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Revised 25 November 2013

Abnormal Brain Structure & Autism


Alan Challoner MA (Phil) MChS

INTRODUCTION
Researchers no longer consider autism to be a rare disorder. At one time, only two to four children per !,!!! were considered autistic, but with milder cases factored in, one in "!! children is now considered to be autistic to some degree. #owe$er it is not infre%uent that the subtle signs of the milder cases are being missed by physicians and other early childhood wor&ers, according to the report published in the 'ecember (!!( issue of the )ournal of Autism and 'e$elopmental 'isorders. Autism also brings about abnormalities in the brain (other than those, which cause it) by interfering with normal de$elopment, both cogniti$e and emotional. *e should also be $ery careful about the ways in which we treat children with autism. +eha$ioural characteristics often are part of their coping strategy. ,heir brain has adapted to the damage it has recei$ed, and their beha$iour reflects the reparation and tolerance of what has happened to them. -t is wrong that their beha$iour should be stylised as pathological and treated with psychotropic drugs.

AETIOLOGY OF AUTIS S!ECTRU DISORDERS


Professor Peter S.atmari in his /ditorial , misses important aetiology of autism spectrum disorders. Although he includes a brief note on en$ironmental ris& factors, he omits to0ic considerations. #e goes on to write that the MMR $accine is not an en$ironmental ris& factor, but omits any reference to the 'P, (whole cell) $accine. -t is now accepted that constituents of the whole cell 'P, $accine can pass the blood1brain barrier. -f they do so, they then can cause sporadic damage to the brain. Abnormal brain structure has been put forward by researchers loo&ing for a cause for autism. ,hese ha$e in$ol$ed the amygdala, the hippocampus, the cerebellum and the caudate nucleus. /ric Courchesne et al ha$e shown that neo2cerebellar damage impairs the ability to rapidly and accurately change attentional maps during shifts of attention between auditory and $isual information as well as between perceptual domains within the $isual modality. 'uring recent studies they ha$e attempted to re$eal the underlying causes of autism using a $ariety of techni%ues. Particular emphasis was placed on techni%ues that ha$e been used by a number of different laboratories, including structural magnetic resonance imaging and post2mortem studies of neuro2anatomy. 3euro2biological and neuropsychological data from indi$iduals across a wide age range were e0amined from a neuro2de$elopmental perspecti$e. 4rom these recent ad$ances they ha$e de$eloped a growth dysregulation hypothesis of autism. ( -n an earlier study, Courchesne et al, in reinforcing the $iew that autism in$ol$es abnormal regulation of brain growth during early life, show that there is an unusual de$elopmental neuro2anatomic phenotype characterised by hyperplasia of cerebellar white matter, neocortical grey matter, and cerebral white matter at the youngest ages with slowed

S"atmari# !$ ,he causes of autism spectrum disorders. /ditorial, BMJ (!!565(78 952 9:
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A%s&oomo'' N# !ierce (# Courc&esne E$ ,he neurobiological basis of autism from a de$elopmental perspecti$e. Dev Psychopathol (!!( Summer :87 525:

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growth thereafter6 slowed growth in the cerebellar hemispheres6 and a smaller $ermis at all ages e0amined.5 ,hey hypothesised the genetic factors most li&ely underlie this growth abnormality, and suggest that future genetic research might usefully e0plore lin&age between autism and genes that are &nown to alter white matter de$elopment. ;ne e0ample of such a gene is p(9, which regulates proliferation of glial and neural cells and affects myelin formation by oligodendrocytes. <oss of the p(9 gene may lead to additional glial and neuronal cell di$isions before withdrawal from cell proliferation cycles. -n mice with this gene &noc&ed out, there was a ("!= increase in glial fibrillary acid protein>staining glia cells in the cerebellum and a 5!= increase in numbers of neurons in CA of the hippocampus.: Another important aetiology is e0citoto0icity, an in$ol$ement that may allow the brain to discard useless connections or reduce poorly functioning neurons. -f neurons are stimulated by to0ins, lac& of o0ygen or are affected by genetic programmes, they release glutamate. ,his process may be in$ol$ed in stro&e, Al.heimer?s disease, and other neuro2degenerati$e conditions, possibly including schi.ophrenia. Alternati$ely, one pathology could trigger the second6 although it is unclear how Pur&in@e neuron loss could trigger e0cessi$e a0onal or glial1myelin growth in cerebellar white matter, e0cessi$e proliferation of e0citatory a0onal pro@ections might be speculated to lead to pathologic e0citoto0icity and Pur&in@e death. /0citoto0icity as a patho2physiologic factor in autism has pre$iously been proposed." ,he coe0istence of both cerebral and cerebellar malde$elopment may e0plain why the impairments in higher cogniti$e functions in autism are per$asi$e and persistent across the life span. A postnatal period of e0treme malde$elopment of these two ma@or brain structures will almost certainly be manifest in aberrant beha$ioural e0pression, and it is during this early period (typically ( to (: months) that parents most often first e0press concern about their child?s de$elopment. 7 'uring this de$elopmental period, the human brain undergoes rapid synaptogenesis, e0pansion of dendritic and a0on arbors, and selection of which neuronal elements to &eep or eliminate. 9 A B ! -n the normally de$eloping brain, shaping of neural architecture and connecti$ity is theorised to be significantly influenced or directed by functional neural acti$ity dri$en by learning and

Courc&esne# E$) (arns# C$ $) Da*is# +$R$) ,iccar-i# R$) Car.er# R$A$) Ti/ue# ,$D$) C&isum# +$0$) oses# !$) !ierce# ($) Lor-# C$) Lincoln# A$0$) !i""o# S$) Sc&reibman# L$) +aas# R$+$) A%s&oomo''# N$A$) & Courc&esne# R$Y. Cnusual brain growth patterns in early life in patients with autistic disorder An MR- study. Neurology (!! 6"98(:">(":. Casaccia1Bonne'il !# Ti%oo R# (i2o%a3a +# Frie-ric& 0# C&ao # (o'' A. ;ligodendrocite precurser differentiation is perturbed in the absence of the cyclin2dependent &inase inhibitor p(9&ip . Genes Dev BB96 8(55">(5:7.. Gor-on 4!$ 3euroto0ic theory of autism. -n8 3aruse #, ;rnit. /M, eds. 3eurobiology of infantile autism8 proceedings of the -nternational Symposium on 3eurobiology of -nfantile Autism, ,o&yo, !> 3o$ember BB!8 satellite meeting of the@oint con$ention of the "th -nternational Child 3eurology Congress and the 5rd Asian and ;ceanian Congress of Child 3eurology.3ew Dor&8 /lse$ier Science, BB(8595>597 Co5 A# C&arman T# Baron1Co&en S# et al. Autism spectrum disorders at (! and :( months of age8 stability of clinical and A'-2R diagnosis. J Child Psychol Psychiatry BBB6"89 B>95(. Sc&a-e 0!# *an Groeni/en 4B$ Structural organi.ation of the human cerebral corte0. -. Maturation of the middle frontal gyrus. Acta Anat B7 6:989(> . +uttenloc&er !R# Dab&ol%ar AS$ Regional differences in synaptogenesis in human cerebral corte0. J Comp Neurol BB96 5A98 79> 9A. 6uart" SR# Se7no3s%i T0$ ,he neural basis of cogniti$e de$elopment8 a constructi$ist manifesto. Behav Brain Sci BBA6(!8 "59>"B7.
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Courc&esne E# C&isum +# To3nsen- 0$ 3eural acti$ity2dependent brain changes in de$elopment8 implications for psychopathology. Dev Psychopathol BB:6787B9>9((.

Revised 25 November 2013

( -n the autistic brain, howe$er, the researchers speculated that growth e0perience. and elaboration of neural architecture and connecti$ity occurs prematurely and without being guided by functional e0periences and adapti$e learning6 that is, in early life the autistic brain e0hibits premature Egrowth without guidance.F

-n addition, the cerebellum and certain cerebral regions may perform analogous, possibly complementary, functions. 4or instance, in the normal brain, cerebellar corte0 is acti$ated by tas&s that commonly acti$ate frontal corte0, such as tas&s in$ol$ing wor&ing memory, attention, or semantic association. 5 : " Adults with cerebellar lesions show impaired performance on similar frontal lobe tas&s, including tests of source memory and e0ecuti$e functions (e.g., shifting attention, cogniti$e planning, and wor&ing memory). 7 9 So, the presence of both cerebral and cerebellar defects from the earliest stages of cogniti$e de$elopment would li&ely result in se$ere and persistent functional deficits. Abnormally ele$ated brain neurotrophins and neuropeptides (brain2deri$ed neurotrophic factor, neurotrophin2:, $asoacti$e intestinal peptide, calcitonin2related gene peptide) ha$e been found in neonatal blood spots of indi$iduals who later de$eloped autism and mental retardation. A ,hese brain growth factors play roles in neural proliferation, migration, differentiation, growth, and circuit organisation, and it was hypothesised that abnormal ele$ations may result in unusual regional growth abnormalities (e.g., o$ergrowth in the cerebrum due to e0cessi$e sparing of neurons and stimulation of growth of neural elements, but, parado0ically, loss of Pur&in@e cells in the cerebellum B). /ric Courchesne et al (idem) further hypothesise that in autism there is a relationship between abnormally ele$ated brain growth factors at birth and the abnormal brain growth patterns described abo$e. Pauline 4ilipe& has said, as a member of a research panel con$ened by the American Academy of 3eurology, G+y ( months of age, most children should be pointing as a non2 $erbal communication gesture and babbling. +y 7 months of age they should ha$e in their $ocabulary words other than Hmummy? and Hdaddy?, and by (: months of age, they should be using phrases.G (! Ioldberg has told us that,
E-n the past, autism was considered a GpsychiatricG disorder. *e now &now that autism is a Gmedical condition,G not a mental disorder. Perhaps one of the reasons no one has come up

6uart" SR# Se7no3s%i T0$ ,he neural basis of cogniti$e de$elopment8 a constructi$ist manifesto. Behav Brain Sci BBA6(!8 "59>"B7.
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Courc&esne E# C&isum +# To3nsen- 0$ 3eural acti$itydependent brain changes in de$elopment8 implications for psychopathology. Dev Psychopathol BB:6787B9>9((. Allen G# Bu5ton RB# 4on/ EC# Courc&esne E$ Attentional acti$ation of the cerebellum independent of motor in$ol$ement. Science BB96(9"8 B:!> B:5. Desmon- 0E# Gabrieli 0D# 4a/ner AD# Ginier BL# Glo*er G+$ <obular patterns of cerebellar acti$ation in $erbal wor&ing memory and finger2tapping tas&s as re$ealed by functional MR-. J Neurosci BB96 98B79">B7A". Raic&le E# Fie" 0A# 8i-een TO, et al. Practice2related changes in human brain functional anatomy during nonmotor learning. Cere! Corte" BB:6 :8A>(7. A%s&oomo'' NA$ -ntramodality shifting attention in children with damage to the cerebellum. J Cogn Neurosci BB:6 785AA> 5BB. Sc&ma&mann 0D# S&erman 0C$ ,he cerebellar cogniti$e affecti$e syndrome. Brain BBA6 ( 8"7 >"9B. Nelson (B# Gret&er 0(# Croen LA, et al. 3europeptides and neurotrophins in neonatal blood of children with autism or mental retardation. Ann Neurol (!! 6:B8"B9>7!7. orrison E# ason CA. Iranule neuron regulation of Pur&in@e cell de$elopment8 stri&ing a balance between neurotrophin and glutamate signaling. J Neurosci BBA6 A85"75>5"95. Fili.e%# !auline$ Journal o# Autism and Developmental Disorders ( BBB6 (B8:592:A()

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with an answer for autism is the way we ha$e thought of it (or rather did not thin& of it, in medicine). /$en though children with classic autism might be helped medically as our &nowledge of the brain?s physiology e0pands, for now it might !e help#ul to separate children a##licted $ith autistic syndrome #rom those $ith classic autism. As children with autistic syndrome increasingly become categorised as a GmedicalG problem, separating them from the many negati$e connotations and hopelessness associated with GclassicG autism could be ad$antageous to promoting research and funding to help these children. -ncreased frontal perfusion may be related to GhyperfrontalityG disorder, and cerebellar hypoperfusion to motility impairment. ,emporal lobe hypoperfusion and other areas of dysfunction remain in spite of multiple $arious therapies used by these children. *e are loo&ing at anatomical mar&ings, defining autism 1 P'' dysfunction, correlating to models proposed by beha$ioural neurologists. Past focus for autistic children has been on trainability, co2operation, and beha$iour, 3;, on impro$ing the cogniti$e processing. A shift to the idea of GrehabilitationG is already in motion6 a full re$iew of techni%ues and goals is urgently needed. Base- on NeuroS!ECT 'in-in/s# im.lications are t&at me-ications or e''orts to 9calm9 t&e brain an- c&il- -o3n# ma2 'urt&er s&ut -o3n t&e areas in 3&ic& 3e 3ant to im.ro*e bloo- 'lo3 an- 'unction an- -o3n re/ulate- bloo- 'lo3$: ;<

,here are also indications that particular parts of the brain can be shown to be damaged in the autistic person. Studies in animals ha$e recorded symptoms typical of autism in young animals with amygdala lesions. Amygdala dysfunction has also been implicated in human disorders ranging from social an0iety to depression and to autism. Another study also suggests that brain damage may bring with it autistic syndrome. More than one area of the brain is responsible for autistic beha$iour in children with tuberous sclerosis and brain lesions, according to an article published in the ;ctober B, (!! issue of Neurology, the scientific @ournal of the American Academy of 3eurology. -n a study of (7 children with tuberous sclerosis comple0 (,SC), a genetic disorder that causes benign lesions or tumours to form in many different organs, including the brain where the lesions are called Gtubers.F Autism is a common occurrence in children with ,SC. Researchers used MR- and P/, e0ams to study how brain lesions resulted in common beha$iours of autism including difficulties in social interaction and communication, and narrow and repetiti$e stereotyped beha$iour. G*e wanted to &now if where the tuber was located or what it was JdoingJ in the brain could predict beha$iours of autism,G said 'iane C. Chugani, Ph', a researcher at the P/, Center at ChildrenJs #ospital of Michigan, 'etroit, Michigan. G*e found that in these children, autism results from a comple0 combination of e$ents in different parts of the brain, rather than from one single source.G 'efects in the cerebellum, the part of the brain responsible for co2ordination, ha$e been induced in guinea pigs, and the result was the de$elopment of some of the traits typical of autism. ,hey were much less inclined to interact with their fellow animals, they did far less sniffing, lic&ing and mating attempts, and showed a reluctance to e0plore or respond to their surroundings.(( ,here are also significant changes that can ta&e place in the brain due to the administration of antipsychotic drugs (AP'). Patients who are chronically treated with antipsychotic drugs show changes in brain structure. ,here is strong support for this $iew from Chege at al who. using resonance imaging findings, ha$e found that there is increasing e$idence to suggest that AP' might affect brain structure directly, particularly the cerebral corte0. ,hey used automated analysis techni%ues to map the regions that show ma0imal impact of chronic => 3ee%s? treatment with either haloperidol or olan.apine
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Gol-ber/# $ 4rontal and ,emporal <obe 'ysfunction in autism and ;ther Related 'isorders8 A'#' and ;C'. Alasbimn )ourna (:)8 )uly BBB. http811www.alasbimn@ournal.cl1re$istas1:1goldberg.htm Reported in %uropean Journal o# Neuroscience, Kol. ! p(799.

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on the rat corte0. Iuided by these imaging findings, they undertoo& a focused postmortem in$estigation with stereology. LMy emphasis) ,heir results showed decreases in the $olume and thic&ness of the anterior cingulate corte0 (ACC) after chronic AP' treatment, regardless of the AP' administered. Postmortem analysis confirmed these $olumetric findings and demonstrated that chronic AP' treatment had no effect on the total number of neurons or S !!MN astrocytes in the ACC but that in contrast there was an increase in the density of these cells. ,his study demonstrates region2specific structural effects of chronic AP' treatment on the rat corte0, primarily but not e0clusi$ely locali.ed to the ACC. At least in the rat, these changes are not due to a loss of either neurons or astrocytes and are li&ely to reflect a loss of neuropil. (5 ,his study highlights the power of this approach to lin& magnetic resonance imaging findings to their histopathological origins. ,he results show such changes after only eight wee&s of treatment and therefore has significance for those who ha$e been prescribed these drugs o$er a longer period.(: +aron2Cohen suggests that there are particular parts of the brain that play a role in social understanding.(" ;ne of those parts is the amygdala. -f a mon&ey has a lesion in the amygdala, for e0ample, its social beha$iour changes. ,he mon&eys no longer &now where they fit in the social group, and donJt &now whether another mon&ey is being friendly, or not. ,his idea of the Gsocial brainG was first written about in the BA!s by <esley +rothers at the Cni$ersity of California, <os Angeles. +aron2Cohen?s wor& in autism has added support to this idea. Kalerie Stone has also contributed to this research. She has written that the ability to infer othersJ mental states, such as their beliefs, &nowledge and desires O is a central cogniti$e faculty underlying our ability to engage in social interaction.(7 Children with the de$elopmental disorder of autism suffer from a deficit in theory of mind. Autistic childrenJs problems with social beha$iour may result from their difficulty ma&ing inferences about othersJ mental states. Certain &inds of neurological patients also show specific deficits in social functioning. #er research in$ol$ed loo&ing for parallels between the social deficits (particularly theory of mind deficits) e0hibited by indi$iduals with autism and patients with frontal lobe or amygdala damage. -n research by Spar&es et al,(9 children with autistic spectrum disorder were found to ha$e significantly increased cerebral $olumes compared with typically de$eloping (,') and de$elopmentally delayed ('') children. Cerebellar $olume for the autistic spectrum disorder group was increased in comparison with a ,' group, but this increase was proportional to o$erall increases in cerebral $olume.

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-n neuroanatomy, a neuro.il, which is sometimes referred to as a neuropile, is a region between neuronal cell bodies in the gray matter of the brain and spinal cord (i.e. the central ner$ous system). -t consists of a dense tangle of a0on terminals, dendrites and glial cell processes. -t is where synaptic connections are formed between branches of a0ons and dendrites. C&e/e$4$) Natesan# S$) o-o# $) Coo.er$ 0D$) 4illiams$ SCR$ & (a.ur$ S. Reduced Cortical Kolume and /le$aled Astrocyte 'ensity in Rats Chronically ,reated with Antipsychotic 'rugsO <in&ing Magnetic Resonance -maging 4indings to Cellular Pathology. Bio&' Psych' published online ( ;ctober (! 5. Baron1Co&en, Simon) Ta/er1Flusber/, +elen & Co&en, Donal-$ L/ds.P Cnderstanding ;ther Minds 2 Perspecti$es from 'e$elopmental Cogniti$e 3euroscience Second /dition. ;CP, BBB. Stone# 8$E$, +aron2Cohen, S., Calder, A.C., Qeane, ). R Doung, A.*. (in press). Ac%uired theory of mind impairments in indi$iduals with bilateral amygdala lesions. Neuropsychologia' S.ar%s BF# Frie-man SD# S&a3 D4# A2l3ar- E+# Ec&elar- D# Artru AA# ara*illa (R# Gie-- 0N# unson 0# Da3son G# Da/er SR$ +rain structural abnormalities in young children with autism spectrum disorder. Neurology (!!( )ul (56"B(()8 A:2B(.

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Measurements of amygdalae and hippocampi in this group of young children with autistic spectrum disorder re$ealed enlargement bilaterally that was proportional to o$erall increases in total cerebral $olume. ,here were similar findings of cerebral enlargement for both girls and boys with autistic spectrum disorder. -n a subgroup of children with autistic spectrum disorder with strictly defined autism, amygdala enlargement was in e0cess of increased cerebral $olume. People with autism spectrum disorder show abnormal processing of faces. Qlin et al employed a well2normed tas& of face recognition to measure this ability in !( young children with autism, per$asi$e de$elopmental disorder not otherwise specified (P''3;S), and non2P'' disorders (mental retardation and language disorders) matched on chronological age and non$erbal mental age, and in a subsample of " children di$ided e%ually in the same three groups matched on chronological age and $erbal mental age. (A ,here were pronounced deficits of face recognition in the autistic group relati$e to the other non$erbally matched and $erbally matched groups. Performance on two comparison tas&s did not re$eal significant differences when $erbal ability was ade%uately controlled. ,hey concluded that young children with autism ha$e face recognition deficits that cannot be attributed to o$erall cogniti$e abilities or tas& demands. -n contrast to controls, there was a lower correlation between performance on face recognition and non$erbal intelligence, suggesting that in autism face recognition is less correlated with general cogniti$e capacity. Ieraldine 'awson reported particular findings in April (!! at the annual meeting of the Society for Research in Child 'e$elopment in Minneapolis. ,hese suggest that impairment in face recognition may turn out to be one of the earliest indicators of abnormal brain de$elopment in autism. G*e &now that e$en new2born babies are drawn to face2li&e stimuli. ,his inborn interest in faces is the start of social de$elopment,G she said. G,his new study tells us something $ery fundamental about abnormalities in autism. -t may be an important clue to actual brain circuits that are not functioning properly. Since all of the children in the study reacted similarly to toys and only the children with autism had problems with face recognition, it tells us autism is not a global problem. Rather, it indicates an abnormality in those brain circuits responsible for social function. -t highlights that autism is a disorder of the social brain.F 'awson said the idea that face recognition may be hard2wired, or something people are born with, is contro$ersial. Rutishauser et al used a range of morphometric, histological, and neuroimaging studies from which they suggest the hypothesis that this abnormality may be lin&ed to the amygdala. ,hey recorded data from single neurons within the amygdalae of two rare neurosurgical patients with autistic spectrum disorder. (B *hile basic electrophysiological response parameters were normal, there were specific and stri&ing abnormalities in how indi$idual facial features dro$e neuronal response. Compared to control patients, a population of neurons in the two autistic spectrum disorder patients responded significantly more to the mouth, but less to the eyes. ,hey also

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(lin# A) S.arro3# SS) -e Bil-t# A) Cicc&etti#8D8 ) Co&en# 0D0) &8ol%mar# RFR$ A 3ormed Study ;f 4ace Recognition -n Autism And Related 'isorders. Journal (# Autism And Developmental Disorders (B(7)8:BB ( BBB) Pmid !75A:7(. Rutis&auser# U) Tu-usciuc# O) 4an/# S) amela%# AN) Ross# IB & A-ol.&s# R. Single23euron Correlates ;f Atypical 4ace Processing -n Autism. Neuron, Kolume A!, -ssue :, AA92ABB, (! 3o$ember (! 5.

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found a second class of face2responsi$e neurons for which responses to faces appeared normal. ,he findings confirm the amygdala s pi$otal role in abnormal face processing by people with autistic spectrum disorder at the cellular le$el and suggest that dysfunction may be traced to a specific subpopulation of neurons with altered selecti$ity for the features of faces. -t would seem therefore that only a specific population of amygdala neurons appears to be abnormal in autism. *ithdrawing from social interaction and communication is a hallmar& of autism, and researchers ha$e identified structural differences in the brains of autism patients that might e0plain the beha$iour.5! -t is not @ust simple face recognition that can be affected following brain in@ury, there can also be a failure in recognition of the emotional presentation of another?s face due to abnormal acti$ation of the social brain during face perception and this is also found in autistic spectrum disorder which is also a neuropathological condition. . Autistic spectrum disorder in$ol$es a fundamental impairment in processing social2 communicati$e information from faces. Se$eral recent studies ha$e challenged earlier findings that indi$iduals with autism spectrum disorder ha$e no acti$ation of the fusiform gyrus (fusiform face area, 44A) when $iewing faces. #ad@i&hani et al e0amined acti$ation to faces in the broader networ& of face2processing modules that comprise what is &nown as the social brain. 5 Csing 5, functional resonance imaging, they measured +;<' signal changes in ! AS' sub@ects and 9 healthy controls passi$ely $iewing non2emotional faces. ,hey replicated their original findings of significant acti$ation of face identity2processing areas (44A and inferior occipital gyrus, -;I) in autistic spectrum disorder. -n addition they identified hypoacti$ation in a more widely distributed networ& of brain areas in$ol$ed in face processing Lincluding the right amygdala, inferior frontal corte0, superior temporal sulcus and face2related somatosensory and premotor corte0P. -n autistic spectrum disorder they found functional correlations between a subgroup of areas in the social brain that belong to the mirror neuron system (-4C, S,S) and other face2 processing areas. ,he se$erity of the social symptoms measured by the Autism 'iagnostic ;bser$ation Schedule was correlated with the right -4C cortical thic&ness and with functional acti$ation in that area. *hen $iewing faces, adults with autistic spectrum disorder show atypical patterns of acti$ation in regions forming the broader face2 processing networ& and social brain, outside the core 44A and -;I regions. ,hese patterns suggest that areas belonging to the mirror neuron system are in$ol$ed in the face2 processing disturbances in AS'. Csing computerised imaging, researchers ha$e obser$ed mini2columnar abnormalities in the frontal and temporal lobes of autistic patients. 5( ,he study by scientists at the Medical College of Ieorgia, the Cni$ersity of South Carolina, and the 'owntown KA Medical Center in Augusta, Ieorgia, is reported in Neurology, the scientific @ournal of the American Academy of 3eurology. A mini2column is a basic organisational unit of brain cells and connecti$e wiring allows an indi$idual to ta&e in information, process it, and respond. ,hus, any changes in si.e, shape
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Casano*a F# Bu5&oe*e-en D!# S3itala AE# Ro2 E$ Minicolumnar pathology in autism. Neurology (!!( 4eb (6 "A(5)8 :(A25(. +a-7i%&ani# N) 0ose.&# R ) Sn2-er# 0 & Ta/er1Flusber/$ +$ Abnormal acti$ation of the social brain during face perception in autism. )uman Brain Mapping (A(")8:: ((!!9) PM-' 9 555A7. ,he frontal lobe of the brain is in$ol$ed with reasoning, planning, parts of speech and mo$ement, emotions and problem2sol$ing. ,he temporal lobe is in$ol$ed with perception and recognition of sound and memory.

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or location of the mini2column will ha$e an effect on the processing capacity of the brain. 4or the study, scientists e0amined the brain tissue of nine autistic patients and nine controls using fi$e measures8 columnar width, peripheral neuropil space, mean inter2neuronal distance, compactness, and grey le$el inde0. According to study author, Manuel 4. Casano$a, M', a neurologist and neuro2pathologist at the 'owntown KA Medical Center in Augusta, Ieorgia, the e0aminations re$ealed that the cell mini2columns of autistic patients are significantly smaller, but there are many more of them. Casano$a reports that e$olution of the brain has &ept mini2column si.e essentially constant while increasing total cortical surface area, which in larger brains has resulted in more columns per brain and thus more processing units and increased comple0ity. ,his would be consistent with an e0isting theory that autistic indi$iduals suffer a chronic state of o$er2arousal, and portray abnormal beha$iours to diminish the arousal. ,he lac& of lateral inhibitors, contained in the corte0, would affect an indi$idualJs ability to discriminate between competing sensory information, (Casano$a, idem). Researchers do not yet &now whether the difference in the number and si.e of the mini2columns is attributable to a gene mutation or some other factor. As mentioned abo$e, Spar&s et al 55 e0plored the specific gross neuro2anatomic substrates of this brain de$elopmental disorder. ,hey e0amined brain morphometric features in a large sample of carefully diagnosed 52 to :2year2old children with autism spectrum disorder (AS') compared with age2matched control groups of typically de$eloping (,') children and de$elopmentally delayed ('') children. Kolumes of the cerebrum, cerebellum, amygdala, and hippocampus were measured from three2dimensional coronal MR images ac%uired from :" children with AS', (7 ,' children, and : '' children. ,he $olumes were analysed with respect to age, se0, $olume of the cerebrum, and clinical status. Children with AS' were found to ha$e significantly increased cerebral $olumes compared with ,' and '' children. Cerebellar $olume for the AS' group was increased in comparison with the ,' group, but this increase was proportional to o$erall increases in cerebral $olume. ,he '' group had smaller cerebellar $olumes compared with both of the other groups. Measurements of amygdalae and hippocampi in this group of young children with AS' re$ealed enlargement bilaterally that was proportional to o$erall increases in total cerebral $olume. ,here were similar findings of cerebral enlargement for both girls and boys with AS'. 4or sub2region analyses, structural abnormalities were obser$ed primarily in boys, although this may reflect low statistical power issues because of the small sample (se$en girls with AS') studied. Among the AS' group, structural findings were independent of non2$erbal -S. -n a subgroup of children with AS' with strictly defined autism, amygdala enlargement was in e0cess of increased cerebral $olume. ,he authors belie$e that these structural findings suggest abnormal brain de$elopmental processes early in the clinical course of autism. Research currently is underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.

AUTIS AND ITS TREAT ENT


Psychiatrists and their predecessors, in the middle ages, pic&ed up those who were de$elopmentally and intellectually disabled and they ha$e been running with them e$er since.

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S.ar%s BF# Frie-man SD# S&a3 D4# A2l3ar- E+# Ec&elar- D# Artru AA# ara*illa (R# Gie-- 0N# unson 0# Da3son G# Da/er SR$ +rain structural abnormalities in young children with autism spectrum disorder. Neurology (!!( )ul (56 "B(()8 A:2B(.

Revised 25 November 2013

Ieneral e0ecuti$e and administrati$e la.iness brought this about and little has been done to ma&e any ade%uate change. Although many fewer of these sub@ects are now in hospital, the transition to community care has not loosened the hold which psychiatrists ha$e on this group of people. A lac& of professional de$elopment and understanding, together with only a fairly recent burgeoning of brain science may ha$e aided this dTbUcle. #owe$er it can only be a lac& of common sense that allows psychiatrists to conflate psychoses and brain damage. 'ue to the problems associated with early brain damage, and the lac& of neuro2 psychological &nowledge, there seems to be a situation where the psychiatrist is unable to understand the person or the person?s condition. #owe$er it is often the case that the psychiatrist is the only a$ailable professional who can attend the person concerned. Most psychiatric faculty members, howe$er, belie$e that there will always remain a specific role for clinicians within the field of Hlearning disability? (whate$er the cause). ,his has e0isted in some guise since the asylums and wor&houses of the early A!!s. ,he fact that about 99= of CQ consultant posts and 9:= of specialist registrar national training numbers are filled, despite general recruitment problems in psychiatry bears reference to this. 5: -n order to @ustify his inter$entions, the psychiatrist has to create the person in the image of what he is able to understand and to treat. *hen the person seems to respond fa$ourably to some aspects of this treatment, the psychiatrist does not attribute this to his good fortune, but for him it reinforces his $iew that the image he has created, Hwill do? as a clinical entity. *hen the person does not respond fa$ourably, the psychiatrist $iews this outcome as an indication of the intractability of the condition he has Hcreated?. ,he past decade has seen a dramatic increase in the use of medications in children and adolescents with psychiatric disorders. 'espite a lac& of clear scientific e$idence for their efficacy and long2term safety, at least to date, psychotropic medications ha$e been used %uite widely in children and adolescents. 5" Researchers discussed these issues in a series of presentations at the APA meeting in (!!!, reporting on no$el antipsychotics and anti2sei.ure medications, as well as medication use in incarcerated youth. Antipsychotics are often used in this co2morbid population, yet few studies are loo&ing for efficacy and safety. -n a study presented by 'r. #ussain, 57 of Prince Albert, Canada, "! children aged 7 to : (9:= being male) with co2morbid diagnosis of A'#' and conduct disorder who had not responded to stimulants alone were randomly assigned to risperidone or olan.apine augmentation. ,he researchers compared the consensus diagnosis, which used all the information from medical records and structured diagnostic inter$iews, to the discharge diagnoses of the independent clinician. ;$erall, there was least agreement for the diagnosis of bipolar disorder, where the clinician was o$er2diagnosing bipolarity. ,he study showed the increased rate of diagnosis of bipolar disorder by clinicians when the best estimate diagnosis by researchers refuted it. Another point to be aware of is that Gbrain2damagedG children may be much more sensiti$e to side effects of drugs than normal children. 'rugs normally used to help an0iety or sleep sometimes ha$e the opposite effect in susceptible children. ,his is not to say that they must ne$er be used, merely that it may be a matter of trial and error to find something that suits

5:

i--leton# Isla & Courtena2# (en$ Psychiatry of learning disability. BMJ Classi#ied6 pp(25, 5 May (!!!. 4eller# Eli"abet& B$ -ssues in Child and Adolescent Psychopharmacology. American Psychiatric Association "5rd Annual Meeting. 'ay 5 2 May 7, (!!!. +ussain ,. 3o$el antipsychotic in A'#' with conduct disorder. Program and abstracts from the "5rd Annual American Psychiatric Association Meeting, May 52 A, (!!!6 Chicago, -llinois. Abstract 5".

5"

57

Revised 25 November 2013

the child. -t may be that some children with brain damage are more susceptible to food additi$es or colourings as well, although this has not been pro$ed. As with the use of any psychopharmacological agent, care should be ta&en in the selection and administration of medications. ,he profile of side effects and ris& as well as potential benefits will of course $ary depending on the agent used and the target symptoms. Since indi$iduals with autism1P'' are often non2$erbal, reliance typically is made on reports and obser$ation of specific beha$iours. ,his can be an ad$antage in many ways in helping to document the efficacy of the selected medication. #owe$er, it is important not to lose sight of the o$erall goal of facilitating the childJs ad@ustment and engagement with educational inter$ention. 4or e0ample, sedation might be misinterpreted as a positi$e therapeutic response. -ssues of informed consent should be carefully considered, particularly as many agents ha$e yet to be appro$ed for use in children6 close follow2up is re%uired. Medications may be useful for symptoms which interfere with participation in educational inter$entions or are a source of impairment or distress to the indi$idual. ,hese medications are not specific to autism and do not treat core aspects of the disorder, and their potential side effects should be carefully considered. ,he neuroleptics, selecti$e serotonin re2upta&e inhibitors, tricyclic antidepressants, lithium and mood stabilisers, and an0iolytics ha$e been used in these patients with only $arying degrees of success. 'ietary and other alternati$e treatments are not clearly established as being efficacious. 4amilies should be helped to ma&e informed decisions about their use of alternati$e treatments. ,reatments that pose some ris& to the child and family should be acti$ely discouraged.

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