0
0

Chapter 10. Schizophrenia

Michael J. Minzenberg, M.D.; Jong H. Yoon, M.D.; Cameron S. Carter, M.D.
DOI: 10.1176/appi.books.9781585623402.329882

Sections

Excerpt

Schizophrenia is a serious and lifelong mental disorder that affects 1% of the population worldwide. It is characterized by a range of striking disturbances in mental functioning that are conceptualized as signs and symptoms that can be grouped into discrete categories. These include symptoms of disruption in the experience of reality, such as hallucinations and delusions, which are grouped as positive symptoms. In addition, many patients with schizophrenia show signs of impoverishment in thinking, emotional experience, and social engagement, which are grouped as negative symptoms. A wide range of other signs and symptoms are also observed in this illness, including disorganized thoughts and behaviors, negative mood states, and behavioral impulsivity.

Your session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 10–1. Natural course of schizophrenia.Note. Asterisks indicate critical periods for early detection or intervention.Source. Keshavan MS, Hogarty GE: "Brain Maturational Processes and Delayed Onset in Schizophrenia." Development and Psychopathology 11:525–543, 1999 (Figure 1 [p. 526]). Copyright 1999. Reprinted with the permission of Cambridge University Press.

FIGURE 10–2. Candidate schizophrenia genes.Linkages that reached genomewide significance on their own (red) or those that have received strong support from more than one sample (blue) are shown. The red arrows refer to the location of chromosomal abnormalities associated with schizophrenia. The yellow arrows and circles show the locations of the genes discussed in the source article (Owen et al. 2005).Source. Reprinted from Owen MJ, Craddock N, O'Donovan MC: "Schizophrenia: Genes at Last?" Trends in Genetics 21:518–525, 2005 (Figure 1 [p. 520]). Copyright 2005, Elsevier Limited. Used with permission.

FIGURE 10–3. Positron emission tomography (PET) images of cognition.The PET image represents the activity recorded from 30 to 60 minutes after injection of 13.3 mCi in a 37-year-old healthy female volunteer. A, B, Sagittal view, illustrating the contrast between cortical and cerebellar activities. C, D, Transaxial view, at the level of the head of caudate, putamen, and thalamus. E, F, Coronal view, at the level of the anterior striatum, illustrating the lower level of activity in the ventral striatum compared with the caudate and putamen. G, H, Coronal view, at the level of the hippocampus, illustrating low levels of activity in thalamus, hippocampus, and parahippocampal gyrus. Putamen and caudate activities are still visualized. NNC 112 = (+)-5-(7-benzofuranyl)-8-chloro-7-hydroxy-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine.Source. Reprinted from Abi-Dargham A, Mawlawi O, Lombardo I, et al.: "Prefrontal Dopamine D1 Receptors and Working Memory in Schizophrenia." Journal of Neuroscience 22:3708–3719, 2002 (Figure 3 [p. 3713]). Copyright 2002, Society for Neuroscience. Used with permission.

FIGURE 10–4. Chandelier cell ultrastructure and physiology.(a) Electron micrographs of two of the multiple boutons (labeled b1 and b2,3) from an electrophysiologically recorded, biocytin-filled axo-axonic cell (AAC) synapsing on the biocytin-filled axonal initial segment (AIS) of a postsynaptic pyramidal cell. Arrows indicate synaptic contacts. Note the morphological differences between the boutons. (b) Firing pattern of two AACs from rat hippocampus in response to a 500-ms depolarizing pulse. Note that (i) shows a nonadapting pattern, whereas (ii) shows a strongly adapting pattern, documenting that AAC physiology is heterogeneous, even within one species and brain area. (c,d) Theta waves (c) and fast ripples (d) in the stratum pyramidale. Extracellularly recorded theta waves and fast ripples are shown in the upper parts of (c,i) and (d,i), respectively, above the simultaneous juxtacellular spike rasters of single AACs in each case. (c,ii) Stratum pyramidale extracellular (black) and pyramidal cell intracellular (blue) theta rhythms, corresponding to histograms of spike firing probability in pyramidal cells (blue) and AACs (red), averaged over several cells. Note that AAC firing is antiphase to pyramidal cell intracellular theta waves and firing but only slightly phase-delayed from extracellular theta waves. (d,ii) Extracellular fast ripples and concomitant spike firing probability in pyramidal cells (blue) and AACs (red), averaged over several cells. Note that AACs increase firing probability just before the fast ripple and depress firing after the fast ripple. Scale bars in (c,i): unit, 0.5 mV; theta, 0.2 mV; time, 300 ms. Scale bars in (d,i): unit, 0.5 mV; fast ripple, 0.1 mV; time, 50 ms.Source. Reprinted from Howard A, Tamas G, Soltesz I: "Lighting the Chandelier: New Vistas for Axo-Axonic Cells." Trends in Neurosciences 28:310–316, 2005 (Figure 3 [p. 313]). Copyright 2005, Elsevier Limited. Used with permission.

FIGURE 10–5. Relation between disorganization symptoms and change in signal intensity in right dorsolateral prefrontal cortex as a function of working memory load for 17 patients with schizophrenia.aNote. fMRI = functional magnetic resonance imaging.aWorking memory was assessed with a sequential-letter task. In the 0-back condition, the target was any letter that matched a prespecified letter. In the 1-back condition, the target was any letter that was identical to the one immediately preceding it. In the 2-back condition, the target was any letter that was identical to the one two trials back. The signal change shown here is the percentage change of the 2-back from the 0-back condition.bIncludes conceptual disorganization, mannerisms and posturing, difficulty abstracting, and poor attention from the Positive and Negative Syndrome Scale (Kay et al. 1987).Source. Reprinted from Perlstein WM, Carter CS, Noll DC, et al.: "Relation of Prefrontal Cortex Dysfunction to Working Memory and Symptoms in Schizophrenia." American Journal of Psychiatry 158:1105–1113, 2001 (Figure 2 [p. 1110]). Copyright 2001, American Psychiatric Publishing, Inc. Used with permission.

FIGURE 10–6. Activation of Heschl's gyrus during auditory hallucinations and in response to acoustical stimulation.(Top) Three-dimensional representations of the activation of Heschl's gyrus in patient 1, showing transversal and coronal sections (left) and a reconstruction of the gray/white matter boundary of the left temporal lobe (right) during hallucinations (a) and acoustical stimulation (b), respectively. (Bottom) Time courses of the blood-oxygen-level-dependent (BOLD) signal for patients 1 (first session) (a and b), 2 (c), and 3 (d), filtered with a high pass of 0.004 Hz and a low pass of 0.05 Hz, from Heschl's gyrus (solid line). The shaded areas indicate experimental conditions (H = hallucinations; S = spoken text; R = reversed speech; T = pulsed tone at 2,000 Hz). For patient 3 (d), the time course of the BOLD signal in Heschl's gyrus (solid line) is shown together with the time course of another area in auditory cortex (x = –57, y = –4, z = 3) that only responds to acoustic stimulation (dotted line) (for acoustical stimulation, the same protocol was used as in [b]).Source. Reprinted from Dierks T, Linden DE, Jandl M, et al.: "Activation of Heschl's Gyrus During Auditory Hallucinations." Neuron 22:615–621, 1999 (Figure 2 [p. 617]). Copyright 1999, Elsevier Limited. Used with permission.
Table Reference Number
TABLE 10–1. Major symptoms in schizophrenia
Table Reference Number
TABLE 10–2. DSM-IV-TR diagnostic criteria for schizophrenia
Table Reference Number
TABLE 10–3. Soft neurological signs most frequently assessed in schizophrenic patients
Table Reference Number
TABLE 10–4. DSM-IV-TR subtypes of schizophrenia
Table Reference Number
TABLE 10–5. Differential diagnosis of schizophrenia
Table Reference Number
TABLE 10–6. Certainty and doubt in schizophrenia neuropathology
Table Reference Number
TABLE 10–7. Relative neurotransmitter receptor affinities for antipsychotics at therapeutic doses
Table Reference Number

Among medical illnesses, schizophrenia is one of the most serious for the afflicted individual, the family of the patient, and society at large.

Schizophrenia, like psychiatric illness in general, occurs as a function of both a genetic predisposition and environmental factors.

Schizophrenia is characterized by cognitive, perceptual, behavioral, and social disturbances and has profound consequences for the individual's capacity for autonomy and function in the community.

Schizophrenia is currently conceived of as a neurodevelopmental disorder, with disturbances in development across a range of epochs, from early gestation through late adolescence.

The pathophysiology of schizophrenia involves several anatomical regions and neurotransmitter and other functional systems in the brain.

The various symptoms and problems in living that schizophrenic patients experience can be treated with the full range of treatment modalities currently available in psychiatry, including pharmacological and psychosocial approaches.

Although many patients with schizophrenia endure relapsing and remitting periods of illness, with a significant decline in function over the early period of illness, many can retain a measure of well-being, symptom control, and autonomy in the community.

Research into the causes, clinical course, and treatment of schizophrenia has shown considerable progress in recent times and shows promise for significant advances in the future treatment of this disorder.

References

Abi-Dargham A, Rodenhiser J, Printz D, et al: Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A 97:8104–8109, 2000
[PubMed]
 
Abi-Dargham A, Mawlawi O, Lombardo I, et al: Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci 22:3708–3719, 2002
[PubMed]
 
Addington J, Addington D: Neurocognitive and social functioning in schizophrenia: a 2.5 year follow-up study. Schizophr Res 44:47–56, 2000
[PubMed]
 
Adityanjee, Aderibigbe YA, Theodoridis D, et al: Dementia praecox to schizophrenia: the first 100 years. Psychiatry Clin Neurosci 53:437–448, 1999
[PubMed]
 
Adler CM, Strakowski SM: Boundaries of schizophrenia. Psychiatr Clin North Am 26:1–23, 2003
[PubMed]
 
Adler LE, Pachtman E, Franks RD, et al: Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry 17:639–654, 1982
[PubMed]
 
Adler LE, Hoffer LJ, Griffith J, et al: Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry 32:607–616, 1992
[PubMed]
 
Akbarian S, Kim JJ, Potkin SG, et al: Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 52:258–266, 1995
[PubMed]
 
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 2nd Edition. Washington, DC, American Psychiatric Association, 1968
 
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition. Washington, DC, American Psychiatric Association, 1980
 
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised. Washington, DC, American Psychiatric Association, 1987
 
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000
 
Andreasen NC: The evolving concept of schizophrenia: from Kraepelin to the present and future. Schizophr Res 28:105–109, 1997
[PubMed]
 
Andreasen NC: Schizophrenia: the fundamental questions. Brain Res Brain Res Rev 31:106–112, 2000
[PubMed]
 
Andreasen NC, Paradiso S, O'Leary DS: "Cognitive dysmetria" as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry? Schizophr Bull 24:203–218, 1998
[PubMed]
 
Angermeyer MC, Goldstein JM, Kuehn L: Gender differences in schizophrenia: rehospitalization and community survival. Psychol Med 19:365–382, 1989
[PubMed]
 
Angst J: Historical aspects of the dichotomy between manic-depressive disorders and schizophrenia. Schizophr Res 57:5–13, 2002
[PubMed]
 
Badner JA, Gershon ES: Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 7:405–411, 2002
[PubMed]
 
Baldessarini RJ, Cohen BM, Teicher MH: Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses. Arch Gen Psychiatry 45:79–91, 1988
[PubMed]
 
Ban TA: Neuropsychopharmacology and the genetics of schizophrenia: a history of the diagnosis of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 28:753–762, 2004
[PubMed]
 
Bellack AS, Mueser KT: Psychosocial treatment for schizophrenia. Schizophr Bull 19:317–336, 1993
[PubMed]
 
Bellack AS, Gold JM, Buchanan RW: Cognitive rehabilitation for schizophrenia: problems, prospects, and strategies. Schizophr Bull 25:257–274, 1999
[PubMed]
 
Benabarre A, Vieta E, Colom F, et al: Bipolar disorder, schizoaffective disorder and schizophrenia: epidemiologic, clinical and prognostic differences. Eur Psychiatry 16:167–172, 2001
[PubMed]
 
Berenbaum H, Oltmanns TF: Emotional experience and expression in schizophrenia and depression. J Abnorm Psychol 101:37–44, 1992
[PubMed]
 
Berman KF, Zec RF, Weinberger DR: Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia, II: role of neuroleptic treatment, attention, and mental effort. Arch Gen Psychiatry 43:126–135, 1986
[PubMed]
 
Berrettini WH: Are schizophrenic and bipolar disorders related? A review of family and molecular studies. Biol Psychiatry 48:531–538, 2000
[PubMed]
 
Bilder RM, Mukherjee S, Rieder RO, et al: Symptomatic and neuropsychological components of defect states. Schizophr Bull 11:409–419, 1985
[PubMed]
 
Bland RC, Parker JH, Orn H: Prognosis in schizophrenia: prognostic predictors and outcome. Arch Gen Psychiatry 35:72–77, 1978
[PubMed]
 
Bombin I, Arango C, Buchanan RW: Significance and meaning of neurological signs in schizophrenia: two decades later. Schizophr Bull 31:962–977, 2005
[PubMed]
 
Brenner CA, Lysaker PH, Wilt MA, et al: Visual processing and neuropsychological function in schizophrenia and schizoaffective disorder. Psychiatry Res 111:125–136, 2002
[PubMed]
 
Bromet EJ, Fennig S: Epidemiology and natural history of schizophrenia. Biol Psychiatry 46:871–881, 1999
[PubMed]
 
Broome MR, Woolley JB, Tabraham P, et al: What causes the onset of psychosis? Schizophr Res 79:23–34, 2005
[PubMed]
 
Brown AS, Begg MD, Gravenstein S, et al: Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 61:774–780, 2004
[PubMed]
 
Bustillo J, Lauriello J, Horan W, et al: The psychosocial treatment of schizophrenia: an update. Am J Psychiatry 158:163–175, 2001
[PubMed]
 
Callicott JH, Bertolino A, Mattay VS, et al: Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex 10:1078–1092, 2000
[PubMed]
 
Cannon M, Jones PB, Murray RM: Obstetric complications and schizophrenia: historical and meta-analytic review. Am J Psychiatry 159:1080–1092, 2002
[PubMed]
 
Cardno AG, McGuffin P: Genetics and delusional disorder. Behav Sci Law 24:257–276, 2006
[PubMed]
 
Carlsson A, Lindqvist M: Effect of chlorpromazine or haloperidol on formation of 3methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol (Copenh) 20:140–144, 1963
[PubMed]
 
Carpenter WT Jr: Maintenance therapy of persons with schizophrenia. J Clin Psychiatry 57 (suppl 9):10–18, 1996
 
Carpenter WT Jr, Strauss JS: The prediction of outcome in schizophrenia, IV: eleven-year follow-up of the Washington IPSS cohort. J Nerv Ment Dis 179:517–525, 1991
[PubMed]
 
Cobb SR, Buhl EH, Halasy K, et al: Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378:75–78, 1995
[PubMed]
 
Cohen JD, Barch DM, Carter C, et al: Context-processing deficits in schizophrenia: converging evidence from three theoretically motivated cognitive tasks. J Abnorm Psychol 108:120–133, 1999
[PubMed]
 
Compton WM, Guze SB: The neo-Kraepelinian revolution in psychiatric diagnosis. Eur Arch Psychiatry Clin Neurosci 245:196–201, 1995
[PubMed]
 
Conley RR, Kelly DL: Management of treatment resistance in schizophrenia. Biol Psychiatry 50:898–911, 2001
[PubMed]
 
Corcoran R, Mercer G, Frith CD: Schizophrenia, symptomatology and social inference: investigating "theory of mind" in people with schizophrenia. Schizophr Res 17:5–13, 1995
[PubMed]
 
Corfas G, Roy K, Buxbaum JD: Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia. Nat Neurosci 7:575–580, 2004
[PubMed]
 
Corrigan PW, Nelson DR: Factors that affect social cue recognition in schizophrenia. Psychiatry Res 78:189–196, 1998
[PubMed]
 
Creese I, Burt DR, Snyder SH: Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483, 1976
[PubMed]
 
Crow TJ: The two-syndrome concept: origins and current status. Schizophr Bull 11:471–486, 1985
[PubMed]
 
Davidson M, Reichenberg A, Rabinowitz J, et al: Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry 156:1328–1335, 1999
[PubMed]
 
Davies G, Welham J, Chant D, et al: A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia. Schizophr Bull 29:587–593, 2003
[PubMed]
 
Davies LM, Drummond MF: Economics and schizophrenia: the real cost. Br J Psychiatry Suppl (25):18–21, 1994
 
Davis JM, Kane JM, Marder SR, et al: Dose response of prophylactic antipsychotics. J Clin Psychiatry 54 (suppl): 24–30, 1993
 
Dickerson FB, Lehman AF: Evidence-based psychotherapy for schizophrenia. J Nerv Ment Dis 194:3–9, 2006
[PubMed]
 
Dierks T, Linden DE, Jandl M, et al: Activation of Heschl's gyrus during auditory hallucinations. Neuron 22:615–621, 1999
[PubMed]
 
Dilk MN, Bond GR: Meta-analytic evaluation of skills training research for individuals with severe mental illness. J Consult Clin Psychol 64:1337–1346, 1996
[PubMed]
 
Earnst KS, Kring AM: Emotional responding in deficit and non-deficit schizophrenia. Psychiatry Res 88:191–207, 1999
[PubMed]
 
Endicott J, Forman JB, Spitzer RL: Research approaches to diagnostic classification in schizophrenia. Birth Defects Orig Artic Ser 14:41–57, 1978
[PubMed]
 
Escamilla MA: Diagnosis and treatment of mood disorders that co-occur with schizophrenia. Psychiatr Serv 52:911–919, 2001
[PubMed]
 
Feighner JP, Robins E, Guze SB, et al: Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 26:57–63, 1972
[PubMed]
 
Fenton WS, Blyler CR, Heinssen RK: Determinants of medication compliance in schizophrenia: empirical and clinical findings. Schizophr Bull 23:637–651, 1997
[PubMed]
 
Frith CD, Corcoran R: Exploring "theory of mind" in people with schizophrenia. Psychol Med 26:521–530, 1996
[PubMed]
 
Geller JL: A report on the "worst" state hospital recidivists in the US. Hosp Community Psychiatry 43:904–908, 1992
[PubMed]
 
Gershon ES, DeLisi LE, Hamovit J, et al: A controlled family study of chronic psychoses: schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 45:328–336, 1988
[PubMed]
 
Gitlin M, Nuechterlein K, Subotnik KL, et al: Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia. Am J Psychiatry 158:1835–1842, 2001
[PubMed]
 
Goldman-Rakic PS: Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci 6:348–357, 1994
[PubMed]
 
Goodwin DW, Alderson P, Rosenthal R: Clinical significance of hallucinations in psychiatric disorders: a study of 116 hallucinatory patients. Arch Gen Psychiatry 24:76–80, 1971
[PubMed]
 
Gottesman II: Schizophrenia Genesis: The Origins of Madness. New York, WH Freeman, 1991
 
Grace AA, Bunney BS, Moore H, et al: Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs. Trends Neurosci 20:31–37, 1997
[PubMed]
 
Green AI, Canuso CM, Brenner MJ, et al: Detection and management of comorbidity in patients with schizophrenia. Psychiatr Clin North Am 26:115–139, 2003
[PubMed]
 
Green M, Walker E: Symptom correlates of vulnerability to backward masking in schizophrenia. Am J Psychiatry 143:181–186, 1986
[PubMed]
 
Green MF: What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153:321–330, 1996
[PubMed]
 
Gunderson JG, Frank AF, Katz HM, et al: Effects of psychotherapy in schizophrenia, II: comparative outcome of two forms of treatment. Schizophr Bull 10:564–598, 1984
[PubMed]
 
Harrison PJ: The neuropathology of schizophrenia: a critical review of the data and their interpretation. Brain 122 (pt 4):593–624, 1999
 
Harrow M, Jobe TH: Longitudinal studies of outcome and recovery in schizophrenia and early intervention: can they make a difference? Can J Psychiatry 50:879–880, 2005
[PubMed]
 
Harvey PD, Keefe RS: Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 158:176–184, 2001
[PubMed]
 
Hegarty JD, Baldessarini RJ, Tohen M, et al: One hundred years of schizophrenia: a meta-analysis of the outcome literature. Am J Psychiatry 151:1409–1416, 1994
[PubMed]
 
Heres S, Davis J, Maino K, et al: Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. Am J Psychiatry 163:185–194, 2006
[PubMed]
 
Hoffman RE, Boutros NN, Hu S, et al: Transcranial magnetic stimulation and auditory hallucinations in schizophrenia. Lancet 355:1073–1075, 2000
[PubMed]
 
Hoffman RE, Gueorguieva R, Hawkins KA, et al: Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Biol Psychiatry 58:97–104, 2005
[PubMed]
 
Hogarty GE, Kornblith SJ, Greenwald D, et al: Personal therapy: a disorder-relevant psychotherapy for schizophrenia. Schizophr Bull 21:379–393, 1995
[PubMed]
 
Hogarty GE, Greenwald D, Ulrich RF, et al: Three-year trials of personal therapy among schizophrenic patients living with or independent of family, II: effects on adjustment of patients. Am J Psychiatry 154:1514–1524, 1997
[PubMed]
 
Hosak L, Libiger J: Antiepileptic drugs in schizophrenia: a review. Eur Psychiatry 17:371–378, 2002
[PubMed]
 
Howard A, Tamas G, Soltesz I: Lighting the chandelier: new vistas for axo-axonic cells. Trends Neurosci 28:310–316, 2005
[PubMed]
 
Ingvar DH, Franzen G: Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia. Acta Psychiatr Scand 50:425–462, 1974
[PubMed]
 
Issakidis C, Sanderson K, Teesson M, et al: Intensive case management in Australia: a randomized controlled trial. Acta Psychiatr Scand 99:360–367, 1999
[PubMed]
 
Jablensky A: Epidemiology of schizophrenia: the global burden of disease and disability. Eur Arch Psychiatry Clin Neurosci 250:274–285, 2000
[PubMed]
 
Javitt DC, Zukin SR: Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148:1301–1308, 1991
[PubMed]
 
Javitt DC, Strous RD, Grochowski S, et al: Impaired precision, but normal retention, of auditory sensory ("echoic") memory information in schizophrenia. J Abnorm Psychol 106:315–324, 1997
[PubMed]
 
Jeste DV, del Carmen R, Lohr JB, et al: Did schizophrenia exist before the eighteenth century? Compr Psychiatry 26:493–503, 1985
[PubMed]
 
Jobe TH, Harrow M: Long-term outcome of patients with schizophrenia: a review. Can J Psychiatry 50:892–900, 2005
[PubMed]
 
Johnstone EC, Crow TJ, Frith CD, et al: Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 2:924–926, 1976
[PubMed]
 
Jones P, Rodgers B, Murray R, et al: Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 344:1398–1402, 1994
[PubMed]
 
Kanaan RA, Kim JS, Kaufmann WE, et al: Diffusion tensor imaging in schizophrenia. Biol Psychiatry 58:921–929, 2005
[PubMed]
 
Kane JM, Honigfeld G, Singer J, et al: Clozapine in treatment-resistant schizophrenics. Psychopharmacol Bull 24:62–67, 1988
[PubMed]
 
Kay SR, Fiszbein A, Opler LA: The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276, 1987
[PubMed]
 
Kety SS, Rosenthal D, Wender PH, et al: Mental illness in the biological and adoptive families of adopted schizophrenics. Am J Psychiatry 128:302–306, 1971
[PubMed]
 
Kirkpatrick B, Conley RC, Kakoyannis A, et al: Interstitial cells of the white matter in the inferior parietal cortex in schizophrenia: an unbiased cell-counting study. Synapse 34:95–102, 1999
[PubMed]
 
Kirkpatrick B, Buchanan RW, Ross DE, et al: A separate disease within the syndrome of schizophrenia. Arch Gen Psychiatry 58:165–171, 2001
[PubMed]
 
Kohler CG, Bilker W, Hagendoorn M, et al: Emotion recognition deficit in schizophrenia: association with symptomatology and cognition. Biol Psychiatry 48:127–136, 2000
[PubMed]
 
Kontaxakis VP, Ferentinos PP, Havaki-Kontaxakis BJ, et al: Randomized controlled augmentation trials in clozapine-resistant schizophrenic patients: a critical review. Eur Psychiatry 20:409–415, 2005
[PubMed]
 
Kraepelin E: Psychiatrie: Ein kurzes Lehrbuch für Studirende und Aerzte, 4th Edition. Leipzig, Germany, Abel (Meiner), 1893
 
Kubicki M, McCarley R, Westin CF, et al: A review of diffusion tensor imaging studies in schizophrenia. J Psychiatr Res 41(1–2):15–30, 2007
[PubMed]
 
Lauriello J, Lenroot R, Bustillo JR: Maximizing the synergy between pharmacotherapy and psychosocial therapies for schizophrenia. Psychiatr Clin North Am 26:191–211, 2003
[PubMed]
 
Lawrie SM, Abukmeil SS: Brain abnormality in schizophrenia: a systematic and quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiatry 172:110–120, 1998
[PubMed]
 
Lehman AF: Vocational rehabilitation in schizophrenia. Schizophr Bull 21:645–656, 1995
[PubMed]
 
Lehman AF: Developing an outcomes-oriented approach for the treatment of schizophrenia. J Clin Psychiatry 60 (suppl 19):30–35; discussion 36–37, 1999
 
Lenroot R, Bustillo JR, Lauriello J, et al: Integrated treatment of schizophrenia. Psychiatr Serv 54:1499–1507, 2003
[PubMed]
 
Lewis CM, Levinson DF, Wise LH, et al: Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am J Hum Genet 73:34–48, 2003
[PubMed]
 
Lewis DA: GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res Brain Res Rev 31:270–276, 2000
[PubMed]
 
Lewis DA, Levitt P: Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 25:409–432, 2002
[PubMed]
 
Liberman RP, Wallace CJ, Blackwell G, et al: Skills training versus psychosocial occupational therapy for persons with persistent schizophrenia. Am J Psychiatry 155:1087–1091, 1998
[PubMed]
 
Liddle PF: The symptoms of chronic schizophrenia: a re-examination of the positive-negative dichotomy. Br J Psychiatry 151:145–151, 1987
[PubMed]
 
Lieberman JA: Prediction of outcome in first-episode schizophrenia. J Clin Psychiatry 54 (suppl):13–17, 1993
 
Lieberman JA, Perkins D, Belger A, et al: The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol Psychiatry 50:884–897, 2001
[PubMed]
 
Lieberman JA, Stroup TS, McEvoy JP, et al: Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1223, 2005
[PubMed]
 
Loscher W, Potschka H: Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci 6:591–602, 2005
[PubMed]
 
Malla A, Payne J: First-episode psychosis: psychopathology, quality of life, and functional outcome. Schizophr Bull 31:650–671, 2005
[PubMed]
 
Manoach DS, Gollub RL, Benson ES, et al: Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry 48:99–109, 2000
[PubMed]
 
May PR, Tuma AH, Dixon WJ, et al: Schizophrenia: a follow-up study of the results of five forms of treatment. Arch Gen Psychiatry 38:776–784, 1981
[PubMed]
 
McEvoy JP, Lieberman JA, Stroup TS, et al: Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 163:600–610, 2006
[PubMed]
 
McGlashan TH: The Chestnut Lodge follow-up study, II: long-term outcome of schizophrenia and the affective disorders. Arch Gen Psychiatry 41:586–601, 1984
[PubMed]
 
McGlashan TH: Duration of untreated psychosis in first-episode schizophrenia: marker or determinant of course? Biol Psychiatry 46:899–907, 1999
[PubMed]
 
McGrath J, Saha S, Welham J, et al: A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med 2:13, 2004
[PubMed]
 
McGue M, Gottesman II: A single dominant gene still cannot account for the transmission of schizophrenia. Arch Gen Psychiatry 46:478–480, 1989
[PubMed]
 
Meltzer HY, Pringuey D: Treatment-resistant schizophrenia: the importance of early detection and treatment. Introduction. J Clin Psychopharmacol 18 (2 suppl 1):1S, 1998
 
Meltzer HY, Li Z, Kaneda Y, et al: Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27:1159–1172, 2003
[PubMed]
 
Miyamoto S, Duncan GE, Marx CE, et al: Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 10:79–104, 2005
[PubMed]
 
Moffitt TE, Caspi A, Rutter M: Strategy for investigating interactions between measured genes and measured environments. Arch Gen Psychiatry 62:473–481, 2005
[PubMed]
 
Mueser KT, McGurk SR: Schizophrenia. Lancet 363:2063–2072, 2004
[PubMed]
 
Murray CJ, Lopez AD: Evidence-based health policy—lessons from the Global Burden of Disease Study. Science 274:740–743, 1996
[PubMed]
 
Naber D, Lambert M, Karow A: [Subjective well-being under antipsychotic treatment and its meaning for compliance and course of disease] [German]. Psychiatr Prax 31 (suppl 2):S230–232, 2004
 
Naz B, Bromet EJ, Mojtabai R: Distinguishing between first-admission schizophreniform disorder and schizophrenia. Schizophr Res 62:51–58, 2003
[PubMed]
 
Newcomer JW: Metabolic risk during antipsychotic treatment. Clin Ther 26:1936–1946, 2004
[PubMed]
 
Nicolson R, Rapoport JL: Childhood-onset schizophrenia: rare but worth studying. Biol Psychiatry 46:1418–1428, 1999
[PubMed]
 
Owen MJ, Craddock N, O'Donovan MC: Schizophrenia: genes at last? Trends Genet 21:518–525, 2005
[PubMed]
 
Palha AP, Esteves MF: The origin of dementia praecox. Schizophr Res 28:99–103, 1997
[PubMed]
 
Penn DL, Mueser KT: Research update on the psychosocial treatment of schizophrenia. Am J Psychiatry 153:607–617, 1996
[PubMed]
 
Penn DL, Waldheter EJ, Perkins DO, et al: Psychosocial treatment for first-episode psychosis: a research update. Am J Psychiatry 162:2220–2232, 2005
[PubMed]
 
Percudani M, Barbui C, Tansella M: Effect of second-generation antipsychotics on employment and productivity in individuals with schizophrenia: an economic perspective. Pharmacoeconomics 22:701–718, 2004
[PubMed]
 
Perlstein WM, Carter CS, Noll DC, et al: Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. Am J Psychiatry 158:1105–1113, 2001
[PubMed]
 
Perry W, Braff DL: Information-processing deficits and thought disorder in schizophrenia. Am J Psychiatry 151:363–367, 1994
[PubMed]
 
Peters E, Day S, McKenna J, et al: Delusional ideation in religious and psychotic populations. Br J Clin Psychol 38 (pt 1):83–96, 1999
 
Phillips LJ, McGorry PD, Yung AR, et al: Prepsychotic phase of schizophrenia and related disorders: recent progress and future opportunities. Br J Psychiatry Suppl 48:S33–44, 2005
 
Pinkham AE, Penn DL, Perkins DO, et al: Implications for the neural basis of social cognition for the study of schizophrenia. Am J Psychiatry 160:815–824, 2003
[PubMed]
 
Popken GJ, Bunney WE Jr, Potkin SG, et al: Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. Proc Natl Acad Sci U S A 97:9276–9280, 2000
[PubMed]
 
Ram R, Bromet EJ, Eaton WW, et al: The natural course of schizophrenia: a review of first-admission studies. Schizophr Bull 18:185–207, 1992
[PubMed]
 
Rasmussen KG, Sampson SM, Rummans TA: Electroconvulsive therapy and newer modalities for the treatment of medication-refractory mental illness. Mayo Clin Proc 77:552–556, 2002
[PubMed]
 
Remington G, Kapur S: D2 and 5-HT2 receptor effects of antipsychotics: bridging basic and clinical findings using PET. J Clin Psychiatry 60 (suppl 10):15–19, 1999
 
Remschmidt H: Early onset schizophrenia as a progressive-deteriorating developmental disorder: evidence from child psychiatry. J Neural Transm 109:101–117, 2002
[PubMed]
 
Risch N: Genetic linkage and complex diseases, with special reference to psychiatric disorders. Genet Epidemiol 7:3–16; discussion 17–45, 1990
 
Robinson D, Woerner MG, Alvir JM, et al: Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 56:241–247, 1999
[PubMed]
 
Robinson DG, Woerner MG, Delman HM, et al: Pharmacological treatments for first-episode schizophrenia. Schizophr Bull 31:705–722, 2005
[PubMed]
 
Saccuzzo DP, Braff DL: Early information processing deficit in schizophrenia: new findings using schizophrenic subgroups and manic control subjects. Arch Gen Psychiatry 38:175–179, 1981
[PubMed]
 
Sakel M: A new treatment of schizophrenia. Am J Psychiatry 93:829–841, 1937
 
Salem JE, Kring AM, Kerr SL: More evidence for generalized poor performance in facial emotion perception in schizophrenia. J Abnorm Psychol 105:480–483, 1996
[PubMed]
 
Sartorius N, Jablensky A, Shapiro R: Two-year follow-up of the patients included in the WHO International Pilot Study of Schizophrenia. Psychol Med 7:529–541, 1977
[PubMed]
 
Schneider F, Gur RC, Koch K, et al: Impairment in the specificity of emotion processing in schizophrenia. Am J Psychiatry 163:442–447, 2006
[PubMed]
 
Seeman P, Lee T, Chau-Wong M, et al: Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261:717–719, 1976
[PubMed]
 
Shelley AM, Ward PB, Catts SV, et al: Mismatch negativity: an index of a preattentive processing deficit in schizophrenia. Biol Psychiatry 30:1059–1062, 1991
[PubMed]
 
Smith DA, Buckley PF: Pharmacotherapy of delusional disorders in the context of offending and the potential for compulsory treatment. Behav Sci Law 24:351–367, 2006
[PubMed]
 
Steen RG, Mull C, McClure R, et al: Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. Br J Psychiatry 188:510–518, 2006
[PubMed]
 
Stefansson H, Sigurdsson E, Steinthorsdottir V, et al: Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet 71:877–892, 2002
[PubMed]
 
Stern RG, Kahn RS, Davidson M: Predictors of response to neuroleptic treatment in schizophrenia. Psychiatr Clin North Am 16:313–338, 1993
[PubMed]
 
Stone MH: Exploratory psychotherapy in schizophrenia-spectrum patients: a reevaluation in the light of long-term follow-up of schizophrenic and borderline patients. Bull Menninger Clin 50:287–306, 1986
[PubMed]
 
Strakowski SM: Diagnostic validity of schizophreniform disorder. Am J Psychiatry 151:815–824, 1994
[PubMed]
 
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
[PubMed]
 
Susser E, Neugebauer R, Hoek HW, et al: Schizophrenia after prenatal famine: further evidence. Arch Gen Psychiatry 53:25–31, 1996
[PubMed]
 
Susser ES, Schaefer CA, Brown AS, et al: The design of the Prenatal Determinants of Schizophrenia Study. Schizophr Bull 26:257–273, 2000
[PubMed]
 
Tandon R: In conclusion: does antipsychotic treatment modify the long-term course of schizophrenic illness? J Psychiatr Res 32:251–253, 1998
[PubMed]
 
Tandon R, Fleischhacker WW: Comparative efficacy of antipsychotics in the treatment of schizophrenia: a critical assessment. Schizophr Res 79:145–155, 2005
[PubMed]
 
Terkelsen KG, Menikoff A: Measuring the costs of schizophrenia: implications for the post-institutional era in the US. Pharmacoeconomics 8:199–222, 1995
[PubMed]
 
Tharyan P, Adams CE: Electroconvulsive therapy for schizophrenia. Cochrane Database Syst Rev (2):CD000076, 2005
 
Tienari P, Wynne LC, Moring J, et al: The Finnish adoptive family study of schizophrenia: implications for family research. Br J Psychiatry Suppl (23):20–26, 1994
 
Torrey EF, Miller J, Rawlings R, et al: Seasonality of births in schizophrenia and bipolar disorder: a review of the literature. Schizophr Res 28:1–38, 1997
[PubMed]
 
Tsuang MT, Winokur G: The Iowa 500: field work in a 35-year follow-up of depression, mania, and schizophrenia. Can Psychiatr Assoc J 20:359–365, 1975
[PubMed]
 
Turkington D, Kingdon D, Weiden PJ: Cognitive behavior therapy for schizophrenia. Am J Psychiatry 163:365–373, 2006
[PubMed]
 
Turner TH: Schizophrenia and mental handicap: an historical review, with implications for further research. Psychol Med 19:301–314, 1989
[PubMed]
 
Turner TH: Schizophrenia as a permanent problem: some aspects of historical evidence in the recency (new disease) hypothesis. Hist Psychiatry 3:413–429, 1992
[PubMed]
 
Volk DW, Austin MC, Pierri JN, et al: Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia. Arch Gen Psychiatry 57:237–245, 2000
[PubMed]
 
U.S. Institute of Medicine: Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenges in the Developing World. Washington, DC, National Academy of Sciences, 2001
 
Walker EF, Savoie T, Davis D: Neuromotor precursors of schizophrenia. Schizophr Bull 20:441–451, 1994
[PubMed]
 
Walker E, Kestler L, Bollini A, et al: Schizophrenia: etiology and course. Annu Rev Psychol 55:401–430, 2004
[PubMed]
 
Weinberger DR, Berman KF, Zec RF: Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia, I: regional cerebral blood flow evidence. Arch Gen Psychiatry 43:114–124, 1986
[PubMed]
 
Wolkowitz OM, Pickar D: Benzodiazepines in the treatment of schizophrenia: a review and reappraisal. Am J Psychiatry 148:714–726, 1991
[PubMed]
 
Wu EQ, Birnbaum HG, Shi L, et al: The economic burden of schizophrenia in the United States in 2002. J Clin Psychiatry 66:1122–1129, 2005
[PubMed]
 
Wyatt RJ, Henter ID: The effects of early and sustained intervention on the long-term morbidity of schizophrenia. J Psychiatr Res 32:169–177, 1998
[PubMed]
 
Xiberas X, Martinot JL, Mallet L, et al: Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Br J Psychiatry 179:503–508, 2001
[PubMed]
 
Zygmunt A, Olfson M, Boyer CA, et al: Interventions to improve medication adherence in schizophrenia. Am J Psychiatry 159:1653–1664, 2002
[PubMed]
 
+

CME Activity

Add a subscription to complete this activity and earn CME credit.
Sample questions:
1.
A number of physicians in the eighteenth and nineteenth centuries made important contributions to the understanding of schizophrenia. Which of the following individuals outlined a set of "first-rank" symptoms in an attempt to establish a discrete criteria set for the diagnosis?
2.
Eugen Bleuler exerted great influence on modern notions of schizophrenia, defining the primary features of schizophrenia as the "four As." Which of the following is not one of Bleuler's "four As"?
3.
DSM-IV-TR (American Psychiatric Association 2000) recognizes five subtypes of schizophrenia: paranoid, disorganized, catatonic, undifferentiated, and residual. Which of these subtypes is associated with better premorbid functioning, older age at onset, and higher social and occupational function after illness onset?
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 20.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 21.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 17.  >
APA Practice Guidelines > Chapter 4.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
PubMed Articles
Schizophrenia genetics comes of age. Neuron 2014;83(4):760-3.
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation