Drug discovery based on genetic and metabolic findings in schizophrenia

Expert Review of Clinical Pharmacology

Volumn 1, Issue 6, 2008, Pages 773-789

  Dwyer, Donard S ^a   Weeks, Kathrine ^a   Aamodt, Eric J ^a  

^a LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

Akt FOXO signaling; Antipsychotic drug; Caenorhabditis elegans; Energy metabolism

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BETA CATENIN; CALCINEURIN; CARBON MONOXIDE; CYCLOSPORIN A; DOPAMINE RECEPTOR; DYSBINDIN; DYSTROBREVIN; EARLY GROWTH RESPONSE FACTOR 3; FOLLITROPIN; GLUCOCORTICOID; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; INSULIN; LSU D 84; MERCURY; NEU DIFFERENTIATION FACTOR; NEUROLEPTIC AGENT; OLANZAPINE; PHENCYCLIDINE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN 14 3 3; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; RAS PROTEIN; RGS4 PROTEIN; SEROTONIN RECEPTOR; SOMATOMEDIN RECEPTOR; TACROLIMUS; TRANSCRIPTION FACTOR FOXO; UNCLASSIFIED DRUG; UNINDEXED DRUG;

BEHAVIOR GENETICS; BRAIN METABOLISM; CONVULSIVE THERAPY; DIABETES MELLITUS; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG RESEARCH; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENERGY METABOLISM; GENE FUNCTION; GENE OVEREXPRESSION; GENETIC SUSCEPTIBILITY; HUMAN; MOTOR DYSFUNCTION; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PATHOGENESIS; PATIENT COMPLIANCE; PROTEIN PROTEIN INTERACTION; PSYCHOSIS; REVIEW; SCHIZOPHRENIA; SIDE EFFECT; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; WEIGHT GAIN;

EID: 70049102159     PISSN: 17512433     EISSN: None     Source Type: Journal    
DOI: 10.1586/17512433.1.6.773     Document Type: Review

References (185)

1. Strange PG. Antipsychotic drugs: importance of dopamine receptors for mechanisms of therapeutic actions and side effects. Pharmacol. Rev. 53, 119-133 (2001).
2. Meltzer HY, Li Z, Kaneda Y, Ichikawa J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 27, 1159-1172 (2003).
3. Leucht S, Pitschel-Walz G, Abraham D, Kissling W. Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr. Res. 35, 51-68 (1999).
4. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA; CATIE investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N. Engl. J. Med. 353, 1209-1223 (2005).
5. Allison DB, Mentore JL, Heo M et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am. J. Psychiatry 156, 1686-1696 (1999).
6. Baptista T, Kin NMK, Beaulieu S, de Baptista EA. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry 35, 205-219 (2002).
7. Casey DE. The relationship of pharmacology to side effects. J. Clin. Psychiatry 58(Suppl 10), 55-62 (1997).
8. Dwyer DS, Donohoe D, Lu X-H, Aamodt EJ. Mechanistic connections between glucose/lipid disturbances and weight gain induced by antipsychotic drugs. Int. Rev. Neurobiol. 65, 211-247 (2005).
9. Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry 44, 660-669 (1987).
10. McGlashan TH, Hoffman RE. Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Arch. Gen. Psychiatry 57, 637-648 (2000).
11. Davis JO, Bracha HS. Famine and schizophrenia: first trimester malnutrition or second trimester beriberi? Biol. Psychiatry 4, 1-3 (1996).
12. Hulshoff Pol HE, Hoek HW, Susser E et al. Prenatal exposure to famine and brain morphology in schizophrenia. Am. J. Psychiatry 157, 1170-1172 (2000).
13. Dwyer DS, Bradley RJ, Kablinger AS, Freeman AM 3rd. Glucose metabolism in relation to schizophrenia and antipsychotic drug treatment. Ann. Clin. Psychiatry 13, 103-113 (2001).
14. Benes FM, Davidson J, Bird ED. Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. Arch. Gen. Psychiatry 43, 31-35 (1986).
15. Arnold SE, Hyman BT, Van Hoesen GW, Damasio AR. Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Arch. Gen. Psychiatry 48, 625-632 (1991).
16. Selemon LD, Goldman-Rakic PS. The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol. Psychiatry 45, 17-25 (2000).
17. Beasley CL, Reynolds GP. Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics. Schizophr. Res. 24, 349-355 (1997).
18. Moberg PJ, Agrin R, Gur RE, Gur RC, Turetsky BI, Doty RL. Olfactory dysfunction in schizophrenia: a qualitative and quantitative review. Neuropsychopharmacology 21, 325-340 (1999).
19. Arnold SE, Han L-Y, Moberg PJ et al. Dysregulation of olfactory receptor neuron lineage in schizophrenia. Arch. Gen. Psychiatry 58, 829-835 (2001).
20. Moises HW, Zoega T, Gottesman II. The glial growth factors deficiency and synaptic stabilization hypothesis of schizophrenia. BMC Psychiatry 2, 8-21 (2002).
21. Lewis DA, Levitt P. Schizophrenia as a disorder of neurodevelopment. Annu. Rev. Neurosci. 25, 409-432 (2002).
22. Coodin S. Body mass index in persons with schizophrenia. Can. J. Psychiatry 46, 549-555 (2001).
23. Simon W, Garvey JT. Glucose tolerance in chronic schizophrenia and senile states. Arch. Neurol. Psychiatry 65, 717-723 (1951).
24. Mukherjee S, Bocola V, Saraceni F, Scapicchio PL. Diabetes mellitus in schizophrenic patients. Compr. Psychiatry 37, 68-73 (1996).
25. Waitzkin L. A survey for unknown diabetics in a mental hospital. II. Men from age fifty. Diabetes 15, 164-172 (1966).
26. Sakel M. The methodological use of hypoglycemia in the treatment of psychoses. Am. J. Psychiatry 94, 111-129 (1938).
27. Ingvar DH, Franzen G. Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia. Acta Psychiatr. Scand. 50, 425-462 (1974).
28. Buchsbaum MS, Haier RJ, Potkin SG et al. Frontostriatal disorder of cerebral metabolism in never-medicated schizophrenics. Arch. Gen. Psychiatry 49, 935-942 (1992).
29. Andreasen NC, Rezai K, Alliger R et al. Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with Xenon-133 single photon emission computed tomography. Arch. Gen. Psychiatry 49, 943-958 (1992).
30. Wolkin A, Jaeger J, Brodie JD et al. Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography. Am. J. Psychiatry 142, 564-571 (1985).
31. 99Tc-ECD-SPECT. Neuro. Endocrinol. Lett. 26, 685-689 (2005).
32. Weinberger DR, Berman KF. Speculation on the meaning of cerebral metabolic hypofrontality in schizophrenia. Schizophr. Bull. 14, 157-168 (1988).
33. Buchsbaum MS, Wu JC, DeLisi LE et al. Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: differences between normal controls and schizophrenic patients. Biol. Psychiatry 22, 479-494 (1987).
34. Olsen L, Hansen T, Jakobsen KD et al. The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples. BMC Med. Genet. 9, 39 (2008).
35. Sengupta S, Parrilla-Escobar MA, Klink R et al. Are metabolic indices different between drug-naive first-episode psychosis patients and healthy controls? Schizophr. Res. 102, 329-336 (2008).
36. Ujike H, Nakata K. Genetic study of schizophrenia: new targets for therapy. Expert Rev. Neurother. 3(1), 41-50 (2003).
37. Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol. Psychiatry 10, 40-68 (2005).
38. Owen MJ, Craddock N, O'Donovan MC. Schizophrenia: genes at last? Trends Genet. 21, 518-525 (2005).
39. Riley B, Kendler KS. Molecular genetic studies of schizophrenia. Eur. J. Hum. Genet. 14, 669-680 (2006).
40. O'Tuathaigh CMP, Babovic D, O'Meara G, Clifford JJ, Croke DT, Waddington JL. Susceptibility genes for schizophrenia: characterization of mutant mouse models at the level of phenotypic behaviour. Neurosci. Biobehav. Rev. 31, 60-78 (2007).
41. The International Schizophrenia Consortium. Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455(7210), 237-241 (2008).
42. Stefansson H, Rujesco D, Cichon S et al. Large recurrent microdeletions associated with schizophrenia. Nature 455(7210), 232-236 (2008).
43. Miyakawa T, Leiter LM, Gerber DJ et al. Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc. Natl Acad. Sci. USA 100, 8987-8992 (2003).
44. Millar JK, Wilson-Annan JC, Anderson S et al. Disruption of two novel genes by a translocation cosegregating with schizophrenia. Hum. Mol. Genet. 6, 1415-1423 (2000).
45. Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ. Schizophrenia and affective disorders - cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical P300 findings in a family. Am. J. Hum. Genet. 69, 428-433 (2001).
46. Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. Convergent evidence for impaired Akt1-GSK3β signaling in schizophrenia. Nat. Genet. 36, 131-137 (2004).
47. Millar JK, Pickard BS, Mackie S et al. DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 310, 1187-1191 (2005).
48. Ozeki Y, Tomoda T, Kleiderlein J et al. Disrupted-in-schizophrenia-1 (DISC-1): Mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Proc. Natl Acad. Sci. USA 100, 289-294 (2003).
49. Brandon NJ, Handford EJ, Schurov I et al. Disrupted in schizophrenia 1 and nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders. Mol. Cell. Neurosci. 25, 42-55 (2004).
50. Taya S, Shinoda T, Tsuboi D et al. DISC1 regulates the transport of the NUDEL/LIS1/14-13-3̇complex through kinesin-1. J. Neurosci. 27, 15-26 (2007).
51. Shinoda T, Taya S, Tsuboi D et al. DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. J. Neurosci. 27, 4-14 (2007).
52. Dwyer DS. Amino acid sequence homology between ligands and their receptors: potential identification of binding sites. Life Sci. 45, 421-429 (1989).
53. Craddock N, O'Donovan MC, Owen MJ. The genetics of schizophrenia and bipolar disorder: dissecting psychosis. J. Med. Genet. 42, 193-204 (2005).
54. James R, Adams RR, Christie S, Buchanan SR, Porteous DJ, Millar JK. Disrupted in schizophrenia 1 (DISC1) is a multicompartmentalized protein that predominantly localizes to mitochondria. Mol. Cell. Neurosci. 26, 112-122 (2004).
55. Millar JK, James R, Christie S, Porteous DJ. Disrupted in schizophrenia 1 (DISC1): subcellular targeting and induction of ring mitochondria. Mol. Cell. Neurosci. 30, 477-484 (2005).
56. Falls DL. Neuregulins: functions, forms and signaling strategies. Exp. Cell Res. 284, 14-30 (2003).
57. Stefansson H, Sigurdsson E, Steinthorsdottir V et al. Neuregulin 1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877-892 (2002).
58. Harrison PJ, Law AJ. Neuregulin 1 and schizophrenia: genetics, gene expression and neurobiology. Biol. Psychiatry 60, 132-140 (2006).
59. Ma L, Huang YZ, Pitcher GM et al. Ligand-dependent recruitment of the ErbB4 signaling complex into neuronal lipid rafts. J. Neurosci. 23, 3164-3175 (2003).
60. Corfas G, Roy K, Buxbaum JD. Neuregulin 1-ErbB signaling and the molecular/cellular basis of schizophrenia. Nat. Neurosci. 7, 575-580 (2004).
61. Canto C, Pich S, Paz JC et al. Neuregulins increase mitochondrial oxidative capacity and insulin sensitivity in skeletal muscle cells. Diabetes 56, 2185-2193 (2007).
62. Suarez E, Bach D, Cadefau J, Palacin M, Zorzano A, Guma A. A novel role of neuregulin in skeletal muscle. Neuregulin stimulates glucose uptake, glucose transporter translocation, and transporter expression in muscle cells. J. Biol. Chem. 276, 18257-18264 (2001).
63. Canto C, Suarez E, Lizcano JM et al. Neuregulin signaling on glucose transport in muscle cells. J. Biol. Chem. 279, 12260-12268 (2004).
64. Kanakry CG, Li Z, Nakai Y, Sei Y, Weinberger DR. Neuregulin-1 regulates cell adhesion via an ErbB2/phosphoinositide-3 kinase/Akt-dependent pathway: potential implications for schizophrenia and cancer. PLoS ONE 2, E1369 (2007).
65. Downward J. The Grb2/Sem-5 adaptor protein. FEBS Lett. 338, 113-117 (1994).
66. Cardno AG, Holmans PA, Rees MI et al. A genomewide linkage study of age at onset in schizophrenia. Am. J. Med. Genet. 105, 439-445 (2001).
67. Crone SA, Lee K-F. Gene targeting reveals multiple essential functions of the neuregulin signaling system during development of the neuroendocrine and nervous systems. Ann. NY Acad. Sci. 971, 547-553 (2002).
68. Straub RE, Jiang Y, MacLean CJ et al. Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. Am. J. Hum. Genet. 71, 337-348 (2002).
69. Numakawa T, Yagasaki Y, Ishimoto T et al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum. Mol. Genet. 13, 2699-2708 (2004).
70. Benson MA, Newey SE, Martin-Rendon E, Hawkes R, Blake DJ. Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. J. Biol. Chem. 276, 24232-24241 (2001).
71. Talbot K, Cho D-S, Ong W-Y et al. Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin. Hum. Mol. Genet. 15, 3041-3054 (2006).
72. Wallis T, Bubb WA, McQuillan JA, Balcar VJ, Rae C. For want of a nail. Ramification of a single gene deletion, dystrophin, in the brain of the mouse. Front. Biosci. 9, 74-84 (2004).
73. Lai W-S, Xu B, Westphal KGC et al. Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning. Proc. Natl Acad. Sci. USA 103, 16906-16911 (2006).
74. Easton RM, Cho H, Roovers K et al. Role for Akt3/protein kinase Bγ in attainment of normal brain size. Mol. Cell. Biol. 25, 1869-1878 (2005).
75. Hajduch E, Litherland GJ, Hundal HS. Protein kinase B (PKB/Akt) - a key regulator of glucose transport? FEBS Lett. 492, 199-203 (2001).
76. Lawlor MA, Alessi DR. PKB/Akt: a key mediator of cell proliferation, survival and insulin responses? J. Cell Sci. 114, 2903-2910 (2001).
77. Plas DR, Thompson CB. Akt-dependent transformation: there is more to growth than just surviving. Oncogene 24, 7435-7442 (2005).
78. Dwyer DS, Lu X-H, Freeman AM III. Neuronal glucose metabolism and schizophrenia: therapeutic prospects? Expert Rev. Neurother. 3(1), 29-40 (2003).
79. Pozuelo Rubio M, Peggie M, Wong BH, Morrice N, MacKintosh C. 14-13-3s regulate fructose-2,6-bisphosphate levels by binding to PKB-phosphorylated cardiac fructose-2,6-bisphosphate kinase/phosphatase. EMBO J. 22, 3514-3523 (2003).
80. Zheng W-H, Kar S, Quirion R. Insulin-like growth factor-1-induced phosphorylation of the forkhead transcription factor FKHRL1 is mediated by Akt kinase in PC12 cells. J. Biol. Chem. 275, 39152-39158 (2000).
81. van der Heide LP, Hoekman MFM, Smidt MP. The ins and outs of Foxo shuttling: mechanisms of Foxo translocation and transcriptional regulation. Biochem. J. 380, 297-309 (2004).
82. Huang H, Tindall DJ. Dynamic FoxO transcription factors. J. Cell Sci. 120, 2479-2487 (2007).
83. Toyooka K, Muratake T, Tanaka T et al. 14-13-3 protein η chain gene (YWHAH) polymorphism and its genetic association with schizophrenia. Am. J. Med. Genet. 88, 164-167 (1999).
84. Wong AH, Macciardi F, Klempan T et al. Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-13-3η gene. Mol. Psychiatry 8, 156-166 (2003).
85. Hayakawa T, Ishiguro H, Toru M, Hamaguchi H, Arinami T. Systematic search for mutations in the 14-13-3 η chain gene on chromosome 22 in schizophrenics. Psychiatr. Genet. 8, 33-36 (1998).
86. Kaelin WG Jr. Proline hydroxylation and gene expression. Annu. Rev. Biochem. 74, 115-128 (2005).
87. Siddiq A, Aminova LR, Ratan RR. Prolyl 4-hydroxylase activity-responsive transcription factors: from hydroxylation to gene expression and neuroprotection. Front. Biosci. 13, 2875-2887 (2008).
88. Airley RE, Mobasheri A. Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy 53, 233-256 (2007).
89. Jiang BH, Liu LZ. AKT signaling in regulating angiogenesis. Curr. Cancer Drug Targets 8, 19-26 (2008).
90. Chowdari KV, Mimics K, Semwall P et al. Association and linkage of RGS4 polymorphisms in schizophrenia. Hum. Mol. Genet. 11, 1373-1380 (2002).
91. Chen X, Dunham C, Kendler S et al. Regulator of G-protein signaling 4 (RGS4) gene is associated with schizophrenia in Irish high density families. Am. J. Med. Genet. 129B, 23-26 (2004).
92. Sobell JL, Richard C, Wirshing DA, Heston LL. Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians. Am. J. Med. Genet. B Neuropsychiatr. Genet. 139, 23-27 (2005).
93. Ross EM, Wilkie TM. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu. Rev. Biochem. 69, 795-827 (2000).
94. + channel. Proc. Natl Acad. Sci. USA 99, 4325-4330 (2002).
95. Thaminy S, Auerbach D, Arnoldo A, Stagljar I. Identification of novel ErbB3-interacting factors using the split-ubiquitin membrane yeast two-hybrid system. Genome Res. 13, 1744-1753 (2003).
96. Abramow-Newerly M, Roy AA, Nunn C, Chidiac P. RGS proteins have a signaling complex: interactions between RGS proteins and GPCRs, effectors, and auxiliary proteins. Cell Signal. 18, 579-591 (2006).
97. Kanzaki M, Watson RT, Artemyev NO, Pessin JE. The trimeric GTP-binding protein (G(q)/JG(11)) α subunit is required for insulin-stimulated GLUT4 translocation in 3T3L1 adipocytes. J. Biol. Chem. 275, 7167-7175 (2000).
98. Shibasaki F, Hallin U, Uchino H. Calcineurin as a multifunctional regulator. J. Biochem. 131, 1-15 (2002).
99. Gerber DJ, Hall D, Miyakawa T et al. Evidence for association of schizophrenia with genetic variation in the 8p21.3 gene, PPP3CC, encoding the calcineurin γ subunit. Proc. Natl Acad. Sci. USA 100, 8993-8998 (2003).
100. Yamada K, Gerber DJ, Iwayama Y et al. Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Proc. Natl Acad. Sci. USA 104, 2815-2820 (2007).
101. Ni YG, Berenji K, Wang N et al. Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling. Circulation 114, 1159-1168 (2006).
102. Shioda N, Han F, Moriguchi S, Fukunaga K. Constitutively active calcineurin mediates delayed neuronal death through Fas-ligand expression via activation of NFAT and FKHR transcriptional activities in mouse brain ischemia. J. Neurochem. 102, 1506-1517 (2007).
103. Screaton RA, Congkright MD, Katoh Y et al. The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 119, 61-74 (2004).
104. Long YC, Glund S, Garcia-Roves PM, Zierath JR. Calcineurin regulates skeletal muscle metabolism via coordinated changes in gene expression. J. Biol. Chem. 282, 1607-1614 (2007).
105. Ryder JW, Bassel-Duby R, Olson EN, Zierath JR. Skeletal muscle reprogramming by activation of calcineurin improves insulin action on metabolic pathways. J. Biol. Chem. 278, 44298-44304 (2003).
106. Dougherty MK, Morrison DK. Unlocking the code of 14-13-3. J. Cell Sci. 117, 1875-1884 (2004).
107. Mackintosh C. Dynamic interactions between 14-13-3 proteins and phosphoproteins regulate diverse cellular processes. Biochem. J. 381, 329-342 (2004).
108. Li MV, Chen W, Poungvarin N, Imamura M, Chan L. Glucose-mediated transactivation of ChREBP requires cooperative actions from Mondo conserved regions and essential trans-acting factor 14-13-3. Mol. Endocrinol. 22 (7), 1658-1672 (2008).
109. Ramm G, Larance M, Guilhaus M, James DE. A role for 14-13-3 in insulin-stimulated GLUT4 translocation through its interaction with the RabGAP AS160. J. Biol. Chem. 281, 29174-29180 (2006).
110. Wang Y, Oh SW, Deplancke B, Luo J, Walhout AJM, Tissenbaum HA. C. elegans 14-13-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech. Ageing Dev. 127, 741-747 (2006).
111. Berdichevsky A, Viswanathan M, Horvitz HR, Guarente L. C. elegans SIR-2.1 interacts with 14-13-3 proteins to activate DAF-16 and extend life span. Cell 125, 1165-1177 (2006).
112. Li, J, Tewari M, Vidal M, Lee SS. The 14-13-3 protein FTT-2 regulates DAF-16 in Caenorhabditis elegans. Dev. Biol. 301, 82-91 (2007).
113. Furuyama T, Kitayama K, Yamashita H, Mori N. Forkhead transcription factor FOXO1 (FKHR)-dependent induction of PDK4 gene expression in skeletal muscle during energy deprivation. Biochem. J. 375, 365-371 (2003).
114. Emerling BM, Weinberg F, Liu J-L, Mak TW, Chandel NS. PTEN regulates p300-dependent hypoxia-inducible factor 1 transciptional activity through Forkhead transcription factor 3a (FOXO3a). Proc. Natl Acad. Sci. USA 105, 2622-2627 (2008).
115. Bakker WJ, Harris IS, Mak TW. FOXO3a is activated in response to hypoxic stress and inhibits HIF-1-induced apoptosis via regulation of CITED2. Mol. Cell 28, 941-953 (2007).
116. Greer EL, Oskoui PR, Banko MR et al. The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor. J. Biol. Chem. 282, 30107-30119 (2007).
117. Thong FS, Bilan PJ, Klip A. The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic. Diabetes 56, 414-423 (2007).
118. Estevez AO, Cowie RH, Gardner KL, Estevez M. Both insulin and calcium channel signaling are required for developmental regulation of serotonin synthesis in the chemosensory ADF neurons of Caenorhabditis elegans. Dev. Biol. 298, 32-44 (2006).
119. Ferri AL, Lin W, Mavromatakis YE, Sasaki H, Whitsett JA, Ang S-L. Foxa1 and Foxa2 regulate multiple phases of midbrain dopaminergic neuron development in a dosage-dependent manner. Development 134, 2761-2769 (2007).
120. Lu X-H, Dwyer DS. Second-generation antipsychotic drugs, olanzapine, quetiapine and clozapine enhance neurite outgrowth in PC12 cells via PI3K/Akt, ERK, and pertussis toxin-sensitive pathways. J. Mol. Neurosci. 27, 43-64 (2005).
121. Ross, CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT. Neurobiology of schizophrenia. Neuron 52, 139-153 (2006).
122. Sletten I, Mou B, Cazenave M, Gershon S. Effects of caloric restriction on behavior and body weight during chlorpromazine therapy. Dis. Nerv. System 28, 519-522 (1967).
123. Plum L, Schubert M, Bruning JC. The role of insulin receptor signaling in the brain. Trends Endocrinol. Metab. 16, 59-65 (2005).
124. Davila D, Piriz J, Trejo JL, Nunez A, Torres-Aleman I. Insulin and insulin-like growth factor I signaling in neurons. Front. Biosci. 12, 3194-3202 (2007).
125. Gerozissis K. Brain insulin, energy and glucose homeostasis: genes, environment and metabolic pathologies. Eur. J. Pharmacol. 585, 38-49 (2008).
126. Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol. 3, 169-178 (2004).
127. Craft S, Asthana S, Newcomer J W et al. Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose. Arch. Gen. Psychiatry 56, 1135-1140 (1999).
128. Fucetola R, Newcomer JW, Craft S, Melson AK. Age- and dose-dependent glucose-induced increases in memory and attention in schizophrenia. Psychiatry Res. 88, 1-13 (1999).
129. Mukherjee S, Schnur DB, Reddy R. Family history of Type 2 diabetes in schizophrenic patients. Lancet 1(8636), 495, (1989).
130. Jacobson AM, Sampson JA, Weinger K, Ryan CM. Diabetes, the brain, and behavior: is there a biological mechanism underlying the association between diabetes and depression? Int. Rev. Neurobiol. 51, 455-479 (2002).
131. Holden RJ. The role of brain insulin in the neurophysiology of serious mental disorders: review. Med. Hypotheses 52, 193-200 (1999).
132. Zhao Z, Ksiezak-Reding H, Riggio S, Hartounian V, Pasinetti GM. Insulin receptor deficits in schizophrenia and in cellular and animal models of insulin receptor dysfunction. Schizophr. Res. 84, 1-14 (2006).
133. Lovestone S, Killick R, Di Forti M, Murray R. Schizophrenia as a GSK-3 dysregulation disorder. Trends Neurosci. 30, 142-149 (2007).
134. Girgis RR, Javitch JA, Lieberman JA. Antipsychotic drug mechanisms: links between therapeutic effects, metabolic side effects and the insulin signaling pathway. Mol. Psychiatry 13, 918-929 (2008).
135. Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am. J. Psychiatry 148, 1301-1308 (1991).
136. Steinpreis RE. The behavioral and neurochemical effects of phencyclidine in humans and animals: some implications for modeling psychosis. Behav. Brain Res. 74, 45-55 (1996).
137. Tripathi A, Panzer MJ. Cyclosporine psychosis. Psychosomatics 34, 101-102 (1993).
138. Corruble E, Buhl C, Esposito D et al. Psychosis associated with elevated trough tacrolimus blood concentrations after combined kidney-pancreas transplant. Int. J. Neuropsychopharmacol. 9, 493-494 (2006).
139. Lewis DA, Smijst RE. Steroid-induced psychiatric syndromes. A report of 14 cases and a review of the literature. J. Affect. Disord. 5, 319-332 (1983).
140. Yanovski JA, Cutler GB Jr. Glucocorticoid action and the clinical features of Cushing's syndrome. Endocrinol. Metab. Clin. North Am. 23, 487-509 (1994).
141. Volgi JR, Baldwin D Jr. Glucocorticoid therapy and diabetes management. Nurs. Clin. North Am. 36, 333-339 (2001).
142. Horner HC, Packan DR, Sapolsky RM. Glucocorticoids inhibit glucose transport in cultured hippocampal neurons and glia. Neuroendocrinology 52, 57-64 (1990).
143. Schuur ER, Loktev AV, Sharma M, Sun Z, Roth RA, Weigel RJ. Ligand-dependent interaction of estrogen receptor-α with members of the forkhead transcription factor family. J. Biol. Chem. 276, 33554-33560 (2001).
144. Leong ML, Maiyar AC, Kim B, O'Keeffe BA, Firestone GL. Expression of the serum- and glucocorticoid-inducible protein kinase, Sgk, is a cell survival response to multiple types of environmental stress stimuli in mammary epithelial cells. J. Biol. Chem. 278, 5871-5882 (2003).
145. Guha M, Srinivasan S, Biswas G, Avadhani NG. Activation of a novel calcineurin-mediated insulin-like growth factor-1 receptor pathway, altered metabolism, and tumor cell invasion in cells subjected to mitochondrial respiratory stress. J. Biol. Chem. 282, 14536-14546 (2007).
146. Wastling JM, Chappell LH. Cyclosporin A: drug treatment in vivo affects the kinetics of [14C] glucose transport in Hymenolepis microstoma in vitro. Parasitology 108, 223-228 (1994).
147. Lei G, Xia Y, Johnson KM. The role of Akt-GSK-3β signaling and synaptic strength in phencyclidine-induced neurodegeneration. Neuropsychopharmacology 33, 1343-1353 (2008).
148. Min SK, A brain syndrome associated with delayed neuropsychiatric sequelae following acute carbon monoxide intoxication. Acta Psychiatr. Scand. 73, 80-86 (1986).
149. Pelclova D, Lukas E, Urban P et al. Mercury intoxication from skin ointment containing mercuric ammonium chloride. Int. Arch. Occup. Environ. Health 75(Suppl.), S54-S59 (2002).
150. Marchbanks RM, Mulcrone J, Whatley SA. Aspects of oxidative metabolism in schizophrenia. Br. J. Psychiatry 167, 293-298 (1995).
151. Blass JP. Glucose/mitochondria in neurological conditions. Int. Rev. Neurobiol. 51, 325-376 (2002).
152. Mauer I, Zierz S, Moller H. Evidence for a mitochondrial oxidative phosphorylation defect in brains from patients with schizophrenia. Schizophr. Res. 48, 125-136 (2001).
153. McDermott E, de Silva P. Impaired neuronal glucose uptake in pathogenesis of schizophrenia - can GLUT1 and GLUT3 deficits explain imaging, post-mortem and pharmacologic findings? Med. Hypotheses 65, 1076-1081 (2005).
154. Markus A, Zhong J, Snider WD. Raf and Akt mediate distinct aspects of sensory axon growth. Neuron 35, 65-76 (2002).
155. Dwyer DS, Dickson A. Neuroprotection and enhancement of neurite outgrowth with small molecular weight compounds from screens of chemical libraries. Int. Rev. Neurobiol. 77, 247-289 (2007).
156. Greer EL, Brunet A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24, 7410-7425 (2005).
157. Henderson ST, Johnson TE. daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr. Biol. 11, 1975-1980 (2001).
158. Schwartz MW, Woods SC, Seeley RJ, Barsh GS, Naskin DG, Leibel RL. Is the energy homeostasis system inherently biased toward weight gain? Diabetes 52, 232-238 (2003).
159. Neel JV. Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? Am. J. Hum. Genet. 14, 363-362 (1962).
160. Wakade CG, Mahadik SP, Waller JL, Chiu FC. Atypical neuroleptics stimulate neurogenesis in adult rat brain. J. Neurosci. Res. 69, 72-79 (2002).
161. Wang HD, Dunnavant FD, Jarman T, Deutch AY. Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 29, 1230-1238 (2004).
162. Bai O, Wei Z, Lu W, Bowen R, Keegan D, Li X-M. Protective effects of atypical antipsychotic drugs on PC12 cells after serum withdrawal. J. Neurosci. Res. 69, 278-283 (2002).
163. Dwyer DS, Lu X-H, Bradley RJ. Cytotoxicity of conventional and atypical antipsychotic drugs in relation to glucose metabolism. Brain Res. 971, 31-39 (2003).
164. Lu X-H, Bradley RJ, Dwyer DS. Olanzapine produces trophic effects in vitro and stimulates phosphorylation of Akt/PKB, ERK1/2, and the mitogen-activated protein kinase p38. Brain Res. 1011, 58-68 (2004).
165. Lieberman JA, Tollefson GD, Charles C et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch. Gen. Psychiatry 62, 361-370 (2005).
166. Molina V, Sanz J, Benito C, Palomo T. Direct association between orbitofrontal atrophy and the response of psychotic symptoms to olanzapine in schizophrenia. Int. Clin. Psychopharmacol. 19, 221-228 (2004).
167. Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 14, 381-395 (2002).
168. Summers SA, Birnbaum MJ. A role for the serine/threonine kinase, Akt, in insulin-stimulated glucose uptake. Biochem. Soc. Trans. 25, 981-988 (1997).
169. Gonzalez-Robayna IJ, Falender AE, Ochsner S, Firestone GL, Richards JS. Follicle-stimulating hormone (FSH) stimulates phosphorylation and activation of protein kinase B (PKB/Akt) and serum and glucocorticoid-induced kinase (Sgk): evidence for A kinase-independent signaling by FSH in granulosa cells. Mol. Endocrinol. 14, 1283-1300 (2000).
170. Communal C, Colucci WS. The control of cardiomyocyte apoptosis via the β-adrenergic signaling pathways. Arch. Mal. Coeur Vaiss. 98, 236-241 (2005).
171. Hagelüken A, Grünbaum L, Nürnberg B, Harhammer R, Schunack W, Seifert R. Lipophilic β-adrenoceptor antagonists and local anesthetics are effective direct activators of G-proteins. Biochem. Pharmacol. 47, 1789-1795 (1994).
172. Odagaki Y, Nishi N, Koyama T. Receptor-mediated and receptor-independent activation of G-proteins in rat brain membranes. Life Sci. 62, 1537-1541 (1998).
173. Lopez-Ilasaca M. Signaling from G-protein-coupled receptors to mitogen-activated protein (MAP)-kinase cascades. Biochem. Pharmacol. 56, 269-277 (1998).
174. Venkatasubramanian G, Chittiprol S, Neelakantachar N et al. Insulin and insulin-like growth factor-1 abnormalities in antipsychotic-naive schizophrenia. Am. J. Psychiatry 164, 1557-1560 (2007).
175. Ward CW, Garrett TPJ, McKern NM et al. The three dimensional structure of the type I insulin-like growth factor receptor. Mol. Pathol. 54, 125-132 (2001).
176. Butcher EC, Berg EL, Kunkel EJ. Systems biology in drug discovery. Nature Biotechnol. 22, 1253-1259 (2004).
177. Csernansky JG. Neurodegeneration in schizophrenia: evidence from in vivo neuroimaging studies. Scientific World J. 7, 135-143 (2007).
178. Woods BT. Is schizophrenia a progressive neurodevelopmental disorder: toward a unitary pathogenic mechanisms. Am. J. Psychiatry 155, 1657-1659 (1998).
179. de Haan L, Bakker JM. Overview of neuropathological theories of schizophrenia: from degeneration to progressive developmental disorder. Psychopathology 37, 1-7 (2004).
180. Hills T, Brockie PJ, Maricq AV. Dopamine and glutamate control area-restricted search behavior in Caenorhabditis elegans. J. Neurosci. 24, 1217-1225 (2004).
181. Wakabayashi T, Osada T, Shingai R. Serotonin deficiency shortens the duration of forward movement in Caenorhabditis elegans. Biosci. Biotechnol. Biochem. 69, 1767-1770 (2005).
182. Donohoe DR, Phan T, Weeks K, Aamodt E, Dwyer DS. Antipsychotic drugs up-regulate tryptophan hydroxylase in ADF neurons of Caenorhabditis elegans: role of calcium-calmodulin-dependent protein kinase II and transient receptor potential vanilloid channel. J. Neurosci. Res. 86, 2553-2563 (2008).
183. Hamdan FF, Ungrin MD, Abramovitz M, Ribiero P. Characterization of a novel serotonin receptor from Caenorhabditis elegans: cloning and expression of two splice variants. J. Neurochem. 72, 1372-1383 (1999).
184. Suo S, Ishiura S, Van Tol HHM. Dopamine receptors in C. elegans. Eur. J. Pharmacol. 500, 159-166 (2004).
185. Donohoe DR, Aamodt EJ, Osborn E, Dwyer DS. Antipsychotic drugs disrupt normal development in Caenorhabditis elegans via additional mechanisms besides dopamine and serotonin receptors. Pharmacol Res. 54, 361-372 (2006).