated duplications at 1q21.1 (17) and 16p13.1 (32) and the autism-associated deletions at 6p11.2 (31), and (iii) autism due to loss of function (or haploinsufficiency) of FMR1 (54), NF1 (55), PTEN (56) and RNF135 (57). By contrast, reduced average values for brain size and cortical thickness, due to some combination of reduced growth and accelerated gray matter loss, have been demonstrated with notable consistency across studies of schizophrenia (58–62), and such reduced head or brain size has also been associated with the schizophrenia-linked CNVs at 1q21.1 and 22q11.21 (17, 63, 64), and with deletions of 16p13.1 (65).
I am more than pleased with these results. Badcock too is. You can read his comments here. What about you? What would it take to convince you? 🙂
Crespi, B., Stead, P., & Elliot, M. (2009). Evolution in Health and Medicine Sackler Colloquium: Comparative genomics of autism and schizophrenia Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0906080106
There is a letter published in the advance online edition of Nature Genetics, that reports that microduplication of genes in the region 16p11.2 are associated with the risk of schizophrenia in a large cohort. It has been earlier shown that microdeletions in the same region confer the risk of Autism.Thus, it seems that the region codes for genes too much of which causes schizophrenia and too little autism. Here is the abstract of the study:
Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 times 10-5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 times 10-7), bipolar disorder (P = 0.017) and autism (P = 1.9 times 10-7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 times 10-13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).
Here is what medical news today (via which I found this article) has to say about the findings:
An international team of researchers led by geneticist Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL), has identified a mutation on human chromosome 16 that substantially increases risk for schizophrenia.
The mutation in question is what scientists call a copy number variant (CNV). CNVs are areas of the genome where the number of copies of genes differs between individuals. The CNV is located in a region referred to by scientists as 16p11.2. By studying the genomes of 4,551 patients and 6,391 healthy individuals, Sebat’s team has shown that having one extra copy of this region is associated with schizophrenia. The study appears online today ahead of print in the journal Nature Genetics.
Schizophrenia and autism: two sides of the same coin?
“This is not the first time that the 16p11.2 region has caught our eye,” says Sebat. It was previously spotted in a 2007 study with Professor Michael Wigler at CSHL — a deletion of the identical region was identified in a girl with autism. Studies by several other groups have shown that losing one copy of 16p11.2 confers high risk of autism and other developmental disorders in children.
Taken together these studies suggest that some genes are shared between schizophrenia and autism, according to Sebat and colleagues. “In some ways, we might consider the two disorders to be at opposite ends of the same neurobiological process” says Shane McCarthy, Ph.D., the lead author of the study, “and this process is influenced by the copy number of genes on chromosome 16.” One hypothesis is that the loss of 16p11.2 leads to the deprivation of key genes involved in brain development, while an extra copy of this region might have the opposite effect.
A correlation between 16p11.2 mutations and head size
It is not known what biological processes are affected by the copy number of 16p11.2, Sebat notes. He believes, however, that the team may have stumbled on to an important clue. By studying the clinical records of patients, they discovered that patients with deletions of the region differ significantly in head size from those with duplications of the same region. Sebat reports, “Head circumference of patients with the deletion were larger than average by more than one standard deviation. Head circumference was slightly below average in patients with the duplication.” These findings, he notes, are consistent with some previous studies that have observed a trend towards larger brain size in autism and an opposite trend toward smaller brain size in schizophrenia.
All this nicely fits in with what I have been proclaiming from the rooftops from the early days of this blog: that autism and Schizophrenia are opposites on the same continuum and the genes involved should also be the same. More copy numbers leading to propensity towards psychosis while lesser number or deletions associated with autistic traits. One more puzzle piece fits in and now we know why the brain size differences exist in autistic and schizophrenic persons and what the poetntial function (mentalizing) of region 16p11.2 may be.
McCarthy, S., Makarov, V., Kirov, G., Addington, A., McClellan, J., Yoon, S., Perkins, D., Dickel, D., Kusenda, M., Krastoshevsky, O., Krause, V., Kumar, R., Grozeva, D., Malhotra, D., Walsh, T., Zackai, E., Kaplan, P., Ganesh, J., Krantz, I., Spinner, N., Roccanova, P., Bhandari, A., Pavon, K., Lakshmi, B., Leotta, A., Kendall, J., Lee, Y., Vacic, V., Gary, S., Iakoucheva, L., Crow, T., Christian, S., Lieberman, J., Stroup, T., Lehtimäki, T., Puura, K., Haldeman-Englert, C., Pearl, J., Goodell, M., Willour, V., DeRosse, P., Steele, J., Kassem, L., Wolff, J., Chitkara, N., McMahon, F., Malhotra, A., Potash, J., Schulze, T., Nöthen, M., Cichon, S., Rietschel, M., Leibenluft, E., Kustanovich, V., Lajonchere, C., Sutcliffe, J., Skuse, D., Gill, M., Gallagher, L., Mendell, N., Craddock, N., Owen, M., O’Donovan, M., Shaikh, T., Susser, E., DeLisi, L., Sullivan, P., Deutsch, C., Rapoport, J., Levy, D., King, M., & Sebat, J. (2009). Microduplications of 16p11.2 are associated with schizophrenia Nature Genetics DOI: 10.1038/ng.474
UPDATE: I just revisited my 20th may 2008 post on the matter and realized how prophetic my musings were. Reproducing part of it below the fold for the benefit of newbies to this blog:
CNVs on the other hand present a different model of disease. One can have one or more types of CNVs (deletions, duplications, multiple duplications etc) associated with the same genetic code sequence and this in my view would lead to spectrum like diseases where one may find variations along a continuum on a particular trait- based on how many copies of the genetic sequence one has. One would remember that I adhere to a spectrum based view of schizophrenia/psychosis and also a spectrum based view of Autism. Moreover I believe that Schizophrenia and Autism are the opposite ends of the spectrum, whose middle is normalcy and that the appropriate traits may have to do with social brain, creativity etc.
now as it happen previous research has also found that CNVs are also found to a higher extent in autistics. Moreover, research has indicated that the same chromosomal regions have CNVs in both Autism and Schizophrenia. To me this is exciting news. Probably the chromosomal region (neurexin related is one such region) commonly involved in both schizophrenia and autism is related to cognitive style, creativity and social thinking. Qualitatively (deletions as opposed to duplications) and quantitatively (more duplications) different type of CNVs may lead to differential eruption of either Schizophrenia or Autism as the same underlying neural circuit gets affected due to CNVs, though in a different qualitative and quantitative way.
A mouse trap reader, using skribit, asked me to write a blog post about the history of madness; that is a dauting task, as she herself mentioned that Foucault wrote an entire book on the subject; so though I promise to write that post, in the meantime here is a post about the history of Autism. After this , the next in series would be a brief history of Schizophrenia.
References to schizophrenia can be found since time immemorial, though the actual term and diagnosis is recent. It is believed that the people haunted by Furies of ancient Greek were actually schizophrenics suffering from delusions and hallucinations. As I contrast Autism and Schizophrenia it is apt that I start here; for similar to the rich historic al tradition, Autism can be equated with the ,blessed Fools’ of old Russia, “who were revered for their unworldiness. The apparent insensitivity to pain, bizarre behaviour, innocence, and lack of social awareness that these “Blessed Fools” showed, suggest that they may have had autism. ” (Happe). Similarly in almost all cultures one can find anecdotes and folktales about foolish boys (note that it is a boy and not a girl as autism has always been more prevalent in boys) who take what their mother said too literally- word for word , rather than figuratively and metaphorically or idiomatically.
The modern diagnosis of autism starts with Leo Kanner. Kanner published his first paper about autistic children in 1943, the full text of which can be found here. Some excerpts from the paper, which has many case studies , should help:
Since 1938, there have come to our attention a number of children whose condition differs so markedly and uniquely from anything reported so far, that each case merits – and, I hope, will eventually receive – a detailed consideration of its fascinating peculiarities.
The outstanding, “pathognomonic,” fundamental disorder is the children’s inability to relate themselves in the ordinary way to people and situations from the begining of life. Their parents referred to them as having always been “self-sufficient”; “like in a shell”; “happiest when left alone”;“acting as if people weren’t there”; “perfectly oblivious to everything about him”; “giving the impression of silent wisdom”; “failing to develop the usual amount of social awareness”;“acting almost as hypnotized.”T his is not, as in schizophrenic children or adults, a departure from an initially present relationship; it is not a “withdrawal”from formerly existing participation. There is from the start an extreme autistic aloneness that, whenever possible, disregards, ignores, shuts out anything that comes to the child from the outside. Direct physical contact or such motion or noise as threatens to disrupt the aloneness is either treated “as if it weren’t there”or, if this is no longer sufficient, resented painfully as distressing interference.
Eight of the eleven children acquired the ability to speak either at the usual age or after some delay. Three (Richard, Herbert, Virginia) have so far remained “mute.”In none of the eight “speaking” children has language over a period of years served to convey meaning to others. They were, with the exception of John F., capable of clear articulation and phonation. Naming of objects presented no difficulty; even long and unusual words were learned and retained with remarkable facility. Almost all the parents reported, usually with much pride, that the children had learned at an early age to repeat an inordinate number of nursery rhymes, prayers, lists of animals, the roster of presidents, the alphabet forward and backward, even foreign-language (French) lullabies. Aside from the recital of sentences contained in the ready-made poems or other remembered pieces, it took a long time before they began to put words together. Other than that, “language”consisted mainly of “naming,”of nouns identifying objects, adjectives indicating colors, and numbers indicating nothing specific.
Their excellent rote memory, coupled with the inability to use language in any other way, often led the parents to stuff them more and more verses, zoologic and botanic names, titles and composers of Victrola record pieces, and the like. Thus, from the start, language-which the children did not use for the purpose of communication-was deflected in a considerable measure to a self-sufficient, semantically and conversationally valueless or grossly distorted memory exercise.
When sentences are finally formed, they are for a long time mostly parrot-like repetitions of heard word combinations. They are sometimes echoed immediately, but they are just as often “stored”by the child and uttered at a later date. One may, if one wishes, speak of delayed echolalia. Affirmation is indicated by literal repetition of a question. “Yes”is a concept that it takes the children many years to acquire. They are incapable of using it as a general symbol of assent. Donald learned to say “Yes”when his father told him that he would put him on his shoulders if he said “Yes.”This word then came to “mean”only the desire to be put on his father’s shoulders. It took many months before he could detach the word “Yes”from this specific situation, and it took much longer before he was able to use it as a general term of affirmation.
The same type of literalness exists also with regard to prepositions. Alfred, when asked, “What is this picture about?”replied:”People are moving about.”
John F. corrected his father’s statement about pictures on the wall; the pictures were “near the wall.” Donald T., requested to put something down, promptly put it on the floor. Apparently the meaning of a word becomes inflexible and cannot be used with any but the originally acquired connotation.
But the child’s noises and motions and all of his performances are as monotonously repetitious as are his verbal utterances. There is a marked limitation int he variety of his spontaneous activies. The child’s behavior is governed by an anxiously obsessive desire for the maintenance of sameness that nobody but the child himself may disrupt on rare occasions. Changes of routine, of furniture arrangement, of a pattern, of the [form] in which every-day acts are carried out, can drive him to despair. When John’s parents got ready to move to a new home, the child was frantic when he saw the moving men roll up the rug in his room. He was acutely upset until the moment when, in the new home, he saw his furniture arranged in the manner as before. He looked pleased, all anxiety was suddenly gone, and he went around affectionately patting each piece. Once blocks, beads, sticks have been put together in a certain way, they are always regrouped in exactly the same way, even though there was no definite design. The children’s memory ws phenomenal in this respect. after the lapse of several days, a multitude of blocks could be rearranged in precisely the same unoganized pattern, with the same color of each block turned up, with each picture or letter on the upper surface of each block facing in the same direction as before. The absence of a block or the presence of a supernumerary block was noticed immediately, and there was an imperative demand for the restoration of the missing piece. If someone removed a block, the child struggled to get it back, going into a panic tantrum until he regained it, and then promptly and with sudden calm after the storm returned to the design and replaced the block.
The children’s relation to people is altogether different. Every one of the children, upon entering the office, immediately went after blocks, toys, or other objects, without paying the least attention to the persons present. It would be wrong to say that they were not aware of the presence of persons. But the people, so long as they left the child alone, figured in about the same manner as did the desk, the bookshelf, or the filing cabinet. When the child was addressed, he was not bothered. He had the choice between not responding at all or, if a question was repeated too insistently, “getting it over with”and continuing with whatever he had been doing. Comings and goings, even of the mother, did not seem to register. Conversation going on in the room elicited no interest. If the adults did not try to enter the child’s domain, he would at times, while moving between them, gently touch a hand or a knee as on other occasions he patted the couch. But he never looked into anyone’s face. If an adult forcibly intruded himself by taking a block away or stepping on an object that child needed, the child struggled and became angry with the hand or the foot, and became angry with the hand or the foot, which was dealt with perse [?] and not as a part of a person. He never addressed a word or a look to the owner of the hand or foot. When the object was retrieved, the child’s mood changed abruptly to one of placitidy. When pricked, he showed fear of the pin but not of the person who pricked him.
Note already that all the currently accepted DSM-IV characteristics of Autism like communicative difficulties, social difficulties and stereotyped or repetitive behavior are already well delineated by Kanner. Here one has to pause and note that autism and autistics were used from the social aloofness first observed and documented in schizophrenics by Kreplin and we seem to have come a full circle now by positing that Autism and schizophrenia are opposites on a continuum. It is also heartening to note that Kanner was also way ahead of his times by focusing on the deficit in ‘mentalizing’ in autistic kids.
Just a year after, Hans Asperger , published his paper on ASD kids, and it is remarkable that despite not knowing about each others papers they came with similar terminology (autistic ) to describe the children and agreed on more points than they disagreed on.
Asperger published the first definition of Asperger Syndrome, in 1944. In four boys, he identified a pattern of behavior and abilities that he called “autistic psychopathy”, meaning autism (self) and psychopathy (personality disease). The pattern included “a lack of empathy, little ability to form friendships, one-sided conversation, intense absorption in a special interest, and clumsy movements.” Asperger called children with AS “little professors” because of their ability to talk about their favorite subject in great detail. It is commonly said that the paper was based on only four boys.
Asperger and Kanner agreed as well as disagreed on many things:
Hans Asperger deserves credit for some very striking insights into autism: some insights which Kanner (1943) lacked and which it has taken us many years of research to rediscover. Before considering these particular observations of Asperger’s, it is worth noting the many features on which the two physicians agreed.
Kanner’s and Asperger’s descriptions are surprisingly similar in many ways, especially when one remembers that each was unaware of the other’s ground-breaking paper. Their choice of the term “autistic” to label their patients is itself a striking coincidence. This choice reflects their common belief that the child’s social problems were the most important and characteristic feature of the disorder. The term “autistic” comes from Bleuler (1908), who used the word (from the Greek “autos” meaning “self”) to describe the social withdrawal seen in adults with schizophrenia. Both Kanner and Asperger believed the social handicap in autism to be innate (in Kanner’s words) or constitutional (as Asperger put it), and to persist through life into adulthood. In addition, Kanner and Asperger both noted the children’s poor eye contact, their stereotypies of word and movement, and their marked resistance to change. The two authors report the common finding of isolated special interests, often in bizarre and idiosyncratic objects or topics. Both seem to have been struck by the attractive appearance of the children they saw. Kanner and Asperger make a point of distinguishing the disorder they describe from schizophrenia, on the basis of three features: the improvement rather than deterioration in their patients, the absence of hallucinations, and the fact that these children appeared to be abnormal from their earliest years, rather than showing a decline in ability after initially good functioning. Lastly, both Kanner and Asperger believed that they had observed similar traits—of social withdrawal or incompetence, obsessive delight in routine, and the pursuit of special interests to the exclusion of all else—in the parents of many of their patients.
There are three main areas in which Asperger’s and Kanner’s reports disagree, if we believe that they were describing the same sort of child. The first and most striking of these is the child’s language abilities. Kanner reported that three of his 11 patients never spoke at all, and that the other children did not use what language they had to communicate: “As far as the communicative functions of speech are concerned, there is no fundamental difference between the eight speaking and the three mute children” (Kanner 1943). While phonology (as demonstrated in accurate echolalia) and vocabulary were often excellent, Kanner concluded that of his 11 cases “In none …has language…served to convey meaning”. The picture in all is of a child with profound communicative difficulties and delay; in seven of the 11 cases so profound that deafness was initially suspected (but ruled out). Asperger, by contrast, reported that each of his four case study patients (and, by implication, most of the unspecified number of such children he treated) spoke fluently. Although two of his patients showed some delay, this was followed in both cases by a rapid mastery of language, and it is difficult to imagine any of his cases having been mistaken for deaf. All four cases, by the age of examination (between 6 and 9 years old), spoke “like little adults”. Asperger notes their “freedom” and “originality” in language use, and reports that two of his four cases had a tendency to tell “fantastic stories”.
Asperger’s description also conflicts with Kanner’s on the subject of motor abilities and co-ordination. Kanner (1943) reported clumsiness in only one case, and remarks on the dexterity of four of his patients. He concluded that “several of the children were somewhat clumsy in gait and gross motor performance, but all were very skilful in terms of finer muscle coordination”—in line with their success on the Seguin form board (in which dexterity plays a part) and their ability to spin objects. Asperger, by contrast, described all four of his patients as clumsy, and recounted their problems not only with school sports (gross co-ordination), but also with fine motor skills such as writing. This feature is part of a larger contrast in Asperger’s and Kanner’s beliefs. Kanner believed the autistic child to have a specific impairment in social understanding, with better relations to objects than to people: while his children showed “excellent, purposeful and ‘intelligent’ relations to objects” their “relations to people [were] altogether different”. Asperger, on the other hand, believed that his patients showed disturbances in both areas: “the essential abnormality in autism is a disturbance of the lively relationship with the whole environment” (Asperger 1944, translated in Frith 1991b).
The last area of disagreement in the clinical pictures painted by Asperger and Kanner is that of the child’s learning abilities. Kanner believed that his patients were best at learning rote fashion, but Asperger felt that his patients performed “best when the child can produce spontaneously”, and suggests that they are “abstract thinkers”. (Happe)
We now know that many of the insights of Asperger were correct especially for those suffering from high-functioning autism or Asperger’s syndrome.
A dark period of autism research was the ‘refrigerator mother‘ hypothesis , which posited based on a psychogenic theory that autism was due to bad parenting. The seeds of this theory can be traced back to Kanner, but Bruno Bettelheim gave it a prominence. this theory as now been widely debunked and discredited and caused undue suffering and guilt to a generation of parents.
Leading researchers in the field after these have been Uta Frith, Leslie, Happe and Simon-Baron-Cohen with his ‘mind-blindness’ theory.
Before concluding please visit the DSM criteria and reassess them as now autism, at least by me and many leading researchers, is conceptualized more as a continuum disorder. Hope the DSM-V has a continuum framework for autism.
Kanner L (1968). Autistic disturbances of affective contact. Acta paedopsychiatrica, 35 (4), 100-36 PMID: 4880460