Neurotoxicity Research

, Volume 18, Issue 3–4, pp 211–228 | Cite as

Clinical Staging in the Pathophysiology of Psychotic and Affective Disorders: Facilitation of Prognosis and Treatment

  • Trevor Archer
  • Richard M. Kostrzewa
  • Tomas Palomo
  • Richard J. Beninger
Article

Abstract

The prevailing utility, and indeed necessity, of clinical staging models applied in considerations of neuropsychiatric disease progressions is discussed from the perspectives of schizophrenia spectrum disorders and affective disorders, cannabis in schizopsychotic disorder, incidences of affect and psychosis, staging disorders in aging and the indices and prevalence of apathy. There would appear to be a strong current consensus that the pursuit of clinical staging of these and other brain disease states has contributed a systematic conceptual instrument to facilitate the better understanding, diagnosis, prognosis and treatment as derived from a multitude of genetic predispositions, symptoms and syndromes, early-onset and prodromal phases, recurrences and relapses, that have complicated the situation of the patient. Through a staging determination of the disorder, elements of diagnosis will describe the progression of symptoms/syndromes through pre-onset, prodromal, first-episode, recurrences and relapses, and treatment resistance thereby facilitating the eventual prognosis, intervention alternatives and treatment. This approach varies from observations of individuals at early stages of development (infancy, childhood, adolescece) to early middle age, in the case of diseases expressed through the aging processes. Essentially, the major contribution of the staging model may lie in the early identification, diagnosis, and treatments of disorders that afflict the brain and central nervous system.

Keywords

Staging Schizophrenia affective disorders Diagnosis Prognosis Treatment Progression Comorbidity Aging Apathy 

References

  1. Addington J, Addington D (2007) Patterns, predictors, and impact of substance use in early psychosis: a longitudinal study. Acta Psychiatr Scand 115:304–309PubMedCrossRefGoogle Scholar
  2. Addington J, Cadenhead KS, Cannon TD, Cornblatt B, McGlashan TH, Perkins DO, Seidman LJ, Tsuang M, Walker EF, Woods SW, Heinssen R, North American Prodrome Longitudinal Study (2007) North American Prodrome Longitudinal Study: a collaborative multisite approach to prodromal schizophrenia research. Schizophr Bull 33:665–672PubMedCrossRefGoogle Scholar
  3. Alexopoulos GS, Meyers BS, Young RC, Kalayam B, Kakuma T, Gabrielle M, Sirey JA, Hull J (2000) Executive dysfunction and long-term outcomes of geriatric depression. Arch Gen Psychiatr 57:285–290PubMedCrossRefGoogle Scholar
  4. Allen P, Seal ML, Valli I, Fusar-Poli P, Perlini C, Day F, Wood SJ, Williams SC, McGuire PK (2009) Altered prefrontal and hippocampal function during verbal encoding and recognition in people with prodromal symptoms of psychosis. Schizophr Bull. PMID:19933712Google Scholar
  5. Almond S, Knapp M, Francois C, Toumi M, Brugha T (2004) Relapse in schizophrenia: costs, clinical outcomes and quality of life. Br J Psychiatr 184:346–351CrossRefGoogle Scholar
  6. Alvarez-Jiménez M, Gleeson JF, Cotton SM, Wade D, Crisp K, Yap MB, McGorry PD (2008) Differential predictors of critical comments and emotional over-involvement in first-episode psychosis. Psychol Med 15:1–10Google Scholar
  7. Alvarez-Jiménez M, Parker AG, Hetrick SE, McGorry PD and Gleeson JF (2009a) Preventing the second episode: a systematic review and meta-analysis of psychosocial and pharmacological trials in first-episode psychosis. Schizophr Bull (in press). PMID:19900962Google Scholar
  8. Alvarez-Jiménez M, Gleeson JF, Cotton S, Wade D, Gee D, Pearce T, Crisp K, Spiliotacopoulos D, Newman B, McGorry PD (2009b) Predictors of adherence to cognitive-behavioural therapy in first-episode psychosis. Can J Psychiatry 54(10):710–718PubMedGoogle Scholar
  9. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4th edn. Washington DCGoogle Scholar
  10. Andersson S, Barder HE, Hellvin T, Lövdahl H, Malt UF (2008) Neuropsychological and electrophysiological indices of neurocognition in bipolar II disorder. Bipolar Disord 10:888–899PubMedCrossRefGoogle Scholar
  11. Andreazza AC, Kapczinski F, Kauer-Sant’Anna M, Walz JC, Bond DJ, Goncales CA, Young LT, Yatham LN (2009) 3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder. Neuroscience 34:263–271Google Scholar
  12. Archer T, Adolphsson B, Karlsson E (2008) Affective personality as cognitive-emotional presymptom profiles regulatory for self-reported health predispositions. Neurotox Res 14:21–44PubMedCrossRefGoogle Scholar
  13. Aronson MK, Wee LO, Dalia LG, Masur D, Blau A, Frishman W (1991) Dementia: age-dependent incidence, prevalence, and mortality in the old old. Arch Intern Med 151:989–992PubMedCrossRefGoogle Scholar
  14. Arranz MJ, Collier D, Sodhi M, Ball D, Roberts G, Price J, Sham P, Kerwin R (1995) Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet 346:281–282PubMedCrossRefGoogle Scholar
  15. Arranz MJ, Munro J, Owen MJ, Spurlock G, Sham PC, Zhao J, Kirov G, Collier DA, Kerwin RW (1998) Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine. Mol Psychiatr 3:61–66CrossRefGoogle Scholar
  16. Arseneault L, Cannon M, Witton J, Murray RM (2004) Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatr 184:110–117CrossRefGoogle Scholar
  17. Benazzi F (2007) Bipolar disorder-focus on bipolar II disorder and mixed depression. Lancet 369:935–945PubMedCrossRefGoogle Scholar
  18. Bender S, Weisbrod M, Resch F (2007) Which perspectives can endophenotypes and biological markers offer in the early recognition of schizophrenia. J Neural Transm 114:1199–1215PubMedCrossRefGoogle Scholar
  19. Berg S (1996) Aging, behavior and terminal illness. In: Brirren JE, Schale KW (eds) Handbook of the psychology of aging, 34th edn. Academic Press, New York, pp 181–197Google Scholar
  20. Berk M, Hallam KT, McGorry PD (2007) The potential utility of a staging model as a course specifier: a bipolar disorder perspective. J Affect Disord 100:279–281PubMedCrossRefGoogle Scholar
  21. Berk M, Malhi GS, Hallam KT, Gama CS, Dodd S, Andreazza AC, Frey BN, Kapczinski F (2009) Early intervention in bipolar disorders: clinical, biochemical and neuroimaging imperatives. J Affect Disorder 114:1–13CrossRefGoogle Scholar
  22. Bersani G, Orlandi V, Kotzalidis GD, Pancheri P (2002) Cannabis and schizophrenia: impact on onset, course, psychopathology, and outcomes. Eur Arch Psychiatr Clin Neurosci 252:86–92CrossRefGoogle Scholar
  23. Bertelsen M, Jeppesen P, Petersen L, Thorup A, Ohlenschlaeger J, le Quach P, Christensen TO, Krarup G, Jorgensen P, Nordentoft M (2008) Five-year follow-up of a randomized multicenter trial of intensive early intervention vs standard treatment for patients with a first episode of psychotic illness: the OPUS trial. Arch Gen Psychiatry 65:762–771PubMedCrossRefGoogle Scholar
  24. Bertelsen M, Jeppesen P, Petersen L, Thorup A, Øhlenschlaeger J, Le Quach P, Østergaard Christensen T, Krarup G, Jørgensen P, Nordentoft M (2009) Course of illness in a sample of 265 patients with first-episode psychosis-five-year follow-up of the Danish OPUS trial. Schizophr Res 107:173–178PubMedCrossRefGoogle Scholar
  25. Bhattacharyya S, Crippa JA, Martin-Santos R, Winton-Brown T, Fusar-Poli P (2009) Imaging the neural effects of cannabinoids: current status and future opportunities for psychopharmacology. Curr Pharm Des 15:2603–2614PubMedCrossRefGoogle Scholar
  26. Birchwood M, Todd P, Jackson C (1998) Early intervention in psychosis. The critical period hypothesis. Brit J Psychiatr [Suppl.] 172:53–59CrossRefGoogle Scholar
  27. Bonaccorso S, Lin AH, Verkerk R, Van Hunsel F, Libbrecht I, Scharpe S, DeClerck L, Biondi M, Janca A, Maes M (1998) Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers. J Affect Disord 48:75–82PubMedCrossRefGoogle Scholar
  28. Bonnin CM, Martinez-Aran A, Torrent C, Pacchiarotti I, Rosa AR, Franco C, Murru A, Sanchez-Moreno J, Vieta E (2010) Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: a long-term follow-up study. J Affect Disord 121:156–160PubMedCrossRefGoogle Scholar
  29. Bonn-Miller M, Zvolensky M, Bernstein A (2007) Marijuana use motives: concurrent relations to frequency of past 30-day use and anxiety sensitivity among young adult marijuana smokers. Addict Behav 32:49–62PubMedCrossRefGoogle Scholar
  30. Borgwardt SJ, Riecher-Rössler A, Dazzan P, Chitnis X, Aston J, Drewe M, Gschwandtner U, Haller S, Pflüger M, Rechsteiner E, D’Souza M, Stieglitz RD, Radü EW, McGuire PK (2007) Regional gray matter volume abnormalities in the at risk mental state. Biol Psychiatr 61:1148–1156CrossRefGoogle Scholar
  31. Borgwardt SJ, McGuire PK, Aston J, Gschwandtner U, Pflüger M, Stieglitz RD, Radü EW, Riecher-Rössler A (2008) Reductions in frontal lobe and parietal volume associated with the onset of psychosis. Schizophr Res 106:108–114PubMedCrossRefGoogle Scholar
  32. Bosanac P, Patton GC, Castle DJ (2010) Early intervention in psychotic disorders: faith before facts? Psychol Med 40:353–358PubMedCrossRefGoogle Scholar
  33. Boter H, Derks EM, Fleischhacker WW, Davidson M, Kahn RS, for the EUFEST Study Group (2010) Generalizability of the results of efficacy trials in first-episode schizophrenia: comparisons between subgroups of participants of the European First Episode Schizophrenia Trial (EUFEST). J Clin Psychiatry 71:58–65Google Scholar
  34. Boter H, Peuskens J, Libiger J, Fleischhacker WW, Davidson M, Galderisi S, Kahn RS, EUFEST study group (2009) Effectiveness of antipsychotics in first-episode schizophrenia and schizophreniform disorder on response and remission: an open randomized clinical trial (EUFEST). Schizophr Res 115:97–103PubMedCrossRefGoogle Scholar
  35. Braida D, Liminta V, Malabarba L, Zani A, Sala M (2007) 5-HT(1A) receptors are involved in the anxiolytic effect of delta(9)-tetrahydrocannabinol and AM404, the anandamide transport inhibitor, in Sprague–Dawley rats. Eur J Pharmacol 555:156–163PubMedCrossRefGoogle Scholar
  36. Brewer WJ, Francey SM, Wood SJ, Jackson HJ, Pantelis C, Phillips LJ, Yung AR, Anderson VA, McGorry (2005) Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis. Am J Psychiatr 162:71–78PubMedCrossRefGoogle Scholar
  37. Broome MR, Matthiasson P, Fusar-Poli P, Woolley JB, Johns LC, Tabraham P, Bramon E, Valmaggia L, Williams SC, Brammer MJ, Chitnis X, McGuire PK (2010) Neural correlates of movement generation in the ‘at-risk mental state’. Acta Psychiatr Scand. PMID:20064129Google Scholar
  38. Burnet PW, Harrison PJ (1995) Genetic variation of the 5-HT2A receptor and response to clozapine. Lancet 346:909PubMedCrossRefGoogle Scholar
  39. Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U, Weiner DM, Brann MR (2005) Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther 315:1278–1287PubMedCrossRefGoogle Scholar
  40. Cannon TD, Cadenhead K, Cornblatt B, Woods SW, Addington J, Walker E, Seidman LJ, Perkins D, Tsuang M, McGlashan T, Heinssen R (2008) Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Arch Gen Psychiat 65:28–37PubMedCrossRefGoogle Scholar
  41. Capuron L, Su S, Miller AH, Bremner JD, Goldberg J, Vogt GJ, Maisano C, Jones L, Murrah NV, Vaccarino V (2009) Depressive symptoms and metabolic syndrome: is inflammation the underlying link? Biol Psychiatry 64:896–900CrossRefGoogle Scholar
  42. Carbone S, Harrigan S, McGorry PD, Curry C, Elkins K (1999) Duration of untreated psychosis and 12-month outcome in first-episode psychosis: the impact of treatment approach. Acta Psychiatr Scand 100:96–104PubMedCrossRefGoogle Scholar
  43. Carlson GA, Findling RL, Post RM, Birmaher B, Blumberg HP, Correll C, DelBello MP, Fristad M, Frazier J, Hammen C, Hinshaw SP, Kowatch R, Leibenluft E, Meyer SE, Pavuluri MN, Wagner KD, Tohen M (2009) AACAP 2006 Research Forum-Advancing research in early-onset bipolar disorder: barriers and suggestions. J Child Adolesc Psychopharmacol 19:3–12PubMedCrossRefGoogle Scholar
  44. Carpenter WT, Bustillo JR, Thaker GK, van Os J, Krueger RF, Green MJ (2009) The psychoses: cluster 3 of the proposed meta-structure for DSM-V and ICD-11. Psychol Med 39:2025–2042PubMedCrossRefGoogle Scholar
  45. Cassens G, Wolfe L, Zola M (1990) Neuropsychology of depression. J Neuropsychiatry Clin Neurosci 2:202–213PubMedGoogle Scholar
  46. Chan RC, Wang Y, Cheung EF, Cui J, Deng Y, Yuan Y, Ma Z, Yu X, Li Z, Gong Q (2009) Sustained attention deficit along the psychosis proneness continuum: a study on the Sustained Attention to Response Task (SART). Cogn Behav Neurol 22:180–185PubMedCrossRefGoogle Scholar
  47. Chase TN (2010) Apathy in neuropsychiatric disease: diagnosis, pathophysiology and treatment. Neurotoxicity ResGoogle Scholar
  48. Chen SF, Shen YC, Chen CH (2009a) HTR2A A-1438G/T102C polymorphisms predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients. Psychopharmacology 205:285–292PubMedCrossRefGoogle Scholar
  49. Chen SF, Shen YC, Chen CH (2009b) Effects of the DRD3 ser9Gly polymorphism on aripiprazole efficacy in schizophrenic patients as modified by clinical factors. Prog Neuropsychopharmacol Biol Psychiatr 33:470–474CrossRefGoogle Scholar
  50. Clarke DE, Reekum R, Simard M, Streiner DL, Freedman M, Conn D (2007) Apathy in dementia: an examination of the psychometric properties of the apathy evaluation scale. J Neuropsychiatry Clin Neurosci 19:57–64PubMedGoogle Scholar
  51. Clerici M, Arosio B, Mundo E, Cattaneo E, Pozzoli S, Dell’osso B, Vergani C, Trabattoni D, Altamura AC (2009) Cytokine polymorphisms in the pathophysiology of mood disorders. CNS Spectr 14:419–425PubMedGoogle Scholar
  52. Colom F, Vieta E (2009) The road to DSM-V: bipolar disorder episode and course specifiers. Psychopathology 42:209–218PubMedCrossRefGoogle Scholar
  53. Colom F, Vieta E, Sánchez-Moreno J, Palomino-Otiniano R, Reinares M, Goikolea JM, Benabarre A, Martínez-Arán A (2009) Group psychoeducation for stabilised bipolar disorders: 5-year outcome of a randomised clinical trial. Br J Psychiatry 194:260–265PubMedCrossRefGoogle Scholar
  54. Compton MT, Furman AC, Kaslow NJ (2004) Lower negative symptom scores among cannabis-dependent patients with schizophrenia spectrum disorders: preliminary evidence from an African-American first-episode sample. Schizophr Res 71:61–64PubMedCrossRefGoogle Scholar
  55. Compton MT, Kelley ME, Ramsay CE, Pringle M, Goulding SM, Esterberg ML, Stewart T, Walker EF (2009) Association of pre-onset cannabis, alcohol, and tobacco use with at onset of prodromal and age at onset of psychosis in first-episode patients. Am J Psychiatr 166:1251–1257PubMedCrossRefGoogle Scholar
  56. Conus P, Berk M, McGorry PD (2006) Pharmacological treatment in the early phase of bipolar disorders: what stage are we at? Aust NZ J Psychiatr 40:199–207Google Scholar
  57. Crespo-Facorro B, Perez-Iglesias R, Ramirez-Bonilla M, Martinez-Garcia O, Llorca J, Vazquez-Barquero JL (2006) A practical clinical trial comparing haloperidol, risperidone, and olanzapine for the acute treatment of first-episode nonaffective psychosis. J Clin Psychiatr 67:1511–1521CrossRefGoogle Scholar
  58. Crespo-Facorro B, Arranz MJ, Mata I, Vazquez-Bourgon J, Perez-Iglesias R, Medina-Gonzalez L, Pelayo-Teran JM, Carrasco-Marin E, Vazquez-Barquero JL (2010, in press) 5-HT2A polymorphisms and negative symptoms response to antipsychotic treatment: evidence of association in first episode psychosis patients. Neurotoxicity ResGoogle Scholar
  59. Crippa JA, Zuardi AW, Martin-Santos R, Bhattacharyya S, Atakan Z, McGuire P, Fusar-Poli P (2009) Cannabis and anxiety: a critical review of the evidence. Hum Psychopharmacol 24:515–523PubMedCrossRefGoogle Scholar
  60. Crossley NA, Mechelli A, Fusar-Poli P, Broome MR, Matthiasson P, Johns LC, Bramon E, Valmaggia L, Williams SCR, McGuire PK (2009) Superior temporal lobe dysfunction and frontotemporal dysconnectivity in subjects at risk of psychosis and first-episode psychosis. Hum Brain Mapp 30:4129–4137PubMedCrossRefGoogle Scholar
  61. Csikszentmihalyi M (2000) Happiness, flow, and economic equality. Am Psychol 55:1163–1164PubMedCrossRefGoogle Scholar
  62. Cullberg J, Levander S, Holmqvist R, Mattsson M, Weiselgren IM (2002) One-year outcome in first episode psychosis patients in the Swedish Parachute project. Acta Psychiatr Scand 106:276–285PubMedCrossRefGoogle Scholar
  63. Cunha AB, Frey BN, Andreazza AC, Goi JD, Rosa AR, Goncales CA, Santin A, Kapczinski F (2006) Serum brain derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes. Neurosci Lett 398:215–219PubMedCrossRefGoogle Scholar
  64. Cunha AB, Andreazza AC, Gomes FA, Frey BN, da Silveira LE, Goncales CA, Kapczinski F (2008) Investigation of serum high-sensitive C-reactive protein levels across all mood states in bipolar disorder. Eur Arch Psychiatr Clin Neurosci 258:300–304CrossRefGoogle Scholar
  65. Daffner KR, Mesulam MM, Cohen LG (1999) Mechanisms underlying diminished novelty-seeking behavior in patients with probable Alzheimer’s disease. Neurocase 12:58–66Google Scholar
  66. Dannon P, Lowengrub K, Amiaz R, Grunhaus l, Kotler M (2004) Comorbid cannabis use and panic disorder: short term and long term follow-up study. Hum Psychopharmacol 19:97–101PubMedCrossRefGoogle Scholar
  67. Dinu IR, Popa S, Bîcu M, Moţa E, Moţa M (2009) The implication of CNR1 gene’s polymorphisms in the modulation of endocannabinoid system effects. Rom J Intern Med 47:9–18PubMedGoogle Scholar
  68. Drijgers RL, Aalten P, Winogrodzzka A, Verhey FR, Leentjens AF (2009) Pharmacological treatment of apathy in neurodegenerative diseases: a systematic review. Dement Geriatr Cogn Disorder 28:13–22CrossRefGoogle Scholar
  69. Duffy A, Alda M, Hajek T, Sherry SB, Grof P (2010) Early stages in the development of bipolar disorder. J Affect Disord 121:127–135PubMedCrossRefGoogle Scholar
  70. Dunbar PR, Hill J, Neale TJ, Mellsop GW (1992) Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia. Psychol Med 22:1051–1057PubMedCrossRefGoogle Scholar
  71. Eagles JM, Beattie JAG, Restall DB, Rawlinson F, Hagen S, Ashcroft GW (1990) Relation between cognitive impairment and early death in the elderly. Br Mad J 300:239–241CrossRefGoogle Scholar
  72. Eastvold AD, Heaton RK, Cadenhead KS (2007) Neurocognitive deficits in the (putative) prodrome and first episode of psychosis. Schizophr Res 93:266–277PubMedCrossRefGoogle Scholar
  73. Edvardsen J, Torgersen S, Roysamb E, Lygren S, Skre I, Onstad S, Oien PA (2008) Heritability of bipolar spectrum disorders: unity or heritability? J Affect Disord 106:229–240PubMedCrossRefGoogle Scholar
  74. Egeland J, Lund A, Landrö NI, Rund BR, Sundet K, Asbjørnsen A, Mjellem N, Roness A, Stordal KI (2005) Cortisol level predicts executive and memory function in depression, symptom level predicts psychmotor speed. Acta Psychiatr Scand 112:434–441PubMedCrossRefGoogle Scholar
  75. Eggan SM, Lewis DA (2007) Immunocytochemical distribution of the cannabinoid CB1 receptor in the primate neocortex: a regional and laminar analysis. Cereb Cort 17:175–191CrossRefGoogle Scholar
  76. Faerden A, Nesvåg R, Barrett EA, Agartz I, Finset A, Friis S, Rossberg JI, Melle I (2008) Assessing apathy: the use of the Apathy Evaluation Scale in first episode psychosis. Eur Psychiatr 23:33–39CrossRefGoogle Scholar
  77. Frommann I, Pukrop R, Brinkmeyer J, Bechdolf A, Ruhrmann S, Berning J, Decker P, Möller HJ, Wölwer W, Gaebel W, Klosterkötter J, Maier W, Wagner M (2010) Neuropsychological profiles in different at-risk states of psychosis: executive control impairment in the early—and additional memory dysfunction in the late—prodromal stateGoogle Scholar
  78. Frye MA, Helleman G, McElroy SL, Altshuler LL, Black DO, Keck PE Jr, Nolen WA, Kupka R, Leverich GS, Grunze H, Mintz J, Post RM, Suppes T (2009) Correlates of treatment-emergent mania associated with antidepressant treatment in bipolar depression. Am J Psychiatr 166:164–172PubMedCrossRefGoogle Scholar
  79. Fusar-Poli P, Byrne M, Valmaggia L, Day F, Tabraham P, Johns L, McGuire P, on behalf of the OASIS Team (2009b) Social dysfunction predicts two years clinical outcome in people at ultra high risk for psychosis. J Psychiatr Res. PMID:19836755Google Scholar
  80. Fusar-Poli P, Allen P, Bhattacharyya S, Crippa JA, Mechelli A, Borgwardt S, Martin-Santos R, Seal ML, O’Carrol C, Atakan Z, Zuardi AW, McGuire P (2009) Modulation of effective connectivity during emotional processing by Δ9-tetrahydrocannabinol and cannabinol. Int J Neuropsychopharmacol 24:1–12Google Scholar
  81. Fusar-Poli P, Howes OD, Allen P, Broome M, Valli I, Asselin MC, Montgomery AJ, Grasby PM, McGuire PK (2009a) Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis. Mol Psychiatr. PMID:19949389Google Scholar
  82. Galderisi S, Davidson M, Kahn RS, Mucci A, Boter H, Gheorghe MD, Rybakowski JK, Libiger J, Dollfus S, López-Ibor JJ, Peuskens J, Hranov LG, Fleischhacker WW, EUFEST group (2009) Correlates of cognitive impairment in first episode schizophrenia: the EUFEST study. Schizophr Res 115:104–114PubMedCrossRefGoogle Scholar
  83. Gardner H, Csikszentmihalyi M, Damon W (2002) Good work: when excellence and ethics meet. Basic Books, New YorkGoogle Scholar
  84. Gilder D, Lau P, Dixon M, Corey L, Phillips E, Ehlers C (2006) Comorbidity of select anxiety, affective, and psychotic disorders with cannabis dependence in southwest california indians. J Addict Dis 25:67–79PubMedCrossRefGoogle Scholar
  85. Gitlin M, Nuechterlein K, Subotnik KL, Ventura J, Mintz J, Fogelson DL, Bartzokis G, Aravagiri M (2001) Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia. Am J Psychiatr 158:1835–1842PubMedCrossRefGoogle Scholar
  86. Goulding SM, McClure-Tone E, Compton MT (2009) Associations between multiple dimensions of schizotypy and sociodemographic variables in a nonpsychiatric sample of young adults. J Nerv Ment Dis 197:786–789PubMedCrossRefGoogle Scholar
  87. Green B, Young R, Kavanagh D (2005) Cannabis use and misuse prevalence among people with psychosis. Br J Psychiatr 187:306–313CrossRefGoogle Scholar
  88. Häfner H (2000) Onset and early course as determinants of the further course of schizophrenia. Acta Psychiatr Scand 102(Suppl. 407):s44–s48CrossRefGoogle Scholar
  89. Häfner H, Maurer K, Löffler W, Riecher-Rössler A (1993) The influence of age and sex on the onset and early course of schizophrenia. Br J Psychiat 162:80–86CrossRefGoogle Scholar
  90. Häfner H, Maurer K, Löffler W, an der Heiden W, Hambrecht M, Schultze-Lutter F (2003) Modelling the early course of schizophrenia. Schizophr Bull 29:325–340PubMedGoogle Scholar
  91. Hambrecht M, Häfner H (2000) Cannabis, vulnerability, and the onset of schizophrenia: an epidemiological perspective. Austr NZ J Psychiatr 34:468–475Google Scholar
  92. Harrigan SM, McGorry PD, Krstev H (2003) Does treatment delay in first-episode psychosis really matter? Psychol Med 33:97–110PubMedCrossRefGoogle Scholar
  93. Harrison I, Joyce EM, Mutsatsa MH, Hutton SB, Huddy V, Kapasi M, Barnes TR (2008) Naturalistic follow-up of co-morbid substance use in schizophrenia: the West London first-episode study. Psychol Med 38:79–88PubMedCrossRefGoogle Scholar
  94. Hazelwood LA, Sanders-Bush E (2004) His452Tyr polymorphism in the human 5-HT2A receptor destabilizes the signaling conformation. Mol Pharmacol 66:1293–1300PubMedGoogle Scholar
  95. Herbert TB, Cohen S (1993) Stress and immunity in humans. Psychosom Med 55:364–379PubMedGoogle Scholar
  96. Hetrick SE, Parker AG, Hickie IB, Purcell R, Yung AR, McGorry PD (2008a) Early identification and intervention in depressive disorders: towards a clinical staging model. Psychother Psychosom 77:263–270PubMedCrossRefGoogle Scholar
  97. Hetrick SE, Simmons M, Merry S (2008b) SSRIs and depression in children and adolescents: the imperative for shared decision-making. Australia Psychiatr 16:354–358CrossRefGoogle Scholar
  98. Hollinghurst S, Kessler D, Peters TJ, Gunnell D (2005) Opportunity cost of antidepressant prescribing in England: analysis of routine data. BMJ 330:999–1000PubMedCrossRefGoogle Scholar
  99. Howes OD, Montgomery AJ, Asselin MC, Murray RM, Valli I, Tabraham P, Bramon-Bosch E, Valmaggia L, Johns L, Broome M, McGuire PK, Grasby PM (2009) Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Arch Gen Psychiatr 66:13–20PubMedCrossRefGoogle Scholar
  100. Hsieh CL, Bowcock AM, Farrer LA, Hebert JM, Huang KN, Cavalli-Sforza LL, Julius D, Francke U (1990) The serotonin subtype 2 locus HTR2 is on human chromosome 13 near genes for esterase D and retinoblastoma-1 and on mouse chromosome 14. Somat Cell Mol Genet 16:567–574PubMedCrossRefGoogle Scholar
  101. Hunsberger JG, Austin DR, Chen G, Manji HK (2009) Cellular mechanisms underlying affective resiliency: the role of glucocorticoid receptor- and mitochondrially-mediated plasticity. Brain Res 1293:76–84PubMedCrossRefGoogle Scholar
  102. Insel TR (2009) Translating scientific opportunity into public health impact: a strategic plan for research on mental illness. Arch Gen Psychiat 66:128–133PubMedCrossRefGoogle Scholar
  103. Irwin M (1999) Immune correlates of depression. Adv Exp Med Biol 461:1–24PubMedCrossRefGoogle Scholar
  104. Isacsson G, Boethius G, Henriksson S, Jones JK, Bergman U (1999) Selective serotonin reuptake inhibitors have broadened the utilization of antidepressant treatment in accordance with recommendations: findings from a Swedish database. Affect Disord 53:15–22CrossRefGoogle Scholar
  105. Isella V, Melzi P, Grimaldi M, Iurlaro S, Piolti R, Ferrarese C, Frattola L, Appollonio I (2002) Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson’s disease. Mov Disord 17:366–371PubMedCrossRefGoogle Scholar
  106. Isella V, Iurlaro S, Piolti R, Ferrarese C, Frattola L, Appollonio I (2003) Physical anhedonia in Parkinson’s disease. J Neurol Neurosurg Psychiatr 74:1308–1311PubMedCrossRefGoogle Scholar
  107. Johansson B, Zarit SH (1997) Early cognitive markers of the incidence of dementia and mortality: a longitudinal population-based study of the oldest old. Int J Ger Psychiatr 12:53–59CrossRefGoogle Scholar
  108. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, Gheorghe MD, Rybakowski JK, Galderisi S, Libiger J, Hummer M, Dollfus S, López-Ibor JJ, Hranov LG, Gaebel W, Peuskens J, Lindefors N, Riecher-Rössler A, Grobbee DE, the EUFEST study group (2008) Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371:1085–1097PubMedCrossRefGoogle Scholar
  109. Kapczinski F, Frey BN, Andreazza AC, Kauer-Sant’Anna M, Cunha AB, Post RM (2008a) Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes. Rev Bras Psiquiatr 30:243–245PubMedGoogle Scholar
  110. Kapczinski F, Vieta E, Andreazza AC, Frey BN, Gomes FA, Tramontina J, Kauer-Sant’anna M, Grassi-Oliveira R, Post RM (2008b) Allostatic load in bipolar disorder: implications for pathophysiology and treatment. Neurosci Biobehav Rev 32:675–692PubMedCrossRefGoogle Scholar
  111. Kapczinski F, Dias VV, Kauer-Sant’Anna M, Frey BN, Grassi-Oliveira R, Colom F, Berk M (2009) Clinical implications of a staging model for bipolar disorders. Expert Rev Neurother 9:957–966PubMedCrossRefGoogle Scholar
  112. Kasper S, Lerman MN, McQuade RD, Saha A, Carson WH, Ali M, Archibald D, Ingenito G, Marcus R, Pigott T (2003) Efficacy and safety of aripipazole vs. haloperidol for long-term maintainence treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol 6:325–337PubMedCrossRefGoogle Scholar
  113. Kelly JP, Wrynn AS, Leonard BE (1997) The olfactory bulbectomized rat as a model of depression: an update. Pharmacol Ther 74:299–316PubMedCrossRefGoogle Scholar
  114. Keshaven MS, Amirsadri A (2007) Early intervention in schizophrenia: current and future perspectives. Curr Psychiat Rep 9:325–328CrossRefGoogle Scholar
  115. Kessing LV, Hansen MG, Andersen PK, Angst (2004) The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders—a life-long perspective. Acta Psychiatr Scand 109:339–344PubMedCrossRefGoogle Scholar
  116. Ketter TA, Houston JP, Adams DH, Risser RC, Al Meyers, Williamson DK, Tohen M (2006) Differential efficacy of olanzepine and lithium in preventing manic or mixed recurrence in patients with bipolar I disorder based on number of previous manic or mixed episodes. J Clin Psychiatr 67:95–101CrossRefGoogle Scholar
  117. Killackey E, McGorry PD (2009) Interventions in the early stages of psychosis. Psychiatr Ann (in press). PMID:18836852Google Scholar
  118. Kim B, Choi EY, Kim CY, Song K, Joo YH (2008) Could HTR2A T102C and DRD3 Ser9Gly predict clinical improvement in patients with acutely exacerbated schizophrenia? Results from treatment responses to risperidone in a naturalistic setting. Hum Psychopharmacol 23:61–67PubMedCrossRefGoogle Scholar
  119. Kiosses DN, Klimstra S, Murphy C, Alexopoulos GS (2001) Executive dysfunction and disability in elderly patients with major depression. Am J Geriatr Psychiatr 9:269–274Google Scholar
  120. Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D (2006) Dissociating apathy and depression in Parkinson’s disease. Neurology 67:33–38PubMedCrossRefGoogle Scholar
  121. Klosterkötter J, Hellmich M, Steinmeyer EM, Schultze-Lutter F (2001) Diagnosing schizophrenia in the initial prodromal phase. Arch Gen Psychiatr 58:158–164PubMedCrossRefGoogle Scholar
  122. Kuzis G, Sabe L, Tiberti C, Dorrego F, Starkstein SE (1999) Neuropsychological correlates of apathy and depression in patients with dementia. Neurology 52:1403–1407PubMedGoogle Scholar
  123. Lane HY, Chang YC, Chiu CC, Chen ML, Hsieh MH, Chang WH (2002) Association of risperidone treatment response with a polymorphism in the 5-HT(2A) receptor gene. Am J Psychiatr 159:1593–1595PubMedCrossRefGoogle Scholar
  124. Larraga L, Saz P, Dewey ME, Marcos G, Lobo A, ZARADEMP Workgroup (2006) Validation of the Spanish version of the EURO-D scale: an instrument for detecting depression in older people. Int J Geriatr Psychiatry 21:1199–1205PubMedCrossRefGoogle Scholar
  125. Larsen TK, McGlashan TH, Johannessen JO, Friis S, Guldberg C, Haahr U, Horneland M, Melle I, Moe LC, Opjordsmoen S, Simonsen E, Vaglum P (2001) Shortened duration of untreated first episode of psychosis: changes in patient characteristics at treatment. Am J Psychiatr 158:1917–1919PubMedCrossRefGoogle Scholar
  126. LeBlanc M, Mérette C, Savard J, Ivers H, Baillargeon L, Morin CM (2009) Incidence and risk factors of insomnia in a population-based sample. Sleep 32:1027–1037PubMedGoogle Scholar
  127. Lechowski L, Benoit M, Chassagne P, Vedel I, Tortrat D, Teillet L, Vellas B (2009) Persistent apathy in Alzheimer’s disease as an independent factor of rapid functional decline: the REAL longitudinal cohort study. Int J Geriatr Psychiatr 24:341–346CrossRefGoogle Scholar
  128. Leentjens AFG, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG (2008) Apathy and Anhedonia Rating Scales in Parkinson’s disease: critique and recommendations. Mov Disord 23:1004–2014Google Scholar
  129. Leentjens AFG, Koester J, Fruh B, Shepard DT, Barone P, Houben JJ (2009) The effect of pramipexole on mood and motivation symptoms in Parkinson’s disease: a meta-analysis of placebo-controlled studies. Clin Ther 61:886–895Google Scholar
  130. Lemke MR, Brecht HM, Koester J, Kraus PH, Reichmann H (2005) Anhedonia, depression, and motor functioning in Parkinson’s diseaseduring treatment with pramipexole. J Neuropsychiatry Clin Neurosci 17:214–220PubMedGoogle Scholar
  131. Lemke MR, Brecht HM, Kraus PH, Reichmann H (2006) Effects of the dopamine agonist pramipexole on depression, anhedonis and motor functioning in Parkinson’s disease. J Neurol Sci 248:266–270PubMedCrossRefGoogle Scholar
  132. Lenze EJ, Munin MC, Dew MA, Marin RS, Butters MA, Skidmore ER, Whyte EM, Begley A, Reynolds CF (2009) Apathy after hip fracture: a potential target for intervention to improve functional outcomes. J Neuropsychiatry Clin Neurosci 21:271–278PubMedGoogle Scholar
  133. Levander E, Frye MA, McElroy S, Suppes T, Grunze H, Nolen WA, Kupka R, Keck PE Jr, Leverich GS, Altshuler LL, Hwang S, Mintz J, Post RM (2007) Alcoholism and anxiety in bipolar illness: differential lifetime anxiety comorbidity in bipolar I women with and without alcoholism. J Affect Disord 101:211–217PubMedCrossRefGoogle Scholar
  134. Leverich GS, Post RM, Keck PE Jr, Altshuler LL, Frye MA, Kupka RW, Nolen WA, Suppes T, McElroy SL, Grunze H, Denicoff K, Moravec MK, Luckenbaugh D (2007) The poor prognosis of childhood-onset bipolar disorder. J Pediatr 150:485–490PubMedCrossRefGoogle Scholar
  135. Lin CH, Tsai SJ, Yu YW, Song HL, Tu PC, Sim CB, Hsu CP, Yang KH, Hong CJ (1999) No evidence for association of serotonin-2A receptor variant (102T/C) with schizophrenia or clozapine response in a Chinese population. NeuroReport 10:57–60PubMedCrossRefGoogle Scholar
  136. Linszen DH, Dingemans PM, Lenior ME (1994) Cannabis use and the course of recent-onset schizophrenic disorders. Arch Gen Psychiatr 51:273–279PubMedGoogle Scholar
  137. Little A (2009) Treatment-resistant depression. Am Fam Physician 80:167–172PubMedGoogle Scholar
  138. Lobo A, Lopez-Anton R, De-La-Camara C, Quintanilla MA, Campayo A, Santabarbara J, Martin A, Saz P, Marcos G, the ZARADEMP Workgroup (2010) Staging of cognitive impairment, incidence of dementia and mortality risk: a simple method based on the Mini Mental Status Examination. Neurotoxicity Res (in press)Google Scholar
  139. Lobo A, Saz P, Marcos G et al (2005) The ZARADEMP-project on the incidence, prevalence and risk factors of dementia (and depression) in the elderly community: II. Methods and first results. Eur J Psychiatr 19:40–54Google Scholar
  140. Lobo A, Saz P, Marcos G, Dia JL, De-la-Camara C, Ventura T, Montañes JA, Lobo-Escolar A, Aznar S, ZARADEMP Workgroup (2007) Prevalence of dementia in a southern European population in two different time periods: the ZARADEMP Project. Acta Psychiatr Scand 116:299–307PubMedCrossRefGoogle Scholar
  141. Lobo-Escolar A, Roy JF, Saz P, De-la-Cámara C, Marcos G, Lobo A, ZARADEMP Workgroup (2008a) Association of hypertension with depression in community-dwelling elderly persons: results from the ZARADEMP Project. Psychother Psychosom 77:323–325PubMedCrossRefGoogle Scholar
  142. Lobo-Escolar A, Saz P, Marcos G, Quintanilla MA, Campayo A, Lobo A, ZARADEMP Workgroup (2008b) Somatic and psychiatric comorbidity in the general elderly population: results from the ZARADEMP Project. J Psychosom Res 65:347–355PubMedCrossRefGoogle Scholar
  143. Lueken U, Seidl U, Völker L, Schweiger E, Kruse A, Schröder J (2007) Development of a short version of the Apathy Evaluation Scale specifically adapted for dementia nursing home residents. Am J Geriatr Psychiatr 15:376–378CrossRefGoogle Scholar
  144. Luzi S, Morrison PD, Powell J, di Forti M, Murray RM (2008) What is the mechanism whereby cannabis use increases risk of psychosis? Neurotox Res 14:105–112PubMedCrossRefGoogle Scholar
  145. Mahli GS, Ivanovski B, Szekeres V, Olley A (2004) Bipolar disorder: it’s all in the mind? The neurological profile of a biological disorder. Can J Psychiatr 49:813–819Google Scholar
  146. Malhotra AK, Goldman D, Ozaki N, Breier A, Buchanan R, Pickar D (1996) Lack of association between polymorphisms in the 5-HT2A receptor gene and the antipsychotic response to clozapine. Am J Psychiatr 153:1092–1094PubMedGoogle Scholar
  147. Malla AK, Norman RM, Williamson P (1993) Stability of positive and negative symptoms in schizophrenia. Can J Psychiatr 38:617–621Google Scholar
  148. Marangell LB, Johnson CR, Kertz B, Zboyan HA, Martinez JM (2002) Olanzapine in the treatment of apathy in previously depressed participants maintained with selective serotonin reuptake inhibitors: an open-label, flexible-dose study. J Clin Psychiatr 63:391–395Google Scholar
  149. Marin RS (1990) Differential diagnosis and classification of apathy. Am J Psychiatr 147:22–30PubMedGoogle Scholar
  150. Marin RS (1991) Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci 3:243–254PubMedGoogle Scholar
  151. Marin RS (1996) Apathy and related disorders of diminished motivation. In: Dickstein LJ, Riba MB, Oldham JM (eds) Review of psychiatry, vol 15. American Psychiatric Press, Washington DC, pp 205–242Google Scholar
  152. Marin RS, Wilkosz PA (2005) Disorders of diminished motivation. J Head Trauma Rehabil 20:377–388PubMedCrossRefGoogle Scholar
  153. Marin RS, Firincigullari S, Biedrzycki RC (1991) Reliability and validity of the Apathy Evaluation Scale. Psychiatr Res 38:143–162CrossRefGoogle Scholar
  154. Marin RS, Biedrzycki RC, Firincigullari S (1993) The sources of convergence between measures of apathy and depression. J Affect Disord 28:117–124PubMedCrossRefGoogle Scholar
  155. Marin RS, Butters MA, Mulsant BH, Pollock BG, Reynolds CF (2003) Apathy and executive function in depressed elderly. J Geriatr Psychiatr Neurol 16:112–118CrossRefGoogle Scholar
  156. Marsh L, McDonald WM, Cummings J, Ravina B, NINDS/NIMH Work Group on Depression, Parkinson’s Disease (2006) Provisional diagnostic criteria for depression in Parkinson’s disease: report of an NINDS/NIMH Work Group. Mov Disord 21:148–158PubMedCrossRefGoogle Scholar
  157. Marshall M, Lewis S, Lockwood A et al (2005) Association between duration of untreated psychosis and in cohorts of first-episode outcome patients: a systematic review. Arch Gen Psychiat 62:975–983PubMedCrossRefGoogle Scholar
  158. Martinez-Aran A, Vieta E, Reinares M, Colom F, Torrent C, Sánchez-Moreno J, Benabarre A, Goikolea JM, Comes M, Salamero M (2004) Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. Am J Psychiatr 161:262–270PubMedCrossRefGoogle Scholar
  159. Masellis M, Basile V, Meltzer HY, Lieberman JA, Sevy S, Macciardi FM, Cola P, Howard A, Badri F, Nothen MM, Kalow W, Kennedy JL (1998) Serotonin subtype 2 receptor genes and clinical response to clozapine in schizophrenic patients. Neuropsychopharmacology 19:123–132PubMedCrossRefGoogle Scholar
  160. Mason O, Startup M, Halpin S et al (2004) Risk factors for transition to first episode psychosis among individuals with ‘at-risk mental states’. Schizophr Res 7:227–237CrossRefGoogle Scholar
  161. Mathew RJ, Wilson WH, Chiu NY, Turkington TG, Degrado TR, Coleman RE (1999) Regional cerebral blood flow and depersonalization after tetrahydrocannabinol administration. Acta Psychiatr Scand 100:67–75PubMedCrossRefGoogle Scholar
  162. Mathew RJ, Wilson WH, Turkington TG, Hawk TC, Coleman RE, DeGrado TR, Provenzale J (2002) Time course of tetrahydrocannabinol-induced changes in regional cerebral blood flow measured with positron emission tomography. Psychiatry Res 116:173–185PubMedCrossRefGoogle Scholar
  163. McGlashan TH (1998) Early detection and intervention of schizophrenia: rationale and research. Br J Psychiat 172:3–6Google Scholar
  164. McGorry PD (2007) Issues for DSM-V: clinical staging, a heuristic pathway to valid nosology and safer, more effective treatment in psychiatry. Am J Psychiat 164:859–860PubMedCrossRefGoogle Scholar
  165. McGorry PD (2010) Staging in neuropsychiatry: a heuristic model for understanding, prevention and treatment. Neurotoxicity Res (in press)Google Scholar
  166. McGorry PD, Yung AR (2003) Early intervention in psychosis: an overdue reform. Aust NZ J Psychiat 37:393–398CrossRefGoogle Scholar
  167. McGorry PD, Edwards J, Mihalopoulos C, Harrigan SM, Jackson HJ (1996) EPPIC: an evolving system of early detection and optimal management. Schizophr Bull 22:305–326PubMedGoogle Scholar
  168. McGorry PD, Yung AR, Phillips L (2001) Ethics and early intervention in psychosis: keeping up the pace and staying in step. Schizophr Res 51:17–29PubMedCrossRefGoogle Scholar
  169. McGorry PD, Hickie IB, Yung AR, Pantelis C, Jackson HJ (2006) Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust NZ J Psychiat 40:616–622Google Scholar
  170. McGorry PD, Purcell R, Hickie IB, Jorm AF (2007) Investing in youth mental health is a best buy. Med J Austral 187(Suppl. 7):s5Google Scholar
  171. McGorry PD, Killackey E, Yung AR (2008a) Early intervention in psychosis: concepts, evidence and future directions. World Psychiat 7:148–156Google Scholar
  172. McGorry PD, Yung AR, Bechdorf A, Amminger P (2008b) Back to the future: predicting and reshaping the course of psychotic disorder. Arch Gen Psychiatr 65:25–27PubMedCrossRefGoogle Scholar
  173. McGorry PD, Johannessen JO, Lewis S, Birchwood M, Malla A, Nordentoft M, Addington A, Yung A (2009a) Early intervention in psychosis: keeping faith with evidence-based health care. Psychol Med. PMID:19886337Google Scholar
  174. McGorry PD, Nelson B, Amminger P, Bechdolf A, Francey SM, Berger G, Riecher-Rössler A, KlosterKötter J, Ruhrmann S, Schultze-Lutter F, Nordentoft M, Hickie I, MsGuire P, Berk M, Chen YH, keshaven MS, Yung AR (2009b) Intervention in individuals at ultra high risk for psychosis: a review and future directions. J Clin Psychiat 70:1206–1212CrossRefGoogle Scholar
  175. McGuire PK (2010) Brain imaging in early stages of psychosis. In: Palomo T, Beninger RJ, Kostrzewa RM, Archer T (eds) Staging neuropsychiatric disorders: implications for etiopathogenesis and treatment. F.P. Graham Publishing, Mountain Home USAGoogle Scholar
  176. Melle I, Larsen TK, Haahr U, Friis S, Johannessen JO, Opjordsmoen S, Simonsen E, Ruud BR, Vaglum P, McGlashan T (2004) Reducing the duration of untreated first-episode psychosis: effects on clinical presentation. Arch Gen Psychiat 61:143–150PubMedCrossRefGoogle Scholar
  177. Melle I, Larsen TK, Friis S, Vaglum P, Johannessen JO, Simonsen E, Haahr U, Opjordsmoen S, Ruud BR, Rossberg JL, Joa I, hegelstad W, Langeveld H, Evensen J, McGlashan T (2009) Early detection of first psychosis: TIPS sample five year outcomes. Schizophr Bull 35(Suppl. 1):s330Google Scholar
  178. Mendlewicz J (2009) Disruption of the circadian timing systems: molecular mechanisms in mood disorders. CNS Drugs 23(Suppl 2):15–26PubMedCrossRefGoogle Scholar
  179. Merikangas KR, Akiskal HS, Angst J (2007) Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatr 64:543–552PubMedCrossRefGoogle Scholar
  180. Meyer U, Feldon J (2009) Neural basis of psychosis-related behaviour in the infection model of schizophrenia. Behav Brain Res 204:322–334PubMedCrossRefGoogle Scholar
  181. Miller AH (2010) Depression and immunity: a role for T cells? Brain Behav Immun 24:1–8PubMedCrossRefGoogle Scholar
  182. Miller TJ, McGlashan TH, Rosen JL et al (2002) Prospective diagnosis of the initial prodrome for schizophrenia based on the Structured Interview for Prodromal Syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiat 159:863–865PubMedCrossRefGoogle Scholar
  183. Modinos G, Mechelli A, Ormel J, Groenewold NA, Aleman A, McGuire PK (2009) Schizotypy and brain structure: a voxel-based morphometry study. Psychol Med 17:1–9Google Scholar
  184. Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G (2007) Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370(9584):319–328PubMedCrossRefGoogle Scholar
  185. Moorhead TW, Stanfield A, Spencer M, Hall J, McIntosh A, Owens DC, Lawrie S, Johnstone E (2009) Progressive temporal lobe grey matter loss in adolescents with schizotypal traits and mild intellectual impairment. Psychiatry Res 174:105–109PubMedCrossRefGoogle Scholar
  186. Moreira FA, Lutz B (2008) The endocannabinoid system: emotion, learning and addiction. Addict Biol 13:196–212PubMedCrossRefGoogle Scholar
  187. Morrison PD, Zois V, McKeown DA, Lee TD, Holt DW, Powell JF, Kapur S, Murray RM (2009) The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol Med 39:1607–1616PubMedCrossRefGoogle Scholar
  188. Moukas G, Stathopoulou A, Gourzis P, Beratis IN, Beratis S (2010) Relationship of “prodromal” symptoms with severity and type of psychopathology in the active phase of schizophrenia. Compr Psychiatry 51:1–7PubMedCrossRefGoogle Scholar
  189. Müller N, Schwarz MJ (2007a) The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Mol Psychiatr 12:988–1000CrossRefGoogle Scholar
  190. Müller N, Schwarz MJ (2007b) The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view. J Neurotransmiss 78 253–256(258–260):262–263Google Scholar
  191. Müller N, Schwarz MJ (2008a) A psychoneuroimmunological perspective to Emil Kraepelins dichotomy: schizophrenia and major depression as inflammatory CNS disorders. Eur Arch Psychiatry Clin Neurosci 258(Suppl 2):97–106PubMedCrossRefGoogle Scholar
  192. Müller N, Schwarz MJ (2008b) COX-2 inhibition in schizophrenia and major depression. Curr Pharm Des 14:1452–1465PubMedCrossRefGoogle Scholar
  193. Müller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Müller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Möller HJ, Arolt V, Riedel M (2006) The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 11:680–684PubMedCrossRefGoogle Scholar
  194. Müller N, Myint AM, Schwarz MJ (2009) The impact of neuroimmune dysregulation on neuroprotection and neurotoxicity in psychiatric disorders—relation to drug treatment. Dialogues Clin Neurosci 11:319–332PubMedGoogle Scholar
  195. Müller N, Myint AM, Schwarz MJ (2010) Inflammatory biomarkers and depression. Neurotoxicity Res (in press)Google Scholar
  196. Murray KM (2010) Cannabis and psychosis. In: Palomo T, Beninger RJ, Kostrzewa RM, Archer T (eds) Staging neuropsychiatric disorders: implication for etiopathogenesis and treatment. Graham publ., Mountain ViewGoogle Scholar
  197. Murray CJ, Lopez AD (1997) Global mortality, disability, and the contributions of risk factors: global burden of disease study. Lancet 349:1436–1442PubMedCrossRefGoogle Scholar
  198. Murray RM, Morrison PD, Henquet C, Di Forti M (2007) Cannabis, the mind and society: the hash realities. Nat Rev Neurosci 8:885–895PubMedCrossRefGoogle Scholar
  199. Myint AM, Steinbusch HW, Goeghegan L, Luchtman D, Kim YK, Leonard BE (2007) Effect of the COX-2 inhibitor celecoxib on behavioural and immune changes in an olfactory bbulbectomised rat model of depression. Neuroimmunomodulation 14:65–71PubMedCrossRefGoogle Scholar
  200. Narrow WE, Kuhl EA, Regier DA (2009) DSM-V perspectives on disentangling disability from clinical significance. World Psychiatr 8:88–89Google Scholar
  201. Nelson B, Simmons MB, Yung AR, Buckby JA, O’Dwyer L, Francey SM, Leicester S, Bapat S, McGorry PD (2008) Identifying the ultra-high risk (prodromal) population: evaluation of training workshops with mental health services. Aust N Z J Psychiatr 42:236–243CrossRefGoogle Scholar
  202. Nery FG, Monkul ES, Hatch JP, Fonseca M, Zunta-Soares GB, Frey BN, Bowden CL, Soares JC (2008) Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study. Hum Psychopharmarcol 23:87–94CrossRefGoogle Scholar
  203. Nothen MM, Rietschel M, Erdmann J, Oberlander H, Moller HJ, Nober D, Propping P (1995) Genetic variation of the 5-HT2A receptor and response to clozapine. Lancet 346:908–909PubMedCrossRefGoogle Scholar
  204. Nowak G, Siwek M, Dudek D, Zieba A, Pilc A (2003) Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Pol J Pharmacol 55:1143–1147PubMedGoogle Scholar
  205. Nudmamud-Thanoi S, Reynolds GP (2004) The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders. Neurosci Lett 372:173–177PubMedCrossRefGoogle Scholar
  206. Padala PR, Burke WJ, Bhatia SC, Petty F (2007) Treatment of apathy with methylphenidate. J Neuropsychiatry Clin Neurosci 19:81–83PubMedGoogle Scholar
  207. Palomo T, Beninger RJ, Kostrzewa RM, Archer T (2008a) Focusing on symptoms rather than diagnosis in brain dysfunction: conscious and nonconscious expression in impulsiveness and decision-making. Neurotoxicity Res 14:1–20CrossRefGoogle Scholar
  208. Palomo T, Kostrzewa RM, Beninger RJ, Archer T (2008b) Schizopsychotic symptom-profiles and biomarkers: beacons in diagnostic labyrinths. Neurotoxicity Res 14:79–96CrossRefGoogle Scholar
  209. Penn DL, Waldheter EJ, Perkins DO, Mueser KT, Lieberman JA (2005) Psychosocial treatment for first-episode psychosis: a research update. Am J Psychiatr 162:2220–2232PubMedCrossRefGoogle Scholar
  210. Perkins DO, Gu H, Boteva K, Lieberman JA (2005) Relationship between duration of untreated psychosis and in cohorts of first-episode outcome schizophrenia: a critical review and meta-analysis. Am J Psychiat 162:1785–1804PubMedCrossRefGoogle Scholar
  211. Pflüger MO, Gschwander U, Stieglitz RD, Riecher-Rössler A (2007) Neuropsychological deficits in individuals with an at risk mental state for psychosis-working memory as a potential trait marker. Schizophr Res 97:14–24CrossRefGoogle Scholar
  212. Pluck GC, Brown RG (2002) Apathy in Parkinson’ disease. J Neurol Neurosurg Psychiatr 73:636–642PubMedCrossRefGoogle Scholar
  213. Post RM (2008) Promising avenues of therapeutics for bipolar illness. Dialogues Clin Neurosci 10:193–201PubMedGoogle Scholar
  214. Post RM (2010) Mechanisms of illness progression in the recurrent affective disorders. Neurotoxicity Res (in press)Google Scholar
  215. Post RM, Leverich GS (2006) The role of psychosocial stress in the onset and progression of bipolar disorder and its comorbidities: the need for earlier and alternative modes of therapeutic intervention. Dev Psychopathol 18:1181–1211PubMedCrossRefGoogle Scholar
  216. Pukrop R, Klosterkötter J (2010) Neurocognitive indicators of clinical high-risk states for psychosis: a critical review of the evidence. Neurotoxicity Res (in press)Google Scholar
  217. Pukrop R, Ruhrmann S, Schultze-Lutter F, Bechdolf A, Brockhaus-Dumke A, Klosterkötter J (2007) Neurocognitive indicators for a conversion to psychosis: comparison of patients in a potentially initial prodromal state who did or did not convert to a psychosis. Schizophr Res 92:116–125PubMedCrossRefGoogle Scholar
  218. Quraishi S, Frangou S (2002) Neuropsychology of bipolar disorder: a review. J Affect Disord 72:209–226PubMedCrossRefGoogle Scholar
  219. Realini N, Rubino T, Parolaro D (2009) Neurobiological alterations at adult age triggered by adolescent exposure to cannabinoids. Pharmacol Res 60:132–138PubMedCrossRefGoogle Scholar
  220. Regier DA, Narrow WE, Kuhl EA, Kupfer DJ (2009) The conceptual development of DSM-V. Am J Psychiatr 166:645–650PubMedCrossRefGoogle Scholar
  221. Reid IC, Cameron IM (2010) The HEAT is on: demonizing antidepressant drugs in Scotland (in press)Google Scholar
  222. Reinares M, Colom F, Sánchez-Moreno J, Torrent C, Martínez-Arán A, Gomes M, Goikolea JM, Benabarre A, Salamero M, Vieta E (2008) Impact of caregiver group psychoeducation on the course and outcome of bipolar patients in remission: a randomized controlled trial. Bipolar Disord 10:511–519PubMedCrossRefGoogle Scholar
  223. Reinares M, Colom F, Rosa AR, Bonnin CM, Franco C, Solé B, Kapczinski F, Vieto E (2009) The impact of staging bipolar disorder on treatment outcome of family psychoeducation. J Affect Disorder. PMID:19853922Google Scholar
  224. Reist C, Mazzanti C, Vu R, Fujimoto K, Goldman D (2004) Inter-relationships of intermediate phenotypes for serotonin function, impulsivity, and a 5.HT2A candidate allelle: His452Tyr. Mol Psychiatr 9:871–878CrossRefGoogle Scholar
  225. Riecher-Rössler A, Gschwandtner U, Aston J, Borgwardt S, Drewe M, Fuhr P, Pflüger M, Radü W, Schindler Ch, Stieglitz RD (2007) The Basel early-detection-of-psychosis (FEPSY)-study—design and preliminary results. Acta Psychiat Scand 115:114–125PubMedCrossRefGoogle Scholar
  226. Riecher-Rössler A, Gschwander U, Borgwardt SJ, Aston J, Pflüger M, Rössler W (2006) Early detection and treatment of schizophrenia: how early? Acta Psychiatr Scand 113:73–80CrossRefGoogle Scholar
  227. Riecher-Rössler A, Pflueger MO, Aston J, Borgwardt SJ, Brewer WJ, Gschwandtner U, Stieglitz RD (2009) Efficacy of using cognitive status in predicting psychosis: a 7-year follow-up. Biol Psychiatry 66:1023–1030PubMedCrossRefGoogle Scholar
  228. Riemer S, Maes M, Christophe A, Rief W (2009) Lowered omega-3 PUFAs are related to major depression, but not to somatization syndrome. J Affect Disord. PMID:19720401Google Scholar
  229. Robert PH, Clairet S, Benoit M, Koutaich J, Bertogliati C, Tible O, Caci H, Borg M, Broker P, Bedoucha P (2002) The apathy inventory: assessment of apathy and awareness in Alzheimer’s disease, Parkinson’s disease and mild cognitive impairment. Int J Geriatr Psychiatr 17:1099–1105CrossRefGoogle Scholar
  230. Robert PH, Onyike CU, Leentjens AF, Dujardin K, Aalten P, Starkstein S, Verhey FR, Yessavage J, Clement JP, Drapier D, Bayle F, Benoit M, Boyer P, Lorca PM, Thibaut F, Gauthier S, Grossberg G, Vellas B, Byrne J (2009) Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur Psychiatry 24:98–104PubMedCrossRefGoogle Scholar
  231. Robinson LJ, Ferrier IN (2006) Evolution of cognitive impairment in bipolar disorder: a systematic review of cross-sectional evidence. Bipolar Disord 8:103–116PubMedCrossRefGoogle Scholar
  232. Robinson D, Woerner MG, Alvir JM, Geisler S, Koreen A, Sheitman B, Chakos M, Mayerhoff D, Bilder R, Goldman R, Lieberman JA (1999) Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatr 56:241–247PubMedCrossRefGoogle Scholar
  233. Robinson D, Woerner MG, Delman HM, Kane JM (2005) Pharmacological treatments for first episode schizophrenia. Schizophr Bull 31:705–722PubMedCrossRefGoogle Scholar
  234. Rodda J, Morgan S, Walker Z (2009) Are cholinesterase inhibitors effective in the management of the behavioural and psychological symptoms of dementia in Alzheimer’s disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int Psychogeriatr 21:813–824PubMedCrossRefGoogle Scholar
  235. Rosa AR, Franco C, Martínez-Aran A, Sánchez-Moreno J, Reinares M, Salamero M, Arango C, Ayuso-Mateos JL, Kapczinski F, Vieta E (2008) Functional impairment in patients with remitted bipolar disorder. Psychother Psychosom 77:390–392PubMedCrossRefGoogle Scholar
  236. Rosa AR, Reinares M, Franco C, Comes M, Torrent C, Sánchez-Moreno J, Martínez-Arán A, Salamero M, Kapczinski F, Vieta E (2009) Clinical predictors of functional outcome of bipolar patients in remission. Bipolar Disord 11:401–409PubMedCrossRefGoogle Scholar
  237. Royall DR (1999) Frontal systems impairment in major depression. Semin Clin Neuropsychiatr 4:13–23Google Scholar
  238. Royall DR, Mahurin RK, Gray K (1992) Bedside assessment of executive cognitive impairment: The Executive Interview (EXIT). J Am Geriatr Soc 40:1221–1226PubMedGoogle Scholar
  239. Ruhrmann S, Schultz-Lutter F, Klosterkotter J (2003) Early detection and intervention in the initial prodromal phase of schizophrenia. Pharmacopsychiat 36(Suppl. 3):S162–S167Google Scholar
  240. Ruhrmann S, Paruch J, Bechdolf A, Pukrop R, Wagner M, Berning J, Schultze-Lutter F, Janssen B, Gaebel W, Möller HJ, Maier W, Klosterkötter J (2008) Reduced subjective quality of life in persons at risk for psychosis. Acta Psychiatr Scand 117:357–368PubMedCrossRefGoogle Scholar
  241. Rummel C, Hamann J, Kissling W, Leucht S (2003) New generation antipsychotics for first episode schizophrenia. Cochrane Database Syst Rev CD004410Google Scholar
  242. Rund BR, Sundet K, Asbjørnsen A, Egeland J, Landrø NI, Lund A, Roness A, Stordal KI, Hugdahl K (2006) Neuropsychological test profiles in schizophrenia and non-psychotic depression. Acta Psychiatr Scand 113:350–359PubMedCrossRefGoogle Scholar
  243. Saz P, Launer LJ, Día JL, De-La-Cámara C, Marcos G, Lobo A (1999) Mortality and mental disorders in a Spanish elderly population. Int J Geriatr Psychiatry 14:1031–1038PubMedCrossRefGoogle Scholar
  244. Saz P, López-Antón R, Dewey ME, Ventura T, Martín A, Marcos G, De La Cámara C, Quintanilla MA, Quetglas B, Bel M, Barrera A, Lobo A (2009) Prevalence and implications of psychopathological non-cognitive symptoms in dementia. Acta Psychiatr Scand 119:107–116PubMedCrossRefGoogle Scholar
  245. Schrag A, Barone P, Brown RG, Leentjens AF, McDonald WM, Starkstein S, Weintraub D, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG (2007) Depression rating scales in Parkinson’s disease: critique and recommendations. Mov Disord 22:1077–1092PubMedCrossRefGoogle Scholar
  246. Scott J, Paykel E, Morriss R, Bentall R, Kinderman P, Johnson T, Abbott R, Hayhurst H (2006) Cognitive-behavioural therapy for severe and recurrent bipolar disorders: randomized controlled trial. Br J Psychiatr 188:310–320Google Scholar
  247. Sheikholeslami H, Kani C, Kani K, Ghafelebashi H (2009) Repetition of suicide-related behavior: a study of the characteristics, psychopathology, suicidality and negative life events in Iran. Int J Psychiatry Med 39:45–62PubMedCrossRefGoogle Scholar
  248. Shen YC, Chen SF, Chen CH, Lin CC, Chen SJ, Chen YJ, Luu SU (2009) Effects of DRD2/ANKKI gene variations and clinical factors on aripipazole efficacy in schizophrenic patients. J Psychiatric Res 43:600–606CrossRefGoogle Scholar
  249. Simic G, Stanic G, Mladinov M, Jovanov-Milosevic N, Kostovic I, Hof PR (2009) Does Alzheimer’s disease begin in the brainstem? Neuropathol Appl Neurobiol 35:532–554PubMedCrossRefGoogle Scholar
  250. Simpson S, Barnes E, Griffiths E, Hood K, Cohen D, Craddock N, Jones I, Smith DJ (2009) The Bipolar Interactive Psychoeducation (BIPED) study: trial design and protocol. BMC Psychiatry 12:9–50Google Scholar
  251. Smieskova R, Fusar-Poli P, Allen P, Bendfeldt K, Stieglitz RD, Radű EW, McGuire PK, Riecher-Rössler A, Borgwardt SJ (2009) The effects of antipsychotics on the brain: what have we learnt from structural imaging of schizophrenia?—a systematic review. Curr Pharm Des 15:2535–2549PubMedCrossRefGoogle Scholar
  252. Spurlock G, Heils A, Holmans P, Williams J, D’Souza UM, Cardno A, Murphy KC, Jones L, Buckland PR, McGuffin P, Lesch KP, Owen MJ (1998) A family based association study of T102C polymorphism in 5-HT2A and schizophrenia plus identification of new polymorphisms in the promotor. Mol Psychiatr 3:42–49CrossRefGoogle Scholar
  253. Starkstein SE (2000) Apathy and withdrawal. Int Psychogeriatr 12(Suppl 1):135–138CrossRefGoogle Scholar
  254. Starkstein SE, Leentjens AF (2008) The nosological position of apathy in clinical practice. J Neurol Neurosurg Psychiatr 79:1088–1092PubMedCrossRefGoogle Scholar
  255. Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leisguarda R, Robinson RG (1992) Reliability, validity, and clinical correlates of apathy in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 4:134–139PubMedGoogle Scholar
  256. Starkstein SE, Jorge R, Mizrahi R (2006) The prevalence, clinical correlates and treatment of apathy in Alzheimer’s disease. Eur J Psychiatr 20:96–106Google Scholar
  257. Stephenson J (2000) Delay in treating schizophrenia may narrow therapeutic window of opportunity. JAMA 283:2091–2092PubMedCrossRefGoogle Scholar
  258. Stewart T, Goulding SM, Esterberg ML, Pringle M, Compton MT (2010)Google Scholar
  259. Su S, Miller AH, Snieder H, Bremner JD, Ritchie J, Maisano C, Jones L, Murrah NV, Goldberg J, Vaccarino V (2009) Common genetic contributions to depressive symptoms and inflammatory markers in middle-aged men: the Twins Heart Study. Psychosom Med 71:152–158PubMedCrossRefGoogle Scholar
  260. Summers M, Papadopoulou K, Bruno S, Cipol L, Ron MA (2006) Bipolar I and Bipolar II disorder: cognition and emotion processing. Psychol Med 36:1799–1809PubMedCrossRefGoogle Scholar
  261. Takahashi T, Yung AR, Yücel M, Wood SJ, Phillips LJ, Harding IH, Soulsby B, McGorry PD, Suzuki M, Velakoulis D, Pantelis C (2008) Prevalence of large cavum septi pellucidi in ultra high-risk individuals and patients with psychotic disorders. Schizophr Res 105:236–244PubMedCrossRefGoogle Scholar
  262. Takahashi T, Wood SJ, Yung AR, Phillips LJ, Soulsby B, McGorry PD, Tanino R, Zhou SY, Suzuki M, Velakoulis D, Pantelis C (2009) Insular cortex gray matter changes in individuals at ultra-high-risk of developing psychosis. Schizophr Res 111:94–102PubMedCrossRefGoogle Scholar
  263. Taylor E (2009) Managing bipolar disorders in children and adolescents. Nat Rev Neurol 5:484–491PubMedCrossRefGoogle Scholar
  264. Therman S, Suvisaari JM, Kalska H, Huttunen MO, Manninen M, Cannon TD (2009) Lack of association between neuropsychological performance and level of psychosis-proneness in an adolescent psychiatric sample. J Nerv Ment Dis 197:669–674PubMedCrossRefGoogle Scholar
  265. Torrent C, Martínez-Arán A, Daban C, Sánchez-Moreno J, Comes M, Goikolea JM, Salamero M, Vieta E (2006) Cognitive impairment in bipolar II disorder. Br J Psychiatr 189:254–259CrossRefGoogle Scholar
  266. Torrent C, Martínez-Arán A, Amann B, Daban C, Tabarés-Seisdedos R, González-Pinto A, Reinares M, Benabarre A, Salamero M, McKenna P, Vieta E (2007) Cognitive impairment in schizoaffective disorder: a comparison with non-psychotic bipolar and healthy subjects. Acta Psychiatr Scand 116:453–460PubMedCrossRefGoogle Scholar
  267. Uzun S, Kozumplik O, Mimica N, Folnegovic-Smalc V (2005) Aripipazole: an overview of a novel antipsychotic. Psychiatr Danub 17:67–75PubMedGoogle Scholar
  268. Vaccarino V, Brennan ML, Miller AH, Bremner JD, Ritchie JC, Lindau F, Veledar E, Su S, Jones L, Jawed F, Dai J, Goldberg J, Hazen SL (2008a) Association of major depressive disorder with serum myeloperoxidase and other markers of inflammation: a twin study. Biol Psychiatry 64:476–483PubMedCrossRefGoogle Scholar
  269. Vaccarino V, Lampert R, Bremner JD, Lee F, Su S, Maisano C, Murrah NV, Jones L, Jawed F, Afzal N, Ashraf A, Goldberg J (2008b) Depressive symptoms and heart rate variability: evidence for a shared genetic substrate in a study of twins. Psychosom Med 70:628–636PubMedCrossRefGoogle Scholar
  270. Vaccarino V, Votaw J, Faber T, Veledar E, Murrah NV, Jones LR, Zhao J, Su S, Goldberg J, Raggi JP, Quyyumi AA, Sheps DS, Bremner JD (2009) Major depression and coronary flow reserve detected by positron emission tomography. Arch Intern Med 169:1668–1676PubMedCrossRefGoogle Scholar
  271. Van Duijn E, Kingma EM, van der Mast RC (2007) Psychopathology in verified Huntington’s disease gene carriers. J Neuropsychiatry Clin Neurosci 19:441–448PubMedGoogle Scholar
  272. Vieta E, Popovic D, Rosa AR, Solé B, Grande I, Frey BN, Martinez-Aran A, Kaczinski F (2009) The clinical implications of cognitive impairment and allostatic load in bipolar disorder. J Clin Psychiatr (in press). PMID:19906078Google Scholar
  273. Vieta E, Reinares M, Rosa AR (2010) Staging bipolar disorder. Neuroyoxicity Res (in press)Google Scholar
  274. Wade D (2005) Cannabis use and schizophrenia. Am J Psychiatr 162:401–402PubMedCrossRefGoogle Scholar
  275. Watkins ER (2009) Depressive rumination and co-morbidity: evidence for brooding as a transdiagnostic process. J Ration Emot Cogn Behav Ther 27:160–175PubMedCrossRefGoogle Scholar
  276. Weiden PJ, Olfson M (1995) Cost of relapse in schizophrenia. Schizophr Bull 21:419–429PubMedGoogle Scholar
  277. Weintraub D, Moberg PJ, Duda JE, Katz IR, Stren MB (2004) Effect of psychiatric and other nonmotor symptoms on disability in Parkinson’s disease. J Am Geriatr Soc 52:784–789PubMedCrossRefGoogle Scholar
  278. Wiersma D, Nienhuis FJ, Slooff CJ, Giel R (1998) Natural course of schizophrenic disorders: a 15-year followup of a Dutch incidence cohort. Schizophr Bull 24:75–85PubMedGoogle Scholar
  279. Williams MM, Roe CM, Morris JC (2009) Stability of the Clinical Dementia Rating, 1979–2007. Arch Neurol 66:773–777PubMedCrossRefGoogle Scholar
  280. Witt K, Daniels C, Herzog J, Lorenz D, Volkmann J, Reiff J, Mehdorn M, Deuschl G, Krack P (2006) Differential effects of l-Dopa and subthalamic stimulation on depressive symptoms and hedonic tone in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 18:397–401PubMedGoogle Scholar
  281. Witthaus H, Kaufmann C, Bohner G, Özgűrdal S, Gudlowski Y, Gallinat J, Ruhrmann S, Brűne M, Heinz A, Klingebiel R, Juckel G (2009) Gray matter abnormalities in subjects at high-risk for schizophrenia and first-episode schizophrenic patients compared to healthy controls. Psychiatr Res 173:163–169CrossRefGoogle Scholar
  282. Wood SJ, Pantelis C, Yung AR, Velakoulis D, McGorry PD (2009) Brain changes during the onset of schizophrenia: implications for neurodevelopmental theories. Med J Aust 190(4 Suppl):S10–S13PubMedGoogle Scholar
  283. Yathan LN, Kapczinski F, Andreazza AC, Young TL, Lam RW, Kauer-Sant’anna M (2009) Accelerated age-related decrease in brain-derived neurotrophic factor levels in bipolar disorder. Int J Neuropsychopharmacol 12:137–139CrossRefGoogle Scholar
  284. Yu YW, Tsai SJ, Yang KH, Lin CH, Chen MC, Hong CJ (2001) Evidence for an association between polymorphism in the serotonin-2A receptor variant (102T/C) and increment of N100 amplitude in schizophrenics treated with clozapine. Neuropsychobiology 43:79–82PubMedCrossRefGoogle Scholar
  285. Yung AR, Phillips LJ, McGorry PD, McFarlane CA, Francey S, Harrigan S, Patton GC, Jackson HJ (1998) Prediction of psychosis: a step towards indicated prevention of schizophrenia. Br J Psychiat Suppl 172:14–20Google Scholar
  286. Yung AR, Phillips LJ, Yuen HP, McGorry PD (2004) Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features. Schizophr Res 67:131–142PubMedCrossRefGoogle Scholar
  287. Yung AR, Nelson B, Stanford C, Simmons NB, Cosgrave EM, Killackey E, Phillips LJ, Bechdolf A, Buckby J, McGorry PD (2008) Validation of “prodromal” criteria to detect individuals at ultra high risk of psychosis: 2 year follow-up. Schizophr Res 105:10–17PubMedCrossRefGoogle Scholar
  288. Yung AR, Nelson B, Baker K, Buckby JA, Baksheev G, Cosgrave EM (2009) Psychotic-like experiences in a community sample of adolescents: implications for the continuum model of psychosis and prediction of schizophrenia. Aust NZ J Psychiat 43:118–128CrossRefGoogle Scholar
  289. Zahodne LB, Young S, Kirsch-Darrow L, Nisenzon A, Fernandez HH, Okun MS, Bowers (2009) Examination of the Lille Apathy Rating Scale in Parkinson’s disease. Mov Disord 24:677–683PubMedCrossRefGoogle Scholar
  290. Zammit S, Moore TH, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G (2008) Effects of cannabis use on outcomes of psychotic disorders: systematic review. Br J Psychiatr 193:357–363CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Trevor Archer
    • 1
  • Richard M. Kostrzewa
    • 2
  • Tomas Palomo
    • 3
  • Richard J. Beninger
    • 4
  1. 1.Department of PsychologyUniversity of GothenburgGothenburgSweden
  2. 2.Department of Pharmacology, Quillen College of MedicineEast Tennessee State UniversityJohnson CityUSA
  3. 3.Servicio Psiquitrico, Hospital Universitario 12 de OctobreMadridSpain
  4. 4.Departments of Psychology and PsychiatryQueen’s UniversityKingstonCanada

Personalised recommendations