2,368
Views
6
CrossRef citations to date
0
Altmetric
Review Articles

Neurological soft signs in patients with schizophrenia: current knowledge and future perspectives in the post-genomics era

, &
Article: 30071 | Received 18 Oct 2015, Accepted 29 Apr 2016, Published online: 08 Jul 2016

References

  • Tandon R, Nasrallah HA, Keshavan MS. Schizophrenia, ‘just the facts’ 4. Clinical features and conceptualization. Schizophr Res. 2009; 110: 1–23.
  • van Os J, Kapur S. Schizophrenia. Lancet. 2009; 374: 635–45.
  • Fatemi SH, Folsom TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull. 2009; 35: 528–48.
  • Rapoport JL, Addington AM, Frangou S, Psych MRC. The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry. 2005; 10: 434–49.
  • Gratten J, Wray NR, Keller MC, Visscher PM. Large-scale genomics unveils the genetic architecture of psychiatric disorders. Nat Neurosci. 2014; 17: 782–90.
  • Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014; 511 : 421–7.
  • Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia: historical and meta-analytic review. Am J Psychiatry. 2002; 159: 1080–92.
  • Keshavan M, Gilbert A, Diwadkar V. Lieberman JA, Stroup TS, Perkins DO. Neurodevelopmental theories. The American Psychiatric Publishing textbook of schizophrenia. 2006; Washington, DC: American Psychiatric Publishing Inc. 69–84.
  • Brown AS. Prenatal infection as a risk factor for schizophrenia. Schizophr Bull. 2006; 32: 200–2.
  • Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010; 167: 261–80.
  • Cannon M, Caspi A, Moffitt TE, Harrington H, Taylor A, Murray RM, etal. Evidence for early-childhood, pan-developmental impairment specific to schizophreniform disorder: results from a longitudinal birth cohort. Arch Gen Psychiatry. 2002; 59: 449–56.
  • Walker EF, Savoie T, Davis D. Neuromotor precursors of schizophrenia. Schizophr Bull. 1994; 20: 441–51.
  • Jones P, Rodgers B, Murray R, Marmot M. Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet. 1994; 344: 1398–402.
  • Murray GK, Jones PB, Moilanen K, Veijola J, Miettunen J, Cannon TD, etal. Infant motor development and adult cognitive functions in schizophrenia. Schizophr Res. 2006; 81: 65–74.
  • Done DJ, Crow TJ, Johnstone EC, Sacker A. Childhood antecedents of schizophrenia and affective illness: social adjustment at ages 7 and 11. BMJ. 1994; 309: 699–703.
  • Olin SC, Mednick SA. Risk factors of psychosis: identifying vulnerable populations premorbidly. Schizophr Bull. 1996; 22: 223–40.
  • Davidson M, Reichenberg A, Rabinowitz J, Weiser M, Kaplan Z, Mark M. Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry. 1999; 156: 1328–35.
  • Sørensen HJ, Mortensen EL, Parnas J, Mednick SA. Premorbid neurocognitive functioning in schizophrenia spectrum disorder. Schizophr Bull. 2006; 32: 578–83.
  • Meier MH, Caspi A, Reichenberg A, Keefe RSE, Fisher HL, Harrington H, etal. Neuropsychological decline in schizophrenia from the premorbid to the postonset period: evidence from a population-representative longitudinal study. Am J Psychiatry. 2014; 171: 91–101.
  • Keshavan MS, Diwadkar VA, Montrose DM, Rajarethinam R, Sweeney JA. Premorbid indicators and risk for schizophrenia: a selective review and update. Schizophr Res. 2005; 79: 45–57.
  • Douaud G, Mackay C, Andersson J, James S, Quested D, Ray MK, etal. Schizophrenia delays and alters maturation of the brain in adolescence. Brain J Neurol. 2009; 132: 2437–48.
  • Dazzan P, Arango C, Fleischacker W, Galderisi S, Glenthøj B, Leucht S, etal. Magnetic resonance imaging and the prediction of outcome in first-episode schizophrenia: a review of current evidence and directions for future research. Schizophr Bull. 2015; 41: 574–83.
  • Compton MT, Chan RCK, Walker EF, Buckley PF. Minor physical anomalies: potentially informative vestiges of fetal developmental disruptions in schizophrenia. Int J Dev Neurosci. 2011; 29: 245–50.
  • Lloyd T, Dazzan P, Dean K, Park SBG, Fearon P, Doody GA, etal. Minor physical anomalies in patients with first-episode psychosis: their frequency and diagnostic specificity. Psychol Med. 2008; 38: 71–7.
  • Golembo-Smith S, Walder DJ, Daly MP, Mittal VA, Kline E, Reeves G, etal. The presentation of dermatoglyphic abnormalities in schizophrenia: a meta-analytic review. Schizophr Res. 2012; 142: 1–11.
  • Fatjó-Vilas M, Gourion D, Campanera S, Mouaffak F, Levy-Rueff M, Navarro ME, etal. New evidences of gene and environment interactions affecting prenatal neurodevelopment in schizophrenia-spectrum disorders: a family dermatoglyphic study. Schizophr Res. 2008; 103: 209–17.
  • Heinrichs DW, Buchanan RW. Significance and meaning of neurological signs in schizophrenia. Am J Psychiatry. 1988; 145: 11–18.
  • Buchanan RW, Heinrichs DW. The Neurological Evaluation Scale (NES): a structured instrument for the assessment of neurological signs in schizophrenia. Psychiatry Res. 1989; 27: 335–50.
  • Chen EY, Shapleske J, Luque R, McKenna PJ, Hodges JR, Calloway SP, etal. The Cambridge Neurological Inventory: a clinical instrument for assessment of soft neurological signs in psychiatric patients. Psychiatry Res. 1995; 56: 183–204.
  • Bombin I. Significance and meaning of neurological signs in schizophrenia: two decades later. Schizophr Bull. 2005; 31: 962–77.
  • Egan MF, Hyde TM, Bonomo JB, Mattay VS, Bigelow LB, Goldberg TE, etal. Relative risk of neurological signs in siblings of patients with schizophrenia. Am J Psychiatry. 2001; 158: 1827–34.
  • Krebs MO, Gut-Fayand A, Bourdel M, Dischamp J, Olié J. Validation and factorial structure of a standardized neurological examination assessing neurological soft signs in schizophrenia. Schizophr Res. 2000; 45: 245–60.
  • Chan RCK, Wang Y, Wang L, Chen EYH, Manschreck TC, Li Z, etal. Neurological soft signs and their relationships to neurocognitive functions: a re-visit with the structural equation modeling design. PLoS One. 2009; 4: e8469.
  • Mouchet-Mages S, Rodrigo S, Cachia A, Mouaffak F, Olie JP, Meder JF, etal. Correlations of cerebello-thalamo-prefrontal structure and neurological soft signs in patients with first-episode psychosis. Acta Psychiatr Scand. 2011; 123: 451–8.
  • Gay O, Plaze M, Oppenheim C, Mouchet-Mages S, Gaillard R, Olié JP, etal. Cortex morphology in first-episode psychosis patients with neurological soft signs. Schizophr Bull. 2013; 39: 820–9.
  • Janssen J, Diaz-Caneja A, Reig S, Bombín I, Mayoral M, Parellada M, etal. Brain morphology and neurological soft signs in adolescents with first-episode psychosis. Br J Psychiatry. 2009; 195: 227–33.
  • Dazzan P, Morgan KD, Orr KG, Hutchinson G, Chitnis X, Suckling J, etal. The structural brain correlates of neurological soft signs in AESOP first-episode psychoses study. Brain J Neurol. 2004; 127: 143–53.
  • Hirjak D, Wolf RC, Stieltjes B, Hauser T, Seidl U, Thiemann U, etal. Neurological soft signs and brainstem morphology in first-episode schizophrenia. Neuropsychobiology. 2013; 68: 91–9.
  • Keshavan MS, Sanders RD, Sweeney JA, Diwadkar VA, Goldstein G, Pettegrew JW, etal. Diagnostic specificity and neuroanatomical validity of neurological abnormalities in first-episode psychoses. Am J Psychiatry. 2003; 160: 1298–304.
  • Zhao Q, Li Z, Huang J, Yan C, Dazzan P, Pantelis C, etal. Neurological soft signs are not ‘soft’ in brain structure and functional networks: evidence from ALE meta-analysis. Schizophr Bull. 2014; 40: 626–41.
  • Chan RCK, Gottesman II. Neurological soft signs as candidate endophenotypes for schizophrenia: a shooting star or a Northern star?. Neurosci Biobehav Rev. 2008; 32: 957–71.
  • Chan RCK, Xu T, Heinrichs RW, Yu Y, Wang Y. Neurological soft signs in schizophrenia: a meta-analysis. Schizophr Bull. 2010; 36: 1089–104.
  • Varambally S, Venkatasubramanian G, Gangadhar BN. Neurological soft signs in schizophrenia – the past, the present and the future. Indian J Psychiatry. 2012; 54: 73–80.
  • Gupta S, Andreasen NC, Arndt S, Flaum M, Schultz SK, Hubbard WC, etal. Neurological soft signs in neuroleptic-naive and neuroleptic-treated schizophrenic patients and in normal comparison subjects. Am J Psychiatry. 1995; 152: 191–6.
  • Scheffer RE. Abnormal neurological signs at the onset of psychosis. Schizophr Res. 2004; 70: 19–26.
  • Flashman LA, Flaum M, Gupta S, Andreasen NC. Soft signs and neuropsychological performance in schizophrenia. Am J Psychiatry. 1996; 153: 526–32.
  • Buchanan RW, Kirkpatrick B, Heinrichs DW, Carpenter WT. Clinical correlates of the deficit syndrome of schizophrenia. Am J Psychiatry. 1990; 147: 290–4.
  • Mohr F, Hubmann W, Cohen R, Bender W, Haslacher C, Hönicke S, etal. Neurological soft signs in schizophrenia: assessment and correlates. Eur Arch Psychiatry Clin Neurosci. 1996; 246: 240–8.
  • Arango C, Kirkpatrick B, Buchanan RW. Neurological signs and the heterogeneity of schizophrenia. Am J Psychiatry. 2000; 157: 560–5.
  • Tiryaki A, Yazici MK, Anil AE, Kabakçi E, Karaağaoğlu E, Göğüş A. Reexamination of the characteristics of the deficit schizophrenia patients. Eur Arch Psychiatry Clin Neurosci. 2003; 253 : 221–7.
  • Mittal VA, Dean DJ, Bernard JA, Orr JM, Pelletier-Baldelli A, Carol EE, etal. Neurological soft signs predict abnormal cerebellar-thalamic tract development and negative symptoms in adolescents at high risk for psychosis: a longitudinal perspective. Schizophr Bull. 2014; 40: 1204–15.
  • Bartkó G, Zádor G, Horváth S, Herczeg I. Neurological soft signs in chronic schizophrenic patients: clinical correlates. Biol Psychiatry. 1988; 24: 458–60.
  • Browne S, Clarke M, Gervin M, Lane A, Waddington JL, Larkin C, etal. Determinants of neurological dysfunction in first episode schizophrenia. Psychol Med. 2000; 30: 1433–41.
  • Green MF. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry. 2006; 67(Suppl 9): 3–8; discussion 36–42.
  • Keefe RSE. The longitudinal course of cognitive impairment in schizophrenia: an examination of data from premorbid through posttreatment phases of illness. J Clin Psychiatry. 2014; 75(Suppl 2): 8–13.
  • Johnstone EC, Macmillan JF, Frith CD, Benn DK, Crow TJ. Further investigation of the predictors of outcome following first schizophrenic episodes. Br J Psychiatry. 1990; 157: 182–9.
  • Wong AH, Voruganti LN, Heslegrave RJ, Awad AG. Neurocognitive deficits and neurological signs in schizophrenia. Schizophr Res. 1997; 23: 139–46.
  • Galderisi S, Bucci P, Mucci A, D'Amato AC, Conforti R, Maj M. Simple schizophrenia’: a controlled MRI and clinical/neuropsychological study. Psychiatry Res. 1999; 91: 175–84.
  • Peralta V, de Jalón EG, Campos MS, Basterra V, Sanchez-Torres A, Cuesta MJ. Risk factors, pre-morbid functioning and episode correlates of neurological soft signs in drug-naive patients with schizophrenia-spectrum disorders. Psychol Med. 2011; 41: 1279–89.
  • Walker E, Lewine RJ. Prediction of adult-onset schizophrenia from childhood home movies of the patients. Am J Psychiatry. 1990; 147: 1052–6.
  • Cannon TD, van Erp TGM, Bearden CE, Loewy R, Thompson P, Toga AW, etal. Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions. Schizophr Bull. 2003; 29: 653–69.
  • Thomann PA, Wüstenberg T, Santos VD, Bachmann S, Essig M, Schröder J. Neurological soft signs and brain morphology in first-episode schizophrenia. Psychol Med. 2009; 39: 371–9.
  • Erlenmeyer-Kimling L, Rock D, Roberts SA, Janal M, Kestenbaum C, Cornblatt B, etal. Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project. Am J Psychiatry. 2000; 157: 1416–22.
  • Sanders RD, Keshavan MS, Schooler NR. Neurological examination abnormalities in neuroleptic-naive patients with first-break schizophrenia: preliminary results. Am J Psychiatry. 1994; 151: 1231–3.
  • Venkatasubramanian G, Latha V, Gangadhar BN, Janakiramaiah N, Subbakrishna DK, Jayakumar PN, etal. Neurological soft signs in never-treated schizophrenia. Acta Psychiatr Scand. 2003; 108: 144–6.
  • Schubert EW, McNeil TF. Neurobehavioral deficits in young adult offspring with heightened risk for psychosis who developed schizophrenia-spectrum disorder. Schizophr Res. 2007; 94: 107–13.
  • Zabala A, Robles O, Parellada M, Moreno DM, Ruiz-Sancho A, Burdalo M, etal. Neurological soft signs in adolescents with first episode psychosis. Eur Psychiatry. 2006; 21: 283–7.
  • Mayoral M, Bombín I, Castro-Fornieles J, González-Pinto A, Otero S, Parellada M, etal. Longitudinal study of neurological soft signs in first-episode early-onset psychosis. J Child Psychol Psychiatry. 2012; 53: 323–31.
  • Mayoral M, Bombín I, Zabala A, Robles O, Moreno D, Parellada M, etal. Neurological soft signs in adolescents with first episode psychosis: two-year followup. Psychiatry Res. 2008; 161: 344–8.
  • Bachmann S, Degen C, Geider FJ, Schröder J. Neurological soft signs in the clinical course of schizophrenia: results of a meta-analysis. Front Psychiatry. 2014; 5: 185.
  • Chen EY, Hui CL, Chan RC, Dunn EL, Miao MY, Yeung WS, etal. A 3-year prospective study of neurological soft signs in first-episode schizophrenia. Schizophr Res. 2005; 75: 45–54.
  • Mrad A, Mechri A, Slama H, Mokni S, Letaief M, Gha L. Correlations between obstetric complications and neurological soft signs in Tunisian patients with schizophrenia. Psychiatry Clin Neurosci. 2010; 64: 645–8.
  • Cantor-Graae E, Ismail B, McNeil TF. Are neurological abnormalities in schizophrenic patients and their siblings the result of perinatal trauma?. Acta Psychiatr Scand. 2000; 101: 142–7.
  • Lane A, Colgan K, Moynihan F, Burke T, Waddington JL, Larkin C, etal. Schizophrenia and neurological soft signs: gender differences in clinical correlates and antecedent factors. Psychiatry Res. 1996; 64: 105–14.
  • Ismail B, Cantor-Graae E, McNeil TF. Neurodevelopmental origins of tardivelike dyskinesia in schizophrenia patients and their siblings. Schizophr Bull. 2001; 27: 629–41.
  • Mäki P, Veijola J, Jones PB, Murray GK, Koponen H, Tienari P, etal. Predictors of schizophrenia – a review. Br Med Bull. 2005; 73–74: 1–15.
  • Isohanni M, Jones PB, Moilanen K, Rantakallio P, Veijola J, Oja H, etal. Early developmental milestones in adult schizophrenia and other psychoses. A 31-year follow-up of the Northern Finland 1966 Birth Cohort. Schizophr Res. 2001; 52: 1–19.
  • Rosso IM, Bearden CE, Hollister JM, Gasperoni TL, Sanchez LE, Hadley T, etal. Childhood neuromotor dysfunction in schizophrenia patients and their unaffected siblings: a prospective cohort study. Schizophr Bull. 2000; 26: 367–78.
  • Cannon M, Jones P, Huttunen MO, Tanskanen A, Huttunen T, Rabe-Hesketh S, etal. School performance in Finnish children and later development of schizophrenia: a population-based longitudinal study. Arch Gen Psychiatry. 1999; 56: 457–63.
  • Schiffman J, Walker E, Ekstrom M, Schulsinger F, Sorensen H, Mednick S. Childhood videotaped social and neuromotor precursors of schizophrenia: a prospective investigation. Am J Psychiatry. 2004; 161: 2021–7.
  • Niemi LT, Suvisaari JM, Tuulio-Henriksson A, Lönnqvist JK. Childhood developmental abnormalities in schizophrenia: evidence from high-risk studies. Schizophr Res. 2003; 60: 239–58.
  • Owens DGC, Johnstone EC. Precursors and prodromata of schizophrenia: findings from the Edinburgh High Risk Study and their literature context. Psychol Med. 2006; 36: 1501–14.
  • Lichtenstein P, Yip BH, Björk C, Pawitan Y, Cannon TD, Sullivan PF, etal. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009; 373: 234–9.
  • Gottesman II. Schizophrenia epigenesis: past, present, and future. Acta Psychiatr Scand Suppl. 1994; 384: 26–33.
  • Blennow G, McNeil TF. Neurological deviations in newborns at psychiatric high risk. Acta Psychiatr Scand. 1991; 84: 179–84.
  • Fish B. Infant predictors of the longitudinal course of schizophrenic development. Schizophr Bull. 1987; 13: 395–409.
  • Mednick SA, Schulsinger F. Some premorbid characteristics related to breakdown in children with schizophrenic mothers. J Psychiatr Res. 1968; 6(Suppl 1): 267–91.
  • Marcus J, Hans SL, Auerbach JG, Auerbach AG. Children at risk for schizophrenia: the Jerusalem Infant Development Study. II. Neurobehavioral deficits at school age. Arch Gen Psychiatry. 1993; 50: 797–809.
  • McNeil TF, Kaij L. Swedish high-risk study: sample characteristics at age 6. Schizophr Bull. 1987; 13: 373–81.
  • Sameroff AJ, Barocas R, Seifer R. Watt NF, Anthony EJ, Wynne LC, Rolf JE. The early development of children born to mentally ill women. Children at risk for schizophrenia: a longitudinal perspective. 1984; New York: Cambridge University Press. 482–514.
  • Marcus J, Auerbach J, Wilkinson L, Burack CM. Infants at risk for schizophrenia. The Jerusalem Infant Development Study. Arch Gen Psychiatry. 1981; 38: 703–13.
  • Mirsky AF, Kugelmass S, Ingraham LJ, Frenkel E, Nathan M. Overview and summary: twenty-five-year followup of high-risk children. Schizophr Bull. 1995; 21: 227–39.
  • McNeil TF, Harty B, Blennow G, Cantor-Graae E. Neuromotor deviation in offspring of psychotic mothers: a selective developmental deficiency in two groups of children at heightened psychiatric risk?. J Psychiatr Res. 1993; 27: 39–54.
  • Rieder RO, Nichols PL. Offspring of schizophrenics. III. Hyperactivity and neurological soft signs. Arch Gen Psychiatry. 1979; 36: 665–74.
  • Marcus J, Hans SL, Lewow E, Wilkinson L, Burack CM. Neurological findings in high-risk children: childhood assessment and 5-year followup. Schizophr Bull. 1985; 11: 85–100.
  • Hans SL, Marcus J, Nuechterlein KH, Asarnow RF, Styr B, Auerbach JG. Neurobehavioral deficits at adolescence in children at risk for schizophrenia: The Jerusalem Infant Development Study. Arch Gen Psychiatry. 1999; 56: 741–8.
  • Isohanni M, Lauronen E, Moilanen K, Isohanni I, Kemppainen L, Koponen H, etal. Predictors of schizophrenia: evidence from the Northern Finland 1966 Birth Cohort and other sources. Br J Psychiatry Suppl. 2005; 48: s4–7.
  • Walther S, Strik W. Motor symptoms and schizophrenia. Neuropsychobiology. 2012; 66: 77–92.
  • Peralta V, Campos MS, De Jalón EG, Cuesta MJ. Motor behavior abnormalities in drug-naïve patients with schizophrenia spectrum disorders. Mov Disord. 2010; 25: 1068–76.
  • Schubert EW, McNeil TF. Prospective study of neurological abnormalities in offspring of women with psychosis: birth to adulthood. Am J Psychiatry. 2004; 161: 1030–7.
  • Kinney DK, Yurgelun-Todd DA, Woods BT. Hard neurologic signs and psychopathology in relatives of schizophrenic patients. Psychiatry Res. 1991; 39: 45–53.
  • Kinney DK, Woods BT, Yurgelun-Todd D. Neurologic abnormalities in schizophrenic patients and their families. II. Neurologic and psychiatric findings in relatives. Arch Gen Psychiatry. 1986; 43: 665–8.
  • Griffiths TD, Sigmundsson T, Takei N, Rowe D, Murray RM. Neurological abnormalities in familial and sporadic schizophrenia. Brain J Neurol. 1998; 121: 191–203.
  • Ismail BT, Cantor-Graae E, Cardenal S, McNeil TF. Neurological abnormalities in schizophrenia: clinical, etiological and demographic correlates. Schizophr Res. 1998; 30: 229–38.
  • Ismail B, Cantor-Graae E, McNeil TF. Neurological abnormalities in schizophrenic patients and their siblings. Am J Psychiatry. 1998; 155: 84–9.
  • Chen YL, Chen YH, Mak FL. Soft neurological signs in schizophrenic patients and their nonpsychotic siblings. J Nerv Ment Dis. 2000; 188: 84–9.
  • Lawrie SM, Byrne M, Miller P, Hodges A, Clafferty RA, Cunningham Owens DG, etal. Neurodevelopmental indices and the development of psychotic symptoms in subjects at high risk of schizophrenia. Br J Psychiatry. 2001; 178: 524–30.
  • Yazici AH, Demir B, Yazici KM, Göğüş A. Neurological soft signs in schizophrenic patients and their nonpsychotic siblings. Schizophr Res. 2002; 58 : 241–6.
  • Gourion D, Goldberger C, Olie JP, Lôo H, Krebs MO. Neurological and morphological anomalies and the genetic liability to schizophrenia: a composite phenotype. Schizophr Res. 2004; 67: 23–31.
  • Niemi LT, Suvisaari JM, Haukka JK, Lönnqvist JK. Childhood predictors of future psychiatric morbidity in offspring of mothers with psychotic disorder: results from the Helsinki High-Risk Study. Br J Psychiatry. 2005; 186: 108–14.
  • Cantor-Graae E, McNeil TF, Rickler KC, Sjöström K, Rawlings R, Higgins ES, etal. Are neurological abnormalities in well discordant monozygotic co-twins of schizophrenic subjects the result of perinatal trauma?. Am J Psychiatry. 1994; 151: 1194–9.
  • Niethammer R, Weisbrod M, Schiesser S, Grothe J, Maier S, Peter U, etal. Genetic influence on laterality in schizophrenia? A twin study of neurological soft signs. Am J Psychiatry. 2000; 157: 272–4.
  • Appels MC, Sitskoorn MM, de Boo M, Klumpers UM, Kemps A, Elderson A, etal. Neurological signs in parents of schizophrenic patients. Neuroreport. 2002; 13: 575–9.
  • Kelly BD, Cotter D, Denihan C, Larkin D, Murphy P, Kinsella A, etal. Neurological soft signs and dermatoglyphic anomalies in twins with schizophrenia. Eur Psychiatry. 2004; 19: 159–63.
  • Solanki RK, Swami MK, Singh P, Gupta S. Identification of vulnerability among first-degree relatives of patients with schizophrenia. East Asian Arch Psychiatry. 2012; 22: 118–25.
  • Snitz BE, Macdonald AW, Carter CS. Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophr Bull. 2006; 32: 179–94.
  • Neelam K, Garg D, Marshall M. A systematic review and meta-analysis of neurological soft signs in relatives of people with schizophrenia. BMC Psychiatry. 2011; 11: 139.
  • Visscher PM, Hill WG, Wray NR. Heritability in the genomics era – concepts and misconceptions. Nat Rev Genet. 2008; 9: 255–66.
  • Sanders RD, Joo YH, Almasy L, Wood J, Keshavan MS, Pogue-Geile MF, etal. Are neurologic examination abnormalities heritable? A preliminary study. Schizophr Res. 2006; 86: 172–80.
  • Hyde TM, Goldberg TE, Egan MF, Lener MC, Weinberger DR. Frontal release signs and cognition in people with schizophrenia, their siblings and healthy controls. Br J Psychiatry. 2007; 191: 120–5.
  • Chen RY, Sham P, Chen EY, Li T, Cheung EF, Hui TC, etal. No association between T102C polymorphism of serotonin-2A receptor gene and clinical phenotypes of Chinese schizophrenic patients. Psychiatry Res. 2001; 105: 175–85.
  • Özçetin A, Poyraz BÇ, Poyraz CA, Bozhüyük E, Bolat N, Balcioğlu I, etal. T102C polymorphism of serotonin-2A receptor gene in Turkish schizophrenia patients: association with cognitive impairment and soft neurological signs. Indian J Psychiatry. 2014; 56 : 359–64.
  • Galderisi S, Maj M, Kirkpatrick B, Piccardi P, Mucci A, Invernizzi G, etal. Catechol-O-methyltransferase Val158Met polymorphism in schizophrenia: associations with cognitive and motor impairment. Neuropsychobiology. 2005; 52: 83–9.
  • Lautenschlager NT, Wu JS, Laws SM, Almeida OP, Clarnette RM, Joesbury K, etal. Neurological soft signs are associated with APOE genotype, age and cognitive performance. J Alzheimers Dis. 2005; 7: 325–30.
  • Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, etal. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet. 2014; 46: 1173–86.
  • Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, etal. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015; 518: 197–206.
  • International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011; 476 : 214–19.
  • Van Den Bossche MJ, Docx L, Morrens M, Cammaerts S, Strazisar M, Bervoets C, etal. Less cognitive and neurological deficits in schizophrenia patients carrying risk variant in ZNF804A. Neuropsychobiology. 2012; 66: 158–66.