Autism review article

1. YaAn Pharmaceutical-Medical Communications Muthukumar Karuppasamy PhD
Autism, taste and high cognitive function
Autism and its pathophysiology:
Autism spectrum disorders (ASD) are neuro-developmental disorders, as defined by
WHO, it is characterized by deficit in social behaviour, social interaction, movement, sensory
processing, communication and language. ASD is a syndrome, not a disease, with plenty of
genetics and non-genetics etiologies and extensive clinical manifestations. The
pathophysiology of ASD is heterogenous and complex in nature (Waterhouse et al., 2016).
Nonetheless, the overgrowth of brain during developmental years, especially cerebral
overgrowth might be the key event in ASD (Courchesne et al., 2001, 2003), consequently,
excessive development of brain targets the early years after birth in children and toddlers,
which is fundamental for social, language, emotion and attention skills.
Having mixed etiologies, pathogenic characteristics and cognitive issues among ASD
patients, a wide range of symptoms are observed in different domains such as cognitive,
communication, language, social and motor (Courchesne et al., 2007). Behavioural evaluation
technique is used to diagnose social and behavioural anomalies in children and toddlers with
ASD, interestingly, research study (Geschwind, 2011) has found that ASD affects boys four
times more than girls. Currently, there are no therapeutic interventions to mitigate social,
behavioural, communication and language abnormalities in ASD. The quest for
neuropathological biomarkers and genetic determinants in the autistic brain has always been
obstructed by the heterogeneity of autistic cases with disparate comorbidities (Kaushik &
Zarbalis, 2016). Nevertheless, research on specific proteins such as PTEN, CHD8, KCTD13
and WDFY3 as neuropathological factors has been in progress to discover the potential

2. YaAn Pharmaceutical-Medical Communications Muthukumar Karuppasamy PhD
treatments for the autism (Goffin et al., 2001; Golzio et al., 2012; Orosco et al., 2014; Bernier
et al., 2014).
Autism & taste:
ASD patients generally have eating issues, they tend to be very selective towards few
foods, which is a characteristic phenomenon in autistic patients (Cermak et al., 2010; Kuschner
et al., 2015; Williams et al., 2000). Selection of specific foods is known as selective or picky
eating, which is a serious issue in ASD patients, around 58–67% of parents of children with
ASD report to picky eating (Tanner et al., 2015).
The differences in taste identification could be due to central than peripheral regions,
few regions such as thalamus, insula and cingulate cortex are mainly involved in taste
discrimination (Bennetto et al., 2007; Kinomura et al., 1994; Tavassoli & Baron-Cohen, 2012).
Children with ASD, around two-thirds, showed some features of selective eating like refusal
of food and food neophobia (Cermak et al., 2010; Williams et al., 2010). In addition, Berkman
et al., (2007) published the eating behavioural problems of ASD patients as compared to control
groups.
Selective eating observed in ASD pateints could result in poor diets and insufficient
nutrition, followed by severe health outcome such as obesity. Not only adverse health outcome
by picky eating, also, this unusual eating behaviours could cause an economical burden and
stress to the parents of children and toddlers with ASD (Phillips et al., 2014). As it is well
known that choosing few foods triggers nutritional issues in ASD patients due to increased
sensory reactivity, however, the neuronal mechanistic pathway is not clearly understood behind
reactivity to taste and restricted food choices (Avery et al., 2018).

3. YaAn Pharmaceutical-Medical Communications Muthukumar Karuppasamy PhD
ASD patients were reported to possess aberrant reactivity to taste, smell and oral
texture, in particular, significant reactivity to taste as compared to controls (Cermak et al.,
2010; Kuschner et al., 2015). In addition, positive relationship between taste reactivity and
sweet tastants response was observed in brain regions such as regions related to gustatory
stimulation (Avery et al., 2018; Veldhuizen et al., 2011; Yeung et al., 2017) left orbitofrontal
cortex (OFC), anterior lateral and posterior medial sub-regions (Murray et al., 2015), bilateral
regions of the dorsal caudate (Small et al., 2003), and right mediodorsal thalamus region.
These studies have unveiled the heightened sensory activation to tastants, taste
reactivity, together with affective and hedonic responses to delicious foods in ASD patients.
Of note, the heightened taste reactivity in association with sensory reactivity and affective
responses may lead into serious health outcomes like type–2 diabetes and cardiovascular
disease. Neurobiological studies were performed to examine the dysfunction of brain regions
for taste reactivity. Brainstem malfunction (Rodier, 2002) and hypoplasia of seventh cranial
nerve nucleus (CN VII), which is commonly known as facial nerve, were reported to possibly
affect taste detective mechanisms in ASD patients.
Brain regions, including thalamus, insula/operculum, OFC and amygdala, mediate the
recognition of tastants and the flavour perception. Of note, the dysfunction of OFC and
amygdala has been implicated in people with ASD (Rodier et al., 1996).
Autism & Synaptic plasticity
In ASD patients, long-term synaptic depression (LSD) is ubiquitous across all brain
regions. LSD is one type of experience-dependent synaptic plasticity and synaptopathies
occurred in people with ASD (Hansel, 2018). The association between synapse and circuit
alterations that was observed in learning related phenotypes is critical for brain function.

4. YaAn Pharmaceutical-Medical Communications Muthukumar Karuppasamy PhD
Synaptic abnormalities in ASD is closely aligned with developmental synapse
pruning pathway, and remarkable changes in synaptic connectivity are characteristic
occurrences in early brain development. The synapse pruning is prolonged process that is
critical for development of brain circuits and cognitive functions.
Impaired synapse pruning is observed in ASD patients and this dysfunction is
associated with mTOR signaling (Hustler & Zhang, 2010; Tang et al., 2014). Research studies
showed that malfunction in synaptic pruning could cause cognitive deficit and the disruption
in excitation-inhibition balance, followed by hyperexcitability (Markram et al., 2007; Ramiro-
Cortes et al., 2013).
Autism & Cognitive function:
Pellicano (2010) reported that children with ASD showed similar cognitive profile
same as controls at the start of the study as well as after three years. Among children with ASD,
the cognitive strength and weakness varied from one to another child.
Autism & Einstein:
The operculum and parietal operculum in the brain is suggested to possess critical
physiological functions such as mathematical thought process, visuospatial cognitive process
and movement issues. Some research studies reported that the parietal operculum region is
missing in Einstein’s brain whereas other researchers indicated otherwise (Witelson et al.,
1999).

5. YaAn Pharmaceutical-Medical Communications Muthukumar Karuppasamy PhD
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