0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

Articles   |    
Gray Matter Volume as an Intermediate Phenotype for Psychosis: Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP)
Elena I. Ivleva, M.D., Ph.D.; Anup S. Bidesi, B.S.; Matcheri S. Keshavan, M.D.; Godfrey D. Pearlson, M.D.; Shashwath A. Meda, Ph.D.; Darko Dodig, M.D.; Amanda F. Moates, Ph.D.; Hanzhang Lu, Ph.D.; Alan N. Francis, M.S.; Neeraj Tandon, B.S.; David J. Schretlen, Ph.D.; John A. Sweeney, Ph.D.; Brett A. Clementz, Ph.D.; Carol A. Tamminga, M.D.
Am J Psychiatry 2013;170:1285-1296. doi:10.1176/appi.ajp.2013.13010126
View Author and Article Information

Dr. Keshavan has received a grant from Sunovion; Dr. Pearlson has received consultant fees from Bristol-Myers Squibb; Dr. Sweeney has received funds from Bristol-Myers Squibb, Eli Lilly, Janssen, Roche, and Takeda; disclosures for Dr. Tamminga, as a Deputy Editor of the American Journal of Psychiatry, were published in the January 2013 issue.

Supported by NIMH (MH077851 to C.A.T., MH078113 to M.S.K., MH077945 to G.D.P., MH077852 to Gunvant K. Thaker, M.D., and MH077862 to J.A.S.). NIMH had no further role in study design; collection, analysis, and interpretation of data; writing of the report; or in the decision to submit the article for publication.

From the University of Texas Southwestern Medical Center, Dallas; Beth Israel Deaconess Hospital, Harvard Medical School, Boston; Institute of Living/Hartford Hospital, Hartford, Conn.; Yale School of Medicine, New Haven; the Department of Psychiatry and Behavioral Sciences and the Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore; and the University of Georgia, Athens, Ga.

Address correspondence to Dr. Ivleva (elena.ivleva@utsouthwestern.edu).

Copyright © 2013 by the American Psychiatric Association

Received January 28, 2013; Revised April 06, 2013; Accepted May 17, 2013.

Abstract

Objective  The study examined gray matter volume across psychosis diagnoses organized by dimensional and DSM-IV categories from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) sample.

Method  In total, 351 probands with psychosis (146 with schizophrenia, 90 with schizoaffective disorder, and 115 with psychotic bipolar I disorder), 369 of their first-degree relatives (134 were relatives of individuals with schizophrenia, 106 of individuals with schizoaffective disorder, and 129 of individuals with psychotic bipolar I disorder), and 200 healthy comparison subjects were assessed. Gray matter volumes from 3-T T1-weighted images were analyzed using the VBM8 toolbox for SPM8, and outcomes were determined at a false discovery rate-corrected threshold of p<0.005.

Results  Across the psychosis dimension, probands (N=351) and relatives with psychosis spectrum disorders (N=34) showed substantial overlapping gray matter reductions throughout the neocortex, whereas relatives without psychosis spectrum (N=332) had normal gray matter volumes relative to comparison subjects. Across DSM-IV diagnoses, schizophrenia and schizoaffective probands showed overlapping gray matter reductions in numerous cortical and subcortical regions, whereas psychotic bipolar probands showed limited gray matter reductions localized to the frontotemporal cortex relative to comparison subjects. All relative groups had gray matter volumes that did not differ from comparison subjects.

Conclusions  Across the dimensional psychosis categories, these findings indicate extensive neocortical gray matter reductions in psychosis probands and relatives with psychosis spectrum disorders, possibly reflecting lifetime psychosis burden, but normal gray matter in nonpsychotic relatives. Traditional DSM-IV psychosis grouping revealed partially divergent gray matter phenotypes for probands with schizophrenia or schizoaffective disorder (extensive neocortical or subcortical gray matter reductions) relative to those with psychotic bipolar disorder (smaller reductions were limited to frontotemporal regions). The dimensional conceptualization of psychosis appears useful in defining more homogenous disease categories that may help identify underlying psychosis biomarkers and develop a biologically driven diagnostic system and targeted treatments.

Abstract Teaser
Figures in this Article

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 1. Groups in the Psychosis Dimension and DSM-IV Analyses in a Study of Gray Matter Volumes in Psychosis

a Four relatives (two relatives of probands with schizophrenia, one relative of a proband with schizoaffective disorder, and one relative of a proband with psychotic bipolar I disorder) were not included in the psychosis dimension analysis as a result of limited diagnostic information that did not allow for their accurate categorization into either the “relatives with psychosis spectrum personality disorders” or “nonpsychotic relatives” groups.

FIGURE 2. Gray Matter Volume Differences Among Psychosis Dimension Groups and Healthy Comparison Subjects

a Panel A shows the regional gray matter volume reductions in the psychosis probands and relatives with psychosis spectrum disorders as compared with healthy comparison subjects. The bar graphs depict cumulative gray matter volume reductions in proband and relatives with psychosis spectrum personality disorders compared with healthy comparison subjects/zero line; voxels of reduction are averaged across the right and the left hemispheres. Panel B shows the regional gray matter volume reductions in probands and relatives with cluster A or psychosis spectrum personality disorders contrasted with nonpsychotic relatives. All imaging contrasts are presented at p<0.005, false discovery rate corrected, k=200 voxels threshold. Images are displayed in neurological convention. Color bars in panel A and panel B indicate t scores.

FIGURE 3. Gray Matter Volume Differences Within the DSM-IV Diagnosis Among Proband Groups and Healthy Comparison Subjects

a Panel A shows regional gray matter volume reductions in probands with schizophrenia, schizoaffective disorder, and psychotic bipolar I disorders relative to healthy comparison subjects. The bar graph depicts cumulative gray matter volume reductions in the three proband groups relative to healthy comparison subjects/zero line; voxels of reduction are averaged across the right and the left hemispheres. Panel B shows the regional gray matter volume reductions in probands with schizophrenia and schizoaffective disorder contrasted with bipolar probands. All imaging contrasts are presented at p<0.005, false discovery rate corrected, k=200 voxels threshold. Images are displayed in neurological convention. Color bars in panel A and panel B indicate t scores.

Anchor for Jump
TABLE 1.Sociodemographic and Clinical Characteristics of the Sample in a Study of Gray Matter Volumes in Psychosis
Table Footer Note

a WRAT=Wide Range Achievement Test; PANSS=Positive and Negative Syndrome Scale; MADRS=Montgomery–Åsberg Depression Rating Scale; GAF=Global Assessment of Functioning.

Table Footer Note

b Post hoc statistics are presented as follows: age: schizophrenia probands compared with relatives of schizophrenia probands, p<0.001; schizophrenia probands compared with relatives of schizoaffective disorder probands, p<0.001; schizophrenia probands compared with relatives of psychotic bipolar I probands, p=0.07 (trend); schizoaffective disorder probands compared with relatives of schizophrenia probands, p=0.002; schizoaffective disorder probands compared with relatives of schizoaffective disorder probands, p=0.01; psychotic bipolar I probands compared with relatives of schizophrenia probands, p<0.001; psychotic bipolar I probands compared with relatives of schizoaffective disorder probands, p<0.001; psychotic bipolar I probands compared with relatives of psychotic bipolar I probands, p=0.06 (trend). Sex: more male individuals among schizophrenia probands compared with schizoaffective disorder probands (χ2=17.84, df=1, p<0.001), psychotic bipolar I disorder probands (χ2=36.85, df=1, p<0.001), relatives of schizophrenia probands (χ2=43.17, df=1, p<0.001), relatives of schizoaffective disorder probands (χ2=30.04, df=1, p<0.001), relatives of psychotic bipolar I probands (χ2=35.21, df=1, p<0.001), and healthy comparison subjects (χ2=18.55, df=1, p<0.001). Handedness: higher proportion of ambidextrous individuals who were relatives of schizoaffective disorder probands compared with relatives of schizophrenia probands (χ2=4.24, df=1, p=0.04), relatives of psychotic bipolar I probands (χ2=4.43, df=1, p=0.04), and healthy comparison subjects (χ2=2.99, df=1, p=0.08) (trend). Race: more African Americans were schizophrenia probands compared with healthy comparison subjects (χ2=11.79, df=1, p<0.001) and psychotic bipolar I probands (χ2=16.28, df=1, p≤0.001); were schizoaffective disorder probands compared with healthy comparison subjects (χ2=5.84, df=1, p=0.01) and psychotic bipolar I probands (χ2=9.99, df=1, p=0.001); and were relatives of schizophrenia probands compared with healthy comparison subjects (χ2=3.55, df=1, p=0.059) (trend). Fewer African Americans were relatives of psychotic bipolar I probands compared with healthy comparison subjects (χ2=7.21, df=1, p=0.007), relatives of schizophrenia probands (χ2=18.04, df=1, p<0.001) and relatives of schizoaffective disorder probands (χ2=6.81, df=1, p=0.009). Education: lower education in schizophrenia probands compared with psychotic bipolar I probands, relatives of schizophrenia probands, relatives of schizoaffective disorder probands, relatives of psychotic bipolar I probands, and healthy comparison subjects (p<0.001 in all cases); and in schizoaffective disorder probands compared with psychotic bipolar I disorder probands (p=0.001), relatives of schizophrenia probands (p<0.001), relatives of schizoaffective disorder probands (p=0.001), relatives of psychotic bipolar I probands (p<0.001), and healthy comparison subjects (p<0.001). WRAT: lower WRAT IQ scores in schizophrenia probands and schizoaffective disorder probands compared with psychotic bipolar I probands, relatives of schizoaffective disorder probands, relatives of schizoaffective disorder probands, relatives of psychotic bipolar I probands, and healthy comparison subjects (p<0.001 in all cases); and in relatives of schizophrenia probands compared with psychotic bipolar I probands (p=0.03). PANSS total: lower scores in psychotic bipolar I probands compared with schizophrenia probands (p<0.001) and schizoaffective disorder probands (p<0.001). PANSS positive symptoms subscale: lower scores in psychotic bipolar I probands compared with schizophrenia probands (p<0.001) and schizoaffective disorder probands (p<0.001). PANSS negative symptoms subscale: lower scores in psychotic bipolar I probands compared with schizophrenia probands (p<0.001) and schizoaffective disorder probands (p<0.001). PANSS general symptoms subscale: higher scores in schizoaffective disorder probands compared with schizophrenia probands (p=0.03) and psychotic bipolar I disorder probands (p<0.001). MADRS: higher scores in schizoaffective disorder probands compared with schizophrenia probands (p<0.001) and psychotic bipolar I disorder probands (p=0.009). GAF: lower scores in all proband and relative groups compared with healthy comparison subjects (p<0.001 in all cases); in schizophrenia probands compared with psychotic bipolar I disorder probands and all relative groups (p<0.001 in all cases); in schizoaffective disorder probands compared with psychotic bipolar I probands and all relative groups (p<0.001 in all cases); in psychotic bipolar I probands compared with all relative groups (p<0.001 in all cases).

Table Footer Note

c Medication data were not recorded in 19 probands (5.41%) and 87 relatives(23.14%).

Anchor for Jump
TABLE 2.Gray Matter Phenotypes Contrasted by the Psychosis Dimension and the DSM-IV Diagnosesa
Table Footer Note

a The arrows indicate gray matter volume reductions in probands and relatives with psychosis spectrum disorders when compared with healthy comparison subjects. The equal signs indicate no differences in gray matter volume between nonpsychotic relatives and categorical diagnoses categorical diagnoses relative groups when compared with healthy comparison subjects.

+

References

Thaker  GK:  Neurophysiological endophenotypes across bipolar and schizophrenia psychosis.  Schizophr Bull 2008; 34:760–773
[CrossRef] | [PubMed]
 
Tamminga  CA;  Ivleva  EI;  Keshavan  MS;  Pearlson  GD;  Clementz  BA;  Witte  B;  Morris  DW;  Elliott  A;  Thaker  GK;  Sweeney  JA:  Clinical phenotypes of psychosis in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP).  Am J Psychiatry 2013; 170:1263–1275
 
Honea  R;  Crow  TJ;  Passingham  D;  Mackay  CE:  Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies.  Am J Psychiatry 2005; 162:2233–2245
[CrossRef] | [PubMed]
 
Ellison-Wright  I;  Glahn  DC;  Laird  AR;  Thelen  SM;  Bullmore  E:  The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis.  Am J Psychiatry 2008; 165:1015–1023
[CrossRef] | [PubMed]
 
Yu  K;  Cheung  C;  Leung  M;  Li  Q;  Chua  S;  McAlonan  G:  Are bipolar disorder and schizophrenia neuroanatomically distinct? an anatomical likelihood meta-analysis.  Front Hum Neurosci 2010; 4:189
[CrossRef] | [PubMed]
 
Kempton  MJ;  Geddes  JR;  Ettinger  U;  Williams  SC;  Grasby  PM:  Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder.  Arch Gen Psychiatry 2008; 65:1017–1032
[CrossRef] | [PubMed]
 
Hallahan  B;  Newell  J;  Soares  JC;  Brambilla  P;  Strakowski  SM;  Fleck  DE;  Kieseppä  T;  Altshuler  LL;  Fornito  A;  Malhi  GS;  McIntosh  AM;  Yurgelun-Todd  DA;  Labar  KS;  Sharma  V;  MacQueen  GM;  Murray  RM;  McDonald  C:  Structural magnetic resonance imaging in bipolar disorder: an international collaborative mega-analysis of individual adult patient data.  Biol Psychiatry 2011; 69:326–335
[CrossRef] | [PubMed]
 
Selvaraj  S;  Arnone  D;  Job  D;  Stanfield  A;  Farrow  TF;  Nugent  AC;  Scherk  H;  Gruber  O;  Chen  X;  Sachdev  PS;  Dickstein  DP;  Malhi  GS;  Ha  TH;  Ha  K;  Phillips  ML;  McIntosh  AM:  Grey matter differences in bipolar disorder: a meta-analysis of voxel-based morphometry studies.  Bipolar Disord 2012; 14:135–145
[CrossRef] | [PubMed]
 
Strasser  HC;  Lilyestrom  J;  Ashby  ER;  Honeycutt  NA;  Schretlen  DJ;  Pulver  AE;  Hopkins  RO;  Depaulo  JR;  Potash  JB;  Schweizer  B;  Yates  KO;  Kurian  E;  Barta  PE;  Pearlson  GD:  Hippocampal and ventricular volumes in psychotic and nonpsychotic bipolar patients compared with schizophrenia patients and community control subjects: a pilot study.  Biol Psychiatry 2005; 57:633–639
[CrossRef] | [PubMed]
 
McDonald  C;  Bullmore  E;  Sham  P;  Chitnis  XA;  Suckling  J;  MacCabe  J;  Walshe  M;  Murray  RM:  Regional volume deviations of brain structure in schizophrenia and psychotic bipolar disorder: computational morphometry study.  Br J Psychiatry 2005; 186:369–377
[CrossRef] | [PubMed]
 
Ivleva  EI;  Bidesi  AS;  Thomas  BP;  Meda  SA;  Francis  A;  Moates  AF;  Witte  B;  Keshavan  MS;  Tamminga  CA:  Brain gray matter phenotypes across the psychosis dimension.  Psychiatry Res 2012; 204:13–24
[CrossRef] | [PubMed]
 
Abrams  DJ;  Rojas  DC;  Arciniegas  DB:  Is schizoaffective disorder a distinct categorical diagnosis? a critical review of the literature.  Neuropsychiatr Dis Treat 2008; 4:1089–1109
[CrossRef] | [PubMed]
 
Cannon  TD;  van Erp  TG;  Huttunen  M;  Lönnqvist  J;  Salonen  O;  Valanne  L;  Poutanen  VP;  Standertskjöld-Nordenstam  CG;  Gur  RE;  Yan  M:  Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls.  Arch Gen Psychiatry 1998; 55:1084–1091
[CrossRef] | [PubMed]
 
Radonić  E;  Rados  M;  Kalember  P;  Bajs-Janović  M;  Folnegović-Smalc  V;  Henigsberg  N:  Comparison of hippocampal volumes in schizophrenia, schizoaffective and bipolar disorder.  Coll Antropol 2011; 35(suppl 1):249–252
 
Palaniyappan  L;  Balain  V;  Liddle  PF:  The neuroanatomy of psychotic diathesis: a meta-analytic review.  J Psychiatr Res 2012; 46:1249–1256
[CrossRef] | [PubMed]
 
Hajek  T;  Cullis  J;  Novak  T;  Kopecek  M;  Blagdon  R;  Propper  L;  Stopkova  P;  Duffy  A;  Hoschl  C;  Uher  R;  Paus  T;  Young  LT;  Alda  M:  Brain structural signature of familial predisposition for bipolar disorder: replicable evidence for involvement of the right inferior frontal gyrus.  Biol Psychiatry 2013; 73:144–152
[CrossRef] | [PubMed]
 
Dickey  CC;  McCarley  RW;  Voglmaier  MM;  Niznikiewicz  MA;  Seidman  LJ;  Hirayasu  Y;  Fischer  I;  Teh  EK;  Van Rhoads  R;  Jakab  M;  Kikinis  R;  Jolesz  FA;  Shenton  ME:  Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter.  Biol Psychiatry 1999; 45:1393–1402
[CrossRef] | [PubMed]
 
Kawasaki  Y;  Suzuki  M;  Nohara  S;  Hagino  H;  Takahashi  T;  Matsui  M;  Yamashita  I;  Chitnis  XA;  McGuire  PK;  Seto  H;  Kurachi  M:  Structural brain differences in patients with schizophrenia and schizotypal disorder demonstrated by voxel-based morphometry.  Eur Arch Psychiatry Clin Neurosci 2004; 254:406–414
[CrossRef] | [PubMed]
 
Hazlett  EA;  Buchsbaum  MS;  Haznedar  MM;  Newmark  R;  Goldstein  KE;  Zelmanova  Y;  Glanton  CF;  Torosjan  Y;  New  AS;  Lo  JN;  Mitropoulou  V;  Siever  LJ:  Cortical gray and white matter volume in unmedicated schizotypal and schizophrenia patients.  Schizophr Res 2008; 101:111–123
[CrossRef] | [PubMed]
 
Honea  RA;  Meyer-Lindenberg  A;  Hobbs  KB;  Pezawas  L;  Mattay  VS;  Egan  MF;  Verchinski  B;  Passingham  RE;  Weinberger  DR;  Callicott  JH:  Is gray matter volume an intermediate phenotype for schizophrenia? a voxel-based morphometry study of patients with schizophrenia and their healthy siblings.  Biol Psychiatry 2008; 63:465–474
[CrossRef] | [PubMed]
 
First  MB;  Spitzer  RL;  Gibbon  M;  Williams  JBW:  Structured Clinical Interview for DSM-IV Axis I Disorders/Patient Edition (SCID-I/P) .  New York,  New York State Psychiatric Institute, Biometrics Research Department, 1996
 
Pfohl  B;  Blum  N;  Zimmerman  M:  Structured Interview for DSM-IV Personality .  Washington DC,  American Psychiatric Press, 1997
 
Kay  SR;  Fiszbein  A;  Opler  LA:  The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.  Schizophr Bull 1987; 13:261–276
[CrossRef] | [PubMed]
 
Montgomery  SA;  Åsberg  M:  A new depression scale designed to be sensitive to change.  Br J Psychiatry 1979; 134:382–389
[CrossRef] | [PubMed]
 
Young  RC;  Biggs  JT;  Ziegler  VE;  Meyer  DA:  A rating scale for mania: reliability, validity and sensitivity.  Br J Psychiatry 1978; 133:429–435
[CrossRef] | [PubMed]
 
Ashburner  J;  Friston  KJ:  Voxel-based morphometry: the methods.  Neuroimage 2000; 11:805–821
[CrossRef] | [PubMed]
 
Ashburner  J:  A fast diffeomorphic image registration algorithm.  Neuroimage 2007; 38:95–113
[CrossRef] | [PubMed]
 
Good  CD;  Johnsrude  IS;  Ashburner  J;  Henson  RN;  Friston  KJ;  Frackowiak  RS:  A voxel-based morphometric study of ageing in 465 normal adult human brains.  Neuroimage 2001; 14:21–36
[CrossRef] | [PubMed]
 
Li  W;  van Tol  MJ;  Li  M;  Miao  W;  Jiao  Y;  Heinze  HJ;  Bogerts  B;  He  H;  Walter  M:  Regional specificity of sex effects on subcortical volumes across the lifespan in healthy aging.  Hum Brain Mapp  (Epub ahead of print, Sept 21, 2012)
 
Rentería  ME:  Cerebral asymmetry: a quantitative, multifactorial, and plastic brain phenotype.  Twin Res Hum Genet 2012; 15:401–413
[CrossRef] | [PubMed]
 
Calhoun  VD;  Adali  T;  Pearlson  GD;  Pekar  JJ:  A method for making group inferences from functional MRI data using independent component analysis.  Hum Brain Mapp 2001; 14:140–151
[CrossRef] | [PubMed]
 
Duvernoy  H:  The Human Brain: Surface, Blood Supply, and Three-Dimensional Sectional Anatomy, 2nd ed .  New York,  Springer Wien, 1999
 
Meisenzahl  EM;  Koutsouleris  N;  Bottlender  R;  Scheuerecker  J;  Jäger  M;  Teipel  SJ;  Holzinger  S;  Frodl  T;  Preuss  U;  Schmitt  G;  Burgermeister  B;  Reiser  M;  Born  C;  Möller  HJ:  Structural brain alterations at different stages of schizophrenia: a voxel-based morphometric study.  Schizophr Res 2008; 104:44–60
[CrossRef] | [PubMed]
 
Andreasen  NC;  Nopoulos  P;  Magnotta  V;  Pierson  R;  Ziebell  S;  Ho  BC:  Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia.  Biol Psychiatry 2011; 70:672–679
[CrossRef] | [PubMed]
 
Selemon  LD;  Rajkowska  G:  Cellular pathology in the dorsolateral prefrontal cortex distinguishes schizophrenia from bipolar disorder.  Curr Mol Med 2003; 3:427–436
[CrossRef] | [PubMed]
 
Bearden  CE;  Thompson  PM;  Dalwani  M;  Hayashi  KM;  Lee  AD;  Nicoletti  M;  Trakhtenbroit  M;  Glahn  DC;  Brambilla  P;  Sassi  RB;  Mallinger  AG;  Frank  E;  Kupfer  DJ;  Soares  JC:  Greater cortical gray matter density in lithium-treated patients with bipolar disorder.  Biol Psychiatry 2007; 62:7–16
[CrossRef] | [PubMed]
 
Moore  GJ;  Cortese  BM;  Glitz  DA;  Zajac-Benitez  C;  Quiroz  JA;  Uhde  TW;  Drevets  WC;  Manji  HK:  A longitudinal study of the effects of lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients.  J Clin Psychiatry 2009; 70:699–705
[CrossRef] | [PubMed]
 
Lieberman  JA;  Tollefson  GD;  Charles  C;  Zipursky  R;  Sharma  T;  Kahn  RS;  Keefe  RS;  Green  AI;  Gur  RE;  McEvoy  J;  Perkins  D;  Hamer  RM;  Gu  H;  Tohen  M; HGDH Study Group:  Antipsychotic drug effects on brain morphology in first-episode psychosis.  Arch Gen Psychiatry 2005; 62:361–370
[CrossRef] | [PubMed]
 
Smieskova  R;  Fusar-Poli  P;  Allen  P;  Bendfeldt  K;  Stieglitz  RD;  Drewe  J;  Radue  EW;  McGuire  PK;  Riecher-Rössler  A;  Borgwardt  SJ:  The effects of antipsychotics on the brain: what have we learnt from structural imaging of schizophrenia? a systematic review.  Curr Pharm Des 2009; 15:2535–2549
[CrossRef] | [PubMed]
 
Ho  BC;  Andreasen  NC;  Ziebell  S;  Pierson  R;  Magnotta  V:  Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia.  Arch Gen Psychiatry 2011; 68:128–137
[CrossRef] | [PubMed]
 
References Container
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 2

Related Content
See Also...
Articles
Books
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 52.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 52.  >
DSM-5™ Clinical Cases > Chapter 2.  >
Dulcan's Textbook of Child and Adolescent Psychiatry > Chapter 24.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 3.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles