Review

Nutrition in autism spectrum disorders: A review of evidences for an emerging central role in aetiology, expression, and management

  • Received: 27 December 2017 Accepted: 09 March 2018 Published: 20 March 2018
  • Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders whose aetiology remains largely unknown, but for which environmental factors appear to be important. Emerging evidences suggest that nutrition may play a major role in the aetiology of ASD; also, specific maternal nutritional-deficiencies appear to be associated with an increased risk in offsprings. In addition, studies are beginning to reveal the beneficial effects of dietary supplementation or restriction in the management of ASD; while at the same time debunking the myths that surround certain purportedly-therapeutic dietary manipulations. In this narrative review (using information from internet databases such as Google scholar, PubMed, Scopus and authoritative texts), we examine the emerging central role of nutrition in relation to aetiology, symptomatology, management, and indices of outcome in ASD; by highlighting available scientific evidences pertaining to the impacts of different dietary manipulations and nutritional supplementation. We also consider the likely future roles of nutrition in ASD, as science continues to grapple with the understanding of a group of neurodevelopmental disorders that are emerging to be largely “nutritional illnesses”.

    Citation: Olakunle James Onaolapo, Adejoke Yetunde Onaolapo. Nutrition in autism spectrum disorders: A review of evidences for an emerging central role in aetiology, expression, and management[J]. AIMS Medical Science, 2018, 5(2): 122-144. doi: 10.3934/medsci.2018.2.122

    Related Papers:

    [1] Simona Silvia Merola, Luca Marchitto, Cinzia Tornatore, Gerardo Valentino . Spray-combustion process characterization in a common rail diesel engine fuelled with butanol-diesel blends by conventional methods and optical diagnostics. AIMS Energy, 2014, 2(2): 116-132. doi: 10.3934/energy.2014.2.116
    [2] Sunbong Lee, Shaku Tei, Kunio Yoshikawa . Properties of chicken manure pyrolysis bio-oil blended with diesel and its combustion characteristics in RCEM, Rapid Compression and Expansion Machine. AIMS Energy, 2014, 2(3): 210-218. doi: 10.3934/energy.2014.3.210
    [3] Husam Al-Mashhadani, Sandun Fernando . Properties, performance, and applications of biofuel blends: a review. AIMS Energy, 2017, 5(4): 735-767. doi: 10.3934/energy.2017.4.735
    [4] Lihao Chen, Hu Wu, Kunio Yoshikawa . Research on upgrading of pyrolysis oil from Japanese cedar by blending with biodiesel. AIMS Energy, 2015, 3(4): 869-883. doi: 10.3934/energy.2015.4.869
    [5] Eric Danso-Boateng, Osei-Wusu Achaw . Bioenergy and biofuel production from biomass using thermochemical conversions technologies—a review. AIMS Energy, 2022, 10(4): 585-647. doi: 10.3934/energy.2022030
    [6] Tien Duy Nguyen, Trung Tran Anh, Vinh Tran Quang, Huy Bui Nhat, Vinh Nguyen Duy . An experimental evaluation of engine performance and emissions characteristics of a modified direct injection diesel engine operated in RCCI mode. AIMS Energy, 2020, 8(6): 1069-1087. doi: 10.3934/energy.2020.6.1069
    [7] Thang Nguyen Minh, Hieu Pham Minh, Vinh Nguyen Duy . A review of internal combustion engines powered by renewable energy based on ethanol fuel and HCCI technology. AIMS Energy, 2022, 10(5): 1005-1025. doi: 10.3934/energy.2022046
    [8] Angelo Minotti . Hybrid energy converter based on swirling combustion chambers: the hydrocarbon feeding analysis. AIMS Energy, 2017, 5(3): 506-516. doi: 10.3934/energy.2017.3.506
    [9] Hussein A. Mahmood, Ali O. Al-Sulttani, Hayder A. Alrazen, Osam H. Attia . The impact of different compression ratios on emissions, and combustion characteristics of a biodiesel engine. AIMS Energy, 2024, 12(5): 924-945. doi: 10.3934/energy.2024043
    [10] Mariana Vale da Silva, Victor Ferreira, Carlos Pinho . Determination of biomass combustion rate in a domestic fixed bed boiler. AIMS Energy, 2021, 9(5): 1067-1096. doi: 10.3934/energy.2021049
  • Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders whose aetiology remains largely unknown, but for which environmental factors appear to be important. Emerging evidences suggest that nutrition may play a major role in the aetiology of ASD; also, specific maternal nutritional-deficiencies appear to be associated with an increased risk in offsprings. In addition, studies are beginning to reveal the beneficial effects of dietary supplementation or restriction in the management of ASD; while at the same time debunking the myths that surround certain purportedly-therapeutic dietary manipulations. In this narrative review (using information from internet databases such as Google scholar, PubMed, Scopus and authoritative texts), we examine the emerging central role of nutrition in relation to aetiology, symptomatology, management, and indices of outcome in ASD; by highlighting available scientific evidences pertaining to the impacts of different dietary manipulations and nutritional supplementation. We also consider the likely future roles of nutrition in ASD, as science continues to grapple with the understanding of a group of neurodevelopmental disorders that are emerging to be largely “nutritional illnesses”.


    In diesel engine, diesel fuel (DF) is injected as liquid in the form of sprays into the combustion chamber. After injection, atomization, vaporization and mixing of fuel vapor with air occurs inside the combustion chamber before ignition. In present scenario, spray combustion is common to diesel as well as gasoline engines. In spray combustion, diffusion flame forms because combustion reactions occur much faster than mixing of fuel with air. The fuel-lean zones are responsible for nitrogen oxides (NOx) formation and fuel-rich zones are responsible for significant soot formation (SF). Therefore incomplete fuel-air mixing leads to incomplete combustion in conventional diesel engines. The trade-off between NOx and particulate matter (PM) emissions is a very serious issue in diesel engine spray combustion [1] as shown in Figure 1. Also, soot particles alongwith other emissions from diesel engine have caused negative impacts on human health end environment [2,3]. Therefore, a breakthrough technology is required for adequate fuel delivery system associated with efficient and clean combustion.

    Figure 1.  Local equivalence ratio with temperature [1].

    One solution to achieve high efficiency as well as reduction in engine emissions was proposed [4,5,6]. In this new concept, fuel is injected into engine cylinder in supercritical (SC) state. In SC phase, fluid has unique thermodynamic and transport properties [7,8]. At higher temperature required for SC state, coking phenomenon occurs in fuels [9]. The formation of coke means thermal decomposition of fuel at high temperatures that result in formation of some heavy products (coke). This coke formation causes choking of injector nozzles [9]. Therefore to avoid this coke formation, some anti-coking agents were used. These anti-coking agents are also called as inert-diluents (ID) such as CO2, H2O, N2 or their mixtures (like exhaust gases). Anti-coking agents can be mixed with the DF followed by heating these mixtures to SC state before injection [6,10]. The SCF mixture upon injection into a combustion chamber quasi-instantaneously diffuses into the hot compressed air and form a single SC phase.

    According to one study [11], DF can be mixed with EGR (exhaust gas recycled) either before or after the injection pumps. Alternatively, DF can be mixed with carbon dioxide before the injection pump. The content of EGR or CO2 can be controlled depending on the rpm and load of engine. Since the DF-EGR or DF-CO2 mixture is delivered as a single homogeneous SC phase to engine combustion chamber followed by a complete combustion leads to significant increase in engine efficiency and substantial reduction in emissions. The mixing of SC fuel-ID with SC air occurs nearly instantaneously due to very high molecular diffusion and combustion is homogeneous and complete. The proposed method also avoids catalytic and filtering devices for after-treatment of exhaust gases. In a similar approach [12], a mixture of DF-H2O (50%) was brought to SC conditions in a DF injection pump to achieve better air-fuel mixing. The mixture then burns in a modified diesel engine with very low NOx and smoke emissions as noticed in Figure 2. In another study [13] on SC fuel injection system, it can be seen through an optical engine fitted with a quartz window that the SC fuel delivery system does not create fuel droplets (i.e., homogeneous SC phase) as depicted in Figure 3.

    Figure 2.  SC Combustion Emissions are much lower than Diesel Combustion Emissions [12].
    Figure 3.  A comparison of standard direct injection of liquid fuel and Transonic’s novel SC injection [13].

    Gasoline is a better choice for studying homogeneous SC spray combustion due to its many useful properties [6]. Dieseline (DL) blend composed of diesel fuel (DF2) and automotive gasoline (AG). Under homogeneous SC spray combustion study, amount of AG in DL blend can be expanded [6]. Therefore in present study, dieseline (DL50) blend is selected which contain 50% AG and 50% DF by v/v. Higher amount of AG in DF is chosen because higher amount of AG reduces estimated Tc of liquid mixture. This reduced Tc of liquid mixtures can be achieved relatively easy in the present experimental setup for producing homogeneous SC spray combustion.

    Duration of combustion (DOC) and rate of heat release (ROHR) are important combustion characteristics of diesel spray combustion in conventional diesel engines [14]. ROHR concept is the basis for phenomenological model of diesel combustion engines [14]. A faster and cleaner diesel combustion process occurs due to short ignition delay and smaller DOC associated with high ROHR and also results in significant decrease in major diesel engine emissions such as PM and NOx.

    Higher power densities and cylinder air pressures in modern high-speed DI diesel engines [15] caused significant increase in piston surface temperature and therefore piston’s role in ignition of sprays becomes important [16]. Modern smaller-sized engines with common-rail injection systems lead to increased spray/piston interactions and therefore results in substantial spray-impingement on piston walls [17,18,19]. In these engines combustion, efficiency and emissions significantly affected due to spray-wall impingement process [17,18,19,20]. Hence, ignition due to hot surfaces plays an important role in combustion phenomenon in small-sizes high-pressures DI diesel engines. Also, for studying basic engine combustion, constant volume chamber are frequently used among others [21,22,23,24,25,26].

    As learnt from above discussion about homogeneous SC spray combustion system, it is clear that homogeneous SC spray combustion system is a promising combustion technology in terms of engine performance. It is also evident from previous studies that combustion characteristics of homogeneous SC sprays of dieseline blend (DL50) are not analyzed qualitatively as well as quantitatively. Therefore, present study investigates combustion characteristics of homogeneous SC spray combustion of DL50 blend under diesel-engine like experimental conditions in constant volume chamber. Moreover, these characteristics of homogeneous SC sprays are compared with conventional diesel sprays under similar experimental conditions. Also, comparative study of soot formation (SF) between normal diesel spray and homogeneous SC spray systems has been investigated in present work under diesel-engine like experimental conditions. Moreover in present work, effects of operating conditions such as injection pressure (IP), hot surface temperature (HST) and cylinder air pressure (CP) are investigated on DOC and SF for both injection systems. Present work will assist in understanding this new combustion system and also helps in developing homogenous SC spray injection system for efficient and clean combustion of future automotive engines.

    The present setup is developed to measure combustion characteristics of homogeneous SC fuel sprays under different experimental conditions. Moreover, homogeneous SC spray combustion is analysed under very lean burning conditions (fuel-air equivalence ratio vary nearly from 0.12 to 0.065). Experimental setup and its block diagram is shown in Figures 4 and 5 respectively. The details and specifications of each component are given in [26,27].

    Figure 4.  Setup and its components [27].
    Figure 5.  Block diagram of experimental setup [27].

    Present setup has combustion chamber of cylindrical shape. Combustion chamber has fuel injector and hot surface plate (electrically heated) which are placed opposite to each other. Fuel injector having pintle nozzle (diameter of 0.15 mm) is placed infront of hot surface plate at some distance from it. Electrical heating and insulation of injector was done for producing SC sprays of DL50 blend [27]. Fuel injection pump was operated manually with the help of lever. Pressure gauge mounted on injection pump measured IP. Another pressure gauge mounted on combustion chamber measured initial CP. Photo transducer mounted on the opposite side of hot surface plate senses light luminosity during combustion of sprays. Detail of photo transducer is available in study [26]. Piezoelectric transducer is mounted on fuel line (Figure 6) and its circuit diagram is given in study [26]. Both transducers indicate their signals on different channel of scopemeter as indicated in Figure 7. Temperature indicators show HST (T1) and temperature of heated DL50 blend (T2) with the help of thermocouples. Another temperature indicator indicates initial cylinder air temperature (T3). Inlet valve for fresh compressed air and exhaust valve for exhaust gases are located at one end of combustion chamber. Compressed fresh air is supplied through multistage compressor. In case of normal diesel spray combustion study, injector is neither heated nor insulated and DF is injected at normal room temperature [26].

    Figure 6.  Piezoelectric transducer for indicating fuel injection process.
    Figure 7.  Channel A, Channel B and Channel C indicate fuel injection, DOC and pressure rise respectively during SC spray combustion on scopemeter.

    Experimental conditions for SC spray combustion are tabulated in Table 1. Different readings are obtained for each set of conditions, average value is calculated from four repeated readings at same condition to reduce errors in measurement and to ensure repeatability of experiments. Estimation of critical properties of DF and DL50 blend is very crucial in obtaining SC fuel spray and is discussed in the following section.

    Table 1.  Experimental conditions.
    Operating Parameters (Controlled parameters) Typical Values
    Fuel IP 100 bar, 200 bar and 300 bar
    Injected Fuel Quantity 0.15 ml at 100bar, 0.14 ml at 200bar, 0.13 ml at 300 bar
    CP 20 bar, 30 bar and 40 bar
    HST 673 K and 723 K
    Dieseline Blend (DL50) 50% DF and 50% AG by v/v
    Estimated Tc of DL50 356.3 ℃ (629.3 K)
    Estimated Pc of DL50 17.74 bar

     | Show Table
    DownLoad: CSV

    To enhance diesel engine performance, a new diesel combustion concept has been proposed called as SC diesel spray combustion. Implementation of this new SC diesel spray combustion concept requires accurate fuel properties in the SC region of fuel [28]. In this new concept, it is a compulsory condition that DF must be heated above its critical temperature for direct injection into engine’s combustion chamber.

    Since DF is composed of hundreds of hydrocarbons, therefore exact determination of critical point of DF is quite difficult. Many correlation were developed based on the availability of characteristics information of hydrocarbon mixtures such as specific gravity (SG) and boiling point (Tb) of DF. Some commonly used correlations for DF are the API method [29], covett correlation [30,31], Kesler and Lee correlation [30,32] Brule correlation [33], Riazi and Daubert correlation [30,34] Sim and Daubert correlation [30,35] Zhou correlation [30,36] and Twu correlation [37]. These correlations can be used for estimation of DF critical point. The Riazi and Daubert correlation and Zhou correlation are recommended due to their simplicity as well as accuracy in the estimation of critical point of DF [28] among others correlations. Hence, Zhou correlation has been used in present work for estimating critical point of DF.

    In study [28], twenty diesel fuel surrogates (DFFs) empolyed for estimating DF chemical and physical properties. The estimated Tc of these DFFs vary significantly from 540 K to 734 K and only those of DFS#5, #17 and #19 were within the estimated Tc range of DF (717 K-745 K) [28]. Therefore, in present study DFS#5, which is n-hexadecane has been used as a representative of DF. The estimation of DF critical point using three correlations (Riazi and Daubert Correlation, Zhou correlation and Sim and Daubert correlation) are given in Table 2. Critical point of DF estimated by Zhou correlation has been considered in present study. The reason being that Tc estimated in present study by Zhou correlation i.e, 714.7 K is nearly same as estimated by Lin et al. [28] using Zhou correlation (715.58 K) for DF. The Pc estimated by Zhou correlation in present study is 19.23 bar and Pc estimated by Lin et al. [28] using Zhou correlation was 21.6 bar, which are also nearly same. Some properties of DF are given below in Table 3.

    Table 2.  Estimated Critical Point of DF.
    Correlations Pc (bar) Tc (K)
    Riazi and Daubert 18.29 724.94
    Zhou 19.23 714.71
    Sim and Daubert 18.26 713.08

     | Show Table
    DownLoad: CSV
    Table 3.  Properties of DF.
    Properties API gravitya (degree) Densitya (kg/m3) Aniline Pointa (℃) Diesel Indexb Flash Pointa (℃) Cloud Pointa (℃) Molecular massc (kg/kmol) Boiling Pointc (K)
    Commercial Diesel Fuel (DF2) 38.98 830 74 64.39 55 6 198 536.4
    a measured properties [38]
    b calculated properties
    c data obtained from chin et al. [39]

     | Show Table
    DownLoad: CSV

    a) Estimation of Critical Temperature of DL50 Blend: The critical temperature of liquid mixture (TCM) is estimated with the help of Kay’s rule [40] as follows:

    $ {T}_{CM} = \sum {X}_{i}{T}_{C, i} $ (1)

    ${T}_{CM} = {X}_{AG}\times {T}_{C, AG}+{X}_{DF2}\times {T}_{C, DF2}$

    ${T}_{CM} = 0.5\times 543.9+0.5\times 714.7 $

    ${T}_{CM} = 629.3K = 356.3\mathit{℃} $

    where $ {X}_{i} $ denotes the mole fraction of respective components and $ {T}_{C, i} $ denotes the Tc of respective components in a given liquid mixture. Since DL50 is a liquid mixture of 50% DF and 50% AG by volume. Critical properties of DF (n-hexadecane) and AG (iso-octane) are given in Tables 4 and 5 respectively. Estimated value of Tc of DL50 blend using Kay’s rule is given in Table 7. Other properties of AG are given in Table 6.

    Table 4.  Properties of n-hexadecane.
    Properties Tca (K) Pca (MPa) Vca (cm3/mol) ωSRKa
    n-hexadecane 723.00 1.400 1034.00 0.7667
    a data obtained from Poling et al. [41].

     | Show Table
    DownLoad: CSV
    Table 5.  Critical properties of AG.
    Tca (K) Pca (MPa) Vca (cm3/mol)
    Automotive Gasoline (AG)/Iso-octane 543.9 2.57 469.70
    a data obtained from Poling et al. [41].

     | Show Table
    DownLoad: CSV
    Table 6.  Properties of AG.
    Properties Molecular Formulaa Molecular Weighta kg/kmol Boiling point Temperaturea (K) SRK acentric factor, ω Densityb kg/m3
    (AG)/Isooctane C8H18 114.23 372.39 0.3045 750
    a data obtained from Poling et al. [41].
    b data obtained from Borgnakke et al. [40].

     | Show Table
    DownLoad: CSV
    Table 7.  Estimated critical pressure and temperature of DL50 blend.
    Dieseline Blend Pc (bar) Tc (℃)
    DL10 (90% DF + 10% AG) 13.92 424.62
    DL20 (80% DF + 20% AG) 14.73 407.54
    DL30 (70% DF + 30% AG) 15.64 390.46
    DL40 (60% DF + 40% AG) 16.59 373.38
    DL50 (50% DF + 50% AG) 17.74 356.3

     | Show Table
    DownLoad: CSV

    b) Estimation of Critical Pressure of DL50 Blend: Thomson et al. [42] recommended the following relation for estimation of critical pressure of a liquid mixture, PCM as

    $ {P}_{CM} = \left(0.291-0.080{\omega }_{SRK, M}\right)\times \left(\frac{{R}_{M}{T}_{CM}}{{V}_{CM}}\right) $ (2)

    where $ {R}_{M} $ is gas constant of mixture, $ {\omega }_{SRK, M} $ is acentric factor of mixture and $ {V}_{CM} $ is critical volume of the mixture.

    where $ {R}_{u} $ is universal gas constant and $ {MW}_{M} $ is molecular weight of mixture. Molecular weight of mixture $ {MW}_{M} $ is given as

    $ {MW}_{M} = \sum {X}_{i}{MW}_{i} $ (3)

    $ {MW}_{M} = {X}_{AG}\times {MW}_{AG}+{X}_{DF2}\times {MW}_{DF2} $

    $ {MW}_{M} = 0.5\times 114.231+0.5\times 198 $

    $ {MW}_{M} = 156.115kg/kmol $

    $ \text{Gas}\ \ \text{ constant }\ \text{ of }\ \text{ mixture,} {R}_{M} = {R}_{u}/{MW}_{M} $ (4)

    $ {R}_{M} = 8.314/156.115 = 0.0533kJ/kgK $

    Critical volume of mixture, $ {V}_{CM} $ is given as

    $ {V}_{CM} = {X}_{i}^{2}{\times V}_{Ci}+{X}_{j}^{2}{\times V}_{Cj}+2\times {V}_{Ci}\times {V}_{Cj}\times {V}_{Cij} $ (5)

    where, $ {V}_{Cij} $ is given as

    $ {V}_{Cij} = \frac{1}{8}{({V}_{Ci}^{1/3}+{V}_{Cj}^{1/3})}^{3} $ (6)

    where $ {V}_{Ci} $ and $ {V}_{Cj} $ are critical volumes of individual component in liquid mixture. $ {X}_{i} $ and $ {X}_{j} $ are mole fractions of individual component in liquid mixture.

    $ {V}_{Ci} = {V}_{AG} = 469.70{cm}^{3}/mol $ (Table 5)

    $ {V}_{Cj} = {V}_{DF2} = 1034{cm}^{3}/mol $ (Table 4)

    $ {V}_{Cij} = \frac{1}{8}{({469.70}^{1÷3}+{1034}^{1÷3})}^{3} = 715.16{cm}^{3}/mol $

    DF may be represented by n-hexadecane because n-hexadecane is a key component of DF and its molecular weight found to be very near to the average molecular weight of DF [28]. n-hexadecane is a good surrogate for DF [9] and can be used as a reference compound for DF [4]. Also Tc of n-hexadecane (723 K) is nearly close to the Tc of DF (725.9 K). DFS like n-hexadecane is recommended in applications where critical point of DF has to be considered [28,43]. Estimated value of Pc of DL50 blend is given in Table 7.

    Now, critical volume of the mixture is estimated as

    $ {V}_{CM} = {0.5}^{2}\times 469.7+{0.5}^{2}\times 1034+2\times 0.5\times 0.5\times 715.16 = 733.51{cm}^{3}/mol $

    $ {v}_{CM} = {V}_{CM}/{MW}_{M} = 733.51/156.115 = 0.00469{m}^{3}/kg $

    Hankinson [44] recommended linear combination for calculating the acentric factor of liquid mixture. Acentric factor, ωSRK, M of the mixture is given as

    $ {\omega }_{SRK, M} = \sum _{i}X{\omega }_{SRK, i}{X}_{i} $ (7)

    $ {\omega }_{SRK, i} $ is acentric factor of individual component in liquid mixture. Acentric factor for n-hexadecane and iso-octane are given below in Tables 4 and 6 respectively.

    $ {\omega }_{SRK, M} = 0.5\times 0.3045+0.5\times 0.7667 $

    $ {\omega }_{SRK, M} = 0.5356 $

    Critical pressure of a liquid mixture, $ {P}_{CM} $ is given as

    $ {P}_{CM} = \left(0.291-0.080{\omega }_{SRK, M}\right)\times \left(\frac{R{T}_{CM}}{{V}_{CM}}\right) $
    $ {P}_{CM} = \left(0.291-0.08\times 0.5356\right)\times \left(\frac{0.0533\times 629.3}{0.00469}\right) $
    $ {P}_{CM} = 1774.72kN/{m}^{2} = 17.74bar $

    Various experiments on DL50 blend have been carried out at different experimental conditions to study homogeneous SC spray combustion through following procedure.

    The various steps followed in taking reading for SC spray combustion of DL50 blend is illustrated through flowchart given in Figure 8.

    Figure 8.  Flowchart indicating details of experimental procedure in SC spray combustion.

    DOC is measured in millisecond (ms) on x-axis by noting difference between point of start and end of combustion as indicated by waveform on channel B (blue colour) shown in Figure 9. Photo transducer senses luminosity of flame due to combustion and indicates it on channel B.

    Figure 9.  Measurement of DOC on Channel B of scopemeter during SC spray combustion.

    Soot formation (SF) during the normal diesel spray and SC spray combustion is estimated at each operating condition. SF is estimated using time integrated natural luminosity (TINL) technique [19,49]. In this technique, pixel area under the curve B is calculated for estimating SF as shown in Figure 10.

    Figure 10.  Image showing area under the curve of channel B for the estimation of SF during SC spray combustion.

    There are two dependent (DOC and SF) and three independent variables (HST, IP and CP) in present work. Error analysis of the variables is done as follows:

    Dependent variables (DV) are measured through scopemeter. The accuracy of scopemeter at 5sec to 10μsec/div for 5 mV/div to 100V/div is ±1.5%. The percentage deviation of data from mean value is obtained at each condition in each combustion process and maximum and minimum values are shown in Tables 8 and 9.

    Table 8.  Error analysis of DV in normal spray combustion.
    DV Maximum Percentage Deviation Minimum Percentage Deviation
    DOC ±11.5% ±5.0%
    SF ±11.1% ±4.5%

     | Show Table
    DownLoad: CSV
    Table 9.  Error analysis of DV in SC spray combustion.
    DV Maximum percentage deviation Minimum percentage deviation
    DOC ±13.5% ±5.6%
    SF ±12.7% ±6.2%

     | Show Table
    DownLoad: CSV

    Uncertainty in calculation of volume of combustion chamber is estimated by method illustrated in [50]. Uncertainty in calculation of volume of combustion chamber is estimated as ±0.218%.

    K-type thermocouple of accuracy ±2.2% measured HST, Tc of DL50 blend and cylinder air temperature whereas Bourdon tube pressure gauges with accuracy from ±0.25% to 1% full scale measured IP and CP.

    Duration of combustion includes all three stages of diesel spray combustion such as premixed combustion, mixing-controlled combustion and after-burning phase. DOC of SC fuel spray is measured through flame luminosity indicated on screen of scopemeter as shown in Figure 9. DOC is defined as duration in ms between point of start of flame formation (start of combustion) and point at which flame extinguishes (end of combustion).

    DOC of normal diesel spray combustion at present experimental conditions is discussed in detail in study [26]. Graphs in Figures 11 and 12 illustrate variation of DOC with IP at HST = 673 K and HST = 723 K respectively and at various CP values for both combustion processes. Plots in Figure 13 and Figure 14 indicate percentage reduction in DOC with IP at HST = 673 K and HST = 723 K respectively and at various CP through histograms. In Figure 13 and Figure 14, yellow and magenta color histograms indicate highest and lowest percentage reduction in DOC respectively. It can be deduced from Figures 11 and 12 that DOC of SC spray combustion is remarkably smaller than DOC of normal diesel spray combustion at all experimental conditions. This is due to reason that SC fluids have desirable thermophysical properties that support fast and homogeneous combustion. Properties of fluids like density, volatility, diffusivity, surface tension, thermal conductivity and viscosity change in SC state significantly [7,28]. In SC spray combustion, fuel is injected into compressed cylinder air inside combustion chamber in SC state. SC fuel sprays are injected as homogeneous single-phase fluid [4] into combustion chamber and has reduced penetration lengths [6], wider spray cone angles [6], higher volatility due to more lighter/volatile components from gasoline, higher diffusivity and reduced surface tension [6]. SC fuel possess high mass transfer properties with diffusion coefficient nearly ten times higher than liquid at critical point [45]. SC state of fuel is characterized by low viscosity, high density and high mass transfer capability [47]. A homogeneous fuel-air mixture rapidly developed under SC conditions [6]. Moreover SC fuel posses high solvating capacity with other liquids [45]. Also, SC fuel spray injection is associated with relatively large spray angles and small spray penetration lengths [47] than liquid fuel spray. Also, raising fuel temperature at constant IP produces smaller spray penetration length and wider spray cone angles [48] and both these factors will improve mixture formation and mixture homogeneity considerably. Raising fuel temperature produces smaller droplets (SMD less than 7 μm) with narrow droplets size distribution (3-9 μm) and subsequently SC fuel injection has no droplets formation [47]. Raising fuel temperature results in reduced ID and DOC [47]. All these desirable changes in thermophysical properties of SC fluids and in spray geometry causes homogeneous, faster and quick mixing of SC fuel sprays with cylinder air. All these favorable properties of SC fuel sprays support faster and homogeneous fuel-air mixing as compared to heterogeneous fuel-air mixing in conventional diesel droplet spray combustion. Faster and homogeneous fuel-air mixing results in faster and homogeneous combustion of SC fuel sprays. Due to significantly faster combustion of SC fuel sprays with compressed cylinder air, DOC is greatly reduced at all operating conditions than conventional normal diesel spray combustion in present study.

    Figure 11.  Variation of DOC with IP at HST of 673 K and at different CP in both combustion systems.
    Figure 12.  DOC against IP at HST of 723 K and at Different CP in both combustion systems.

    Spray development affects the mixture preparation inside combustion chamber significantly and this can be explained through the non-dimensional numbers like Reynolds number, Weber number, Ohnesorge number and Knudsen number. In case of heated fuel injection system, Reynolds number is relatively large than cold fuel injection. Weber number and Ohnesorge number of heated fuel injection are an order of magnitude higher than cold fuel injection due to significantly diminished surface tension in heated fuel injection (Weber and Ohnesorge number are inversely proportional to surface tension) [48]. SC state fuel has turbulent and diffusion mixing characteristics with surrounding air. Also in case of SC fuel injection, spray core is diffused and continuous as compared to discrete surface of unheated fuel injection [48]. In case of SC spray injection than liquid fuel injection, mixture charge homogeneity considerably increased [51]. Also, it is reported [51] that SC fuel spray changes its state from SC to vapor phase on injection into combustion chamber and leads to the rapid expansion of jet. The rapid expansion of jets as well as wider spray angles and longer penetrations lengths causes more air entrainment into jet and results in enhanced fuel-air mixing and this mechanism is responsible for increased mixture homogeneity in combustion chamber. Nevertheless, SC spray injection has shorter ignition delay with spontaneous ignition at various locations inside combustion chamber and premixed combustion phase is followed by diffusion combustion with overall shorter DOC [45].

    In the present study, SC fuel spray injection mainly occurs in subcritical environment (with respect to injectant’s Tc). The compressed cylinder air was at pressures (20 bar, 30 bar and 40 bar) above injectant’s Pc (17.74 bar) but at temperatures (nearly 350 ℃) lower than DL50 blend’s Tc (356 ℃). Therefore compressed cylinder air was at subcritical condition with respect to injectant’s Tc. It is reported that in case of SC fuel spray injection in subcritical conditions inside combustion chamber, surface tension effects becomes negligible on fuel-air mixing and smooth jet-gas interface with few formation of ligaments and clusters occurs at near nozzle regions [52]. However, far downstream of the injector nozzle several droplets may form and detached from the main body of jet. This occurs due to heat transfer from the jet to surrounding medium and increase in surface tension at lower ambient charge temperature. However, when fuel is injected in high temperature and pressure chamber conditions (typical diesel engine conditions at TDC) exceeding the critical point of injected fuel there were no evidences of ligaments and droplets formation due to absence of surface tension [53].

    It can be noticed in Figures 13 and 14 that at all experimental conditions, percentage reduction in DOC in SC spray combustion with respect to normal diesel spray combustion is above 35%. Faster and homogeneous combustion of SC fuel sprays produces dramatically lowered exhaust emissions mainly PM and NOx [12,45,51,54]. Therefore, SC spray injection and combustion system is a clean and efficient combustion technology for automotive engines [55]. This combustion technology will significantly reduce harmful exhaust emissions in the environment.

    Figure 13.  Variation of percentage reduction in DOC with IP at HST of 673 K and at Various CP.
    Figure 14.  Variation of percentage reduction in DOC with IP at HST of 723 K and at Various CP.

    As discussed above, in case of SC spray injection, impingement of SC sprays on hot surface sufficiently reduced due to lesser spray tip penetration lengths and wider cone angles of SC fuel sprays [6] and these factors may causes hot air combustion of SC fuel sprays rather than hot surface ignition. However, normal (non-supercritical) spray combustion occurs due to hot surface ignition of impinging diesel sprays. Since ID of SC fuel sprays [56] is very small (nearly 2-3 ms) as compared to ID of normal diesel sprays (nearly 6-24 ms) therefore corresponding premixed combustion phase after completion of ID period in case of SC fuel sprays will be significantly smaller. Therefore, mixing-controlled combustion phase is observed to dominate SC spray combustion in present work. Mixing-controlled combustion nature of SC sprays combustion is also confirmed by the fact that SC spray combustion process is significantly affected by IP rather than CP as pointed in Figures 11 and 12. Since, hot air combustion is also significantly affected by IP [14,57]. Higher IP enhances homogeneous mixing of fuel-air and consequently reduces mixing-controlled combustion or diffusing burning phase and ultimately DOC reduces as shown in Figures 11 and 12 for SC sprays. With increase in IP of SC sprays, DOC continuously decreases and it is minimum at 300 bar IP at both values of HST (673 K and 723 K). Also, it is found from Figures 13 and 14 that there is a dip in percentage reduction in DOC at 200 bar IP. This may be due to the fact that IP effect on DOC mitigates in normal diesel spray combustion as IP increases [26]. However, in case of SC spray combustion, effect of IP on DOC becomes more stronger at higher IP and therefore combustion is observed to be faster at 300 bar IP. Higher IP of the fuel generates faster combustion rates [58,59] and faster combustion rate results in rapid combustion which have short DOC of fuel jets [45,60]. Higher IP leads to larger penetration of fuel jet and hence better mixing of fuel and air inside combustion chamber. Moreover, spray/jet structure or shape is not affected by the quantity of fuel injected into combustion chamber [6]. Moreover, phenomenon occurring in diesel injector leads to the development of increased turbulence near-nozzle regions, which causes disintegration of fuel jets and increased spray cone angles [61]. All above factors resulted in nearly complete and faster combustion of the fuel sprays inside combustion chamber at higher IP.

    Also, it can be noted that there is a marginal effect of CP on the DOC for SC fuel sprays as shown in Figure 11 and Figure 12. The same effect can be observed in Figure 13 and Figure 14 by noting the difference in values of percentage reduction in DOC with increase in CP of air at both HST values. Since, CP of air mainly affects the ID and has minor effect on fuel-air mixing and hence on mixing-controlled combustion phase [14], therefore DOC is insignificantly affected by CP of air inside combustion chamber. Also, it can be noticed from Figure 13 and Figure 14 that percentage reduction in DOC slightly decreases with increase in CP. Percentage reduction in DOC is high at lower CP (20 bar) and low at higher CP (40 bar) for both temperatures (HST = 673 and HST = 723 K).

    It is observed from Figures 11 and 12 or Figures 13 and 14 that DOC of SC fuel sprays is also affected by HST. It is found that DOC of SC fuel sprays insignificantly reduced with increase in HST from 673 K to 723 K at various CP values. However, effect of increase in HST from 673 K to 723 K on DOC of normal diesel sprays is significant at all CP values [26]. The insignificant effect of increasing HST on DOC of SC fuel spray combustion may due to the reason that SC fuel spray combustion occurs in hot compressed air inside combustion chamber and moreover because of reduced penetration lengths and wider cone or spray angles of SC fuel sprays. Hence, there is no impingement of SC fuel sprays on hot surface unlike that of normal diesel spray (impinging on hot surface) and consequently combustion of SC fuel sprays is less affected by HST. However, small decrease in DOC of SC fuel sprays with increase in HST is attributed to the increase in compressed cylinder air temperature with increase in HST. Any increase in HST causes increase in compressed cylinder air temperature. It is interesting to note that at typical normal operating conditions of small bore high speed DI diesel engine (high IP, CP and HST), reduction in DOC is found to be lowest.

    The combustion process can also be characterized by the flame or natural luminosity [17]. The flame luminosity includes two phenomena i.e., soot incandescence and chemiluminescence. The soot incandescence is the major source of flame luminosity [17,49]. The intensity of chemiluminescence is much weaker than the intensity of soot incandescence [62]. Flame (natural) luminosity indicates soot emissions because soot incandescence depends on soot concentration and temperature [62] and soot incandescence is main part of flame luminosity. Flame or natural luminosity is the indicator of soot formation [49].

    Flame or natural luminosity is measured in terms of spatially integrated flame luminosity (SINL). SINL value is calculated by integrating pixel values over entire flame image. SINL is a combination of the soot concentration and temperature [19,64]. Therefore higher values of SINL indicate higher formation of soot particles [19,65]. To better quantify the flame luminosity characteristics of entire spray combustion process, time integrated natural luminosity (TINL) is employed [49]. The TINL is an indicator of soot formation (SF) during whole combustion duration [19,49].

    TINL values are evaluated through the integration of SINL with time [49]. In present study, TINL value is calculated as area under the entire flame curve B as shown in Figure 10. The flame luminosity curve B is obtained as a function of time over the complete combustion process or DOC. Therefore area under the curve B indicates the level of SF during whole combustion process and it is denoted as TINL. TINL values are indicated in auxiliary units (a.u.).

    It can be seen in Figure 16 that TINL values are high at higher HST (723 K) as compared to lower HST (623 K) at all CP. The reason may be that as HST increases the temperature gradients near the hot surface decrease and ID shortens and this leads to insufficient mixing of fuel-air and fuel-rich combustion products. Therefore high SF (higher TINL value) occurs at higher HST [17]. It can also be seen from Figure 16 that TINL values are lower at higher CP (40 bar) as compared to lower CP (20 bar) at all values of HST. In other words, TINL values decrease with increase in CP from 20 bar to 40 bar. In the condition of lower CP, wall temperature has a greater influence on flame luminosity as indicated by TINL values in Figure 16. This is because when the CP is lower, ID will be longer, fuel-air mixing during ID will be proper and HST dominates the combustion process [17].

    Figure 15.  Variation of Percentage Reduction in SF with HSTs at different CPs and at 300 bar IP.
    Figure 16.  Variation of SF with HST at different CP and at IP of 300 bar in both combustion systems.

    In the condition of higher CP, ID will be shorter and fuel-air mixing during ID will be insufficient, the flame will be very close to the hot surface and therefore has difficulty of air entrainment [17,66] and also has the probability of liquid-wetting of hot surface. Therefore because of these reasons combustion near the hot surface will be rich combustion and has higher SF [17,67] and these reasons weaken the effect of HST on TINL or flame luminosity at higher CP. Feng et al. [17] also reported similar trends of flame luminosity variation with heated wall temperatures and cylinder pressures for higher IP (600 bar to 1600 bar) in CVCC. SF (flame luminosity) significantly increases as a result of impinging sprays in comparison to free sprays as reported in literature [68,69,70].

    In present study on SC fuel spray combustion, TINL values are calculated for 300 bar IP case only for both combustion systems to quantify and compare SF levels in these two combustion processes under similar operating conditions. Graphs in Figure 15 show the variation of percentage reduction in SF in SC fuel sprays than normal diesel sprays with HST at various CP values and at constant IP of 300 bar. Increase in percentage reduction in SF with increase in HST is presented by change of color of bars (yellow histograms indicate highest percentage reduction in soot). It can be noticed from Figure 15 that at a given IP and at all CP and HST values, SF levels in case of SC spray combustion are greatly reduced to much lower values than SF levels in normal diesel spray combustion. It is evident from these plots in Figure 15 that SF levels or TINL values are reduced atleast by nearly 90% in SC spray combustion than normal diesel droplet spray combustion. The similar reduction in SF is also reported by some researchers in case of SC spray injection and combustion process [12,48,51,54]. Heated fuel injection resulted in reduce soot emissions [47]. Since SF generally depends on the combustion of lower air-fuel ratios mixtures. The lower local air-fuel ratios or rich mixtures mainly produced due to the maldistribution of fuel in the surrounding air, wall wetting or impingement of fuel sprays and fuel droplets [51]. Injection of fuel as SC fuel into compressed air appears to have reduced these causes of SF in present study and therefore results in significant reduction in SF in SC fuel spray combustion process. Also, since SC fuel injection contains no liquid fuel droplets and hence shows significant decrease in SF [45].

    Simultaneous reduction of both NOx and PM is reported when SC fuel spray combustion occurred in engines or in other combustors [12,54]. In present study, only SF is quantified and compared with the help of TINL values but on the basis of previous studies [12,54,71] it can be state that simultaneous reduction of NOx will also occurred in SC spray combustion of DL50 blend. NOx formation will be significantly lower in SC spray combustion since SC spray combustion occurs at lower combustion temperature than normal diesel droplet spray combustion’s temperature [71,72]. Temperature spikes and fuel rich regions are absent in homogeneous single-phase SC spray combustion [4] unlike that of normal diesel spray combustion and hence significant reduction of both major diesel engine emissions (NOx and soot) and improved efficiency is ensured in this new combustion technology.

    SC spray combustion takes place in larger volume than only around fuel spray envelope as well as combustion occurs at lower temperature and hence avoids NOx formation [71,72]. Moreover, simultaneous reduction of both NOx and soot may due to the enhanced premixing associated with the SC injection of fuel into combustion chamber [73]. SC fuel spray combustion not only produces lower levels of NOx and soot but also generates smaller levels of other gaseous emissions such as CO, HC and CO2 as compared to conventional diesel droplet spray combustion process [4,12,45,51,74]. However in conventional engines, EGR systems besides other techniques significantly affected combustion and emissions formation [75]. In a study [4], SC fuel spray combustion produced reduced harmful emissions like PM, NOx, SOx, CO, aldehydes and polyaromatic hydrocarbons (PAHs) alongwith improved efficiency.

    Plots in Figure 16 show the comparison of SF levels in both combustion systems at fixed IP of 300 bar and at different CP and HST values. TINL values are calculated at each operating condition for both combustion systems and plotted against HST to quantify the SF levels under similar operating conditions in CVCC. Each plot of Figure 15 shows substantial reduction in SF level for SC spray combustion than normal diesel spray combustion. The reasons for dramatic reduction in SF in SC spray combustion are given in previous paragraphs. It can also be observed in Figure 16 that in case of SC spray combustion, SF level slightly reduces with the increase in CP. Moreover, it can be observed in Figure 16 that with increase in HST, SF level decreases gradually in SC spray combustion. The decrease in SF with increase in HST may due to the reason that increase in HST results in corresponding increase in temperature of cylinder air and therefore oxidation of fuel-rich regions enhances with rising cylinder air temperature. The reduction in SF with increase in CP may be due to the fact that increasing CP increases density of cylinder air and this causes enhancement in fuel-air mixing process as well as mixture becomes more homogeneous and also avoids local fuel-rich mixtures regions, similar findings regarding soot formation are reported in [76]. All these factors reduce SF at higher CP.

    Combustion and soot formation characteristics of homogeneous SC sprays in CVCC are studied under diesel engine-like experimental conditions. It is found that DOC of SC sprays are substantially lower than DOC of normal diesel sprays (percentage reduction in DOC is more than 35% in SC spray combustion than normal diesel spray combustion) under all present conditions. Smaller DOC means homogeneous, single-phase and faster combustion of SC sprays due to more homogeneous and enhanced mixing of SC sprays with cylinder air. Percentage reduction in DOC of SC sprays is found to be highest (>80%) at higher IP of 30 MPa. This means that even more faster combustion of SC sprays than normal diesel sprays occurs at higher IP. SC spray combustion appears to be a hot-air combustion. Also, it has been observed that percentage reduction in soot formation in SC spray combustion than normal diesel spray combustion is more than 90% at all conditions. At normal diesel engine operating condition, percentage reduction in DOC and soot formation of nearly 82% and 96% respectively are achieved. In SC spray combustion, soot formation reduced slightly with increase in CP and HST. On the basis of present work, it is felt that the new concept of homogenous SC spray injection and combustion can prove out to be a promising technology (cleaner and efficient) for improving engine performance and can be recommended for future generation automotive engines.

    Although there are some limitations of present study such as use of lower injection pressures, higher concentrations of gasoline in DF and investigation of soot formation only. Therefore, as a part of future work, lower concentrations of gasoline (<50%) in DF and higher injection pressures above 30 MPa can be explored and study of other exhaust emissions such as hydrocarbons, oxides of nitrogen, carbon monoxides may be investigated.

    This work is supported by Technical Education Quality Improvement Program-III, MHRD, Govt. of India.

    The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

    [1] Happé F (2015) Autism as a neurodevelopmental disorder of mind-reading. Abstr Book 3: 197–209.
    [2] Dover CJ, Le Couteur AL (2007) How to diagnose Autism. Arch Dis Child 92: 540–545. doi: 10.1136/adc.2005.086280
    [3] Jukić V, Arbanas G (2013) Diagnostic and Statistical Manual of Mental Disorders; Fifth Edition (DSM-5).Int J 57: 15461548.
    [4] Fombonne E (2009) Epidemiology of pervasive developmental disorders. Pediatr Res 65: 591–598. doi: 10.1203/PDR.0b013e31819e7203
    [5] Fombonne E, Quirke S, Hagen A (2009) Prevalence and interpretation of recent trends in rates of pervasive developmental disorders. McGill J Med 12: 73.
    [6] Weintraub K (2011) Autism counts. Nature 479: 22–24. doi: 10.1038/479022a
    [7] Nazeer A, Ghaziuddin M (2012) Autism spectrum disorders: Clinical features and diagnosis. Pediatr Clin North Am 59: 19–25. doi: 10.1016/j.pcl.2011.10.007
    [8] Zablotsky B, Black LI, Maenner MJ, et al. (2015) Estimated prevalence of autism and other developmental disabilities following questionnaire changes in the 2014 national health interview survey. Natl Health Stat Rep 2015: 1–20.
    [9] Hansen SN, Schendel DE, Parner ET (2015) Explaining the increase in the prevalence of autism spectrum disorders the proportion attributable to changes in reporting practices. JAMA Pediatr 169: 56–62. doi: 10.1001/jamapediatrics.2014.1893
    [10] Mostafa GA, ALayadhi LY (2012) Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: Relation to autoimmunity. J Neuroinflammation 9: 1–7.
    [11] Duan XY, Jia FY, Jiang HY (2013) Relationship between vitamin D and autism spectrum disorder. Chin J Contemp Pediatr 15: 698–702.
    [12] Newschaffer CJ, Croen LA, Daniels J, et al. (2007) The epidemiology of autism spectrum disorders. Annu Rev Public Health 28: 235–258. doi: 10.1146/annurev.publhealth.28.021406.144007
    [13] Christison GW, Ivany K (2006) Elimination diets in autism spectrum disorders: Any wheat amidst the chaff? J Dev Behav Pediatr 27: S162–S171. doi: 10.1097/00004703-200604002-00015
    [14] Meyer U, Feldon J, Dammann O (2011) Schizophrenia and autism: Both shared and disorder-specific pathogenesis via perinatal inflammation? Pediatr Res 69: 26R–33R.
    [15] Wagner CL, Taylor SN, Dawodu A, et al. (2012) Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus. Nutrients 4: 208–230.
    [16] Abdulbari B, Oaa AHA, Saleh NM (2013) Association between vitamin D insufficiency and adverse pregnancy outcome: Global comparisons. Int J Womens Health 5: 523.
    [17] Georgieff MK (2007) Nutrition and the developing brain: Nutrient priorities and measurement. Am J Clin Nutr85: 614S620S.
    [18] Al-Farsi YM, Waly MI, Deth RC, et al. (2013) Impact ofnutrition on serum levels of docosahexaenoic acid among Omani children with autism. Nutrition 29: 11421146.
    [19] Bell JG, Mackinlay EE, Dick JR, et al. (2004) Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins Leukotrienes Essent Fatty Acids 71: 201204.
    [20] Amminger GP, Berger GE, Schafer MR, et al. (2007) Omega-3 fatty acids supplementation in children with autism: A double-blind randomized, placebo-controlled pilot study. Biol Psychol 61: 551553.
    [21] Meguid NA, Atta HM, Gouda AS, et al. (2008) Role of polyunsaturated fatty acids in the management of Egyptian children with autism. Clin Biochem 41: 10441048.
    [22] Meiri G, Bichovsky Y, Belmaker RH (2009) Omega 3 fatty acid treatment in autism. J Child Adolesc Psychopharmacol 19: 449451.
    [23] El-Ansary AK, Ben BAG, Al-Ayahdi LY (2011) Impaired plasma phospholipids and relative amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia. Lipids Health Dis 10: 63. doi: 10.1186/1476-511X-10-63
    [24] Yui K, Koshiba M, Nakamura S, et al. (2012) Effects of large doses of arachi-donic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders: A double-blind, placebo-controlled, randomized trial. J Clin Psychopharmacol 32: 200206.
    [25] Gómezpinilla F (2008) Brainfoods: The effect of nutrients on brain function. Nat Rev Neurosci 9: 568578.
    [26] Willis LM, Shukitt-Hale BJ (2009) Recent advances in berry supplementation and age-related cognitive decline. Curr Opin Clin Nutr Metab Care 12: 91–94. doi: 10.1097/MCO.0b013e32831b9c6e
    [27] Gu Y, Nieves JW, Stern Y, et al. (2010) Food combination and Alzheimer disease risk: A protective diet. Arch Neurol 67: 699706.
    [28] Nyaradi A, Li J, Hickling S, et al. (2013) The role of nutrition in children's neurocognitive development, from pregnancy through childhood. Front Hum Neurosci 7: 97.
    [29] Prado EL, Dewey KG (2014) Nutrition and brain development in early life. Nutr Rev 72: 267284.
    [30] Keunen K, Elburg RMV, Bel FV, et al. (2014) Impact of nutrition on brain development and its neuroprotective implications following preterm birth. Pediatr Res 77: 148155.
    [31] Georgieff MK, Rao R, (2001) The role of nutrition in cognitive development. In: Nelson CA, Luciana M, Eds.,Handbook in developmental cognitive neuroscience.Cambridge, MA: MIT Press, 491–504.
    [32] Hultman CM, Sparén P, Cnattingius S (2002) Perinatal risk factors for infantile autism. Epidemiology 13: 417423.
    [33] Dionne G, Boivin M, Seguin JR. et al. (2008) Gestational diabetes hinders language development in offspring. Pediatrics 122: 10731079.
    [34] Leonard H, Klerk N, Bourke J, et al. (2006) Maternal health in pregnancy and intellectual disability in the offspring: A population-based study. Ann Epidemiol 16: 448454.
    [35] Dodds L, Fell DB, Shea S, et al. (2011) The role of prenatal, obsteric and neonatal factors in the development of autism. J Autism Dev Disord 41: 891902.
    [36] Burdge GC, Lillycrop KA (2014) Fatty acids and epigenetics. Curr Opin Clin Nutr Metab Care 17: 156–161. doi: 10.1097/MCO.0000000000000023
    [37] Delong GR (1993) Effects of nutrition on brain development in humans. Am J Clin Nutr 57: S286S290.
    [38] Morgane PJ, Mokler DJ, Galler JR (2002) Effects of prenatal protein malnutrition on the hippocampal formation. Neurosci Biobehav Rev 26: 471–483. doi: 10.1016/S0149-7634(02)00012-X
    [39] Rosales FJ, Reznick JS, Zeisel SH (2009) Understanding the role of nutrition in the brain and behavioral development of toddlers and preschool children: Identifying and addressing methodological barriers. Nutr Neurosci 12: 190–202. doi: 10.1179/147683009X423454
    [40] Mccann JC, Ames BN (2005) Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. Am J Clin Nutr 82: 281–295.
    [41] Innis SM (2007) Dietary (n-3) fatty acids and brain development. J Nutr 137: 855–859. doi: 10.1093/jn/137.4.855
    [42] Wu A, Ying Z, Gomezpinilla F (2007) Omega-3 fatty acids supplementation restores mechanisms that maintain brain homeostasis in traumatic brain injury. J Neurotrauma 24: 1587–1595.
    [43] De Souza AS, Fernandes FS (2011) Effects of maternal malnutrition and postnatal nutritional rehabilitation on brain fatty acids, learning, and memory. Nutr Rev 69: 132–144.
    [44] Lozoff B, Georgieff MK (2006) Iron deficiency and brain development. Semin Pediatr Neurol 13: 158–165.
    [45] Zimmermann MB (2011) The role of iodine in human growth and development. Semin Cell Dev Biol 22: 645–652.
    [46] Greenwood CE, Winocur G (2005) High-fat diets, insulin resistance and declining cognitive function. Neurobiol Aging 26: 42–45.
    [47] Molteni R, Barnard RJ, Ying Z, et al. (2002) A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 112: 803–814.
    [48] Rice D, Barone S (2000) Critical periods of vulnerability for the developing nervous system: Evidence from humans and animal models. Environ Health Perspect 108: 511533.
    [49] Couperus JW,Nelson CA,(2006) Early brain development and plasticity. In: McCartney K, Phillips D, Eds.,The Blackwell Handbook of Early Childhood Development.Malden, MA: Blackwell Publsihing,85105.
    [50] Benton D (2010) The influence of dietary status on the cognitive performance of children. Mol Nutr Food Res 54: 457–470.
    [51] Levitsky DA, Strupp BJ (1995) Malnutrition and the brain: Changing concepts, changing concerns. J Nutr 125: 2212S–2220S. doi: 10.1093/jn/125.suppl_8.2212S
    [52] Penido AB, Rezende GH, Abreu RV, et al. (2012) Malnutrition during central nervous system growth and development impairs permanently the subcortical auditory pathway. Nutr Neurosci 15: 31–36. doi: 10.1179/1476830511Y.0000000022
    [53] Roseboom TJ, Painter RC, Van Abeelen AF, et al. (2011) Hungry in the womb: What are the consequences? Lessons from the Dutch famine. Maturitas 70: 141–145.
    [54] Kerac M, Postels DG, Mallewa M, et al. (2014) The interaction of malnutrition and neurologic disability in Africa. Semin Pediatr Neurol 21: 42–49. doi: 10.1016/j.spen.2014.01.003
    [55] Jacka FN, Pasco JA, Mykletun A, et al. (2010) Association of western and traditional diets with depression and anxiety in women. Am J Psychiatry 167: 305–311. doi: 10.1176/appi.ajp.2009.09060881
    [56] Jacka FN, Pasco JA, Mykletun A, et al. (2011) Diet quality in bipolar disorder in a population-based sample of women. J Affective Disord 129: 332–337. doi: 10.1016/j.jad.2010.09.004
    [57] Forsyth AK, Williams PG, Deane FP (2011) Nutrition status of primary care patients with depression and anxiety. Aust J Primary Health 18: 172–176.
    [58] Scarmeas N, Stern Y, Tang MX, et al. (2006) Mediterranean diet and risk for Alzheimer's disease. Ann Neurol 59: 912–921. doi: 10.1002/ana.20854
    [59] Francesco S, Francesca C, Rosanna A, et al. (2008) Adherence to Mediterranean diet and health status: A meta-analysis. BMJ 337: a1344. doi: 10.1136/bmj.a1344
    [60] Scarmeas N, Stern Y, Mayeux R, et al. (2009) Mediterranean diet and mild cognitive impairment. Arch Neurol 66: 216–225.
    [61] Eilander A, Gera T, Sachdev HS, et al. (2010) Multiple micronutrient supplementation for improving cognitive performance in children: Systematic review of randomised controlled trials. Am J Clin Nutr 91: 115–130. doi: 10.3945/ajcn.2009.28376
    [62] Schoenthaler SJ, Amos S, Doraz W, et al. (1997) The effect of randomized vitamin-mineral supplementation on violent and non-violent antisocial behavior among incarcerated juveniles. J Nutr Environ Med 7: 343–352. doi: 10.1080/13590849762475
    [63] Schoenthaler SJ, Bier ID (1999) Vitamin-mineral intake and intelligence: A macrolevel analysis of randomised controlled trials. J Altern Complementary Med 5: 125–134. doi: 10.1089/acm.1999.5.125
    [64] Zaalberg A, Nijman H, Bulten E, et al. (2010) Effects of nutritional supplements on aggression, rule-breaking, and psychopathology among young adult prisoners. Aggressive Behav 36: 117–126. doi: 10.1002/ab.20335
    [65] Buffington SA, Di PG, Auchtung TA, et al. (2016) Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell 165: 1762–1775. doi: 10.1016/j.cell.2016.06.001
    [66] Bazinet RP, Layé S (2014) Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci 15: 771–785. doi: 10.1038/nrn3820
    [67] Innis S, De-La-Presa-Owens S (2001) Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain. J Nutr 131: 118–122. doi: 10.1093/jn/131.1.118
    [68] Pardo CA, Eberhart CG (2007) The neurobiology of autism. Brain Pathol 17: 434–447. doi: 10.1111/j.1750-3639.2007.00102.x
    [69] Chalon S (2006) Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukotrienes Essent Fatty Acids 75: 259–269. doi: 10.1016/j.plefa.2006.07.005
    [70] Zimmer L, Delpal S, Guilloteau D, et al. (2000) Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. Neurosci Lett 284: 25–28. doi: 10.1016/S0304-3940(00)00950-2
    [71] Aïd S, Vancassel S, Poumès-Ballihaut C, et al. (2003) Effect of a diet-induced n-3 PUFA depletion on cholinergic parameters in the rat hippocampus. J Lipid Res 44: 1545–1551. doi: 10.1194/jlr.M300079-JLR200
    [72] Takeuchi T, Iwanaga M, Harada E (2003) Possible regulatory mechanism of DHA-induced anti-stress reaction in rats. Brain Res 964: 136–143. doi: 10.1016/S0006-8993(02)04113-6
    [73] Fedorova I, Alvheim AR, Hussein N, et al. (2009) Deficit in prepulse inhibition in mice caused by dietary n-3 fatty acid deficiency. Behav Neurosci 123: 1218–1225. doi: 10.1037/a0017446
    [74] Larrieu T, Hilal LM, Fourrier C, et al. (2014) Nutritional omega-3 modulates neuronal morphology in the prefrontal cortex along with depression-related behaviour through corticosterone secretion. Transl Psychiatry 4: e437. doi: 10.1038/tp.2014.77
    [75] Larrieu T, Madore C, Joffre C, et al. (2012) Nutritional n-3 polyunsaturated fatty acids deficiency alters cannabinoid receptor signalling pathway in the brain and associated anxiety-like behavior in mice. J Physiol Biochem 68: 671–681. doi: 10.1007/s13105-012-0179-6
    [76] Jones ML, Mark PJ, Waddell BJ (2013) Maternal omega-3 fatty acid intake increases placental labyrinthine antioxidant capacity but does not protect against fetal growth restriction induced by placental ischaemia-reperfusion injury. Reproduction 146: 539–547. doi: 10.1530/REP-13-0282
    [77] Li Q, Leung YO, Zhou I, et al. (2015) Dietary supplementation with n-3 fatty acids from weaning limits brain biochemistry and behavioural changes elicited by prenatal exposure to maternal inflammation in the mouse model. Transl Psychiatry 5: e641. doi: 10.1038/tp.2015.126
    [78] Labrousse VF, Nadjar A, Joffre C, et al. (2012) Short-term long chain Omega3 diet protects from neuroinflammatory processes and memory impairment in aged mice. PLoS One 7: e36861. doi: 10.1371/journal.pone.0036861
    [79] Kerr M (2008) Neurodevelopmental delays associated with iron-fortified formula for healthy infants. Med Psychiatry Mental Health.
    [80] Stein Z, Susser M, Saenger G, et al. (1975) Famine and human development: The Dutch hunger winter of 1944–1945. Q Rev Biol 7: 1944–1945.
    [81] Hoek HW, Susser E, Buck KA, et al. (1996) Schizoid personality disorder after prenatal exposure to famine. Am J Psychiatry 153: 1637–1639. doi: 10.1176/ajp.153.12.1637
    [82] Susser E, Neugebauer R, Hoek HW, et al. (1996) Schizophrenia after prenatal famine: Further evidence. Arch Gen Psychiatry 53: 25–31. doi: 10.1001/archpsyc.1996.01830010027005
    [83] Susser E, Hoek HW, Brown A (1998) Neurodevelopmental Disorders after Prenatal Famine: The Story of the Dutch Famine Study. Am J Epidemiol 147: 214–216.
    [84] Millichap JG, Yee MM (2012) The Diet Factor in Attention-Deficit/hyperactivity disorder. Paediatrics 129: 330. doi: 10.1542/peds.2011-2199
    [85] Surén P, Roth C, Bresnahan M, et al. (2013) Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. J Am Med Assoc 309: 570–577. doi: 10.1001/jama.2012.155925
    [86] Grant WB, Soles CM (2009) Epidemiologic evidence supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism. Dermatoendocrinology 1: 223–228. doi: 10.4161/derm.1.4.9500
    [87] Blaylock RL (2009) Possible central mechanism in autism spectrum disorders, part 3: The role of excitotoxin food additives and the synergistic effects of other environmental toxins. Altern Ther Health Med 15: 56–60.
    [88] Macfabe DF, Cain DP, Rodriguez-Capote K, et al. (2007) Neurobiological effects of intraventricular propionic acid in rats: Possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders.Behav Brain Res176: 149169.
    [89] Macfabe DF, Cain NE, Boon F, et al. (2011) Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder. Behav Brain Res 217: 47–54. doi: 10.1016/j.bbr.2010.10.005
    [90] El-Ansary AK, Bacha AB, Kotb M (2012) Etiology of autistic features: The persisting neurotoxic effects of propionic acid. J Neuroinflammation 9: 74.
    [91] Bourgeron T (2007) The possible interplay of synaptic and clock genes in autism spectrum disorders. Cold Spring Harb Symp Quant Biol 72: 645–654. doi: 10.1101/sqb.2007.72.020
    [92] Bourgeron T (2009) A synaptic trek to autism. Curr Opin Neurobiol 19: 231–234. doi: 10.1016/j.conb.2009.06.003
    [93] Bourgeron T (2015) From the genetic architecture to synaptic plasticity in autism spectrum disorder. Nat Rev Neurosci 16: 551–563. doi: 10.1038/nrn3992
    [94] Oberman LM, Ifertmiller F, Najib U, et al. (2016) Abnormal echanisms of plasticity and metaplasticity in autism spectrum disorders and fragile X syndrome. J Child Adolesc Psychopharmacol 26: 617–624. doi: 10.1089/cap.2015.0166
    [95] Georgieff MK, Brunette KE, Tran PV (2015) Early life nutrition and neural plasticity. Dev Psychopathol 27: 411–423. doi: 10.1017/S0954579415000061
    [96] Madore C, Nadjar A, Delpech JC, et al. (2014) Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes. Brain Behav Immun 41: 22–31. doi: 10.1016/j.bbi.2014.03.021
    [97] Lafourcade M, Larrieu T, Mato S, et al. (2011) Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nat Neurosci 14: 345–350. doi: 10.1038/nn.2736
    [98] Thomazeau A, Boschbouju C, Manzoni O, et al. (2016) Nutritional n-3 PUFA deficiency abolishes endocannabinoid gating of hippocampal long-term potentiation. Cereb Cortex 27: 2571–2579.
    [99] Fatemi SH, Aldinger KA, Ashwood P, et al. (2012) Consensus paper: Pathological role of the cerebellum in autism. Cerebellum 11: 777–807. doi: 10.1007/s12311-012-0355-9
    [100] Harada M, Taki MM, Nose A, et al. (2011) Non-invasive evaluation of the gabaergic/glutamatergic system in autistic patients observed by mega-editing proton MR spectroscopy using a clinical 3 tesla instrument. J Autism Dev Disord 41: 447–454. doi: 10.1007/s10803-010-1065-0
    [101] Blatt GJ, Fatemi SH (2011) Alterations in gabaergic biomarkers in the autism brain: Research findings and clinical implications. Anat Rec 294: 1646–1652. doi: 10.1002/ar.21252
    [102] Hogart A, Leung KN, Wang NJ, et al. (2009) Chromosome 15q11-13 duplication syndrome brain reveals epigenetic alterations in gene expression not predicted from copy number. J Med Genet 46: 86–93.
    [103] Xu LM, Li JR, Huang Y, et al. (2012) Autismkb: An evidence-based knowledgebase of autism genetics. Nucleic Acids Res 40: 1016–1022. doi: 10.1093/nar/gkr1145
    [104] Jamain S, Betancur C, Quach H, et al. (2002) Linkage and association of the glutamate receptor 6 gene with autism. Mol Psychiatry 7: 302–310. doi: 10.1038/sj.mp.4000979
    [105] Yang Y, Pan C (2013) Role of metabotropic glutamate receptor 7 in autism spectrum disorders: A pilot study. Life Sci 92: 149–153. doi: 10.1016/j.lfs.2012.11.010
    [106] Yip J, Soghomonian JJ, Blatt GJ (2007) Decreased GAD67 mrna levels in cerebellar purkinje cells in autism: Pathophysiological implications. Acta Neuropathol 113: 559–568. doi: 10.1007/s00401-006-0176-3
    [107] Aldred S, Moore KM, Fitzgerald M, et al. (2003) Plasma amino acid levels in children with autism and their families. J Autism Dev Disord 33: 93–97. doi: 10.1023/A:1022238706604
    [108] Shinohe A, Hashimoto K, Nakamura K, et al. (2006) Increased serum levels of glutamate in adult patients with autism. Prog Neuropsychopharmacology Biol Psychiatry 30: 1472–1477. doi: 10.1016/j.pnpbp.2006.06.013
    [109] Sutcliffe JS, Delahanty RJ, Prasad HC, et al. (2005) Allelic heterogeneity at the serotonin transporter locus (slc6a4) confers susceptibility to autism and rigid-compulsive behaviors. Am J Hum Genet 77: 265–279.
    [110] Levitt P (2011) Serotonin and the autisms: A red flag or a red herring? Arch Gen Psychiatry 68: 1093–1094. doi: 10.1001/archgenpsychiatry.2011.98
    [111] Muller CL, Anacker AM, Veenstravanderweele J (2016) The serotonin system in autism spectrum disorder: From biomarker to animal models. Neuroscience 321: 24–41. doi: 10.1016/j.neuroscience.2015.11.010
    [112] Mccracken JT, Mcgough J, Shah B, et al. (2002) Risperidone in children with autism and serious behavioral problems. N Engl J Med 347: 314–321. doi: 10.1056/NEJMoa013171
    [113] Pavăl D (2017) A Dopamine Hypothesis of Autism Spectrum Disorder. Dev Neurosci 39: 355–360. doi: 10.1159/000478725
    [114] Nakamura K, Sekine Y, Ouchi Y, et al. (2010) Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Arch Gen Psychiatry 67: 59–68. doi: 10.1001/archgenpsychiatry.2009.137
    [115] Kałuzna-Czaplińska J, Socha E, Rynkowski J (2010) Determination of homovanillic acid and vanillylmandelic acid in urine of autistic children by gas chromatography/mass spectrometry. Med Sci Monit 16: CR445–CR450.
    [116] Anderson GH, Johnston JL (1983) Nutrient control of brain neurotransmitter synthesis and function. Can J Physiol Pharmacol 61: 271–281. doi: 10.1139/y83-042
    [117] Fernstrom JD, Fernstrom MH (2007) Tyrosine, phenylalanine, and catecholamine synthesis and function in the brain. J Nutr 137: 1539S–1547S. doi: 10.1093/jn/137.6.1539S
    [118] Schmidt RJ, Tancredi DJ, Krakowiak P, et al. (2014) Maternal intake of supplemental iron and risk of autism spectrum disorder. Am J Epidemiol 180: 890–900. doi: 10.1093/aje/kwu208
    [119] Eyles DW, Burne TH, Mcgrath JJ (2013) Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol 34: 47–64. doi: 10.1016/j.yfrne.2012.07.001
    [120] Whitehouse AJ, Holt BJ, Serralha M, et al. (2013) Maternal vitamin D levels and the autism phenotype among offspring. J Autism Dev Disord 43: 1495. doi: 10.1007/s10803-012-1676-8
    [121] Tylavsky FA, Kocak M, Murphy LE, et al. (2015) Gestational vitamin 25(OH)D status as a risk factor for receptive language development: A 24-month, longitudinal, observational study. Nutrients 7: 9918–9930. doi: 10.3390/nu7125499
    [122] Morales E, Guxens M, Llop S, et al. (2012) Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics 130: e913–e920. doi: 10.1542/peds.2011-3289
    [123] Keim SA, Bodnar LM, Klebanoff MA (2014) Maternal and cord blood 25(OH)-vitamin D concentrations in relation to child development and behaviour. Paediatr Perinat Epidemiol 28: 434–444. doi: 10.1111/ppe.12135
    [124] Magnusson C, Rai D, Goodman A, et al. (2012) Migration and autism spectrum disorder: Population-based study. Br J Psychiatry 201: 109–115. doi: 10.1192/bjp.bp.111.095125
    [125] Holick MF (2007) Vitamin D deficiency. N Engl J Med 357: 266–281. doi: 10.1056/NEJMra070553
    [126] Vinkhuyzen AA, Eyles DW, Burne TH, et al. (2016) Gestational vitamin D deficiency and autism-related traits: The Generation R Study. Mol Psychiatry 23: 240246.
    [127] Liu X, Liu J, Xiong X, et al. (2016) Correlation between Nutrition and Symptoms: Nutritional Survey of Children with Autism Spectrum Disorder in Chongqing, China. Nutrients 8: 294. doi: 10.3390/nu8050294
    [128] Egan AM, Dreyer ML, Odar CC, et al. (2013) Obesity in young children with autism spectrum disorders: Prevalence and associated factors. Child Obes 9: 125–131. doi: 10.1089/chi.2012.0028
    [129] Adams JB, Vogelaar AT, (2005) Nutritional abnormalities in autism and effects of nutritional supplementation, In: ASA's 36th National Conference on Autism Spectrum Disorders, Nashville, TN.
    [130] Strambi M, Longini M, Hayek J, et al. (2006) Magnesium profile in autism. Biol Trace Elem Res 109: 97–104. doi: 10.1385/BTER:109:2:097
    [131] Pineless SL, Avery RA, Liu GT (2010) Vitamin B12 optic neuropathy in autism. Pediatrics 126: e967–e970. doi: 10.1542/peds.2009-2975
    [132] Gong ZL, Luo CM, Wang L, et al. (2014) Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. Neuroreport 25: 23–27.
    [133] Kocovska E, Andorsdottir G, Weihe P, et al. (2014) Vitamin d in the general population of young adults with autism in the faroe islands. J Autism Dev Disord 44: 2996–3005. doi: 10.1007/s10803-014-2155-1
    [134] Filipek PA, Juranek J, Nguyen MT, et al. (2004) Relative carnitine deficiency in autism. J Autism Dev Disord 34: 615–623. doi: 10.1007/s10803-004-5283-1
    [135] Adams JB (2013) Summary of Dietary, Nutritional, and Medical Treatments for Autism-based on over 150 published research studies. Autism Reasearch Institute Publication 40-Version. Available from: http://autism.asu.edu.
    [136] Berry RC, Novak P, Withrow N, et al. (2015) Nutrition Management of Gastrointestinal Symptoms in Children with Autism Spectrum Disorder: Guideline from an Expert Panel. J Acad Nutr Diet 115: 1919–1927. doi: 10.1016/j.jand.2015.05.016
    [137] Stewart PA, Hyman SL, Schmidt BL, et al. (2015) Dietary Supplementation in Children with Autism Spectrum Disorders: Common, Insufficient, and Excessive. J Acad Nutr Diet 115: 1237–1248. doi: 10.1016/j.jand.2015.03.026
    [138] Santosh PJ, Singh J (2016) Drug treatment of autism spectrum disorder and its comorbidities in children and adolescents. BJ Psych Adv 22: 151–161.
    [139] Brondino N, Fusar-Poli L, Panisi C, et al. (2016) Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies. J Autism Dev Disord 46: 825–839. doi: 10.1007/s10803-015-2619-y
    [140] Kumar B, Prakash A, Sewal RK, et al. (2012) Drug therapy in autism: A present and future perspective. Pharmacol Rep 64: 1291–1304. doi: 10.1016/S1734-1140(12)70927-1
    [141] Doyle CA, Mcdougle CJ (2012) Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan. Dialogues Clin Neurosci 14: 263–279.
    [142] Croen LA, Grether JK, Yoshida CK, et al. (2011) Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 68: 1104–1112. doi: 10.1001/archgenpsychiatry.2011.73
    [143] Aman MG, Arnold LE, Mcdougle CJ, et al. (2005) Acute and long-term safety and tolerability of risperidone in children with autism. J Child Adolesc Psychopharmacol 15: 869–884. doi: 10.1089/cap.2005.15.869
    [144] Mcdougle CJ, Scahill L, Aman MG, et al. (2005) Risperidone for the core symptom domains of autism: Results from the study by the autism network of the research units on pediatric psychopharmacology. Am J Psychiatry 16: 1142–1148.
    [145] Buitelaar JK, Willemsen-Swinkels SHN (2000) Medication treatment in subjects with autistic spectrum disorders. Eur Child Adolesc Psychiatry 9: S85–S97. doi: 10.1007/s007870070022
    [146] Aoki Y, Yahata N, Watanabe T, et al. (2014) Oxytocin improves behavioural and neural deficits in inferring others' social emotions in autism. Brain 137: 3073–3086. doi: 10.1093/brain/awu231
    [147] Watanabe T, Abe O, Kuwabara H, et al. (2014) Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: A randomized trial. JAMA Psychiatry 71: 166–175. doi: 10.1001/jamapsychiatry.2013.3181
    [148] Geraghty ME, Bates-Wall J, Ratliff-Schaub K, et al. (2010) Nutritional interventions and therapies in autism: A spectrum of what we know: Part 2. Ican Infant Child Adolesc Nutr 2: 120–133.
    [149] Geraghty ME, Depasquale GM, Lane AE (2010) Nutritional intake and therapies in autism: A spectrum of what we know: Part 1. Ican Infant Child Adolesc Nutr 2: 62–69. doi: 10.1177/1941406409358437
    [150] Marti LF (2014) Dietary interventions in children with autism spectrum disorders-an updated review of the research evidence. Curr Clin Pharmacol 9: 335–349. doi: 10.2174/15748847113086660074
    [151] Kawicka A, Regulska-Ilow B (2013) How nutrition status, diet and dietary supplements can affect autism. A review. Rocz Panstw Zakl Hig 64: 1–12.
    [152] Curtis LT, Patel K (2008) Nutritional and environmental approaches to preventing and treating autism and attention deficit hyperactivity disorder (ADHD): A review. J Altern Complement Med 14: 79–85. doi: 10.1089/acm.2007.0610
    [153] Kidd PM (2002) Autism, an extreme challenge to integrative medicine. Part II: Medical Management. Altern Med Rev 7: 472–499.
    [154] Kidd PM (2002) Autism, an extreme challenge to integrative medicine. Part 1: The knowledge base. Altern Med Rev 7: 292316.
    [155] Pilla SSDD, Ravisankar P, Penugonda V, et al. (2014) Dietary interventions in Autism Spectrum Disorders. AP J Psychol Med 15: 24–31.
    [156] Joanna KCE, Rynkowski JB (2011) Vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children. Nutr Res 31: 497–502. doi: 10.1016/j.nutres.2011.06.002
    [157] Mousainbosc M, Roche M, Polge A, et al. (2006) Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. II. Pervasive developmental disorder-autism. Magnesium Res 19: 53–62.
    [158] Adams JB, Holloway C (2004) Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med 10: 1033–1039. doi: 10.1089/acm.2004.10.1033
    [159] Adams JB, Audhya T, Mcdonoughmeans S, et al. (2011) Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr 11: 111. doi: 10.1186/1471-2431-11-111
    [160] Cannell JJ (2008) Autism and vitamin D. Med Hypotheses 70: 750–759. doi: 10.1016/j.mehy.2007.08.016
    [161] Jia F, Wang B, Shan L, et al. (2015) Core symptoms of autism improved after vitamin D supplementation. Pediatrics 135: e196–e198. doi: 10.1542/peds.2014-2121
    [162] Saad K, Abdel-Rahman AA, Elserogy YM, et al. (2018) Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder. J Child Psychol Psychiatry 59: 20–29. doi: 10.1111/jcpp.12652
    [163] Jia F, Shan L, Wang B, et al. (2017) Bench to bedside review: Possible role of vitamin D in autism spectrum disorder. Psychiatry Res 260: 360–365.
    [164] Politi P, Cena H, Emanuele E (2011) Dietary Supplementation of Omega-3 Polyunsaturated Fatty Acids in Autism. Handb Behav Food Nutr 88: 1787–1796.
    [165] Malow BA, Adkins KW, Mcgrew SG, et al. (2012) Melatonin for sleep in children with autism: A controlled trial examining dose, tolerability, and outcomes. J Autism Dev Disord 42: 1729–1737. doi: 10.1007/s10803-011-1418-3
    [166] Reading R (2011) Melatonin in autism spectrum disorders: A systematic review and meta-analysis. Dev Med Child Neurol 53: 783–792. doi: 10.1111/j.1469-8749.2011.03980.x
    [167] Critchfield JW, Van HS, Ash M, et al. (2011) The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract 2011: 161358.
    [168] Hsiao EY, Mcbride SW, Hsien S, et al. (2013) The microbiota modulates gut physiology and behavioral abnormalities associated with autism. Cell 155: 1451–1463. doi: 10.1016/j.cell.2013.11.024
    [169] Shaaban SY, El Gendy YG, Mehanna NS, et al. (2017) The role of probiotics in children with autism spectrum disorder: A prospective, open-label study. Nutr Neurosci 2017: 1–6.
    [170] Gvozdjáková A, Kucharská J, Ostatníková D, et al. (2014) Ubiquinol improves symptoms in children with autism. Oxid Med Cell Longevity 2014: 798957.
    [171] Geier DA, Kern JK, Davis G, et al. (2011) A prospective double-blind, randomized clinical trial of levocarnitine to treat autism spectrum disorders. Med Sci Monit 17: P115–P123.
    [172] Hardan AY, Fung LK, Libove RA, et al. (2012) A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry 71: 956–961. doi: 10.1016/j.biopsych.2012.01.014
    [173] Chez MG, Buchanan CP, Aimonovitch MC, et al. (2002) Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol 17: 833–837. doi: 10.1177/08830738020170111501
    [174] Elder JH (2008) The gluten-free, casein-free diet in autism: An overview with clinical implications. Nutr Clin Pract 23: 583–588. doi: 10.1177/0884533608326061
    [175] Mulloy TA, Lang R, Reilly OM, et al. (2009) Gluten-free and casein-free diets in the treatment of autism spectrum disorders: A systematic review. Res Autism Spectrum Disord 4: 328–339.
    [176] Cade R, Privette M, Fregly M, et al. (2000) Autism and Schizophrenia: Intestinal disorders. Nutr Neurosci 3: 57–72. doi: 10.1080/1028415X.2000.11747303
    [177] Whiteley P, Haracopos D, Knivsberg AN, et al. (2010) The ScanBrit randomized, controlled, single-blind study of a gluten- and casein- free dietary intervention for children with autism spectrum disorders. Nutr Neurosci 13: 87–100. doi: 10.1179/147683010X12611460763922
    [178] Evangeliou A, Vlachonikolis I, Mihailidou H, et al. (2003) Application of a ketogenic diet in children with autistic behavior: Pilot study. J Child Neurol 18: 113–118. doi: 10.1177/08830738030180020501
    [179] Rossignol DA (2009) Novel and emerging treatments for autism spectrum disorders: A systematic review. Ann Clin Psychiatry 21: 213–236.
    [180] Elrashidy O, Elbaz F, Elgendy Y, et al. (2017) Ketogenic diet versus gluten free casein free diet in autistic children: A case-control study. Metab Brain Dis 32: 1935–1941. doi: 10.1007/s11011-017-0088-z
    [181] Strickland E (2009) Eating for Autism: The 10-step Nutrition Plan to Treat Your Child's Autism, Asperger's, or ADHD. Philadelphia, PA: Da Capo Press.
  • This article has been cited by:

    1. Nishant Kumar, Vinod Singh Yadav, Application of response surface methodology to optimize the emissions and performance of a dual fuel engine using diesel and dimethyl ether, 2024, 43, 1944-7442, 10.1002/ep.14233
  • Reader Comments
  • © 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(12611) PDF downloads(2158) Cited by(9)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog