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The effect of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis

Published online by Cambridge University Press:  02 July 2009

A. Dutt ,
C. McDonald ,
E. Dempster ,
D. Prata ,
M. Shaikh ,
I. Williams ,
K. Schulze ,
N. Marshall ,
M. Walshe  and
M. Allin
...Show all authors
A. Dutt*
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
C. McDonald
Affiliation:
Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Republic of Ireland
E. Dempster
Affiliation:
MRC, Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, London, UK
D. Prata
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Shaikh
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
I. Williams
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
K. Schulze
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
N. Marshall
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Walshe
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
M. Allin
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
D. Collier
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
R. Murray
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
E. Bramon
Affiliation:
NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK
*
*Address for correspondence: A. Dutt, MRCPsych, Division of Psychological Medicine and Psychiatry P063, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK. (Email: Anirban.Dutt@kcl.ac.uk)
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Abstract

Background

Morphometric endophenotypes which have been proposed for psychotic disorders include lateral ventricular enlargement and hippocampal volume reductions. Genetic epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders. This study examined associations between these candidate genes and morphometric endophenotypes for psychosis.

Method

A total of 383 subjects (128 patients with psychosis, 194 of their unaffected relatives and 61 healthy controls) from the Maudsley Family Psychosis Study underwent structural magnetic resonance imaging and genotyping. The effect of candidate genes on brain morphometry was examined using linear regression models adjusting for clinical group, age, sex and correlations between members of the same family.

Results

The results showed no evidence of association between variation in COMT genotype and lateral ventricular, and left or right hippocampal volumes. Neither was there any effect of the BDNF, 5-HTTLPR, NRG1 and DTNBP1 genotypes on these regional brain volumes.

Conclusions

Abnormal hippocampal and lateral ventricular volumes are among the most replicated endophenotypes for psychosis; however, the influences of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on these key brain regions must be very subtle if at all present.

Keywords

Bipolarendophenotypesgeneshippocampusschizophreniaventricles
Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 11 , November 2009 , pp. 1783 - 1797
Copyright
Copyright © Cambridge University Press 2009

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References

Agartz, I, Sedvall, GC, Terenius, L, Kulle, B, Frigessi, A, Hall, H, Jönsson, EG (2006). BDNF gene variants and brain morphology in schizophrenia. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 141, 513–523.CrossRefGoogle Scholar
Badner, JA, Gershon, ES (2002). Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Molecular Psychiatry 7, 405–411.CrossRefGoogle Scholar
Bearden, CE, Soares, JC, Klunder, AD, Nicoletti, M, Dierschke, N, Hayashi, KM, Narr, KL, Brambilla, P, Sassi, RB, Axelson, D, Ryan, N, Birmaher, B, Thompson, PM (2008). Three-dimensional mapping of hippocampal anatomy in adolescents with bipolar disorder. Journal of the American Academy of Child and Adolescent Psychiatry 47, 515–525.CrossRefGoogle ScholarPubMed
Boks, MP, Leask, S, Vermunt, JK, Kahn, RS (2007). The structure of psychosis revisited: the role of mood symptoms. Schizophrenia Research 93, 178–185.CrossRefGoogle ScholarPubMed
Braff, D, Schork, NJ, Gottesman, II (2007 a). Endophenotyping schizophrenia. American Journal of Psychiatry 164, 705–707.CrossRefGoogle ScholarPubMed
Braff, DL, Freedman, R, Schork, NJ, Gottesman, II (2007 b). Deconstructing schizophrenia: an overview of the use of endophenotypes in order to understand a complex disorder. Schizophrenia Bulletin 33, 21–32.CrossRefGoogle ScholarPubMed
Bramon, E, Croft, RJ, McDonald, C, Virdi, GK, Gruzelier, JG, Baldeweg, T, Sham, PC, Frangou, S, Murray, RM (2004). Mismatch negativity in schizophrenia: a family study. Schizophrenia Research 67, 1–10.CrossRefGoogle ScholarPubMed
Bramon, E, Dempster, E, Frangou, S, McDonald, C, Schoenberg, P, MacCabe, JH, Walshe, M, Sham, P, Collier, D, Murray, RM (2006). Is there any association between the COMT gene and P300 endophenotypes? European Psychiatry 21, 70–73.CrossRefGoogle ScholarPubMed
Bramon, E, Sham, PC (2001). The common genetic liability between schizophrenia and bipolar disorder: a review. Current Psychiatry Reports 3, 332–337.CrossRefGoogle ScholarPubMed
Breen, G, Prata, D, Osborne, S, Munro, J, Sinclair, M, Li, T, Staddon, S, Dempster, D, Sainz, R, Arroyo, B, Kerwin, RW, St Clair, D, Collier, D (2006). Association of the dysbindin gene with bipolar affective disorder. American Journal of Psychiatry 163, 1636–1638.CrossRefGoogle ScholarPubMed
Broome, MR, Woolley, JB, Tabraham, P, Johns, LC, Bramon, E, Murray, GK, Pariante, C, McGuire, PK, Murray, RM (2005). What causes the onset of psychosis? Schizophrenia Research 79, 23–34.CrossRefGoogle ScholarPubMed
Burdick, KE, Goldberg, TE, Funke, B, Bates, JA, Lencz, T, Kucherlapati, R, Malhotra, AK (2007). DTNBP1 genotype influences cognitive decline in schizophrenia. Schizophrenia Research 89, 169–172.CrossRefGoogle ScholarPubMed
Cannon, TD (2005). The inheritance of intermediate phenotypes for schizophrenia. Current Opinion in Psychiatry 18, 135–140.CrossRefGoogle ScholarPubMed
Cannon, TD, Keller, MC (2006). Endophenotypes in the genetic analyses of mental disorders. Annual Review of Clinical Psychology 2, 267–290.CrossRefGoogle ScholarPubMed
Cardno, AG, Rijsdijk, FV, Sham, PC, Murray, RM, McGuffin, P (2002). A twin study of genetic relationships between psychotic symptoms. American Journal of Psychiatry 159, 539–545.CrossRefGoogle ScholarPubMed
Chakos, MH, Schobel, SA, Gu, H, Gerig, G, Bradford, D, Charles, C, Lieberman, JA (2005). Duration of illness and treatment effects on hippocampal volume in male patients with schizophrenia. British Journal of Psychiatry 186, 26–31.CrossRefGoogle ScholarPubMed
Chen, X, Wang, X, O'Neill, AF, Walsh, D, Kendler, KS (2004). Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families. Molecular Psychiatry 9, 962–967.CrossRefGoogle ScholarPubMed
Cho, HJ, Meira-Lima, I, Cordeiro, Q, Michelon, L, Sham, P, Vallada, H, Collier, DA (2005). Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis. Molecular Psychiatry 10, 771–781.CrossRefGoogle ScholarPubMed
Chua, SE, Cheung, C, Cheung, V, Tsang, JT, Chen, EY, Wong, JC, Cheung, JP, Yip, L, Tai, KS, Suckling, J, McAlonan, GM (2007). Cerebral grey, white matter and CSF in never-medicated, first-episode schizophrenia. Schizophrenia Research 89, 12–21.CrossRefGoogle ScholarPubMed
Church, SM, Cotter, D, Bramon, E, Murray, RM (2002). Does schizophrenia result from developmental or degenerative processes? Journal of Neural Transmission 63 (Suppl.), S129–S147.Google Scholar
Craddock, N, O'Donovan, MC, Owen, MJ (2006). Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophrenia Bulletin 32, 9–16.CrossRefGoogle ScholarPubMed
Craddock, N, Owen, MJ (2007). Rethinking psychosis: the disadvantages of a dichotomous classification now outweigh the advantages. World Psychiatry 6, 84–91.Google ScholarPubMed
Craddock, N, Owen, MJ, O'Donovan, MC (2006). The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Molecular Psychiatry 11, 446–458.CrossRefGoogle ScholarPubMed
Crespo-Facorro, B, Roiz-Santiáñez, R, Pelayo-Terán, JM, Pérez-Iglesias, R, Carrasco-Marín, E, Mata, I, González-Mandly, A, Jorge, R, Vázquez-Barquero, JL (2007). Low-activity allele of catechol-O-methyltransferase (COMTL) is associated with increased lateral ventricles in patients with first episode non-affective psychosis. Progress in Neuro-psychopharmacology and Biological Psychiatry 31, 1514–1518.CrossRefGoogle ScholarPubMed
Dean, K, Bramon, E, Murray, RM (2003). The causes of schizophrenia: neurodevelopment and other risk factors. Journal of Psychiatric Practice 9, 442–454.CrossRefGoogle ScholarPubMed
DeLisi, LE (2008). The concept of progressive brain change in schizophrenia: implications for understanding schizophrenia. Schizophrenia Bulletin 34, 312–321.CrossRefGoogle ScholarPubMed
Dempster, E, Toulopoulou, T, McDonald, C, Bramon, E, Walshe, M, Filbey, F, Wickham, H, Sham, PC, Murray, RM, Collier, DA (2005). Association between BDNF Val66 Met genotype and episodic memory. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 134, 73–75.CrossRefGoogle Scholar
Dubertret, C, Hanoun, N, Adès, J, Hamon, M, Gorwood, P (2005). Family-based association study of the 5-HT transporter gene and schizophrenia. International Journal of Neuropsychopharmacology 8, 87–92.CrossRefGoogle ScholarPubMed
Dutta, R, Greene, T, Addington, J, McKenzie, K, Phillips, M, Murray, RM (2007). Biological, life course, and cross-cultural studies all point toward the value of dimensional and developmental ratings in the classification of psychosis. Schizophrenia Bulletin 33, 868–876.CrossRefGoogle ScholarPubMed
Egan, MF, Goldberg, TE, Kolachana, BS, Callicott, JH, Mazzanti, CM, Straub, RE, Goldman, D, Weinberger, DR (2001). Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proceedings of the National Academy of Sciences USA 98, 6917–6922.CrossRefGoogle ScholarPubMed
Endicott, J, Spitzer, RL (1978). A diagnostic interview: the schedule for affective disorders and schizophrenia. Archives of General Psychiatry 35, 837–844.CrossRefGoogle ScholarPubMed
Fan, JB, Sklar, P (2005). Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia. Molecular Psychiatry 10, 928–938.CrossRefGoogle ScholarPubMed
Farmer, A, Elkin, A, McGuffin, P (2007). The genetics of bipolar affective disorder. Current Opinion in Psychiatry 20, 8–12.CrossRefGoogle ScholarPubMed
Frangou, S, Sharma, T, Sigmudsson, T, Barta, P, Pearlson, G, Murray, RM (1997). The Maudsley Family Study. 4. Normal planum temporale asymmetry in familial schizophrenia. A volumetric MRI study. British Journal of Psychiatry 170, 328–333.CrossRefGoogle ScholarPubMed
Funke, B, Malhotra, AK, Finn, CT, Plocik, AM, Lake, SL, Lencz, T, DeRosse, P, Kane, JM, Kucherlapati, R (2005). COMT genetic variation confers risk for psychotic and affective disorders: a case control study. Behavioral and Brain Functions (http://www.behavioralandbrainfunctions.com/content/pdf/1744-9081-1-19.pdf). Accessed 28 July 2008.Google Scholar
Gelernter, J, Kranzler, H, Cubells, JF (1997). Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects. Human Genetics 101, 243–246.CrossRefGoogle ScholarPubMed
Georgieva, L, Dimitrova, A, Ivanov, D, Nikolov, I, Williams, NM, Grozeva, D, Zaharieva, I, Toncheva, D, Owen, MJ, Kirov, G, O'Donovan, MC (2008). Support for neuregulin 1 as a susceptibility gene for bipolar disorder and schizophrenia. Biological Psychiatry 64, 419–427.CrossRefGoogle Scholar
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.CrossRefGoogle ScholarPubMed
Gruber, O, Falkai, P, Schneider-Axmann, T, Schwab, SG, Wagner, M, Maier, W (2008). Neuregulin-1 haplotype HAPICE is associated with lower hippocampal volumes in schizophrenic patients and in non-affected family members. Journal of Psychiatric Research 43, 1–6.CrossRefGoogle ScholarPubMed
Hajek, T, Carrey, N, Alda, M (2005). Neuroanatomical abnormalities as risk factors for bipolar disorder. Bipolar Disorders 7, 393–403.CrossRefGoogle ScholarPubMed
Halliday, GM (2001). A review of the neuropathology of schizophrenia. Clinical and Experimental Pharmacology and Physiology 28, 64–65.CrossRefGoogle ScholarPubMed
Harrison, PJ, Weinberger, DR (2005). Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Molecular Psychiatry 10, 40–68.CrossRefGoogle ScholarPubMed
Ho, BC, Andreasen, NC, Dawson, JD, Wassink, TH (2007). Association between brain-derived neurotrophic factor Val66Met gene polymorphism and progressive brain volume changes in schizophrenia. American Journal of Psychiatry 164, 1890–1899.CrossRefGoogle ScholarPubMed
Ho, BC, Milev, P, O'Leary, DS, Librant, A, Andreasen, NC, Wassink, TH (2006). Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers. Archives of General Psychiatry 63, 731–740.CrossRefGoogle ScholarPubMed
Hoda, F, Nicholl, D, Bennett, P, Arranz, M, Aitchison, KJ, al-Chalabi, A, Kunugi, H, Vallada, H, Leigh, PN, Chaudhuri, KR, Collier, DA (1996). No association between Parkinson's disease and low-activity alleles of catechol O-methyltransferase. Biochemical and Biophysical Research Communications 228, 780–784.CrossRefGoogle ScholarPubMed
Ikeda, M, Iwata, N, Suzuki, T, Kitajima, T, Yamanouchi, Y, Kinoshita, Y, Ozaki, N (2006). No association of serotonin transporter gene (SLC6A4) with schizophrenia and bipolar disorder in Japanese patients: association analysis based on linkage disequilibrium. Journal of Neural Transmission 113, 899–905.CrossRefGoogle ScholarPubMed
Ikeda, M, Takahashi, N, Saito, S, Aleksic, B, Watanabe, Y, Nunokawa, A, Yamanouchi, Y, Kitajima, T, Kinoshita, Y, Kishi, T, Kawashima, K, Hashimoto, R, Ujike, H, Inada, T, Someya, T, Takeda, M, Ozaki, N, Iwata, N (2008). Failure to replicate the association between NRG1 and schizophrenia using Japanese large sample. Schizophrenia Research 101, 1–8.CrossRefGoogle ScholarPubMed
Isohanni, M, Lauronen, E, Moilanen, K, Isohanni, I, Kemppainen, L, Koponen, H, Miettunen, J, Mäki, P, Räsänen, S, Veijola, J, Tienari, P, Wahlberg, KE, Murray, GK (2005). Predictors of schizophrenia: evidence from the Northern Finland 1966 Birth Cohort and other sources. British Journal of Psychiatry 48 (Suppl.), S4–S7.CrossRefGoogle ScholarPubMed
Joo, EJ, Lee, KY, Jeong, SH, Ahn, YM, Koo, YJ, Kim, YS (2006). The dysbindin gene (DTNBP1) and schizophrenia: no support for an association in the Korean population. Neuroscience Letters 407, 101–106.CrossRefGoogle ScholarPubMed
Joo, EJ, Lee, KY, Jeong, SH, Chang, JS, Ahn, YM, Koo, YJ, Kim, YS (2007). Dysbindin gene variants are associated with bipolar I disorder in a Korean population. Neuroscience Letters 418, 272–275.CrossRefGoogle Scholar
Kanazawa, T, Glatt, SJ, Kia-Keating, B, Yoneda, H, Tsuang, MT (2007). Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder. Psychiatric Genetics 17, 165–170.CrossRefGoogle ScholarPubMed
Kempton, MJ, Geddes, JR, Ettinger, U, Williams, SC, Grasby, PM (2008). Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. Archives of General Psychiatry 65, 1017–1032.CrossRefGoogle ScholarPubMed
Ketter, TA, Wang, PW, Becker, OV, Nowakowska, C, Yang, Y (2004). Psychotic bipolar disorders: dimensionally similar to or categorically different from schizophrenia? Journal of Psychiatric Research 38, 47–61.CrossRefGoogle ScholarPubMed
Kumari, V, Cooke, M (2006). Use of magnetic resonance imaging in tracking the course and treatment of schizophrenia. Expert Review of Neurotherapeutics 6, 1005–1016.CrossRefGoogle ScholarPubMed
Kwon, OB, Longart, M, Vullhorst, D, Hoffman, DA, Buonanno, A (2005). Neuregulin-1 reverses long-term potentiation at CA1 hippocampal synapses. Journal of Neuroscience 225, 9378–9383.CrossRefGoogle Scholar
Law, A (2003). Schizophrenia, IV: neuregulin-1 in the human brain. American Journal of Psychiatry 160, 1392.CrossRefGoogle ScholarPubMed
Lawrie, SM, Abukmeil, SS (1998). Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry 172, 110–120.CrossRefGoogle ScholarPubMed
Lawrie, SM, Hall, J, McIntosh, AM, Cunningham-Owens, DG, Johnstone, EC (2008). Neuroimaging and molecular genetics of schizophrenia: pathophysiological advances and therapeutic potential. British Journal of Pharmacology 153 (Suppl.), S120–S124.CrossRefGoogle ScholarPubMed
Li, D, Collier, DA, He, L (2006). Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Human Molecular Genetics 15, 1995–2002.CrossRefGoogle ScholarPubMed
Lieberman, JA (1999). Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biological Psychiatry 46, 729–739.CrossRefGoogle ScholarPubMed
Lieberman, JA, Tollefson, GD, Charles, C, Zipursky, R, Sharma, T, Kahn, RS, Keefe, RS, Green, AI, Gur, RE, McEvoy, J, Perkins, D, Hamer, RM, Gu, H, Tohen, M; HGDH Study Group (2005). Antipsychotic drug effects on brain morphology in first-episode psychosis. Archives of General Psychiatry 62, 361–370.CrossRefGoogle ScholarPubMed
Maier, W (2008). Common risk genes for affective and schizophrenic psychoses. European Archives of Psychiatry and Clinical Neuroscience 2 (Suppl.), S37–S40.CrossRefGoogle Scholar
Malaspina, D (2006). Schizophrenia: a neurodevelopmental or a neurodegenerative disorder. Journal of Clinical Psychiatry 67, e07.Google ScholarPubMed
Mansour, HA, Talkowski, ME, Wood, J, Pless, L, Bamne, M, Chowdari, KV, Allen, M, Bowden, CL, Calabrese, J, El-Mallakh, RS, Fagiolini, A, Faraone, SV, Fossey, MD, Friedman, ES, Gyulai, L, Hauser, P, Ketter, TA, Loftis, JM, Marangell, LB, Miklowitz, DJ, Nierenberg, AA, Patel, J, Sachs, GS, Sklar, P, Smoller, JW, Thase, ME, Frank, E, Kupfer, DJ, Nimgaonkar, VL (2005). Serotonin gene polymorphisms and bipolar 1 disorder: focus on the serotonin transporter. Annals of Medicine 37, 590–602.CrossRefGoogle ScholarPubMed
Martorell, L, Costas, J, Valero, J, Gutierrez-Zotes, A, Phillips, C, Torres, M, Brunet, A, Garrido, G, Carracedo, A, Guillamat, R, Vallès, V, Guitart, M, Labad, A, Vilella, E (2008). Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia. Schizophrenia Research 100, 308–315.CrossRefGoogle ScholarPubMed
Massana, G, Salgado-Pineda, P, Junqué, C, Pérez, M, Baeza, I, Pons, A, Massana, J, Navarro, V, Blanch, J, Morer, A, Mercader, JM, Bernardo, M (2005). Volume changes in gray matter in first-episode neuroleptic-naive schizophrenic patients treated with risperidone. Journal of Clinical Psychopharmacology 25, 111–117.CrossRefGoogle ScholarPubMed
Mata, I, Arranz, MJ, Patiño, A, Lai, T, Beperet, M, Sierrasesumaga, L, Clark, D, Perez-Nievas, F, Richards, L, Ortuño, F, Sham, P, Kerwin, RW (2004). Serotonergic polymorphisms and psychotic disorders in populations from North Spain. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 126B, 88–94.CrossRefGoogle ScholarPubMed
Mata, I, Perez-Iglesias, R, Roiz-Santiañez, R, Tordesillas-Gutierrez, D, Gonzalez-Mandly, A, Luis Vazquez-Barquero, J, Crespo-Facorro, B (2009). A neuregulin 1 variant is associated with increased lateral ventricle volume in patients with first-episode schizophrenia. Biological Psychiatry 65, 535–540.CrossRefGoogle ScholarPubMed
McDonald, C, Grech, A, Toulopoulou, T, Schulze, K, Chapple, B, Sham, P, Walshe, M, Sharma, T, Sigmundsson, T, Chitnis, X, Murray, RM (2002). Brain volumes in familial and non-familial schizophrenic probands and their unaffected relatives. American Journal of Medical Genetics (Neuropsychiatric Genetics) 114, 616–625.CrossRefGoogle ScholarPubMed
McDonald, C, Marshall, N, Sham, PC, Bullmore, ET, Schulze, K, Chapple, B, Bramon, E, Filbey, F, Quraishi, S, Walshe, M, Murray, RM (2006). Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives. American Journal of Psychiatry 163, 478–487.CrossRefGoogle ScholarPubMed
McDonald, C, Zanelli, J, Rabe-Hesketh, S, Ellison-Wright, I, Sham, P, Kalidindi, S, Murray, RM, Kennedy, N (2004). Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder. Biological Psychiatry 56, 411–417.CrossRefGoogle ScholarPubMed
Molina, V, Reig, S, Sanz, J, Palomo, T, Benito, C, Sánchez, J, Pascau, J, Desco, M (2007). Changes in cortical volume with olanzapine in chronic schizophrenia. Pharmacopsychiatry 40, 135–139.CrossRefGoogle ScholarPubMed
Morgan, KD, Dazzan, P, Orr, KG, Hutchinson, G, Chitnis, X, Suckling, J, Lythgoe, D, Pollock, SJ, Rossell, S, Shapleske, J, Fearon, P, Morgan, C, David, A, McGuire, PK, Jones, PB, Leff, J, Murray, RM (2007). Grey matter abnormalities in first-episode schizophrenia and affective psychosis. British Journal of Psychiatry 51 (Suppl.), S111–S116.CrossRefGoogle ScholarPubMed
Munafò, MR, Bowes, L, Clark, TG, Flint, J (2005). Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case–control studies. Molecular Psychiatry 10, 765–770.CrossRefGoogle ScholarPubMed
Murray, RM, Sham, P, Van Os, J, Zanelli, J, Cannon, M, McDonald, C (2004). A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder. Schizophrenia Research 71, 405–416.CrossRefGoogle ScholarPubMed
Neves-Pereira, M, Cheung, JK, Pasdar, A, Zhang, F, Breen, G, Yates, P, Sinclair, M, Crombie, C, Walker, N, St Clair, DM (2005). BDNF gene is a risk factor for schizophrenia in a Scottish population. Molecular Psychiatry 10, 208–212.CrossRefGoogle Scholar
Neves-Pereira, M, Mundo, E, Muglia, P, King, N, Macciardi, F, Kennedy, JL (2002). The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. American Journal of Human Genetics 71, 651–655.CrossRefGoogle ScholarPubMed
Nunokawa, A, Watanabe, Y, Muratake, T, Kaneko, N, Koizumi, M, Someya, T (2007). No associations exist between five functional polymorphisms in the catechol-O-methyltransferase gene and schizophrenia in a Japanese population. Neuroscience Research 58, 291–296.CrossRefGoogle Scholar
Ohnishi, T, Hashimoto, R, Mori, T, Nemoto, K, Moriguchi, Y, Iida, H, Noguchi, H, Nakabayashi, T, Hori, H, Ohmori, M, Tsukue, R, Anami, K, Hirabayashi, N, Harada, S, Arima, K, Saitoh, O, Kunugi, H (2006). The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia. Brain 129, 399–410.CrossRefGoogle ScholarPubMed
Peper, JS, Brouwer, RM, Boomsma, DI, Kahn, RS, Hulshoff Pol, HE (2007). Genetic influences on human brain structure: a review of brain imaging studies in twins. Human Brain Mapping 28, 464–473.CrossRefGoogle ScholarPubMed
Peralta, V, Cuesta, MJ (2007). A dimensional and categorical architecture for the classification of psychotic disorders. World Psychiatry 6, 100–101.Google ScholarPubMed
Pfefferbaum, A, Sullivan, EV, Swan, GE, Carmelli, D (2000). Brain structure in men remains highly heritable in the seventh and eighth decades of life. Neurobiology of Aging 21, 63–74.CrossRefGoogle ScholarPubMed
Prasad, KM, Keshavan, MS (2008). Structural cerebral variations as useful endophenotypes in schizophrenia: do they help construct ‘extended endophenotypes’? Schizophrenia Bulletin 34, 774–790.CrossRefGoogle ScholarPubMed
Prata, DP, Breen, G, Munro, J, Sinclair, M, Osborne, S, Li, T, Kerwin, R, St Clair, D, Collier, DA (2006). Bipolar 1 disorder is not associated with the RGS4, PRODH, COMT and GRK3 genes. Psychiatric Genetics 16, 229–230.CrossRefGoogle Scholar
Reveley, AM, Reveley, MA, Chitkara, B, Clifford, C (1984). The genetic basis of cerebral ventricular volume. Psychiatry Research 13, 261–266.CrossRefGoogle ScholarPubMed
Rijsdijk, FV, van Haren, NE, Picchioni, MM, McDonald, C, Toulopoulou, T, Hulshoff Pol, HE, Kahn, RS, Murray, R, Sham, PC (2005). Brain MRI abnormalities in schizophrenia: same genes or same environment? Psychological Medicine 35, 1399–1409.CrossRefGoogle ScholarPubMed
Riley, B, Kendler, KS (2006). Molecular genetic studies of schizophrenia. European Journal of Human Genetics 14, 669–680.CrossRefGoogle ScholarPubMed
Rosa, A, Cuesta, MJ, Fatjó-Vilas, M, Peralta, V, Zarzuela, A, Fañanás, L (2006). The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with risk for psychosis: evidence from a family-based association study. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 141, 135–138.CrossRefGoogle Scholar
Saleem, Q, Ganesh, S, Vijaykumar, M, Reddy, YC, Brahmachari, SK, Jain, S (2000). Association analysis of 5HT transporter gene in bipolar disorder in the Indian population. American Journal of Medical Genetics (Neuropsychiatric Genetics) 96, 170–172.3.0.CO;2-1>CrossRefGoogle ScholarPubMed
Sand, PG, Eichhammer, P, Langguth, B, Hajak, G (2006). COMT association data in schizophrenia: new caveats. Biological Psychiatry 60, 663–664.CrossRefGoogle ScholarPubMed
Sanders, AR, Duan, J, Levinson, DF, Shi, J, He, D, Hou, C, Burrell, GJ, Rice, JP, Nertney, DA, Olincy, A, Rozic, P, Vinogradov, S, Buccola, NG, Mowry, BJ, Freedman, R, Amin, F, Black, DW, Silverman, JM, Byerley, WF, Crowe, RR, Cloninger, CR, Martinez, M, Gejman, PV (2008). No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics. American Journal of Psychiatry 165, 497–506.CrossRefGoogle Scholar
Scherk, H, Falkai, P (2006). Effects of antipsychotics on brain structure. Current Opinion in Psychiatry 19, 145–150.CrossRefGoogle ScholarPubMed
Schulze, K, McDonald, C, Frangou, S, Sham, P, Grech, A, Toulopoulou, T, Walshe, M, Sharma, T, Sigmundsson, T, Taylor, M, Murray, RM (2003). Hippocampal volume in familial and nonfamilial schizophrenic probands and their unaffected relatives. Biological Psychiatry 53, 562–570.CrossRefGoogle ScholarPubMed
Seidman, LJ, Faraone, SV, Goldstein, JM, Kremen, WS, Horton, NJ, Makris, N, Toomey, R, Kennedy, D, Caviness, VS, Tsuang, MT (2002). Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives. Archives of General Psychiatry 59, 839–849.CrossRefGoogle ScholarPubMed
Seidman, LJ, Wencel, HE (2003). Genetically mediated brain abnormalities in schizophrenia. Current Psychiatry Report 5, 135–144.CrossRefGoogle ScholarPubMed
Shenton, ME, Dickey, CC, Frumin, M, McCarley, RW (2001). A review of MRI findings in schizophrenia. Schizophrenia Research 49, 1–52.CrossRefGoogle ScholarPubMed
Shi, J, Gershon, ES, Liu, C (2008). Genetic associations with schizophrenia: meta-analyses of 12 candidate genes. Schizophrenia Research 104, 96–107.CrossRefGoogle ScholarPubMed
Sklar, P, Gabriel, SB, McInnis, MG, Bennett, P, Lim, YM, Tsan, G, Schaffner, S, Kirov, G, Jones, I, Owen, M, Craddock, N, DePaulo, JR, Lander, ES (2002). Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Molecular Psychiatry 7, 579–593.CrossRefGoogle ScholarPubMed
Steen, RG, Mull, C, McClure, R, Hamer, RM, Lieberman, JA (2006). Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. British Journal of Psychiatry 188, 510–518.CrossRefGoogle ScholarPubMed
Stefanis, N, Frangou, S, Yakeley, J, Sharma, T, O'Connell, P, Morgan, K, Sigmundsson, T, Taylor, M, Murray, RM (1999). Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications. Biological Psychiatry 46, 697–702.CrossRefGoogle ScholarPubMed
Stefansson, H, Sarginson, J, Kong, A, Yates, P, Steinthorsdottir, V, Gudfinnsson, E, Gunnarsdottir, S, Walker, N, Petursson, H, Crombie, C, Ingason, A, Gulcher, JR, Stefansson, K, St Clair, D (2003). Association of neuregulin 1 with schizophrenia confirmed in a Scottish population. American Journal of Human Genetics 72, 83–87.CrossRefGoogle Scholar
Stefansson, H, Sigurdsson, E, Steinthorsdottir, V, Bjornsdottir, S, Sigmundsson, T, Ghosh, S, Brynjolfsson, J, Gunnarsdottir, S, Ivarsson, O, Chou, TT, Hjaltason, O, Birgisdottir, B, Jonsson, H, Gudnadottir, VG, Gudmundsdottir, E, Bjornsson, A, Ingvarsson, B, Ingason, A, Sigfusson, S, Hardardottir, H, Harvey, RP, Lai, D, Zhou, M, Brunner, D, Mutel, V, Gonzalo, A, Lemke, G, Sainz, J, Johannesson, G, Andresson, T, Gudbjartsson, D, Manolescu, A, Frigge, ML, Gurney, ME, Kong, A, Gulcher, JR, Petursson, H, Stefansson, K (2002). Neuregulin 1 and susceptibility to schizophrenia. American Journal of Human Genetics 71, 877–892.CrossRefGoogle ScholarPubMed
Strasser, HC, Lilyestrom, J, Ashby, ER, Honeycutt, NA, Schretlen, DJ, Pulver, AE, Hopkins, RO, Depaulo, JR, Potash, JB, Schweizer, B, Yates, KO, Kurian, E, Barta, PE, Pearlson, GD (2005). Hippocampal and ventricular volumes in psychotic and nonpsychotic bipolar patients compared with schizophrenia patients and community control subjects: a pilot study. Biological Psychiatry 57, 633–639.CrossRefGoogle ScholarPubMed
Styner, M, Lieberman, JA, McClure, RK, Weinberger, DR, Jones, DW, Gerig, G (2005). Morphometric analysis of lateral ventricles in schizophrenia and healthy controls regarding genetic and disease-specific factors. Proceedings of the National Academy of Sciences USA 102, 4872–4877.CrossRefGoogle ScholarPubMed
Szeszko, PR, Lipsky, R, Mentschel, C, Robinson, D, Gunduz-Bruce, H, Sevy, S, Ashtari, M, Napolitano, B, Bilder, RM, Kane, JM, Goldman, D, Malhotra, AK (2005). Brain-derived neurotrophic factor Val66Met polymorphism and volume of the hippocampal formation. Molecular Psychiatry 10, 631–636.CrossRefGoogle ScholarPubMed
Taylor, WD, Züchner, S, Payne, ME, Messer, DF, Doty, TJ, MacFall, JR, Beyer, JL, Krishnan, KR (2007). The COMT Val158Met polymorphism and temporal lobe morphometry in healthy adults. Psychiatry Research 155, 173–177.CrossRefGoogle ScholarPubMed
Tunbridge, EM, Harrison, PJ, Weinberger, DR (2006). Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biological Psychiatry 60, 141–151.CrossRefGoogle ScholarPubMed
Walterfang, M, Wood, SJ, Velakoulis, D, Pantelis, C (2006). Neuropathological, neurogenetic and neuroimaging evidence for white matter pathology in schizophrenia. Neuroscience and Biobehavioral Reviews 30, 918–948.CrossRefGoogle ScholarPubMed
Wang, PW, Ketter, TA (2000). Biology and recent brain imaging studies in affective psychoses. Current Psychiatry Reports 2, 298–304.CrossRefGoogle ScholarPubMed
Weickert, CS, Straub, RE, McClintock, BW, Matsumoto, M, Hashimoto, R, Hyde, TM, Herman, MM, Weinberger, DR, Kleinman, JE (2004). Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain. Archives of General Psychiatry 61, 544–555.CrossRefGoogle ScholarPubMed
Whitworth, AB, Kemmler, G, Honeder, M, Kremser, C, Felber, S, Hausmann, A, Walch, T, Wanko, C, Weiss, EM, Stuppaeck, CH, Fleischhacker, WW (2005). Longitudinal volumetric MRI study in first- and multiple-episode male schizophrenia patients. Psychiatry Research 140, 225–237.CrossRefGoogle ScholarPubMed
Wickham, H, Murray, RM (1997). Can biological markers identify endophenotypes predisposing to schizophrenia? International Review of Psychiatry 9, 355–364.CrossRefGoogle Scholar
Williams, HJ, Glaser, B, Williams, NM, Norton, N, Zammit, S, MacGregor, S, Kirov, GK, Owen, MJ, O'Donovan, MC (2005). No association between schizophrenia and polymorphisms in COMT in two large samples. American Journal of Psychiatry 162, 1736–1738.CrossRefGoogle ScholarPubMed
Williams, HJ, Owen, MJ, O'Donovan, MC (2007). Is COMT a susceptibility gene for schizophrenia? Schizophrenia Bulletin 33, 635–641.CrossRefGoogle ScholarPubMed
Williams, NM, Preece, A, Spurlock, G, Norton, N, Williams, HJ, Zammit, S, O'Donovan, MC, Owen, MJ (2003). Support for genetic variation in neuregulin 1 and susceptibility to schizophrenia. Molecular Psychiatry 8, 485–487.CrossRefGoogle ScholarPubMed
Wood, SJ, Pantelis, C, Velakoulis, D, Yücel, M, Fornito, A, McGorry, PD (2008). Progressive changes in the development toward schizophrenia: studies in subjects at increased symptomatic risk. Schizophrenia Bulletin 34, 322–329.CrossRefGoogle ScholarPubMed
Wood, SJ, Velakoulis, D, Smith, DJ, Bond, D, Stuart, GW, McGorry, PD, Brewer, WJ, Bridle, N, Eritaia, J, Desmond, P, Singh, B, Copolov, D, Pantelis, C (2001). A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia. Schizophrenia Research 52, 37–46.CrossRefGoogle ScholarPubMed
Wright, IC, Rabe-Hesketh, S, Woodruff, PW, David, AS, Murray, RM, Bullmore, ET (2000). Meta-analysis of regional brain volumes in schizophrenia. American Journal of Psychiatry 157, 16–25.CrossRefGoogle ScholarPubMed