Neuropathology of infantile autism

Kemper, Thomas L.; Bauman, Margaret L.

doi:10.1038/sj.mp.4001165

Cited by 240 publications

(289 citation statements)

References 8 publications

(6 reference statements)

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“…This model focuses specifically at the time of neural tube closure on gestational day 12.5, which is believed to be a particularly vulnerable time point for insults that may produce autistic symptoms. Indeed, striking similarities were observed between such VPA-treated rat offspring and autism, including: (i) a reduced number of motor cells in cranial nerve motor nuclei in the brain stem (Rodier et al, 1996), (ii) a reduced number of Purkinje cells in the cerebellum, observed both in VPA-treated offspring (Rodier et al, 1997;Ingram et al, 2000) and autism (Ritvo et al, 1986;Kemper and Bauman, 1998), (iii) decreased social interactions, increased repetitive behaviors, lower sensitivity to pain, impaired sensorimotor gating and increased anxiety described in VPA-treated offspring (Schneider and Przewlocki, 2005;Schneider et al, 2006) and commonly found in the autistic spectrum (American Psychiatric Association, 1994;Muris et al, 1998;McAlonan et al, 2002;Perry et al, 2007). Our results confirm many of the previous behavioral findings on this particular VPA rat model of autism (Schneider and Przewlocki, 2005;Schneider et al, 2006) and show that this animal model is indeed reproducible.…”

Section: Discussionmentioning

confidence: 99%

“…Both microscopic and macroscopic studies reveal alterations in the morphology of the amygdala in autism (Kemper and Bauman, 1998;Aylward et al, 1999;Sparks et al, 2002;Schumann et al, 2004;Schumann and Amaral, 2006), indicating a dysfunction in this region that might possibly contribute to the autistic pathology. The current 'amygdala theory of autism' is based on the lost capability to evaluate socioemotional information and lost drive for social interaction derived from lesioning studies in monkeys and a few functional imaging studies in humans (Baron-Cohen et al, 2000;Sweeten et al, 2002;Pelphrey et al, 2004;Bachevalier and Loveland, 2006;Schultz, 2005), which implies that a hypofunctioning amygdala underlies autism.…”

Section: A Novel Role Suggested For the Amygdala In Autismmentioning

confidence: 99%

“…Several brain structures and pathways have been suggested to underlie this disorder, among them the amygdala (Bachevalier, 1994;Baron-Cohen et al, 1999;Adolphs et al, 2001), which exhibits a number of abnormalities. Whereas earlier postmortem studies on autistic patients indicated an increased number of cells with reduced cell size in the cortical, medial, and central nuclei of the amygdala (Kemper and Bauman, 1998), more recent and modern stereological counts of neurons in the amygdala revealed a reduced number of neurons, particularly in the lateral nucleus (Schumann and Amaral, 2006). The total amygdala volume is enlarged during early infancy (Sparks et al, 2002;Schumann et al, 2004), but can be reduced in adulthood (Aylward et al, 1999).…”

Section: Introductionmentioning

confidence: 97%

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Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism

Markram

Rinaldi

Mendola

et al. 2007

Neuropsychopharmacol

314

252

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A core feature of autism spectrum disorders is the impairment in social interactions. Among other brain regions, a deficit in amygdala processing has been suggested to underlie this impairment, but whether the amygdala is processing fear abnormally in autism, is yet not clear. We used the valproic acid (VPA) rat model of autism to (a) screen for autism-like symptoms in rats, (b) test for alterations in amygdala-dependent fear processing, and (c) evaluate neuronal reactivity and synaptic plasticity in the lateral amygdala by means of in vitro single-cell electrophysiological recordings. VPA-treated animals displayed several symptoms common to autism, among them impaired social interactions and increased repetitive behaviors. Furthermore, VPA-treated rats were more anxious and exhibited abnormally high and longer lasting fear memories, which were overgeneralized and harder to extinguish. On the cellular level, the amygdala was hyperreactive to electrical stimulation and displayed boosted synaptic plasticity as well as a deficit in inhibition. We show for the first time enhanced, overgeneralized and resistant conditioned fear memories in an animal model of autism. Such hyperfear could be caused by the hyperreactivity and hyperplasticity found in the lateral amygdala, which may in turn be due to a deficit in the inhibitory system of the amygdala. We hypothesize an 'aversive world' syndrome that could, even if not a primary cause of the disorder itself, underlie some core symptoms in autism, such as impairments in social interactions and resistance to rehabilitation.

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Section: Discussionmentioning

confidence: 99%

Section: A Novel Role Suggested For the Amygdala In Autismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism

Markram

Rinaldi

Mendola

et al. 2007

Neuropsychopharmacol

314

252

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“…Several studies have found increased brain size, brain structure differences, and reduced numbers of neurons in children with ASD, compared with control subjects. [93][94][95] Although no direct cause of these abnormalities is known, it has been suggested that a dysregulation in neurotransmission could result in altered development. Differences in neurotransmitters (including serotonin and GABA) and in glutamate signaling pathways have been demonstrated in ASD (see review by Lam et al 96 ).…”

Section: Neurotransmittersmentioning

confidence: 99%

Immune Dysfunction in Autism: A Pathway to Treatment

2010

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Summary: Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Clinicians, schools, and service agencies worldwide have reported a dramatic increase in the number of children identified with autism. Despite expanding research, the etiology and underlying biological processes of autism remain poorly understood, and the relative contribution from genetic, epigenetic, and environmental factors remains unclear. Although autism affects primarily brain function (especially affect, social functioning, and cognition), it is unknown to what extent other organs and systems are disrupted. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment. A better understanding of the involvement of the immune response in autism, and of how early brain development is altered, may have important therapeutic implications.

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“…So what evidence is there of neuroanatomical dysfunction in the frontal lobes in autism? Structural studies of the autistic brain are limited, although several cortical and subcortical abnormalities have been identified [45]. Transient delayed postnatal maturation of the frontal lobes [46], serotinergic abnormalities in prefrontal cortex [47] and structural abnormality in orbitofrontal cortex [48] have all been reported.…”

mentioning

confidence: 99%

Executive dysfunction in autism☆

Hill¹

2004

Trends in Cognitive Sciences

1,136

826

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Abstract'Executive function' is an umbrella term for functions such as planning, working memory, impulse control, inhibition and mental flexibility, as well as for the initiation and monitoring of action. The primacy of executive dysfunction in autism is a topic of much debate, as are recent attempts to examine subtypes of executive function within autism and other neurodevelopmental disorders that are considered to implicate frontal lobe function. This article will review cognitive behavioural studies of planning, mental flexibility and inhibition in autism. It is concluded that more detailed research is needed to fractionate the executive system in autism by assessing a wide range of executive functions as well as their neuroanatomical correlates in the same individuals across the lifespan.2 Executive dysfunction in autism.Goldsmiths Research Online.'Executive function' is traditionally used as an umbrella term for functions such as planning, working memory, impulse control, inhibition and shifting set as well as the initiation and monitoring of action [1]. These functions share the need to disengage from the immediate environment to guide actions. Executive functions are typically impaired in patients with acquired damage to the frontal lobes as well as in a range of neurodevelopmental disorders that are likely to involve congenital deficits in the frontal lobes. Such clinical disorders include attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder, Tourette syndrome, phenylketonuria, schizophrenia and autism spectrum disorder. It should be noted that executive dysfunction can be observed in those with acquired damage to non-frontal brain areas.Autism spectrum disorder is a developmental disorder characterised by impaired social interaction and communication as well as repetitive behaviours and restricted interests. It is a lifelong disorder and affects at least 0.6% of the population with males being affected three times more often than females [2,3]. Estimates of learning disability vary. In a recent review of epidemiological studies the percentage of individuals with a learning disability is given as 70% [4]. Although different labels are used to define people at each end of the spectrum (e.g. autism, Asperger syndrome), 'autism' will be used in this review to refer to the whole spectrum.In recent years three key cognitive theories and their variants have been investigated in an attempt to understand the link between the brain and behaviour in autism. The most well-known of these is the theory of mind deficit hypothesis [5][6][7][8][9][10], and another account is that of weak central coherence [11][12][13][14][15] (see Box 1). Although these two accounts together can explain many of the deficits and assets associated with autism, repetitive behaviours and restricted interests might best be explained by a third cognitive theory: that of executive dysfunction. Executive dysfunction in autismOver the past twenty years several executive functions have been studied in autism. In this rev...

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Neuropathology of infantile autism

Cited by 240 publications

References 8 publications

Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism

Abnormal Fear Conditioning and Amygdala Processing in an Animal Model of Autism

Immune Dysfunction in Autism: A Pathway to Treatment

Executive dysfunction in autism☆

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