Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD

p120 Catenin Is Required for the Stress Response in <em>Drosophila</em>

The nodal modulation of the diurnal (K1 and O1) and semi-diurnal (M2, and K2) tidal constituents at the coasts of the Mediterranean Sea and the eastern Atlantic is estimated and its spatial variability mapped. Fourteen hourly tide gauge records each spanning more than 18 years are considered in this analysis. Ten tide gauges are located in the Mediterranean Sea and four in the Bay of Biscay. The nodal modulation of the most energetic tidal constituent (M2) reaches up to 5 cm at the eastern Atlantic coasts, while within the Mediterranean Sea its modulation is in general less than 1.2 cm. The largest K2 nodal modulation found is 3.7 cm in the eastern Atlantic coasts. In the Mediterranean Sea, smaller modulation amplitudes, ranging between 0.4 and 1.4 cm are found. The K1 tide constituent has the largest amplitude nodal modulation within the Mediterranean Sea of 1.9 cm in the north Adriatic Sea, which is also larger than the modulation of this constituent at the eastern Atlantic coasts. The O1 tide constituent has the highest amplitude nodal modulation (1.4 cm) at the eastern Atlantic coasts. In the Mediterranean Sea the maximum value is 1 cm in the north Adriatic Sea.The derived nodal modulations of the diurnal and semi-diurnal constituents follow, in general, the equilibrium tidal theory. The tidal amplitudes for all four components do not indicate significant secular trends for most tide gauges. The tidal phases indicate significant negative trends for all four tidal constituents within the central and eastern Mediterranean Sea.<br/