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Maternal Immune Activation in Nonhuman Primates Alters Social Attention in Juvenile Offspring

      Abstract

      Background

      Sickness during pregnancy is associated with an increased risk of offspring neurodevelopmental disorders. Rodent models have played a critical role in establishing causal relationships and identifying mechanisms of altered brain and behavior development in pups prenatally exposed to maternal immune activation (MIA). We recently developed a novel nonhuman primate model to bridge the gap between human epidemiological studies and rodent models of prenatal immune challenge. Our initial results demonstrated that rhesus monkeys given the viral mimic synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-l-lysine) during pregnancy produce offspring with abnormal repetitive behaviors, altered communication, and atypical social interactions.

      Methods

      We utilized noninvasive infrared eye tracking to further evaluate social processing capabilities in a subset of the first trimester MIA-exposed offspring (n = 4) and control animals (n = 4) from our previous study.

      Results

      As juveniles, the MIA offspring differed from control animals on several measures of social attention, particularly when viewing macaque faces depicting the fear grimace facial expression. Compared with control animals, MIA offspring had a longer latency before fixating on the eyes, had fewer fixations directed at the eyes, and spent less total time fixating on the eyes of the fear grimace images.

      Conclusions

      In the rhesus monkey model, exposure to MIA at the end of the first trimester results in abnormal gaze patterns to salient social information. The use of noninvasive eye tracking extends the findings from rodent MIA models to more human-like behaviors resembling those in both autism spectrum disorder and schizophrenia.

      Keywords

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      References

        • Brown A.S.
        Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism.
        Dev Neurobiol. 2012; 72: 1272-1276
        • Hallmayer J.
        • Cleveland S.
        • Torres A.
        • Phillips J.
        • Cohen B.
        • Torigoe T.
        • et al.
        Genetic heritability and shared environmental factors among twin pairs with autism.
        Arch Gen Psychiatry. 2011; 68: 1095-1102
        • Hagberg H.
        • Gressens P.
        • Mallard C.
        Inflammation during fetal and neonatal life: Implications for neurologic and neuropsychiatric disease in children and adults.
        Ann Neurol. 2012; 71: 444-457
        • Rosenberg R.E.
        • Law J.K.
        • Yenokyan G.
        • McGready J.
        • Kaufmann W.E.
        • Law P.A.
        Characteristics and concordance of autism spectrum disorders among 277 twin pairs.
        Arch Pediatr Adolesc Med. 2009; 163: 907-914
        • Brown A.S.
        • Schaefer C.A.
        • Quesenberry Jr, C.P.
        • Liu L.
        • Babulas V.P.
        • Susser E.S.
        Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring.
        Am J Psychiatry. 2005; 162: 767-773
        • Brown A.S.
        • Schaefer C.A.
        • Wyatt R.J.
        • Goetz R.
        • Begg M.D.
        • Gorman J.M.
        • Susser E.S.
        Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: A prospective birth cohort study.
        Schizophr Bull. 2000; 26: 287-295
        • Sorensen H.J.
        • Mortensen E.L.
        • Reinisch J.M.
        • Mednick S.A.
        Association between prenatal exposure to bacterial infection and risk of schizophrenia.
        Schizophr Bull. 2009; 35: 631-637
        • Babulas V.
        • Factor-Litvak P.
        • Goetz R.
        • Schaefer C.A.
        • Brown A.S.
        Prenatal exposure to maternal genital and reproductive infections and adult schizophrenia.
        Am J Psychiatry. 2006; 163: 927-929
        • Buka S.L.
        • Cannon T.D.
        • Torrey E.F.
        • Yolken R.H.
        Maternal exposure to herpes simplex virus and risk of psychosis among adult offspring.
        Biol Psychiatry. 2008; 63: 809-815
        • Brown A.S.
        • Begg M.D.
        • Gravenstein S.
        • Schaefer C.A.
        • Wyatt R.J.
        • Bresnahan M.
        • et al.
        Serologic evidence of prenatal influenza in the etiology of schizophrenia.
        Arch Gen Psychiatry. 2004; 61: 774-780
        • Brown A.S.
        • Sourander A.
        • Hinkka-Yli-Salomaki S.
        • McKeague I.W.
        • Sundvall J.
        • Surcel H.M.
        Elevated maternal C-reactive protein and autism in a national birth cohort.
        Mol Psychiatry. 2014; 19: 259-264
        • Abdallah M.W.
        • Larsen N.
        • Mortensen E.L.
        • Atladottir H.O.
        • Norgaard-Pedersen B.
        • Bonefeld-Jorgensen E.C.
        • et al.
        Neonatal levels of cytokines and risk of autism spectrum disorders: An exploratory register-based historic birth cohort study utilizing the Danish Newborn Screening Biobank.
        J Neuroimmunol. 2012; 252: 75-82
        • Atladottir H.O.
        • Thorsen P.
        • Ostergaard L.
        • Schendel D.E.
        • Lemcke S.
        • Abdallah M.
        • Parner E.T.
        Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders.
        J Autism Dev Disord. 2010; 40: 1423-1430
        • Goines P.E.
        • Croen L.A.
        • Braunschweig D.
        • Yoshida C.K.
        • Grether J.
        • Hansen R.
        • et al.
        Increased midgestational IFN-gamma, IL-4 and IL-5 in women bearing a child with autism: A case-control study.
        Mol Autism. 2011; 2: 13
        • Fatemi S.H.
        • Emamian E.S.
        • Sidwell R.W.
        • Kist D.A.
        • Stary J.M.
        • Earle J.A.
        • Thuras P.
        Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice.
        Mol Psychiatry. 2002; 7: 633-640
        • Fatemi S.H.
        • Sidwell R.
        • Kist D.
        • Akhter P.
        • Meltzer H.Y.
        • Bailey K.
        • et al.
        Differential expression of synaptosome-associated protein 25 kDa [SNAP-25] in hippocampi of neonatal mice following exposure to human influenza virus in utero.
        Brain Res. 1998; 800: 1-9
        • Fatemi S.H.
        • Reutiman T.J.
        • Folsom T.D.
        • Huang H.
        • Oishi K.
        • Mori S.
        • et al.
        Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: Implications for genesis of neurodevelopmental disorders.
        Schizophr Res. 2008; 99: 56-70
        • Short S.J.
        • Lubach G.R.
        • Karasin A.I.
        • Olsen C.W.
        • Styner M.
        • Knickmeyer R.C.
        • et al.
        Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey.
        Biol Psychiatry. 2010; 67: 965-973
        • Willette A.A.
        • Lubach G.R.
        • Knickmeyer R.C.
        • Short S.J.
        • Styner M.
        • Gilmore J.H.
        • Coe C.L.
        Brain enlargement and increased behavioral and cytokine reactivity in infant monkeys following acute prenatal endotoxemia.
        Behav Brain Res. 2011; 219: 108-115
        • Coyle P.
        • Tran N.
        • Fung J.N.
        • Summers B.L.
        • Rofe A.M.
        Maternal dietary zinc supplementation prevents aberrant behaviour in an object recognition task in mice offspring exposed to LPS in early pregnancy.
        Behav Brain Res. 2009; 197: 210-218
        • Fortier M.E.
        • Joober R.
        • Luheshi G.N.
        • Boksa P.
        Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring.
        J Psychiatr Res. 2004; 38: 335-345
        • Fortier M.E.
        • Luheshi G.N.
        • Boksa P.
        Effects of prenatal infection on prepulse inhibition in the rat depend on the nature of the infectious agent and the stage of pregnancy.
        Behav Brain Res. 2007; 181: 270-277
        • Traynor T.R.
        • Majde J.A.
        • Bohnet S.G.
        • Krueger J.M.
        Intratracheal double-stranded RNA plus interferon-gamma: A model for analysis of the acute phase response to respiratory viral infections.
        Life Sci. 2004; 74: 2563-2576
        • Boksa P.
        Effects of prenatal infection on brain development and behavior: A review of findings from animal models.
        Brain Behav Immun. 2010; 24: 881-897
        • Meyer U.
        • Feldon J.
        To poly(I:C) or not to poly(I:C): Advancing preclinical schizophrenia research through the use of prenatal immune activation models.
        Neuropharmacology. 2012; 62: 1308-1321
        • Meyer U.
        • Feldon J.
        • Dammann O.
        Schizophrenia and autism: Both shared and disorder-specific pathogenesis via perinatal inflammation?.
        Pediatr Res. 2011; 69: 26R-33R
        • Patterson P.H.
        Immune involvement in schizophrenia and autism: Etiology, pathology and animal models.
        Behav Brain Res. 2009; 204: 313-321
        • Meyer U.
        • Feldon J.
        Neural basis of psychosis-related behaviour in the infection model of schizophrenia.
        Behav Brain Res. 2009; 204: 322-334
        • Laibl V.R.
        • Sheffield J.S.
        Influenza and pneumonia in pregnancy.
        Clin Perinatol. 2005; 32: 727-738
        • Longman R.E.
        • Johnson T.R.
        Viral respiratory disease in pregnancy.
        Curr Opin Obstet Gynecol. 2007; 19: 120-125
        • Selten J.P.
        • Frissen A.
        • Lensvelt-Mulders G.
        • Morgan V.A.
        Schizophrenia and 1957 pandemic of influenza: Meta-analysis.
        Schizophr Bull. 2010; 36: 219-228
        • Meyer U.
        Prenatal poly(i:C) exposure and other developmental immune activation models in rodent systems.
        Biol Psychiatry. 2014; 75: 307-315
        • Gallagher D.
        • Norman A.A.
        • Woodard C.L.
        • Yang G.
        • Gauthier-Fisher A.
        • Fujitani M.
        • et al.
        Transient maternal IL-6 mediates long-lasting changes in neural stem cell pools by deregulating an endogenous self-renewal pathway.
        Cell Stem Cell. 2013; 13: 564-576
        • Smith S.E.
        • Li J.
        • Garbett K.
        • Mirnics K.
        • Patterson P.H.
        Maternal immune activation alters fetal brain development through interleukin-6.
        J Neurosci. 2007; 27: 10695-10702
        • Giovanoli S.
        • Engler H.
        • Engler A.
        • Richetto J.
        • Voget M.
        • Willi R.
        • et al.
        Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice.
        Science. 2013; 339: 1095-1099
        • Piontkewitz Y.
        • Arad M.
        • Weiner I.
        Abnormal trajectories of neurodevelopment and behavior following in utero insult in the rat.
        Biol Psychiatry. 2011; 70: 842-851
        • Garay P.A.
        • Hsiao E.Y.
        • Patterson P.H.
        • McAllister A.K.
        Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development.
        Brain Behav Immun. 2013; 31: 54-68
        • Malkova N.V.
        • Yu C.Z.
        • Hsiao E.Y.
        • Moore M.J.
        • Patterson P.H.
        Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism.
        Brain Behav Immun. 2012; 26: 607-616
        • Shi L.
        • Fatemi S.H.
        • Sidwell R.W.
        • Patterson P.H.
        Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring.
        J Neurosci. 2003; 23: 297-302
        • Garbett K.A.
        • Hsiao E.Y.
        • Kalman S.
        • Patterson P.H.
        • Mirnics K.
        Effects of maternal immune activation on gene expression patterns in the fetal brain.
        Transl Psychiatry. 2012; 2: e98
        • Watson K.K.
        • Platt M.L.
        Of mice and monkeys: Using non-human primate models to bridge mouse- and human-based investigations of autism spectrum disorders.
        J Neurodev Disord. 2012; 4: 21
        • Capitanio J.P.
        • Emborg M.E.
        Contributions of non-human primates to neuroscience research.
        Lancet. 2008; 371: 1126-1135
        • Phillips K.A.
        • Bales K.L.
        • Capitanio J.P.
        • Conley A.
        • Czoty P.W.
        • t Hart B.A.
        • et al.
        Why primate models matter.
        Am J Primatol. 2014; 76: 801-827
        • Levy H.B.
        • Baer G.
        • Baron S.
        • Buckler C.E.
        • Gibbs C.J.
        • Iadarola M.J.
        • et al.
        A modified polyriboinosinic-polyribocytidylic acid complex that induces interferon in primates.
        J Infect Dis. 1975; 132: 434-439
        • Caskey M.
        • Lefebvre F.
        • Filali-Mouhim A.
        • Cameron M.J.
        • Goulet J.P.
        • Haddad E.K.
        • et al.
        Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans.
        J Exp Med. 2011; 208: 2357-2366
        • Bauman M.D.
        • Iosif A.M.
        • Smith S.E.
        • Bregere C.
        • Amaral D.G.
        • Patterson P.H.
        Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring.
        Biol Psychiatry. 2014; 75: 332-341
        • King B.H.
        • Lord C.
        Is schizophrenia on the autism spectrum?.
        Brain Res. 2011; 1380: 34-41
        • Pelphrey K.A.
        • Sasson N.J.
        • Reznick J.S.
        • Paul G.
        • Goldman B.D.
        • Piven J.
        Visual scanning of faces in autism.
        J Autism Dev Disord. 2002; 32: 249-261
        • Toh W.L.
        • Rossell S.L.
        • Castle D.J.
        Current visual scanpath research: A review of investigations into the psychotic, anxiety, and mood disorders.
        Compr Psychiatry. 2011; 52: 567-579
        • Schneider M.L.
        • Roughton E.C.
        • Koehler A.J.
        • Lubach G.R.
        Growth and development following prenatal stress exposure in primates: An examination of ontogenetic vulnerability.
        Child Dev. 1999; 70: 263-274
        • Schneider M.L.
        • Moore C.F.
        • Roberts A.D.
        • Dejesus O.
        Prenatal stress alters early neurobehavior, stress reactivity and learning in non-human primates: A brief review.
        Stress. 2001; 4: 183-193
        • Schneider M.L.
        • Moore C.F.
        • Kraemer G.W.
        Moderate level alcohol during pregnancy, prenatal stress, or both and limbic-hypothalamic-pituitary-adrenocortical axis response to stress in rhesus monkeys.
        Child Dev. 2004; 75: 96-109
        • Roberts A.D.
        • Moore C.F.
        • DeJesus O.T.
        • Barnhart T.E.
        • Larson J.A.
        • Mukherjee J.
        • et al.
        Prenatal stress, moderate fetal alcohol, and dopamine system function in rhesus monkeys.
        Neurotoxicol Teratol. 2004; 26: 169-178
        • Converse A.K.
        • Moore C.F.
        • Moirano J.M.
        • Ahlers E.O.
        • Larson J.A.
        • Engle J.W.
        • et al.
        Prenatal stress induces increased striatal dopamine transporter binding in adult nonhuman primates.
        Biol Psychiatry. 2013; 74: 502-510
        • Riby D.M.
        • Hancock P.J.
        Do faces capture the attention of individuals with Williams syndrome or autism? Evidence from tracking eye movements.
        J Autism Dev Disord. 2009; 39: 421-431
        • Tomasello M.
        • Call J.
        Social knowledge and interaction.
        in: Tomasello M. Call J. Primate Cognition. Oxford University Press, New York1997: 191-230
        • Chang S.W.
        • Brent L.J.
        • Adams G.K.
        • Klein J.T.
        • Pearson J.M.
        • Watson K.K.
        • Platt M.L.
        Neuroethology of primate social behavior.
        Proc Natl Acad Sci U S A. 2013; 110: 10387-10394
        • Deaner R.O.
        • Khera A.V.
        • Platt M.L.
        Monkeys pay per view: Adaptive valuation of social images by rhesus macaques.
        Curr Biol. 2005; 15: 543-548
        • Bower S.
        • Suomi S.J.
        • Paukner A.
        Evidence for kinship information contained in the rhesus macaque (Macaca mulatta) face.
        J Comp Psychol. 2012; 126: 318-323
        • Ferrari P.F.
        • Paukner A.
        • Ionica C.
        • Suomi S.J.
        Reciprocal face-to-face communication between rhesus macaque mothers and their newborn infants.
        Curr Biol. 2009; 19: 1768-1772
        • Davis M.
        • Whalen P.J.
        The amygdala: Vigilance and emotion.
        Mol Psychiatry. 2001; 6: 13-34
        • Bannerman R.L.
        • Milders M.
        • de Gelder B.
        • Sahraie A.
        Orienting to threat: Faster localization of fearful facial expressions and body postures revealed by saccadic eye movements.
        Proc Biol Sci. 2009; 276: 1635-1641
        • Whalen P.J.
        Fear, vigilance, and ambiguity: Initial neuroimaging studies of the human amygdala.
        Curr Dir Psychol Sci. 1998; 7: 177-188
        • Whalen P.J.
        • Rauch S.L.
        • Etcoff N.L.
        • McInerney S.C.
        • Lee M.B.
        • Jenike M.A.
        Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge.
        J Neurosci. 1998; 18: 411-418
        • Adolphs R.
        • Tranel D.
        • Damasio H.
        • Damasio A.
        Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala.
        Nature. 1994; 372: 669-672
        • Adolphs R.
        • Tranel D.
        • Damasio H.
        • Damasio A.R.
        Fear and the human amygdala.
        J Neurosci. 1995; 15: 5879-5891
        • Adolphs R.
        • Tranel D.
        • Hamann S.
        • Young A.W.
        • Calder A.J.
        • Phelps E.A.
        • et al.
        Recognition of facial emotion in nine individuals with bilateral amygdala damage.
        Neuropsychologia. 1999; 37: 1111-1117
        • Spezio M.L.
        • Huang P.Y.
        • Castelli F.
        • Adolphs R.
        Amygdala damage impairs eye contact during conversations with real people.
        J Neurosci. 2007; 27: 3994-3997
        • Gothard K.M.
        • Battaglia F.P.
        • Erickson C.A.
        • Spitler K.M.
        • Amaral D.G.
        Neural responses to facial expression and face identity in the monkey amygdala.
        J Neurophysiol. 2007; 97: 1671-1683
        • Hoffman K.L.
        • Gothard K.M.
        • Schmid M.C.
        • Logothetis N.K.
        Facial-expression and gaze-selective responses in the monkey amygdala.
        Curr Biol. 2007; 17: 766-772
        • Adolphs R.
        • Gosselin F.
        • Buchanan T.W.
        • Tranel D.
        • Schyns P.
        • Damasio A.R.
        A mechanism for impaired fear recognition after amygdala damage.
        Nature. 2005; 433: 68-72
        • Kordower J.H.
        • Piecinski P.
        • Rakic P.
        Neurogenesis of the amygdaloid nuclear complex in the rhesus monkey.
        Brain Res Dev Brain Res. 1992; 68: 9-15
        • Walker-Smith G.J.
        • Gale A.G.
        • Findlay J.M.
        Eye movement strategies involved in face perception.
        Perception. 1977; 6: 313-326
        • Ekman P.
        • Friesen W.V.
        Unmasking the Face: A Guide to Recognizing Emotions from Facial Cues.
        Prentice-Hall, Oxford, UK1975
        • Machado C.J.
        • Bliss-Moreau E.
        • Platt M.L.
        • Amaral D.G.
        Social and nonsocial content differentially modulates visual attention and autonomic arousal in rhesus macaques.
        PloS One. 2011; 6: e26598
        • Leonard T.K.
        • Blumenthal G.
        • Gothard K.M.
        • Hoffman K.L.
        How macaques view familiarity and gaze in conspecific faces.
        Behav Neurosci. 2012; 126: 781-791
        • Mandell D.S.
        • Novak M.M.
        • Zubritsky C.D.
        Factors associated with age of diagnosis among children with autism spectrum disorders.
        Pediatrics. 2005; 116: 1480-1486
        • Ziermans T.B.
        • Schothorst P.F.
        • Sprong M.
        • van Engeland H.
        Transition and remission in adolescents at ultra-high risk for psychosis.
        Schizophr Res. 2011; 126: 58-64
        • Couture S.M.
        • Penn D.L.
        • Losh M.
        • Adolphs R.
        • Hurley R.
        • Piven J.
        Comparison of social cognitive functioning in schizophrenia and high functioning autism: More convergence than divergence.
        Psychol Med. 2010; 40: 569-579
        • Sasson N.J.
        • Pinkham A.E.
        • Carpenter K.L.
        • Belger A.
        The benefit of directly comparing autism and schizophrenia for revealing mechanisms of social cognitive impairment.
        J Neurodev Disord. 2011; 3: 87-100
        • Solomon M.
        • Olsen E.
        • Niendam T.
        • Ragland J.D.
        • Yoon J.
        • Minzenberg M.
        • Carter C.S.
        From lumping to splitting and back again: Atypical social and language development in individuals with clinical-high-risk for psychosis, first episode schizophrenia, and autism spectrum disorders.
        Schizophr Res. 2011; 131: 146-151
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        American Psychiatric Publishing, Arlington, VA2013
        • Dalton K.M.
        • Nacewicz B.M.
        • Johnstone T.
        • Schaefer H.S.
        • Gernsbacher M.A.
        • Goldsmith H.H.
        • et al.
        Gaze fixation and the neural circuitry of face processing in autism.
        Nat Neurosci. 2005; 8: 519-526
        • Kliemann D.
        • Dziobek I.
        • Hatri A.
        • Steimke R.
        • Heekeren H.R.
        Atypical reflexive gaze patterns on emotional faces in autism spectrum disorders.
        J Neurosci. 2010; 30: 12281-12287
        • Klin A.
        • Jones W.
        • Schultz R.
        • Volkmar F.
        • Cohen D.
        Visual fixation patterns during viewing of naturalistic social situations as predictors of social competence in individuals with autism.
        Arch Gen Psychiatry. 2002; 59: 809-816
        • Neumann D.
        • Spezio M.L.
        • Piven J.
        • Adolphs R.
        Looking you in the mouth: Abnormal gaze in autism resulting from impaired top-down modulation of visual attention.
        Soc Cogn Affect Neurosci. 2006; 1: 194-202
        • Spezio M.L.
        • Adolphs R.
        • Hurley R.S.
        • Piven J.
        Abnormal use of facial information in high-functioning autism.
        J Autism Dev Disord. 2007; 37: 929-939
        • Kennedy D.P.
        • Adolphs R.
        Perception of emotions from facial expressions in high-functioning adults with autism.
        Neuropsychologia. 2012; 50: 3313-3319
        • Allen D.N.
        • Frantom L.V.
        • Strauss G.P.
        • van Kammen D.P.
        Differential patterns of premorbid academic and social deterioration in patients with schizophrenia.
        Schizophr Res. 2005; 75: 389-397
        • Ballon J.S.
        • Kaur T.
        • Marks II,
        • Cadenhead K.S.
        Social functioning in young people at risk for schizophrenia.
        Psychiatry Res. 2007; 151: 29-35
        • Chudleigh C.
        • Naismith S.L.
        • Blaszczynski A.
        • Hermens D.F.
        • Hodge M.A.
        • Hickie I.B.
        How does social functioning in the early stages of psychosis relate to depression and social anxiety?.
        Early Interv Psychiatry. 2011; 5: 224-232
        • Cornblatt B.A.
        • Auther A.M.
        • Niendam T.
        • Smith C.W.
        • Zinberg J.
        • Bearden C.E.
        • Cannon T.D.
        Preliminary findings for two new measures of social and role functioning in the prodromal phase of schizophrenia.
        Schizophr Bull. 2007; 33: 688-702
        • Amminger G.P.
        • Schafer M.R.
        • Klier C.M.
        • Schlogelhofer M.
        • Mossaheb N.
        • Thompson A.
        • et al.
        Facial and vocal affect perception in people at ultra-high risk of psychosis, first-episode schizophrenia and healthy controls.
        Early Interv Psychiatry. 2012; 6: 450-454
        • Bora E.
        • Pantelis C.
        Theory of mind impairments in first-episode psychosis, individuals at ultra-high risk for psychosis and in first-degree relatives of schizophrenia: Systematic review and meta-analysis.
        Schizophr Res. 2013; 144: 31-36
        • Ventura J.
        • Wood R.C.
        • Jimenez A.M.
        • Hellemann G.S.
        Neurocognition and symptoms identify links between facial recognition and emotion processing in schizophrenia: Meta-analytic findings.
        Schizophr Res. 2013; 151: 78-84
        • Pinkham A.E.
        • Gur R.E.
        • Gur R.C.
        Affect recognition deficits in schizophrenia: Neural substrates and psychopharmacological implications.
        Expert Rev Neurother. 2007; 7: 807-816
        • Edwards J.
        • Jackson H.J.
        • Pattison P.E.
        Emotion recognition via facial expression and affective prosody in schizophrenia: A methodological review.
        Clin Psychol Rev. 2002; 22: 789-832
        • Kohler C.G.
        • Walker J.B.
        • Martin E.A.
        • Healey K.M.
        • Moberg P.J.
        Facial emotion perception in schizophrenia: A meta-analytic review.
        Schizophr Bull. 2010; 36: 1009-1019
        • Hoekert M.
        • Kahn R.S.
        • Pijnenborg M.
        • Aleman A.
        Impaired recognition and expression of emotional prosody in schizophrenia: Review and meta-analysis.
        Schizophr Res. 2007; 96: 135-145
        • Loughland C.M.
        • Williams L.M.
        • Harris A.W.
        Visual scanpath dysfunction in first-degree relatives of schizophrenia probands: Evidence for a vulnerability marker?.
        Schizophr Res. 2004; 67: 11-21
        • Williams L.M.
        • Loughland C.M.
        • Green M.J.
        • Harris A.W.
        • Gordon E.
        Emotion perception in schizophrenia: An eye movement study comparing the effectiveness of risperidone vs. haloperidol.
        Psychiatry Res. 2003; 120: 13-27
        • Loughland C.M.
        • Williams L.M.
        • Gordon E.
        Schizophrenia and affective disorder show different visual scanning behavior for faces: A trait versus state-based distinction?.
        Biol Psychiatry. 2002; 52: 338-348
        • Loughland C.M.
        • Williams L.M.
        • Gordon E.
        Visual scanpaths to positive and negative facial emotions in an outpatient schizophrenia sample.
        Schizophr Res. 2002; 55: 159-170
        • Williams L.M.
        • Loughland C.M.
        • Gordon E.
        • Davidson D.
        Visual scanpaths in schizophrenia: Is there a deficit in face recognition?.
        Schizophr Res. 1999; 40: 189-199
        • Hsiao E.Y.
        • McBride S.W.
        • Hsien S.
        • Sharon G.
        • Hyde E.R.
        • McCue T.
        • et al.
        Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.
        Cell. 2013; 155: 1451-1463