1. Bussing R, Siddiqi S, Janicke DM, Harbert MJ, Trauner D, Taylor T, Stein MT. Late {{Onset Autistic Symptoms and Other Fluctuating Behaviors}}. {J Dev Behav Pediatr};2009 (Dec);30(6):593-596.

CASE:: Suzanna was born to a 26-year-old woman who used cocaine, alcohol, and cigarettes and experienced domestic violence throughout her pregnancy. Suzanna was placed in foster care with her current adoptive family after her birth. Her initial evaluation at 4 years revealed a global developmental delay (physical: 6 months; social and communication: 12 months). Improvements in development seemed to be in response to subsequent interventions. At 5 years, she had borderline intellectual functioning, an expressive or receptive language disorder, and attention-deficit hyperactivity disorder.Suzanna experienced an abrupt developmental decline at 6 1/2 years old. She lost cognitive abilities, and she no longer carried on conversations. Although she was no longer interactive with most people, she remained affectionate with her parents. Her mother thought that Suzanna had visual and auditory hallucinations. In addition, she developed encopresis and hand flapping. A neurological evaluation, including a test for Rett Syndrome, was negative. Her Full Scale IQ dropped from 73 to 50 with decreased adaptive functioning and clinically significant problems with hyperactivity, attention, and functional communication.Suzanna’s development stabilized temporarily during an 18-month period. A second period of declining function included « zombie-like » behavior, anxiety, and hallucinations. Weekly sessions in child psychiatry included treatment with risperidone, methylphenidate, and supportive therapy for mother and child. After some clinical improvements in behavior, attention, and functioning, a psychological assessment confirmed the persistence of moderate mental retardation. A multidisciplinary team considered a diagnosis of childhood disintegrative disorder.

2. Correia CT, Almeida JP, Santos PE, Sequeira AF, Marques CE, Miguel TS, Abreu RL, Oliveira GG, Vicente AM. {{Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions}}. {Pharmacogenomics J};2009 (Dec 8)

Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics (CYP2D6 and ABCB1) and pharmacodynamics (HTR2A, HTR2C, DRD2, DRD3, HTR6) of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. Using the generalized estimating equation method these genes were tested for association with drug efficacy, assessed with the Autism Treatment Evaluation Checklist, and with safety and tolerability measures, such as prolactin levels, body mass index (BMI), waist circumference and neurological adverse effects, including extrapyramidal movements. Our results confirm that risperidone therapy was very effective in reducing some autism symptoms and caused few serious adverse effects. After adjusting for confounding factors, the HTR2A c.-1438G>A, DRD3 Ser9Gly, HTR2C c.995G>A and ABCB1 1236C>T polymorphisms were predictors for clinical improvement with risperidone therapy. The HTR2A c.-1438G>A, HTR2C c.68G>C (p.C33S), HTR6 c.7154-2542C>T and BDNF c.196G>A (p.V66M) polymorphisms influenced prolactin elevation. HTR2C c.68G>C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference. We thus identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Although association results require replication, given the small sample size, the study makes a preliminary contribution to the personalized therapy of risperidone in autism.The Pharmacogenomics Journal advance online publication, 8 December 2009; doi:10.1038/tpj.2009.63.

3. Fatemi SH. {{Multiple pathways in prevention of immune-mediated brain disorders: Implications for the prevention of autism}}.{ J Neuroimmunol};2009 (Dec 10);217(1-2):8-9.

4. Gordon Bell J, Miller D, Macdonald DJ, Mackinlay EE, Dick JR, Cheseldine S, Boyle RM, Graham C, O’Hare AE. {{The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake}}. {Br J Nutr};2009 (Dec 9):1-8.

The erythrocyte and plasma fatty acid compositions of children with autism were compared in a case-control study with typically developing (TD) children and with children showing developmental delay (DD). Forty-five autism subjects were age-matched with TD controls and thirty-eight with DD controls. Fatty acid data were compared using paired t tests. In addition, blood fatty acids from treatment-naive autism subjects were compared with autism subjects who had consumed fish oil supplements by two-sample t tests. Relatively few differences were seen between erythrocyte fatty acids in autism and TD subjects although the former had an increased arachidonic acid (ARA):EPA ratio. This ratio was also increased in plasma samples from the same children. No changes in n-3 fatty acids or ARA:EPA ratio were seen when comparing autism with DD subjects but some SFA and MUFA were decreased in the DD subjects, most notably 24 : 0 and 24 : 1, which are essential components of axonal myelin sheaths. However, if multiple comparisons are taken into account, and a stricter level of significance applied, most of these values would not be significant. Autism subjects consuming fish oil showed reduced erythrocyte ARA, 22 : 4n-6, 22 : 5n-6 and total n-6 fatty acids and increased EPA, 22 : 5n-3, 22 : 6n-3 and total n-3 fatty acids along with reduced n-6:n-3 and ARA:EPA ratios. Collectively, the autism subjects did not have an underlying phospholipid disorder, based on erythrocyte fatty acid compositions, although the increased ARA:EPA ratio observed suggested that an imbalance of essential highly unsaturated fatty acids may be present in a cohort of autism subjects.

5. Low J, Goddard E, Melser J. {{Generativity and imagination in autism spectrum disorder: evidence from individual differences in children’s impossible entity drawings}}. {Br J Dev Psychol};2009 (Jun);27(Pt 2):425-444.

This study examined the cognitive underpinnings of spontaneous imagination in autism spectrum disorder (ASD) by way of individual differences. Children with ASD (N = 27) and matched typically developing (TD) children were administered Karmiloff-Smith’s (1990) imaginative drawing task, along with measures that tapped specific executive functions (generativity, visuospatial planning, and central coherence processing style) and false belief theory of mind (ToM) understanding. The ASD group drawings displayed deficits in imaginative content and a piecemeal pictorial style. ASD participants also showed group deficits in generativity, planning and ToM, and exhibited weak coherence. Individual differences in generativity were related to imaginative drawing content in the ASD group, and the association was mediated through planning ability. Variations in weak coherence were separately related to a piecemeal drawing style in the ASD group. Variations in generativity were also linked with imaginative drawing content in the TD group; the connection unfolded when it received pooled variance from receptive language ability, and thereupon mediated through false belief reasoning to cue imaginative content. Results are discussed in terms of how generativity plays a broad and important role for imagination in ASD and typical development, albeit in different ways.

6. Nadig A, Vivanti G, Ozonoff S. {{Adaptation of object descriptions to a partner under increasing communicative demands: a comparison of children with and without autism}}. {Autism Res};2009 (Dec 8)

This study compared the object descriptions of school-age children with high-functioning autism (HFA) with those of a matched group of typically developing children. Descriptions were elicited in a referential communication task where shared information was manipulated, and in a guessing game where clues had to be provided about the identity of an object that was hidden from the addressee. Across these tasks, increasingly complex levels of audience design were assessed: (1) the ability to give adequate descriptions from one’s own perspective, (2) the ability to adjust descriptions to an addressee’s perspective when this differs from one’s own, and (3) the ability to provide indirect yet identifying descriptions in a situation where explicit labeling is inappropriate. Results showed that there were group differences in all three cases, with the HFA group giving less efficient descriptions with respect to the relevant context than the comparison group. More revealing was the identification of distinct adaptation profiles among the HFA participants: those who had difficulty with all three levels, those who displayed Level 1 audience design but poor Level 2 and Level 3 design, and those demonstrated all three levels of audience design, like the majority of the comparison group. Higher structural language ability, rather than symptom severity or social skills, differentiated those HFA participants with typical adaptation profiles from those who displayed deficient audience design, consistent with previous reports of language use in autism.

7. Parker-Athill E, Luo D, Bailey A, Giunta B, Tian J, Shytle RD, Murphy T, Legradi G, Tan J. {{Flavonoids, a prenatal prophylaxis via targeting JAK2/STAT3 signaling to oppose IL-6/MIA associated autism}}. {J Neuroimmunol};2009 (Dec 10);217(1-2):20-27.

Maternal immune activation (MIA) can affect fetal brain development and thus behavior of young and adult offspring. Reports have shown that increased Interleukin-6 (IL-6) in the maternal serum plays a key role in altering fetal brain development, and may impair social behaviors in the offspring. Interestingly, these effects could be attenuated by blocking IL-6. The current study investigated the effects of luteolin, a citrus bioflavonoid, and its structural analog, diosmin, on IL-6 induced JAK2/STAT3 (Janus tyrosine kinase-2/signal transducer and activator of transcription-3) phosphorylation and signaling as well as behavioral phenotypes of MIA offspring. Luteolin and diosmin inhibited neuronal JAK2/STAT3 phosphorylation both in vitro and in vivo following IL-6 challenge as well as significantly diminishing behavioral deficits in social interaction. Importantly, our results showed that diosmin (10mg/kgday) was able to block the STAT3 signal pathway; significantly opposing MIA-induced abnormal behavior and neuropathological abnormalities in MIA/adult offspring. Diosmin’s molecular inhibition of JAK2/STAT3 pathway may underlie the attenuation of abnormal social interaction in IL-6/MIA adult offspring.

8. Yerys BE, Wallace GL, Sokoloff JL, Shook DA, James JD, Kenworthy L. {{Attention deficit/hyperactivity disorder symptoms moderate cognition and behavior in children with autism spectrum disorders}}. {Autism Res};2009 (Dec 8)

Recent estimates suggest that 31% of children with autism spectrum disorders (ASD) meet diagnostic criteria for attention deficit/hyperactivity disorder (ADHD), and another 24% of children with ASD exhibit subthreshold clinical ADHD symptoms. Presence of ADHD symptoms in the context of ASD could have a variety of effects on cognition, autistic traits, and adaptive/maladaptive behaviors including: exacerbating core ASD impairments; adding unique impairments specific to ADHD; producing new problems unreported in ASD or ADHD; having no clear impact; or producing some combination of these scenarios. Children with ASD and co-morbid ADHD symptoms (ASD+ADHD; n=21), children with ASD without ADHD (ASD; n=28), and a typically developing control group (n=21) were included in the study; all groups were matched on age, gender-ratio, IQ, and socioeconomic status. Data were collected on verbal and spatial working memory, response inhibition, global executive control (EC), autistic traits, adaptive functioning, and maladaptive behavior problems. In this sample, the presence of ADHD symptoms in ASD exacerbated impairments in EC and adaptive behavior and resulted in higher autistic trait, and externalizing behavior ratings. ADHD symptoms were also associated with greater impairments on a lab measure of verbal working memory. These findings suggest that children with ASD+ADHD symptoms present with exacerbated impairments in some but not all domains of functioning relative to children with ASD, most notably in adaptive behavior and working memory. Therefore, ADHD may moderate the expression of components of the ASD cognitive and behavioral phenotype, but ASD+ADHD may not represent an etiologically distinct phenotype from ASD alone.