K

: .

, 2012

K

K
T
,

K

K
T
,

.
..1
...3
..5
7
.......7
......8
......9
.11
..11
.....12
....13
.....15
.......17
......19
......21
.........23

.....23
.........26

........26
.............30

.........33

........36

.....39

.45
...47
....47
......49

..50
...................................................................................................51
...51
(PANSS)...52
Calgary(CDS)..53
.54
.................................................................................................................55
56
....59
..62
.66
.....68
73
.83
85
SUMMARY87
..89

 ,


,

Mmmmm

.
,
, ,
,
,


,

.
,
.
,
.
. ,
,
,
.
,
. ,
.
.
.
. ,
,
.
.
.

A.



, , .
,

(Buchanan & Carpenter 2005).
,

4
.
,
,

(Carpenter 2003).
,

.


Emil
Kraepelin,
, ,
(Kraepelin 1893).

,
.


, (Dodds 1996).
,
(460 .. -377 ..),
. , .
4 , , ,
, 4 : , ,
(, , . 1993).
, (25 ..- 50 ..)
, ,
(Stone 2006),
(129-199 ..)
, .
,
. ,
,
(Stone 2006). ,

, : ...
, (,
, . 1997).
, (6 . ..),
(7 . ..), , (980 1037) (1126-1198), ,
(Howells 1993), , ,
,
.
, .
5


.
Johann Weyer, o
De
Praestigiis Daemonum (Stone 2006).

, James Tilly Matthews,
Bethlem Hospital,
, ,
(Haslam
1810).
20 . Emil Kraepelin dementia praecox - ,
,
. Kraepelin
,
, (Kraepelin 1893).
, o Eugen Bleuler
,
. 4:
, , , (Bleuler 1911).
Kurt Schneider 1 2
. 1 , ,
. : ,
,
(Schneider 1959).
, , Bleuler
, ,
(Stone 2006).



, ,
,
.

O 0,5%
0,27%-0,83%, (Eaton 1985).
0,20 1000 ,
, 0,11-0,70 1000 (Eaton 1991).
,
.
,

10 (Sartorius . 1986),
. ,
,
, .
.

(Rajkumar 1993, McGrath & Susser 2009).

.
, 2-4 ,

(Torrey & Miller 2001).

,
(Eaton & Chen 2006). ,
,
, ,
, ,
,
7

 ,
(Brown . 2005).

2-4
.

,
(Eaton . 2000, Van Os . 2004, March
. 2008).
(March . 2008).

, ,
, ,
(Pedersen & Mortensen 2001).

, ,
.
, ,
, ,
(Tandon . 2008).

(March . 2008).

,
(Brown . 2005, Veling .
2008). , ,
, (March
. 2008).
,
, 1 2 ,
(Eaton & Harisson 2000, Boydell & Murray
2003).


1.

.
25 (Cannon
. 2000).
4,02, 7,76,
3,89, , Rhesus,
(Geddes . 1999, Cannon . 2002, Gilmore
& Murray 2006). -
4,56 (Zornberg . 2000).

1 2 ,
, .
21%, 21%
,
(Bagalkote . 2000). ,
( 5-15%)
(Mortensen . 1999).
, ,
(Munk-Jrgensen & Ewald 2001).
, 5,2
2 (Brown .
2000), , , ,
(Torrey . 1988, OCallaghan .
1994).

.

,
(Susser & Lin 1992).

(Hoek
. 1996). ,
, , , ,

 , stress,
(Brown . 2005).
, stress, ,
,
.
- (Brown . 2005).

, -,
, -
stress (Gilmore & Murray 2006).
2.

,
. O , 2,96,
55 , 20-24
. , ,
DNA
, de novo
.
.

,
,
, ..
(Malaspina . 2001, McGrath & Susser 2009).
3.

, BDV
HERV-W. ,
26 (Gattaz . 2004).

10



.
(Saha . 2007),
2,6.
, 12,9,
, ,
, , HIV .

, , ,
. ,

(Mortensen 2003).

. 20-50%
, 10-13% . 7%
(Heil &
Lnnqvist 2003).

, (Caldwell & Gottesman 1990),
, , (Allebeck . 1987),
(Heil & Lnnqvist 2003).
,
, 64%,
(Heil . 1997).
, 20%50% , (Haas 1997). ,
.
1 1 , 1 .
,

(Heil & Lnnqvist 2003).

11


,
(Murray . 2003).
70-90% , 40-50%
25-30% (Ziedonis &
George 1997, Dervaux & Laqueille 2008),
(Diwan . 1998). ,
20% (Koskinen . 2009),
35% (Blanchard . 2000).
H
, 88%
(Hambrecht & Hfner 1996).
(D Souza
. 2009), 1,4 (Moore . 2007).

12



.
,

, .
(Tandon . 2008).

, , .

(Sullivan
. 2003, Riley & Kendler 2005).
80% (Merikangas & Risch 2003, Schwab & Wildenauer 2009).

,
,
(linkage analysis) (association
analysis) (Alaerts & Del-Favero 2009).


.

, .

: ,
,
,

13

, .
(Schwab & Wildenauer 2009).

(GWA, Genome Wide Association),
(SNPs)
, . ,
DNA (CNVs, Copy Number
Variations) (Owen . 2009).

-
- (Schwab & Wildenauer 2009).
,
, ,
, ,
. ,

, , ,
(Craddock . 2007,
McClellan . 2007).
.
,
8p, 13q, 22q (Badner & Gershon 2002), 1q, 2q, 3p, 5q,
6p, 11q, 14p, 20q (Lewis . 2003, Alaerts & Del-Favero 2009).

-

.
(AKT1, BDNF, GRM3, DTNBP1)
,
(Nicodemus . 2008).

14




.

,

.
CT MRI
,
, , ,
,
,
-, Heschl,
[planum temporale] ,
, ,
, (Nelson . 1998,
Wright . 2000).
,
(Selemon . 1998).
.
(Shenton
. 2001). ,
(Van
Horn & McManus 1992, Lawrie . 2008). A
(Vita . 2006, Steen . 2006,
Gur . 2007).
PET, SPECT, fMRI,
, ,
, ,
,
.
,
(Belger 2006).
,
(Lawrie
2008).
15



(Lawrie . 1999, 2001, Job . 2005),

.



, (McNeil .
2000).
,
,
, (Corcoran
. 2003, Quickfall & Crockford 2006). ,
,

,
,

(Lawrie . 2008).

16



, ,
, .

,
(Fatemi & Folsom 2009).
,
,
.
,

, , ,
, (Murray & Bramon 2005, Keshavan
. 2006).
,
, , ,

(Shenton . 2001,
Lahuis . 2003). ,
, 1 2
,
1 (Lloyd
. 2008), ,
,
2 (Avila . 2003).
,

, , , ,
.
,
,
,
,
(Murray & Bramon 2005).

.
17

 ,
(Nicodemus . 2008, Carter 2008),
,
( ).


,
, ,
,
(Keshavan . 2006).
,
( ), ,
, , , LSD,
, ,
,
.
,

,
.

(Murray & Bramon 2005).

,
. ,
, . ,
,
.
, 23,5% ,
(Fatemi & Folsom 2009).

18



,
. ,

. 5
. ,
, : D1, D5 D2, D3, D4
(Remington 2008). .
D1 , ,
, D5 ,
D2 , D3, D4
(Joyce & Meador-Woodruff 1997).

,

D2 . , ,
,
,
(Snyder 1976) - (Davis
. 1991)
,

.

,
(Pycock . 1980).
,
, . ,
, , ,
, ,
.
.
,
,
(Howes & Kapur 2009).

19


, , GABA ,

, ,
(Stone . 2007).
,
, AMPA NMDA, ,
G . NMDA
GABA
, (Stone . 2007). H
, NMDA ,
,
, .. ,
(Stone 2009). ,
,
,
(Javitt & Laruelle 2006).
,
(Olney . 1999),
NMDA
.
,
(Stone . 2007).

,
,
(David . 2005, Hatzipetros & Yamamoto 2006).

20



in vivo .
,
(Bruton . 1990, Harrison 1999). ,
, ,
(Crow . 1989).
(Harrison 1999). ,


.
,
,
.
(.. ),
(Arnold . 1998, Jarskog & Robbins 2006). ,
,
GABA
,
(Jarskog & Robbins 2006),
,
,
(Harrison
1999). ,
(Roberts & Tamminga 2005).

(Crow 1998).
,
,
2
, (Jacob & Beckmann 1989, Akil &
Lewis 1997).

(Whalley . 2005, 2009, Lewis & Sweet 2009).
PET, SPECT
fMRI
, : 21

 - -
- (Jarskog & Robbins 2006).

22




, , , ,
(Lindenmayer & Khan 2006).

Kraepelin, Bleuler Schneider. ,
,
Emil Kraepelin,
Eugene Bleuler Kurt
Schneider, (Tandon
. 2009).
T , DSM-IV-TR (APA 2000) ICD-10 (WHO
1992)
, ,
. , ICD-10
1 Schneider.

, , , ,
. ,

.

.
,

,
,
.
,
. ICD-10
,
(Kirkpatrick & Cenk 2005).

23

DSM-IV-TR: :
. : ( ) ,
( ,
):
1.
2.
3. (.. )
4.
5. (.. , , )
:


. / :
,
, ,
(
, ,
).
. :
.
( )
.
,

(.. ,
).
. :

1) ,
, 2)
,

.
. / :

.
. :
,
(
, ).

24

ICD-10:
I. , ,
(1), (2),

(
).
1. :
. , , .
. , ,
, , . .
. ,

.
. ,
.
2. :
. ,
,
, .
. , , ,
.
. , , , ,
, , .
. , , ,
.
. :
,
(1) (2)
.
,
, .

25


,

DSM-IV (SCIDI/P, Structured clinical interview for DSM-IV axis I disorders- patient edition) (First
. 1995).
,
BPRS (Brief Psychiatric Rating Scale) (Overall & Gorham
1962) PANSS (Positive And Negative Syndrome Scale) (Kay . 1987),
7 , 7 16
. PANSS
, (Nakaya . 1999, Lykouras . 2000,
Peralta & Cuesta 2001).
SAPS (ndreasen 1984) SANS ( Scale for the Assessment of
Negative Symptoms) (ndreasen 1983)
, . CDS (Calgary
Depression Scale) (Addington . 1990, 1991)
.


.
,
,
(Nakaya . 1999, Lykouras . 2000, Peralta & Cuesta
2001).
H
,
.

, /
, ,
, / ( 2006).
,
.

26


(Fish 1984).
, ,
. , ,
, .

.
, , , ,
, , ,
, .
,
, .

. ,
50-70%
(Hoffman . 2003, Lindenmayer & Khan 2006).

,
.

.
, , , , ,
.
, , ,
,
(Tandon . 2000, 2009).
, ,
, ,
.
(Andreasen 1979).
,
.
(Tandon . 2009).

, , ,
(Tandon . 2009).
,
(Penn .
2008).
27

 , , ,
,
(Keefe . 2007), , ,
(Whalley . 2007).

. , , ,
, .
:
,
, ,
, ,
(Tandon . 2009).
, ,
,
(Mller . 2004).
,
/ ,

(Morrens . 2007).
,
, (Ungvari .
2007). ,
25% (Cortese .
2005).
,
.
, ,
, ,
.
. .
,

(Tandon . 2009).
,
(Atasanova . 2008),

(Malaspina . 2003).
,
,
28

,
, (Bombin . 2005,
Tosato & Dazzan 2005). ,

.

(Keshavan . 2008).

29



.
, ,
,
,
.
,
,

.
.

,
, , ,
, (Ellison . 1998,
Silverstein . 2002, Tandon . 2009).
, ,
, ,
, (Cornblatt
. 1999, Keshavan . 2006). ,
, , ,
(Cloninger & Svrakic 2009),


(Ritsner & Susser 2004,
Bora & Veznedaroglou 2007, Smith . 2008). ,
(Camisa
. 2005).

.

,

, (Fanous & Kendler 2004).
,
,
30

 , , - ,
(Hare . 2011, Yasouda . 2011).

,
(Erche . 2010, Reichborn-Kjennerud
. 2010). ,
, , ,

(Fanous & Kendler 2004, Tsuang . 2005).
,
.
,
, ,
, ,
(Tsuang . 2005).

(Meehl
1962).
DSM-IV-TR,
. 20-50%
,
10%.
,
(Faraone . 2001).


. 1,5-5
(Kendler . 1993,
Battaglia & Torgersen 1996). , ,
,
, , .

: , ,
, - (Vollema & Van den Bosch
1995).
,
,
(Dickey . 2002). T,

31

 , Val - (COMT),
(Avramopoulos . 2002, Fanous & Kendler 2004).

,
, ,
.
,

(Tsuang . 2005).

. H
,
,
(Pallanti 2004, Fogelson . 2007).

, ,
,
,
(Asarnow . 2001, Fogelson . 2007).
.
McMillan . (2009)

,
,
-, , ,
, .

, .


.

32



,
(Yung & McGorry 1996).

, , ,
(Cornblatt . 1999).

, Duration of Untreated Illness (DUI),
, Duration of Untreated Psychosis (DUP),
(Norman . 2005, Owens &
Johnstone 2006). ,
,
.

. 80-90%
(Hfner . 1994). H
5 (Hfner
2000, Klosterktter . 2008). ,
15 (Hfner .
1993). , ()
0<4 , , 4 <1 , , >1 ,
18%, 15% 68% (Hfner 2000). ,
73%
- , 7%
20% . ,
-
,
, ,
, ,
.

(Gourzis . 2002),
, ,
,


33

. , ,
, ,
, ,
.
(Moukas . 2010),

.
,

, ,

,
.
,
.
(Parnas . 1998, Mller & Husby 2000, Nelson . 2008)

.
,
, ,
,
,
.
(Klosterktter . 2005, Parnas . 2005)


.

.
PACE (Personal assessment and Crisis Evaluation)
(McGorry . 2002)
CAARMS (Comprehensive Assessment of At Risk Mental
States), .
, PRIME (Prevention through Risk
Identification, Management and Education) (McGlashan . 2003),
PACE, SOPS (Scale Of Prodromal
Symptoms) SIPS (Structured Interview for Prodromal
symptoms). K
. ,
34

 21-41% (Yung . 1996, 2004, Yung

2004). , 54% (Miller
. 2002).

35



,

, 1.4 (Aleman . 2003,
Tandon . 2008). H
1980 .

/
(Hambrecht . 1992, Aleman
. 2003).
.
30 90%
67% (Loranger 1984, Gureje 1991). H
15-24,
55-64 (Munk-Jrgensen 1987).
4-6
3-4 , (RiecherRssler . 1992b, Hfner . 1989).

,
(Beratis . 1994, 1997). ,
, 45% , ,
,
25%, 14%, 13% 3,7% . ,
18% 5,5%
, 7,8%
1,3% .
, 22,6
23,1 . ,
, 2 ,
16 , 17,9 .
, 26,4 ,
33 , 6,6 . ,
,
30 . ,
72% , 41%
36

. , ,
35 , 46% .
,
,

. ,
, , ,
,
(Thara . 1994, Lee . 1998, Leung & Chue 2000, Usal
. 2002).
,
,
(Larsen . 1996).

,
(Riecher-Rssler . 1992b, Hfner 2003).
,
(Goldstein .
1990, Rund . 2004)
(Goldstein & Link 1988, Hfner . 1994).
,
(Lindamer . 1999). ,
,
(Gureje 1991, Lindamer . 1999).
Lindamer .,
,
.
, ,
(Lindamer . 1999).
,
, , ,
.
,
, .
(Hfner . 1994, Gureje
1991, Beratis . 1994)
.
D2 (Hruska 1986, Dipaolo & Falardeau 1985).

37

 , ,

, , D2 , .
,
(Hfner
. 1991, 1994).
,
,
,
, (Riecher-Rssler .
1992b).
,
.
,
(Balu & Lucki 2009).

,
(Tanapat . 1999, De Nicola .
2006). T , ERa ERb,
5-HT1A ,
(Mazzuco . 2006, Birzniece . 2001).
.
,
, (Spritzer & Galea 2007,
Brannval . 2005).
, .
stress, , , ,
(Goel & Bale 2009).
, ,

, , , -
, , (Manson
2008), ,
.
,
(Becker . 2005,
Quinn . 2007).

38


, ,
. Kraepelin, dementia
praecox , ,
, (Kraepelin
1893). ,
,
. Kraepelin
,
,
.

(Harris & Jeste 1988).
Manfred Bleuler
, 40
(Bleuler 1943). 126 ,
15% (Howard . 2000). ,
,
,

. DSM-III (APA 1980)

44 ,
(Palmer . 2001).
, DSM III-R (APA 1987)
, ,
44 ,
(Rabins
. 1984). , DSM-IV-TR (APA 2000) ICD-10
(WHO 1992) .
,
DSM-IV-TR (APA 2000)
, ,
, ,

(Harris & Jeste 1988, Howard . 2000).

39

,
.

, ,
,
, ,
,
(ndreasen 1999). ,
60 .
,
, 40 60 ,
, 60 (Palmer
. 2001, Howard . 2000).

40 23,5% (Howard
. 2000, Harris & Jeste 1988),
45 64 0,6% (Keith . 1991, Howard .
2000).
, :
1,9:1 45:2 (Howard . 2000).

, , ,
. Lohr
. (1997)

,
Alzheimer. ,
,
. ,
,
10%-15%,
(Jeste . 1997, Palmer
. 2001).

,
,

(Brodaty . 1999, Palmer . 2001, Jeste . 1997,
Castle & Murray 1993). Sato . (2004)
40

 ,
,

, .
,
(Palmer . 2001). H
.
,

. ,
.
,

. , ,
. Jeste .
(1997)
- - -,
: , ,
,
, ,
. ,
,
. ,
,

.
,
,
.

(Corey-Bloom . 1995).

, .
,
, ,
(Jeste . 1997, 1998). (Rajji . 2009)
,
,
. ,
41

 (Jeste . 1997).

(Heinrichs & Zakzanis
1998, Green . 2004). ,

(DeLisi 1992).

, , .

60,
, (Howard . 2000).

40,

. , ,
,
,

. ,

,
,
(Palmer . 2001).
Beratis . (1994),

, 200 .
,
, .
,
.
9 , 11-20 , , 17,7
16,1 .
,
42 , 26 ,
33,5 26,7 . 72%
30, ,
41% 30 , 46% 35 .
20-24 40-44 .

42

40-44.
, 22,6 23,1
, 25 .

.

,
.
,

. ,
,
.

43

44

B.

45

46


,
(Palmer
. 2001, Hfner . 1993).
,
30
35 . ,
<30,
, . 35 ,
(Beratis . 1994). ,
,
:
1)

2) ,
3)



.

, 15-3-2005
7-5-2008. 88
,
. , 21 35 ,
60 <30 , 7
30Y<35 . 30 <35
, .
,
.



.
47


DSM-IV-TR (APA 2000),
DSM-IV (SCID-I/P) (First . 1995), ,
.
, 20
,
. , 1-5
, ,
20 , :
1) -Structured Clinical Interview for
Positive and Negative Syndrome Scale (PANSS) (Kay . 1987),
(Lykouras . 2000),
2) Calgary -Calgary
Depression Scale for Schizophrenia (Addington . 1990, 1991),
(Kontaxakis . 2000).
,

.
DSM-IV
(Structured Clinical Interview for DSM-IV Axis II Personality Disorders, SCID-II)
(First . 1997), ' 18
.
18,


.
.
,
,

DSM-IV. ,
.

DSM-III-R,
,
(Gourzis . 2002), ,
-, -, - ( 1).

,
48

 .

.
.

.

,
PANSS Calgary,
, ,
,
two-tailed Wilcoxon rank-sum, .
, ,
, ,
, ,
2.
(p-value) 0,05.
,
Bonferroni
,
PANSS. ,
p<0,007
, p<0,003 .

, ,
, ,
.
NCSS
Statistical software 2007, Kaysville, Utah, USA.

49


H
k.
(k<0), ( 0,0<k <0,2), (0,2 k<0,4) (0,4k <0,6), (0,6
k<0,8) (0,8 k1,0). H
(k=1,0).
PANSS
, 0,71k0,84. ,
, 0,76k1,0.
, k=1,0.
SCID-II ,
0,64 k1,0.
(0,00001<p<0,0478).

50

1. 2. 3.

1. 2. 3.

1. 2. 3. 4.

1.

6.

2.

7. ...

3. ...

8. ...

4.

9.

5. ...

...

;
;

1.

2.

51

 ( PANSS)

1,
2,
3
4,
5,
6, /
7,

1,
2,
3, ()
4, /
5,
6,
7,

1,
2,
3,
4,
5, ()
6,
7,
8,
9,
10,
11,
12,
13,
14,

15,
16,

52

 Calgary (Calgary Depression

Scale, CDS)

1.
2.
3.
4. ,
5.
6.
7.
8.
9.

53

,

-
/

/ /
-

54



30
35 .
, ,
, 40, 45 50 (Rabins . 1984, Jeste .
1997, Brodaty . 1999, Howard . 2000, Sato . 2004).
40 60
,
60 ,
(Howard . 2000). ,
, 40
(Howard . 2000). Castle Murray (1993)
2
, 21 39 , 3
, 22, 37 62 . 77%
30 (an der Heiden & Hfner
2000). , ,

, , ,
30 (<30 , =60),
35 (35 , =21) 70%
41% 30 , 10%
46% 35 (Beratis
. 1994).

. (N=46), 25
(54%) , 15 (33%) 6 (13%)
, 5 (63%), 2 (25%) 1 (13%)
(N=8), . ,
, 6
(43%), 5 (36%), 3 (21%) 8 (62%), 4 (31%), 1 (8%)
(N=14) (N=13), .
, :
39,7338,41 56,1349,03
, 43,0440,02 39,3840,73
, .

55

1.
, 3 ,
(p=0.032).
(p=0.533) ( 2).

1. ().

27,54

5,25

47,50

7,21

30,71

8,68

27,96

5,00

45,92

7,24

36,47

10,59

27,70

5,20

46,72

7,23

32,61

9,68

2. ().

4,66

Min

Max

20,89

12

23,86

3,86

21,58

4,63

56

Min

Max

29

38,75

4,00

35

45

19

29

40,46

6,25

35

57

12

29

39,81

5,46

35

57



( 3).

(p=0,000001).
, ,
(p=0,0012).

,
,
(p=0,06 p=0,07, ).

3.
.

42(91,3%)

12(85,7%)

54(90,0%)

5(62,5%)

2(15,4%)

7(33,3%)

61(75,30%)

2(4,3%)

1(7,1%)

3(5,0%)

1(12,5%)

7(53,8%)

8(38,1%)

11(13,58%)

2(4,3%)

1(7,1%)

3(5,0%)

2(25,0%)

4(30,8%)

6(28,6%)

9(11,11%)

46(100%)

14(100%)

60(100%)

8(100%)

13(100%)

21(100%)

81(100%)

( 4).

57



(p=0,0009). H
(p=0,001),
( 5).
,
, ,
( 6).
4.
.

1(2,2%)

1(1,7%)

1(1,23%)

4(8,7%)

1(7,1%)

5(8,3%)

6(75,0%)

7(53,8%)

13(61,9%)

18(22,2%)

27(58,7%)

4(28,6%)

31(51,6%)

2(25,0%)

4(30,8%)

6(28,6%)

37(45,7%)

6(13,1%)

4(28,6%)

10(16,7%)

1(7,7%)

1(4,8%)

11(13,6%)

8(17,4%)

5(35,7%)

13(21,7%)

1(7,7%)

1(4,8%)

14(17,3%)

46(100%)

14(100%)

60(100%)

8(100%)

13(100%)

21(100%)

81(100%)

5. .

34(73,9%)

12(85,7%)

46(76,7%)

2(25%)

8(61,5%)

10(47,6%)

56(69,1%)

5(10,9%)

1(7,1%)

6(10,0%)

6(7,4%)

7(15,2%)

1(7,1%)

8(13,3%)

6(75%)

5(38,5%)

11(52,4%)

19(23,5%)

46(100%)

14(100%)

60(100%)

8(100%)

13(100%)

21(100%)

81(100%)

58

 6. .

35(76,1%)

13(92,9%)

48(80,0%)

7(87,5%)

11(84,6%)

18(85,7%)

66(81,5%)

6(13,0%)

1(7,1%)

7(11,7%)

7(8,6%)

5(10,9%)

5(8,3%)

1(12,5%)

2(15,4%)

3(14,3%)

8(9,9%)

46(100%)

14(100%)

60(100%)

8(100%)

13(100%)

21(100%)

81(100%)

, , -
( 7).
(p=0,007).

7. .

32(69,6%)

8(57,1%)

40(66,6%)

8(100%)

5(41,7%)

13(65,0%)

54(67,5%)

14(30,4%)

6(42,85%)

20(33,3%)

7(58,3%)

7(35,0%)

26(32,5%)

46(100%)

14(100%)

60(100%)

8(100%)

12(100%)

20(100%)

80(100%)

59



,
, ( 8).

,
.
(p=0,01).

, .
.

,
. ,
,
, , (p=0,01)
(p=0,054, trend) ( 8).
, .

60

 8. (= , = )

4(8,7%)

19(41,3%)

6(42,9%)

11(78,6%)

10(16,7%)

30(50,0%)

1(12,5%)

3(37,5%)

4(30,8%)

7(53,8%)

5(23,8%)

10(47,6%)

15(18,5%)

40(49,4%)

23(50,0%)

13(28,3%)

7(50,0%)

3(21,4%)

30(50,0%)

16(26,7%)

4(50,0%)

2(25,0%)

7(53,8%)

5(38,5%)

11(52,4%)

7(33,3%)

41(50,6%)

23(28,4%)

16(34,8%)

12(26,1%)

1(7,1%)

17(28,3%)

12(50,0%)

2(25,0%)

2(25,0%)

1(7,7%)

1(7,7%)

3(14,3%)

3(14,3%)

20(24,7%)

15(18,5%)

3(6,5%)

2(4,3%)

3(5,0%)

2(3,3%)

1(12,5%)

1(12,5%)

1(7,7%)

2(9,5%)

1(4,8%)

5(6,2%)

3(3,7%)

46(100%)

46(100%)

14(100%)

14(100%)

60(100%)

60(100%)

8(100%)

8(100%)

13(100%)

13(100%)

21(100%)

21(100%)

81(100%)

81(100%)

16(34,8%)

35(76,1%)

12(85,7%)

13(92,9%)

28(46,7%)

48(80,0%)

3(37,5%)

5(62,5%)

12(92,3%)

12(92,3%)

15(71,4%)

17(81,0%)

43(53,1%)

65(80,2%)

13(28,3%)

5(10,9%)

1(7,1%)

1(7,1%)

14(23,3%)

6(10,0%)

1(12,5%)

2(25,0%)

1(4,8%)

2(9,5%)

15(18,5%)

8(9,9%)

12(26,1%)

4(8,7%)

1(7,1%)

13(21,7%)

4(6,7%)

3(37,5%)

1(12,5%)

1(7,7%)

1(7,7%)

4(19,0%)

2(9,5%)

17(21,0%)

6(7,4%)

5(10,9%)

2(4,3%)

5(8,3%)

2(3,3%)

1(12,5%)

1(4,8%)

6(7,4%)

2(2,5%)

46(100%)

46(100%)

14(100%)

14(100%)

60(100%)

60(100%)

8(100%)

8(100%)

13(100%)

13(100%)

21(100%)

21(100%)

81(100%)

81(100%)

61



,
, ,
( 9), ,
( 10).
,
-
, (p=0,017),
(p=0,002). O
(p=0,036).

(p=0,053, trend). ,
-
(p=0,056), (p=0,075),

(p=0,060)

(p=0,067)

.
(p=0,053)
(p=0,073) .
, ,
(p=0,023),

(p=0,005)

(p=0,020)

, . ,
, A,
(p=0,010), (p=0,047), ,

(p=0,048), .
,
, ,
, ,
,
,
(Vollema & Van den Bosch
1995).

62

 9.
.
(= , =
).
1.

(N=23)

(=8)

0,35

0,88

0,26

0,54

1,00

1,19

0,075

0,82

1,11

2,50

2,44

0,060

0,26

0,86

1,37

2,20

0,067

1,26

1,54

2,62

1,84

0,056(
)

0,04

0,20

1,50

1,85

0,002

2.

0,168

(=10)

(=13)

0,90

1,28

0,07

0,27

0,053

0,90

1,10

0,23

0,60

0,073

(=33)

(=21)

0,51

1,03

0,04

0,21

0,036

0,06

0,24

0,85

1,62

0,017

63

 10. ,
, .
(= ,
= ).
(=33)

(=23)

(=10)

1,69

1,45

0,60

1,34

0,010

1,08

0,66

0,60

1,07

0,047

0,39

0,89

0,26

0,61

0,90

0,080
1,10

0,048

(=21)
(=8)

(=13)

1,00

1,19

0,07

0,27

0,023

2,50

2,45

0,23

0,60

0,005

1,37

2,19

0,020

DSM-IV-TR,
11. .

64

 11.
DSM-IV-TR.

(=54)

(=23)

(=8)

(=10)

(=13)

.-

13

65



,

, , .


( : 2,221,48 1,281,18 , p=0,008).

(p= 0,020) (p= 0,026)
( 12).
( : 34,88 39,70
37,9541,50 , ,
).
,

( : 2,391,46
1,121,00 , p=0,018). ,

,
.
, .
,
, ,
.
,
,
,
2,5 : : 41,1 42,39 12,8
14,17 , p=0,006.

.
, ,
,
, .

66

 12. (=
)
(N=59)
No(%)

(N=21)
No(%)

42(71,2)
2(3,4)
26(44,1)
9(15,3)
3(5,1)
0
12(20,3)
14(23,7)

9(42,9)
3(14,3)
7(33,3)
0
0
0
4(19)
2(9,5)

0,020

23(39)

2(9,5)

0,026

22(37,3)
44(74,6)
3(5,1)
4(6,8)
7(11,9)
9(15,3)

7(33,3)
16(76,2)
1(4,8)
2(9,5)
3(14,3)
1(4,8)

14(23,7)
35(39,3)
25(42,4)

1(4,8)
10(47,6)
4(19)

5(8,5)
0
4(6,8)
0
2(3,4)
0

0
0
0
0
0
1(4,8)

26(44,1)
13(22)
9(15,3)
27(45,8)
27(45,8)
16(27,1)
21(35,6)
10(16,9)
12(20,3)
18(30,5)
9(15,3)
5(8,5)
18(30,5)
4(6,8)

7(33,3)
2(9,5)
3(14,3)
12(57,1)
14(66,7)
1(4,8)
7(33,3)
4(19)
1(4,8)
11(52,4)
2(9,5)
2(9,5)
5(23,8)
1(4,8)

67



PANSS, ,
Calgary Depression Scale for
Schizophrenia (CDSS), ,
, ,
, .

(CDSS>6), (
13).

13. .

11(23,9%)

4(28,6%)

15(25,0%)

4(50,0%)

3(23,1%)

7(33,3%)

22(27,2%)

35(76,1%)

10(71,4%)

45(75,0%)

4(50,0%)

10(76,9%)

14(66,7%)

59(72,8%)

46(100,0%)

14(100,0%)

60(100,0%)

8(100,0%)

13(100,0%)

21(100,0%)

81(100,0%)

,

PANSS (p=0,029),
(p=0,006),
. ,
/
(p=0,008), .
,
(p=0,0007)
( 14).
68

 ,
.
, ,

,
(p=0,002, p=0,003 p=0,011 ). ,

,
(p=0,031 p=0,062, ). ,
.
,
(p=0,008) ( 15).
.
PANSS. ,
(p=0,004)
( 15).
, ,
( 16). ,

(p=0,014 p=0,016, ).

(p=0,033). ,

(p=0,005).

69

 14. PANSS
(= ).

PANSS

(N=60)

(N=21)

6,30

0,88

6,47

0,51

1,
2,

2,65

0,91

2,61

0,58

4,41

1,70

4,71

1,52

4,

3,58

1,19

3,95

0,74

5,

3,61

1,94

3,52

1,80

6, /

5,41

1,22

6,19

0,87

0,008

7,

4,13

1,74

4,04

1,39

30,11

4,71

31,52

3,40

1,

2,65

0,98

2,04

0,92

0,020

2,

3,20

0,98

2,71

0,78

0,050

3, ()

2,93

1,10

2,42

0,92

4, /

5,

2,88

0,97

2,47

0,81

3,83

1,36

3,57

0,97

6,

7,

2,75

1,56

1,71

0,84

0,006

3,23

0,81

3,14

0,65

21,48

5,72

18,09

4,21

0.028

1,

3,28

1,75

3,28

1,84

2,

4,00

1,39

4,33

1,27

3,

2,61

1,54

2,14

1,31

4,

3,38

1,13

3,85

0,79

0,023

5, ()

6,

1,73

0,98

1,38

0,74

2,81

1,52

2,80

1,25

7,

2,11

1,34

1,52

0,87

8,

3,95

1,34

3,90

1,81

9,

4,45

1,09

4,09

1,13

10,

2,48

0,96

2,61

0,80

11,

3,43

1,04

3,42

1,03

12,

5,08

1,16

5,66

0,96

13,

2,45

1,24

1,57

0,97

0,0007

14,

15,

3,75

1,64

3,57

1,39

3,23

1,04

3,09

0,53

16,

4,30

1,51

4,80

1,77

53,58

9,91

52,09

7,97

70

 15. PANSS ,
. (=
).

1.

(N=46)

(N=8)

2,63
3,15

0,92
0,86

1,50
2,50

0,53
0,53

0,002
0,031( )

2,84

0,94

2,12

0,83

0,062( )

2,63

1,45

1,25

0,46

0,003

21,21

5,33

16,37

3,29

0,011

2,26

1,08

1,25

0,46

0,008( )

1,
2,

3,
()
6,

13,

2.

(N=14)

(N=13)

3,07

1,54

1,76

1,16

0,004( )

13,

71

 16. PANSS ,
.
(=
).

1.

(=46)

11,

15,

(=14)

3,23

0,97

4,07

1,07

0,014( )

3,04

0,94

3,85

1,16

0,016( )

2.
(=8)

(=13)

1,

6,87

0,35

6,23

0,43

0,005

1,

1,50

0,53

2,38

0,96

0,033( )

72



,
,
(Castle & Murray 1993, Jeste . 1995, Hfner .
1998, Schultz . 2000, Sato . 2004).

,
, .

(Kirkpatrick & Cenk 2005).

(Beratis . 1994)
.
(Beratis . 1994)
, 30
35 ,
, 77%, 30
(an der Heiden & Hfner 2000).
,
,

(March . 2008).
,
, .

, 2,4 (Marcelis
. 1998, Mortensen . 1999, McGrath & Susser 2009),
, 15
(Pedersen & Mortensen 2001, Tandon . 2008).

.
(Marcelis . 1998, Pedersen 2006)
(Pedersen 2006), .

. ,
73

, ,
D, stress ,
(Tandon
. 2008).
.
(Hfner
. 1998) , ,

, ,
.

,
,


(Riecher-Rossler . 1992, Hfner . 1993). ,
,
,
(Zimmerman
& Coryell 1989).

,
, ,
.

,

,

(Asarnow . 2001, Fogelson . 2007).

,
(McMillan . 2009),
(Pallanti . 2000). ,
,
, ,
, ,
, (Cloninger & Svrakic
2009),
74


(Bora & Veznedaroglou 2007, Smith . 2008).
,
,
,
. ,
,
. , ,
, .
,
. -
,
, ,
(Fine . 1992, Skodol 2005).
, -,
,
,
, ,
, (Skodol 2005).
- ,
(Skodol 2005),
. , o

. O
, ,
,
,
.
,

,
,
(Vollema & Van den Bosch 1995), .
,
,
.
,
,
75

 .
,
,
, ,
(Ellison . 1998).
, ,

.
,
, / .

, .

,
(Jackson . 1995,
McGorry . 2002, Cannon . 2002, Woods . 2003, McGlashan
. 2006).
,
(Yung . 1998, Miller . 1999, Klosterktter . 2001,
2005).
,
(Huber & Gross 1989, Parnas . 1998, 2005,
Hfner . 1998, Mller & Husby 2000, Gourzis . 2002, Nelson .
2008, Schultz-Lutter 2009).
. Hfner .
(1998)
, .

, .
(Hfner . 1993, 1994, 1998, Brodaty
. 1999),
(Pearlson . 1989, Jeste . 1997),
(Jeste . 1997, Palmer . 2001)
(Castle & Murray 1993, Mayer . 1993)
.
,
,
. Sato . (2004)
76

 ,
,

.
,

,

(Castle & Murray 1993, Jeste . 1995, Hfner
. 1998, Sato . 2004). ,

,
.
(Kirkpatrick &
Cenk 2005)
(Kendler . 1985). , ,
.
, ,
. ,
,

,
. , ,
.
, ,
,
.
,
,
,
,
. , ,
,
.
Hfner . (1998), ,

.
, .

77

 ,
/ .
,
. ,
,
, Hfner . (1998),
Mayer . (1993), Castle . (1993).

(Castle & Murray 1993, Hfner
. 1998, Sato . 2004), (Brodaty . 1999, Jeste
. 1999, Schultz . 2000, Palmer . 2001). ,
.

.
, ,
,
,
, .
,
,
.

,
.
Sato . (2004). ,
,
, , ,
,
,

. Mayer . (1993)
,
,
, ,
.
(Beratis . 1994),

: 30 ,
35 . , ,
78

 72% 30 ,
35 ,
30 35 , 41% 46% ,
.
,
,
, , .
, ,
(Hfner . 1998, Kulkarni 2009).
- ,
D2 (Seeman & Lang 1990),
, (Hfner .
1991). ,
.
(Toga . 2006).

7 60 ,
(Sowell . 2003). ,

. ,
, 20 50 (Bartzokis .
2001).
,
47 (Bartzokis 2002). ,
,
(Benes . 1994),
.
(Melkangi . 1998),

(Davis . 2003).
,

, ,

. ,
,
,
, 35 ,
.
79

, ,

, . ,
.
BDNF (Brain Derived
Neurotrophic Factor) 25 (Krebs .
2000),
, 1-bp ,
, 40 (Borglum . 2001). BDNF
,

, ,

, (Krebs . 2000, Borglum .
2001).

, ,
,
. Jeste . (1997)
-
.
,
,
.
,
, , , ,

(Mega & Cummings 2001).


, ,
, , .


. ,
,
,
,

80


.
,
,
,
,
, 10-50%
(Eaton 1985), . ,

.
,
,
,
.

.

81

82




, .

, .
.
.
,
,
.
,
/ . ,
.
,

.
,
.
- ,
. ,
, .
,

,

. ,
,
.
.
,
,

. ,
, .
, ,

83

 ,
, .
,

, ,
. ,
,

. ,
. ,
,
. ,

,
.
,

, , ,
,
,
.
,

.

84



88
, ,
15-3-2005 7-5-2008. , 60, 46 14 ,
, 30 , 21, 8 13
, , 35 .
,
, ,
, ,

, ,
, .
SCID-I/P, PANSS, Calgary Depression Scale, SCID-II,
.
Wilcoxon rank-sum
2
.
, ,

.
.
,
,
. ,

. ,
.
,

.
. ,
,
-
. ,
,
.

85

 , ,
.
,
,
. ,


.
, .
,
,
. ,
/
. ,
,
.
. ,
.
,
.


, , ,

, .

86

SUMMARY
The demographic features and symptomatology of young and late onset
paranoid schizophrenia were studied in a sample of 88 patients who were
consecutively hospitalized in the Psychiatric Department of the University Hospital of
Patras, from 3-15-2005 to 5-7-2008. The sample consisted of 60 patients, 46 men and
14 women, with young onset paranoid schizophrenia, before the age of 30, and 21 late
onset patients, 8 men and 13 women, with onset of the illness after the age of 35 years
old.
Demographic features, rates of smoking and alcohol and cannabis use,
premorbid personality disorder features, the number and type of prodromal symptoms,
the duration of the prodromal period and the symptomatologies of the active phase
were compared between young and late onset groups, in the total sample and
separately for the two sexes, and between the two sexes in each age group. SCID-I/P,
PANSS, Calgary Depression Scale, SCID-II, and a clinical interview for the
prodromal symptoms were applied.
Statistical analysis was performed by applying the Wilcoxon rank-sum and
chi-square tests.
Young onset patients, particularly men, were more likely to have been born in
urban regions, compared with late onset patients. Late onset women were most
frequently married, compared with all other groups.
There was not any significant difference regarding use of nicotine, alcohol or
cannabis between young and late onset patients. In the young onset group, men more
frequently used alcohol and cannabis than women. Similarly, late onset men smoked
and tended to use cannabis more often than late onset women.
In the premorbid period, young onset patients have significantly more traits of
avoidant personality disorder compared with late onset patients. This finding tended
to be significant in the female sample, as well. Late onset patients had significantly
more traits of passive-aggressive personality disorder than young onset patients, in the
total and male sample. In the young onset group, men had significantly more traits of
paranoid and schizotypal personality disorder than women, whereas women had more
traits of the depressive personality disorder. In the late onset group, men had more
histrionic, narcissistic and antisocial traits than women.
In the prodromal phase, young onset patients present with significantly more
negative prodromal symptoms, in the total and the male sample. In the total sample,
marked isolation and impairment of concentration are observed at a significantly

87

higher rate in the young onset group, than in late onset patients. Also, in the young
onset group, women had significantly shorter duration of prodromal period than men.
During the active phase, young onset patients had significantly heavier total
score of negative symptomatology, heavier lack of spontaneity and heavier
disturbances of volition. On the other hand, late onset patients tended to suffer from
heavier suspiciousness/ideas of persecution. In the male sample, young onset patients
had heavier total negative symptomatology, blunted affect and lack of spontaneity.
There were not any significant differences in the female sample. In the late onset
group, men had heavier delusions than women. There was not any significant
difference regarding depressive symptoms among the groups.
Our findings indicate the modulatory effect of age of onset and sex on the
clinical presentation of paranoid schizophrenia, in the premorbid period, prodromal
and active phases, possibly following the developmental and maturational procedures
that take place in the brain, throughout the life span, in the two sexes.

88

Addington D, Addington J, Schissel B. A depression rating scale for schizophrenics.

Schizophr Res 1990;3:247-251.
Addington A, Addington J, Maticka-Tyndale E, et al. Reliability and validity of a
depression rating scale for schizophrenics. Schizophr Res 1991;5:123-134.
Akil M, Lewis DA. Cytoarchitecture of the entorhinal cortex in schizophrenia. Am J
Psychiatry 1997;154:1010-1012.
Alaerts M, Del-Favero J. Searching genetic risk factors for schizophrenia and bipolar
disorder: Learn from the Past and Back to the Future. Hum Mutat 2009;30:1139-1152.
Aleman A, Kahn RS, Selten JP. Sex differences in the risk of schizophrenia: evidence
from meta-analysis. Arch Gen Psychiatry 2003;60:565-571.
Allebeck P, Varla A, Kristjiansson E, Wistedt B. Risk factors for suicide among patients
with schizophrenia. Acta Psychiatr Scand 1987;76:414-419.
American Psychiatric Association. DSM-III: Diagnostic and Statistical Manual of Mental
Disorders. 3rd ed. Washington, DC: The American Psychiatric Association, 1980.
American Psychiatric Association. DSM-III-R: Diagnostic and Statistical Manual of
Mental Disorders. 3rd ed., revised. Washington, DC: The American Psychiatric
Association, 1987.
American Psychiatric Association. DSM-IV-TR: Diagnostic and Statistical of Mental
Disorders. 4th ed., Text Revision. Washington, DC: The American Psychiatric
Association, 2000.
Andreasen NC. Thought, language, and communication disorders: I. Clinical assessment,
definition of terms, and evaluation of their reliability. Arch Gen Psychiatry 1979;39:784788.
Andreasen NC. Scale for the Assessment of Negative Symptoms(SANS). Iowa City,
University of Iowa,1983.
Andreasen NC. Scale for the Assessment of Positive Symptoms(SAPS). Iowa City,
University of Iowa,1984.
Andreasen NC. I dont believe in late onset schizophrenia. In: Late-Onset schizophrenia.
Howard R, Rabins PV, Castle DJ, eds. Philadelphia: Wrightson Biomedical Publishing,
1999.
. . , . , 1997.

89

Arnold SE, Trojanowski JQ, Gur RE, Blackwell P, Han LY, Choi C. Absence of
neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients
with schizophrenia. Arch Gen Psychiatry 1998;55:225-232.
Asarnow RF, Nuechterlein KH, Fogelson D, et al. Schizophrenia and schizophreniaspectrum personality disorders in first-degree relatives of children with schizophrenia: the
UCLA family study. Arch Gen Psychiatry 2001;58(6):581-588.
Atanasova B, Graux J, El Hage W, et al. Olfaction: a potential cognitive marker of
psychiatric disorders. Neurosci Biobehav Rev 2008;32:1315-1325.
Avila MT, Sherr J, Valentine LE, Blaxton TA, Thaker GK. Neurodevelopmental
interactions conferring risk for schizophrenia: a study of dermatoglyphic markers in
patients and relatives. Schizophr Bull 2003;29(3):595-605.
Avramopoulos D, Stefanis NC, Hantoumi I, Smyrnis N, Evdokimidis I, Stefanis CN.
Higher scores of self reported schizotypy in healthy young males carrying the COMT
high activity allele. Mol Psychiatry 2002;7(7):706-711.
Badner JA, Gershon ES. Meta-analysis of whole genome linkage scans of bipolar
disorder and schizophrenia. Mol Psychiatry 2002;7:405-411.
Bagalkote H, Pang D, Jones PB. Maternal Influenza and schizophrenia in the offspring.
Int J Ment Health 2000;29:3-21.
Balu DT, Lucki I. Adult hippocampal neurogenesis: Regulation, functional implications,
and contribution to disease pathology. Neurosci Biobehav Rev 2009;33:232-252.
Bartzokis G, Beckson M, Lu PH, Nuechterlein K, Edwards N, Mintz J. Age-related
changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging
study. Arch Gen Psychiatry 2001;58:461-465.
Bartzokis G. Schizophrenia: Breakdown in the well-regulated lifelong process of brain
development and maturation. Neuropsychopharmacology 2002;27:672-683.
Battaglia M, Torgersen S: Schizotypal disorder: at the crossroads of genetics and
nosology. Acta Psychiatr Scand 1996;94:303-310.
Becker JB, Arnold AP, Berkley KJ, et al. Strategies and methods for research on sex
differences in brain and behavior. Endocrinology 2005;146:1650-1673.
Belger A, Dichter G. Structural and functional neuroanatomy. In: Textbook of
schizophrenia. Lieberman JA, Stroup TS, Perkins DO, eds. Washington DC: American
Psychiatric Publishing, 2006.
Benes FM, Turtle M, Khan Y, Farol P. Myelination of a key relay zone in the
hippocampal formation occurs in the human brain during childhood, adolescence and
adulthood. Arch Gen Psychiatry 1994;51:477-484.
Beratis S, Gabriel J, Hoidas S. Age at onset in subtypes of schizophrenic disorders.
Schizophr Bull 1994;20(2):287-296.
90

Beratis S, Gabriel J, Hoidas S. Gender differences in the frequency of schizophrenic

subtypes in unselected hospitalized patients. Schizophr Res 1997;23:239-244.
Birzniece V, Johansson IM, Wang MD, Seckl JR, Backstrom T, Olsson T. Serotonin 5HT(1A) receptor mRNA expression in dorsal hippocampus and raphe nuclei after gonadal
hormone manipulation in female rats. Neuroendocrinology 2001;74:135-142.
Blanchard JJ, Brown SA, Horan WP, et al. Substance use disorders in schizophrenia:
review, integration, and a proposed model. Clin Psychol Rev 2000;20:207-234.
Bleuler E. Dementia Praecox, oder die Gruppe der Schizophrenien [Dementia Praecox, or
the Group of the Schizophrenias]. Leipzig, Germany, Franz Deuticke, 1911.
Bleuler M. Die spatschizophrenen Krankheitsbilder. Fortschritte der Neurologie und
Psychiatrie 1943;15:259-290.
Bombin I, Arango C, Buchanan RW. Significance and meaning of neurological signs in
schizophrenia: two decades later. Schizophr Bull 2005;31:962-977.
Bora E, Veznedaroglou B. Temperament and character dimensions of the relatives of
schizophrenia patients and controls: The relationship between schizotypal features and
personality. Eur psychiatry 2007;22:27-31.
Borglum AD, Hampson M, Kjeldsen TE, et al. Dopa decarvoxylase genotypes may
influence age at onset of schizophrenia. Mol Psychiatry 2001;6:712-717.
Boydell J, Murray R. Urbanization, migration and risk of schizophrenia. In: The
Epidemiology of Schizophrenia. Murray RM, Jones PB, Susser E, Van Os J, Cannon M,
eds. Cambridge University Press, 2003.
Brannvall K, Bogdanovic N, Korhonen L, Lindholm D. 19-Nortestosterone influences
neural stem cell proliferation and neurogenesis in the rat brain. Eur J Neurosci
2005;21:871-878.
Brodaty H, Sachdev P, Rose N, Rylands K, Prenter L. Schizophrenia with onset after age
50 years. I: Phenomenology and risk factors. Br J Psychiatry 1999;175:410-415.
Brodaty H, Sachdev P, Koschera A, Monk D, Cullen B. Long-term outcome of late-onset
schizophrenia: 5-year follow-up study. Br J Psychiatry 2003;183:213-219.
Brown AS, Cohen P, Greenwald S, et al. Nonaffective psychosis after prenatal exposure
to rubella. Am J Psychiatry 2000;157:438-443.
Brown AS, Bresnahan M, Susser ES. Schizophrenia: Environmental Epidemiology. In:
Comprehensive Textbook of Psychiatry, 8th ed. Sadock BJ, Sadock VA, eds. Lippincott
Williams & Wilkins, Philadelphia, 2005.
Bruton CJ, Crow TJ, Frith CD, Johnstone EC, Owens DG, Roberts GW. Schizophrenia
and the brain: a prospective clinico-neuropathological study. Psychol Med 1990;20:285304.

91

Buchanan RW, Carpenter WT. Concept of Schizophrenia. In: Comprehensive Textbook

of Psychiatry, 8th ed. Sadock BJ, Sadock VA, eds. Lippincott Williams & Wilkins,
Philadelphia, 2005.
Caldwell CB, Gottesman II. Schizophrenics kill themselves too: a review of risk factors
for suicide. Schizophr Bull 1990;16:571-588.
Camisa KM, Bockbrader MA, Lysaker P, Rae LL, Brenner CA, O Donnell BF.
Personality traits in schizophrenia and related personality disorders. Psychiatry Res
2005;133:23-33.
Cannon M, Jones PB, Murray RM. Obstretic complications and schizophrenia: historical
and meta-analytic review. Am J Psychiatry 2002;159:1080-1092.
Cannon TD, Rosso IM, Hollister JM, et al. A prospective cohort study of genetic and
perinatal influences in the etiology of schizophrenia. Schizophr Bull 2000;26:351-366.
Cannon TD, Huttunen MO, Dahlstrm M, Larmo I, Rsnen P, Juriloo A. Antipsychotic
drug treatment in the prodromal phase of schizophrenia. Am J Psychiatry 2002;159:12301232.
Cannon TD, Van Erp TG, Bearden CE, et al. Early and Late Neurodevelopmental
Influences in the Prodrome to Schizophrenia: Contributions of Genes, Environment, and
their Interactions. Schizophr Bull 2003;29(4):653-669.
Carpenter W. Foreword. In: The Epidemiology of schizophrenia. Murray RM, Jones PB,
Susser E, Van Os J, Canon M, eds. Cambridge University Press, 2003.
Carter CJ. Schizophrenia susceptibility genes directly implicated in the life cycles of
pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii.
Schizophr Bull 2009;35(6):1163-1182.
Castle DJ, Murray RM. The epidemiology of late-onset schizophrenia. Schizophr Bull
1993;19(4):691-700.
Cloninger CR, Svrakic DM. Personality Disorders. In: Comprehensive Textbook of
Psychiatry, 9th ed. Sadock BJ, Sadock VA, Ruiz P, eds. Lippincott Williams & Wilkins,
Philadelphia, 2009.
Corcoran C, Walker E, Huot R, et al. The stress cascade and schizophrenia: etiology and
onset. Schizophr Bull 2003;29:671-692.
Corey-Bloom J, Jernigan T, Archibald S, Harris MJ, Jeste DV. Quantitative magnetic
resonance imaging in late life schizophrenia. Am J Psychiatry 1995;152:447-449.
Cornblatt B, Obuchowski M, Roberts S et al. Cognitive and behavioral precursors of
schizophrenia. Dev Psychopathol 1999;11:487-508.
Cortese L, Caliguri MP, Malla AK, et al. Relationship of neuromotor disturbances to
psychosis symptoms in first-episode neuroleptic-nave schizophrenia patients. Schizophr
Res 2005;75:65-75.
92

Craddock N, O Donovan MC, Owen MJ. Phenotypic and genetic complexity of

psychosis Invited commentary on Schizophrenia: a common disease caused by multiple
rare alleles. Br J Psychiatry 2007;190:200-203.
Crow TJ, Ball J, Bloom SR, et al..Schizophrenia as an anomaly of development of
cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of
the disease. Arch Gen Psychiatry 1989;46(12):1145-1150.
Crow TJ. Schizophrenia as a failure of hemispheric dominance for language. Trends
Neurosci 1998;21:145-147.
David HN, Ansseau M, Abraini JH. Dopamine-Glutamate reciprocal modulation of
release and motor responses in the rat caudate-putamen and nucleus accumbens of intact
animals. Brain Res Rev 2005;50(2):336-360.
Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and
reconceptualization. Am J Psychiatry 1991;148:1474-1486.
Davis KL, Stewart DG, Friedman JI, et al. White matter changes in schizophrenia. Arch
Gen Psychiatry 2003;60:443-456.
Delisi LE. The significance of age of onset for schizophrenia. Schizophr Bull
1992;18:209-15.
De Nicola AF, Saravia FE, Beauquis J, Pietranera L, Ferrini MG. Estrogens and
neuroendocrine hypothalamic-pituitary-adrenal axis function. Front Horm Res
2006;35:157-168.
Dervaux A, Laqueille X. Smoking and schizophrenia: epidemiological and clinical
features. Encephale 2008;34(3):299-305.
Dickey CC, McCarley RW, Shenton ME. The brain in schizotypal personality disorder: a
review of structural MRI and CT findings. Harv Rev Psychiatry 2002;10:1-15.
DiPaolo T, Falardeau P. Modulation of brain and pituitary dopamine receptors by
estrogens and prolactin. Prog Neuro-psychopharm Biol Psychiatry 1985;9:473-480.
Diwan A, Castine M, Pomerleau CS, et al. Differential prevalence of cigarette smoking in
patients with schizophrenic vs mood disorders. Schizophr Res 1998;33:113-118.
Dodds ER. . . - . ,
1996.
D Souza DC, Sewell RA, Ranganathan Mohini. Cannabis and psychosis/schizophrenia:
human studies. Eur Arch Psychiatry Clin Neurosci 2009;259(7):413-431.
Eaton WW. The Epidemiology of schizophrenia. Epidemiol Rev 1985;7:105-126.
Eaton WW. Update on the epidemiology of schizophrenia. Epidemiol Rev 1991;13:320328.

93

Eaton WW, Mortensen PB, Frydenberg M. Obstetric factors, urbanization and psychosis.
Schizophr Res 2000;43:117-23.
Eaton WW, Harisson G. Ethnic disadvantage and schizophrenia. Acta Psychiatr Scand
2000;102(suppl):38-43.
Eaton WW, Chen CY. Epidemiology. In: Textbook of Schizophrenia. Lieberman JA,
Stroup TS, Perkins DO, eds. American Psychiatric Publishing, Washington DC, 2006.
Ellison Z, Van Os J, Murray R. Special feature: Childhood personality characteristics of
schizophrenia: Manifestations of, or risk factors for, the disorder? J Personal Dis
1998;12(3):247-261.
Ersche KD, Turton AJ, Pradhan S, Bullmore ET, Robbins TW. Drug addiction
endophenotypes: impulsive versus sensation-seeking personality traits. Biol Psychiatry
2010;68(8):770-3.
Fanous AH, Kendler KS. The genetic relationship of personality to major depression and
schizophrenia. Neurotox Res 2004;6(1):43-50.
Faraone SV, Green AI, Seidman LJ, Tsuang MT. Schizotaxia: Clinical Implications
and New Directions for Research. Schizophr Bull 2001;27(1):1-18.
Fatemi SH, Folsom TD. The Neurodevelopmental Hypothesis of schizophrenia,
Revisited. Schizophr Bull 2009;35(3):528-548.
Fine MA, Overholser JC, Berkoff K. Diagnostic validity of the passive-aggressive
personality disorder: suggestions for reform. Am J Psychother 1992;46(3):470-484.
First MB, Spitzer RL, Gibbon M, Williams JBV. Structured clinical interview for DSMIV axis I disorders- patient edition (SCID I/P), version 2.0. New York: Biometrics
Research Department, New York State Psychiatric Institute, 1995.
First MB, Gibbon M, Spitzer RL, Williams JBV, Benjamin LS. Structured clinical
interview for DSM-IV axis II personality disorders(SCID-II). New York: Biometrics
Research Department, New York State Psychiatric Institute, 1997.
Fish F. Schizophrenia, 3rd ed. Hamilton M, ed. Williams & Wilkins, Baltimore, 1984.
Fogelson DL, Nuechterlein KH, Asarnow RA, et al. Avoidant personality disorder is a
separable schizophrenia spectrum personality disorder even when controlling for the
presence of paranoid and schizotypal personality disorders. Schizophr Res 2007;91(13):192-199.
Gattaz WF, Abrahao AR, Foccacia R. Childhood meningitis, brain maturation and the
risk of psychosis. Eur Arch Psychiatry Clin Neurosci 2004;254:23-26.
Geddes JR, Verdoux H, Takei N, et al. Schizophrenia and complications of pregnancy
and labor: an individual patient data meta-analysis. Schizophr Bull 1999;25:413-423.

94

Gilmore JH, Murray RM. Prenatal and Perinatal Factors. In: Textbook of Schizophrenia.
Lieberman JA, Stroup TS, Perkins DO, eds. American Psychiatric Publishing,
Washington DC, 2006.
Goel N, Bale TL. Examining the intersection of sex and stress in modeling
neuropsychiatric disorders. J Neuroendocrinol 2009;21(4):415-420.
Goldstein JM, Link BG. Gender and the expression of schizophrenia. Psychiatr Res
1988;2:141-155.
Goldstein JM, Santangelo SL, Simpson JC, et al. The role of gender in identifying
subtypes of schizophrenia: a latent class analytic approach. Schizophr Bull 1990;16:263275.
Gourzis P, Katrivanou A, Beratis S. Symptomatology of the initial prodromal phase in
schizophrenia. Schizophr Bull 2002;28(3):415-429.
Green MF, Kern RS, Heaton RK. Longitudinal studies of cognition and functional
outcome in schizophrenia: Implications for MATRICS. Schizophr Res 2004:72:41-51.
Gur RE, Keshavan MS, Lawrie SM. Deconstructing psychosis with human brain
imaging. Schizophr Bull 2007;33:921-931.
Gureje O. Gender and schizophrenia: age at onset and sociodemographic attributes. Acta
Psychiatr Scand 1991;83:402-405.
Haas GL. Suicidal behavior in schizophrenia. In: Review of suicidology. Maris RW,
Silverman MM, Canetto SS, eds. Guilford Press, New York, 1997.
Hfner H, Riecher-Rssler A, Maurer K, Lffler W, Munk-Jrgensen P, Strmgren E.
How does gender influence age at first hospitalization for schizophrenia? Psychol Med
1989;19:903-918.
Hfner H, Behrens S, De Vry J, et al. An animal model for the effects of estradiol on
dopamine-mediated behavior: implications for sex differences in schizophrenia.
Psychiatry Res 1991;38:125-234.
Hfner H, Maurer K, Lffler W, Riecher-Rssler A. The Influence of Age and Sex on the
Onset and Early Course of Schizophrenia. Br J Psychiatry 1993;162:80-86.
Hfner H, Maurer K, Lffler W, et al. The Epidemiology of Early Schizophrenia.
Influence of age and gender on onset and early course. Br J Psychiatry 1994;164(suppl
23):29-38.
Hfner H, Hambrecht M, Lffler W, Munk-Jrgensen P, Riecher-Rssler A. Is
schizophrenia a disorder of all ages? A comparison of first episodes and early course
across the life-cycle. Psychol Med 1998;28:351-365.
Hfner H. Onset and early course as determinants of the further course of schizophrenia.
Acta Psychiatr Scand 2000;102(Suppl. 407):44-48.

95

Hfner H. Gender differences

2003;28(suppl 2):17-54.

in

schizophrenia.

Psychoneuroendocrinology

Hambrecht M, Maurer K, Hfner H. Evidence for a gender bias in epidemiological

studies of schizophrenia. Schizophr Res 1992;8:223-231.
Hambrecht M, Hfner H. Substance abuse and the onset of schizophrenia. Biol Psychiatry
1996;40:1155-1163.
Hare E, Contreras J, Raventos H, et al. Genetic structure of personality factors and bipolar
disorder in families segregating bipolar disorder. J Affect Disord. 2011 Sep 6. [Epub
ahead of print]
Harris MJ, Jeste DV. Late-Onset Schizophrenia: An Overview. Schizophr Bull
1988;14(1):39-54.
Harrison PJ. The neuropathology of schizophrenia. A critical review of the data and their
interpretation. Brain 1999;122:593-624.
Haslam J. Illustrations of Madness. London, J Callow, 1810.
Hatzipetros T, Yamamoto BK. Dopaminergic and GABAergic modulation of glutamate
release from rat subthalamic nucleus efferents to the substantia nigra. Brain Res
2006;1076(1):60-67.
an der Heiden W, Hfner H. The epidemiology of onset and course of schizophrenia. Eur
Arch Psychiatry Clin Neurosci 2000;250:292-303.
Heil H, Isomets ET, Henriksson MM, Heikkinen MH, Marttunen MJ, Lnnqvist JK.
Suicide and schizophrenia: a nationwide psychological autopsy study on age- and sexspecific clinical characteristics of 92 suicide victims with schizophrenia. Am J Psychiatry
1997;154:1235-1242.
Heil H, Lnnqvist JK. The clinical epidemiology of suicide in schizophrenia. In: The
Epidemiology of Schizophrenia. Murray RM, Jones PB, Susser E, Van Os J, Cannon M,
eds. Cambridge University Press, Cambridge, UK, 2003.
Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative
review of the evidence. Neuropsychology 1998;12:426-445.
Hoek HW, Susser E, Buck KA, et al. Schizoid personality disorder after prenatal
exposure to famine. Am J Psychiatry 1996;153:1637-1639.
Hoffman RE, Hawkins KA, Gueorguieva R, et al. Transcranial magnetic stimulation of
left temporoparietal cortex and medication-resistant auditory hallucinations. Arch Gen
Psychiatry 2003;60:49-56.
van Horn JD, McManus IC. Ventricular enlargement in schizophrenia: a meta-analysis of
studies of the ventricle:-brain ratio (VBR). Br J Psychiatry 1992;160:687-697.

96

Howard R, Rabins PV, Seeman MV, Jeste DV, and the International Late-Onset
Schizophrenia Group. Late-Onset Schizophrenia and Very-Late-Onset SchizophreniaLike Psychosis: An International Consensus. Am J Psychiatry 2000;157:172-178.
Howells JG. Introduction. In: The Concept of Schizophrenia. Howells JG, ed. American
Psychiatric Press, Washington DC, 1993.
Howes OD, Kapur S. The Dopamine Hypothesis of Schizophrenia: Version III-The Final
Common Pathway. Schizophr Bull 2009;35(3):549-562.
Hruska RE. Elevation of striatal dopamine receptors by estrogen: dose and time studies. J
Neurochemistry 1986;47:1908-1915.
Huber G, Gross G. The concept of basic symptoms in schizophrenic and schizoaffective
psychoses. Recenti Prog Med 1989;80:646-652.
. : -. , . , 1993.
Jackson HJ, McGorry PD, Dudgeon P. Prodromal symptoms of schizophrenia in firstepisode psychosis: Prevalence and specificity. Compr Psychiatry 1995;36:241-150.
Jacob H, Beckmann H. Gross and histological criteria for developmental disorders in
brains of schizophrenics. J R Soc Med 1989;82:466-469.
Jarskog LF, Robbins TW. Neuropathology and neural circuits implicated in
schizophrenia. In: Textbook of schizophrenia. Lieberman JA, Stroup TS, Perkins DO,
eds. American Psychiatric Publishing, Washington DC, 2006.
Javitt DC, Laruelle M. Neurochemical theories. In: Textbook of schizophrenia.
Lieberman JA, Stroup TS, Perkins DO, eds. American Psychiatric Publishing,
Washington DC, 2006.
Jeste DV, Harris MJ, Krull A, Kuck J, McAdams A, Heaton R. Clinical and
neuropsychological Characteristics of Patients with Late-Onset Schizophrenia. Am J
Psychiatry 1995;152:722-730.
Jeste DV, Symonds LL, Harris MJ, Paulsen JS, Palmer BW, Heaton RK. Nondementia
Nonpraecox Dementia Praecox? Late-Onset Schizophrenia. Am J Geriatr Psychiatry
1997;5:302-317.
Jeste DV, McAdams LA, Palmer BW, et al. Relationship of neuropsychological and MRI
measures to age of onset of schizophrenia. Acta Psychiatr Scand 1998;98:156-164.
Job D, Whalley HC, Johnstone EC, Lawrie SM. Grey matter changes over time in high
risk subjects developing schizophrenia. Neuroimage 2005;25:1023-1030.
Joyce JN, Meador-Woodruff JH. Linking the family of D2 receptors to neuronal circuits in
human brain: insights into schizophrenia. Neuropsychopharmacology 1997;16:375-384.
Kay SR , Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for
schizophrenia. Schizophr Bull 1987;13:261-274.

97

Keefe RSE, Bilder RM, Davis SM, et al. Neurocognitive effects of antipsychotic
medications in patients with schizophrenia in the CATIE trial. Arch Gen Psychiatry
2007;64:633-647.
Keith SJ, Regier DA, Rae DS: Schizophrenic disorders. In: Psychiatric Disorders in
America: The Epidemiologic Catchment Area Study. Robins LN, Regier DA, eds. Free
Press, New York, 1991.
Kendler KS, Gruenberg AM, Tsuang MT. Subtype stability in schizophrenia. Am J
Psychiatry 1985;142:827-832.
Kendler KS, McGuire M, Gruenberg AM, O Hare A, Spellman M, Walsh D. The
Roscommon Family Study. III. Schizophrenia-related personality disorders in relatives.
Arch Gen Psychiatry 1993;50:781-788.
Keshavan MS, Gilbert AR, Diwadkar VA. Neurodevelopmental Theories. In: Textbook
of schizophrenia. Lieberman JA, Stroup TS, Perkins DO, eds. American Psychiatric
Publishing, Washington DC, 2006.
Keshavan MS, Tandon R, Boutros N, Nasrallah HA. Schizophrenia, just the facts. What
we know in 2008. Part 3: Pathophysiology. Schizophr Res 2008;106:89-107.
Kirkpatrick B, Cenk T. Schizophrenia: Clinical features and psychopathology concepts.
In: Comprehensive Textbook of Psychiatry, 8th ed. Sadock BJ, Sadock VA, eds.
Lippinkott Williams & Wilkins, Philadelphia, 2005.
Klosterktter J, Hellmich M, Steinmeyer EM, Schultze-Lutter F. Diagnosing
schizophrenia in the initial prodromal phase. Arch Gen Psychiatry 2001;58(2):158-164.
Klosterktter J, Ruhrmann S, Schultze-Lutter F, et al.The European Prediction of
Psychosis Study( EPOS): integrating early recognition and intervention in Europe. World
Psychiatry 2005;4:161-167.
Klosterktter J, Schultze-Lutter F, Ruhrmann S. Kraepelin and psychotic prodromal
conditions. Eur Arch Psychiatry Clin Neurosci 2008;258(Suppl 2):74-84.
Kontaxakis V, Havaki-Kontaxaki B, Margariti M, et al. The Greek Version of Calgary
Depression Scale for Schizophrenia. Psychiatry Res 2000;94:163-171.
Koskinen J, Lohonen J, Koponen H, et al. Prevalence of alcohol use disorders in
schizophrenia- a systematic review and meta-analysis. Acta Psychiatr Scand
2009;210:85-96.
Kraepelin E. Psychiatrie. 4th ed. Ein Lehbruch fur Studirende und Arzte. Leipzig,
Germany, Abel, 1893.
Krebs MO, Guilin O, Bourdel MC et al. Brain Derived Neurotrophic Factor (BDNF) gene
variants association with age at onset and therapeutic response in schizophrenia. Mol
Psychiatry 2000;5:558-562.
Kulkarni J. Oestrogen-a new treatment approach for schizophrenia? MJA 2009;190:3738.
98

Lahuis B, Kemner C, Van Engeland H. Magnetic resonance imaging studies on autism

and childhood-onset schizophrenia in children and adolescents- a review. Acta
Neuropsychiatr 2003;15:140.
Larsen TK, McGlashan TH, Johannessen JO, et al. First-episode schizophrenia, II:
premorbid patterns by gender. Schizophr Bull 1996;22:257-269.
Lawrie SM, Abukmeil SS. Brain abnormality in schizophrenia. A systematic and
quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiatry
1998;172:110-120.
Lawrie SM, Whalley HC, Kestelman JN, et al. Magnetic resonance imaging of brain in
people at high risk of developing schizophrenia. Lancet. 1999;353:30-33.
Lawrie SM, Whalley HC, Abukmeil SS, et al. Brain structure, genetic liability and
psychotic symptoms in subjects at high risk of developing schizophrenia. Biol Psychiatry.
2001;49:811-823.
Lawrie SM, McIntosh AM, Hall J, Owens DGC, Johnstone EC. Brain structure and
function changes during the development of schizophrenia: The evidence from studies of
subjects at increased genetic risk. Schizophr Bull 2008;34(2):330-340.
Lee PW, Lieh-Mak F, Wong MC, et al. The 15-year outcome of Chinese patients with
schizophrenia in Hong Kong. Can J Psychiatry 1998;43:706-713.
Leung A, Chue P. Sex differences in schizophrenia, a review of the literature. Acta
Psychiatr Scand Suppl 2000;401:3-38.
Lewis CM, Levinson DF, Wise LH, et al. Genome scan meta-analysis of schizophrenia
and bipolar disorder, part II: Schizophrenia. Am J Hum Genet 2003;73:34-48.
Lewis DA, Sweet RA. Schizophrenia from a neural circuitry perspective: advancing
toward rational pharmacological therapies. J Clin Invest 2009;119:706-716.
Lindamer LA, Lohr JB, Harris MJ, McAdams LA, Jeste DV. Gender-related clinical
differences in older patients with schizophrenia. J Clin Psychiatry 1999;60:61-67.
Lindenmayer JP, Khan A. Psychopathology. In: Textbook of schizophrenia. Lieberman
JA, Stroup TS, Perkins DO, eds. American Psychiatric Publishing, Washington DC, 2006.
Lloyd T, Dazzan P, Dean K, et al. Minor physical anomalies in patients with first-episode
psychosis: their frequency and diagnostic specificity. Psychol Med 2008;38:71-77.
Lohr JB, Alder M, Flynn K, Harris MJ, McAdams LA. Minor physical anomalies in older
patients with late-onset schizophrenia, early-onset schizophrenia, depression and
Alzheimers disease. Am J Geriatr Psychiatry 1997;5:318-323.
Loranger AW. Sex difference in age at onset of schizophrenia. Arch Gen Psychiatry
1984;41:157-161.
Lykouras L, Oulis P, Psarros K, et al. Five-factor model of schizophrenic
psychopathology: how valid is it? Eur Arch Psychiatr Clin Neurosci 2000;250:93-100.
99

alaspina D, Harlap S, Fennig S, et al. Advancing paternal age and the risk of
schizophrenia. Arch Gen Psychiatry 2001;58:361-367.
Malaspina D, Coleman E. Olfaction and social drive in schizophrenia. Arch Gen
Psychiatry 2003;60:578-584.
Manson JE. Prenatal exposure to sex steroid hormones and behavioral/cognitive
outcomes. Metabol Clin Exp 2008;57(Suppl 2):S16-S21.
Marcelis M, Navarro-Mateu F, Harrison G, et al. Urbanization and psychosis: a study of
1942-1978 birth cohorts in the Netherlands. Psychol Med 1998;28:871-879.
March D, Hatch SL, Morgan C, et al. Psychosis and place. Epidemiol Rev 2008;30:84100.
Mayer C, Kelterborn G, Naber D. Age of onset in schizophrenia: Relations to
psychopathology and gender. Br J Psychiatry 1993;162:665-671.
Mazzuco CA, Lieblich SE, Bingham BI, Williamson MA, Viau V, Galea LA. Both
estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in
the dentate gyrous of adult female rats. Neuroscience 2006;141:1793-1800.
McClellan JM, Susser E, King MC. Schizophrenia: a common disease caused by multiple
rare alleles. Br J Psychiatry 2007;190:194-199.
McGlashan TH, Zipursky RB, Perkins D, et al. The PRIME North America randomized
double-blind clinical trial of olanzapine vs placebo in patients at risk of being
prodromally symptomatic for psychosis, I: study rationale and design. Schizophr Res
2003;61:7-18.
McGlashan TH, Zipursky RB, Perkins D, et al. Randomized, double-blind trial of
olanzapine versus placebo in patients prodromally symptomatic for psychosis. Am J
Psychiatry 2006;163:790-799.
McGorry PD, Yung AR, Philips LJ, Yen HP, Francey S, Cosgrave EM. Randomized
controlled trial of interventions designed to reduce the risk of progression to first episode
psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry
2002;59:921-928.
McGrath JJ, Susser ES. New directions in the epidemiology of schizophrenia. MJA
2009;190:S7-S9.
McMillan KA, Enns MW, Cox BJ, Sareen J. Comorbidity of axis I and II mental
disorders with schizophrenia and psychotic disorders: Findings from the National
Epidemiology Survey on alcohol and related conditions. Can J Psychiatry
2009;54(7):477-486.
McNeil TF, Cantor-Graae E, Weinberger DR. Relationship of obstetric complications and
differences in size of brain structures in monozygotic twin pairs discordant for
schizophrenia. Am J Psychiatry 2000;157:203-212.
Meehl PE. Schizotaxia, schizotypy, schizophrenia. Am Psychol 1962;17:827-838.
100

Mega MS, Cummings JL. Frontal and prefrontal circuits. In: The frontal lobes and
neuropsychiatric illness. Salloway SP, Malloy PF, Duffy JD, eds. American Psychiatric
Publishing, Washington DC, 2001.
Melkangi RC, Magnaghi I, Cavaretta L, Martini L, Piva F. Age-induced decrease of
glycoprotein PO and myelin basic protein gene expression in the rat sciatic nerve. Repair
by steroid derivatives. Neuroscience 1998;85:569-578.
Merikangas KR, Risch N. Will the genomics revolution revolutionize psychiatry? Am J
Psychiatry 2003;160:625-635.
Miller TJ, McGlashan TH, Woods SW, et al. Symptom assessment in schizophrenic
prodromal states. Psychiatr Q 1999;70(4):273-287.
Miller TJ, McGlashan TH, Rosen JL, et al: Prospective diagnosis for the initial prodrome
for schizophrenia based on the Structured Interview for Prodromal Syndromes:
preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry
2002;159:863-865.
Mller P, Husby R. The initial prodrome in schizophrenia: searching for naturalistic core
dimensions of experience and behavior. Schizophr Bull 2000;26:217-232.
Moore TH, Zammit S, Lingford-Hughes A, et al. Cannabis use and risk of psychotic or
affective mental health outcomes: a systematic review. Lancet 2007;370:319-328.
Morrens M, Hulstijn W, Sabbe B. Psychomotor slowing in schizophrenia. Schizophr Bull
2007;33:1038-1053.
Mortensen PB, Pedersen CB, Westergaard T, et al. Effects of family history and place and
season of birth on the risk of schizophrenia. N Engl J Med 1999;340:603-608.
Mortensen PB. Mortality and physical illness in schizophrenia. In: The Epidemiology of
schizophrenia. Murray RM, Jones PB, Susser E, Van Os J, Canon M, eds. Cambridge
University Press, 2003.
Moukas G, Stathopoulou A, Gourzis P, Beratis IN, Beratis S. Relationship of
prodromal symptoms with severity and type of psychopathology in the active phase of
schizophrenia. Compr Psychiatry 2010;51:1-7.
Muller JE, Koen L, Soraya S, et al. Anxiety disorders and schizophrenia. Curr Psychiatry
Rep 2004;6:255-261.
Munk-Jrgensen P: First-admission rates and marital status of schizophrenics.
Psychiatr Scand 1987;76:210-216.

Acta

Munk-Jrgensen P, Ewald H. Epidemiology in neurobiological research: exemplified by

the influenza-schizophrenia theory. Br J Psychiatry 2001;40(suppl):30-32.
Murray RM, Grech A, Phillips P, Johnson S. What is the relationship between substance
abuse and schizophrenia? In: The Epidemiology of schizophrenia. Murray RM, Jones PB,
Susser E, Van Os J, Canon M, eds. Cambridge University Press, 2003.

101

Murray RM, Bramon A. Developmental model of schizophrenia. In: Comprehensive

Textbook of Psychiatry, 8th ed. Sadock BJ, Sadock VA, eds. Lippincott Williams &
Wilkins, Philadelphia, 2005.
Nakaya M, Suwa H, Ohmori K. Latent structures underlying schizophrenic symptoms: a
five-dimensional model. Schizophr Res 1999;39:39-50.
Nelson MD, Saykin AJ, Flashman LA, Riordan HJ. Hippocampal volume reduction in
schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Arch
Gen Psychiatry 1998;55:433-440.
Nelson B, Yung AR, Bechdolf A, McGorry PD. The Phenomenological Critique and
Self-disturbance: Implications for Ultra-High Risk (Prodrome) Research. Scizophr Bull
2008;34(2):381-392.
Nicodemus KK, Marenco S, Batten AJ, et al. Serious obstetric complications interact with
hypoxia-regulated/vascular-expression genes to influence schizophrenia risk. Mol
Psychiatry 2008;13:873-877.
Norman RMG, Lewis SW, Marshall M. Duration of untreated psychosis and its
relationship to clinical outcome. Br J Psychiatry(Suppl.) 2005;187:S19-S23.
OCallaghan, Sham PC, Takei N, et al. The relationship of schizophrenic births to 16
infectious diseases. Br J Psychiatry 1994;163:353-356.
Olney JW, Newcomer JW, Farber NB. NMDA receptor hypofunction model of
schizophrenia. J Psychiatry Res 1999;33(6):523-533.
van Os J, Pedersen CB, Mortensen PB. Confirmation of synergy between urbanicity and
familial liability in the causation of psychosis. Am J Psychiatry 2004;161:2312-2314.
van Os J, Rutten B PF, Poulton R. Gene-environment interactions in schizophrenia:
Review of epidemiological findings and future directions. Schizophrenia Bull
2008;34(6):1066-1082.
van Os J, Kapur S. Schizophrenia. Lancet 2009;374:635-645.
. . . , , 2006.
Overall JE, Gorham DR. The brief psychiatric rating scale. Psychol Rep 1962;10:799812.
Owen MJ, Williams HJ, O Donovan MC. Schizophrenia genetics: advancing on two
fronts. Curr Opin Genet Dev 2009;19:266-270.
Owens DGC, Johnstone EC. Precursors and prodromata of schizophrenia: findings from
the Edinburgh High Risk Study and their literature context. Psychol Med 2006;36:15011514.
Pallanti S, Quercioli L, Pazzagli A. Social anxiety and premorbid personality disorders in
paranoid schizophrenic patients treated with clozapine. CNS Spectr 2000;5(9):29-43.

102

Palmer BW, McClure FS, Jeste DV. Schizophrenia in late life: Findings challenge
traditional concepts. Harv Rev Psychiatry 2001;9:51-58.
Parnas J, Jansson L, Sass LA, Handest P. Self-experience in the prodromal phases of
schizophrenia: a pilot-study of first admissions. Neurol Psychiatry Brain Res 1998;6:97106.
Parnas J, Mller P, Kircher T, et al. EASE: Examination of Anomalous Self-Experience.
Psychopathology 2005;38:236-258.
Pearlson GD, Kreger L, Rabins PV, et al. A chart review study of late-onset and earlyonset schizophrenia. Am J Psychiatry 1989;146(12):1568-1574.
Pedersen CB, Mortensen PB. Evidence of a dose-response relationship between
urbanicity during upbringing and schizophrenia risk. Arch Gen Psychiatry 2001;58:10391046.
Pedersen CB. No evidence of time trends in the urban-rural differences in schizophrenia
risk among five million people born in Denmark from 1910 to 1986. Psychol Med
2006;36:211-219.
Penn DL, Sanna LJ, Roberts DL. Social cognition in schizophrenia: an overview.
Schizophr Bull 2008;34:408-411.
Peralta V, Cuesta MJ. How many and which are the psychopathological dimensions in
schizophrenia? Issues influencing their ascertainment. Schizophr Res 2001;49:269-285.
Pycock CJ, Kervin RW, Carter CJ. Effect of lesion of cortical dopamine terminals on
subcortical dopamine receptors in rats. Nature 1980;286(5768):74-76.
Quickfall J, Crockford D. Brain neuroimaging in cannabis use: a review. J
Neuropsychiatry Clin Neurosci 2006;18:318-332.
Quinn JJ, Hitchcott PK, Umeda EA, Arnold AP, Taylor JR. Sex chromosome
complement regulates habit formation. Nat Neurosci 2007;10:1398-1400.
Rabins PV, Pauker S, Thomas J: Can schizophrenia begin after age 44? Compr Psychiatry
1984;25:290-293.
Rajji TK, Ismail Z, Mulsant BH. Age at onset and cognition in schizophrenia: metaanalysis. Br J Psychiatry 2009;195:286-293.
Rajkumar SR. Incidence of schizophrenia in an urban community in Mandras. Indian J
Psychiatry 1993;35:18-21.
Reichborn-Kjennerud T. The genetic epidemiology of personality disorders. Dialogues
Clin Neurosci. 2010;12(1):103-14.
Remington G. Alterations of dopamine and serotonin transmission in schizophrenia. Prog
Brain Res 2008;172:117-140.

103

Riecher-Rssler A, Fatkenheuer B, Lffler W, Maurer K, Hfner H. Is age of onset in

schizophrenia influenced by marital status? Soc Psychiatry Psychiatr Epidemiol
1992;27:122-128.
Riecher-Rssler A, Hfner H, Maurer K, et al. Schizophrenic symptomatology varies
with serum estradiol levels during menstrual cycle. Schizophr Res 1992; 6(special
issue):114.
Riley BP, Kendler KS. Schizophrenia: Genetics. In: Comprehensive Textbook of
Psychiatry, 8th ed. Sadock BJ, Sadock VA, eds. Lippincott Williams & Wilkins,
Philadelphia, 2005.
Ritsner M, Susser E. Temperament types are associated with weak self-construct,
elevated distress and emotion-oriented coping in schizophrenia: evidence for a complex
vylnerability marker? Psychiatry Res 2004;128:219-228.
Roberts RC, Tamminga CA. Schizophrenia: Neuropathology. In: Comprehensive
Textbook of Psychiatry, 8th ed. Sadock BJ, Sadock VA, eds. Lippincott Williams &
Wilkins, Philadelphia, 2005.
Rund BR, Melle I, Friis S, et al. Neuro-cognitive dysfunction in first-episode psychosis:
correlates with symptoms, premorbid adjustment, and duration of untreated psychosis.
Am J Psychiatry 2004;161:466-472.
Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the
differential mortality gap worsening over time? Arch Gen Psychiatry 2007;64:1123-1131.
Sartorius N, Jablensky A, Korten A, et al. Early manifestations and first-contact incidence
of schizophrenia in different cultures. Psychol Med 1986;16:909-928.
Sato T, Bottlender R, Schrter A, Mller HJ. Psychopathology of early-onset versus lateonset schizophrenia revisited: an observation of 473 neuroleptic-nave patients before and
after first admission treatments. Schizophr Res 2004;67:175-183.
Schneider K. Clinical Psychopathology, translated by Hamilton MW. Grune & Stratton,
New York, 1959.
Schultz SK, Ho BC, Andreasen NC. Clinical features characterizing young-onset and
intermediate onset schizophrenia. J Neuropsychiatry Clin Neurosci 2000;12:502-505.
Schultze-Lutter F. Subjective Symptoms of Schizophrenia in Research and the Clinic:
The Basic Symptom Concept. Schizophr Bull 2009;35(1):5-8.
Schwab SG, Wildenauer DB. Update on key previously proposed candidate genes for
schizophrenia. Curr Opin Psychiatry 2009;22:147-153.
Seeman MV, Lang M. The role of estrogens in schizophrenia gender differences.
Schizophr Bull 1990;16:185-194.
Selemon LD, Rajkowska G, Goldman-Rakik PS: Elevated neuronal density in prefrontal
area 46 in brains from schizophrenic patients: application of a three-dimensional,
stereologic counting method. J Comp Neurol 1998;392:402-412.
104

Shenton ME, Dickey CC, Frumin M, et al. A review of MRI findings in schizophrenia.
Schizophr Res 2001;49:1-52.
Silverstein ML, Mavrolefteros G, Close D. Premorbid Adjustment and
Neuropsychological Performance in Schizophrenia. Schizophr Bull 2002;28(1):157-165.
Skodol AE. Manifestations, Clinical Diagnosis, and Comorbidity. In: Textbook of
Personality Disorders. Oldham JM, Skodol AE, Bender DS, eds. American Psychiatric
Publishing, Washington DC, 2005.
Smith MJ, Cloninger CR, Harms MP, Csernansky JG. Temperament and character as
schizophrenia related endophenotypes in non-psychotic siblings. Schizophr Res 2008;
104:198-205.
Snyder SH. The dopamine hypothesis of schizophrenia: focus on the dopamine receptor.
Am J Psychiatry 1976;133:197-202.
Sowell ER, Thompson PM, Toga AW. Mapping cortical change across the human life
span. Nat Neurosci 2003;6:309-315.
Spritzer MD, Galea LA. Testosterone and dihydrotestosterone, but not estradiol, enhance
survival of new hippocampal neurons in adult male rats. Dev Neurobiol 2007;67:13211333.
Steen RG, Mull C, McClure R, Hamer RM, Lieberman JA. Brain volume in first-episode
schizophrenia: systematic review and meta-analysis of magnetic resonance imaging
studies. Br J Psychiatry 2006;188:510-518.
Stone JM, Morrison PD, Pilowsky LS. Glutamate and dopamine dysregulation in
schizophrenia: a synthesis and selective review. J Psychopharm 2007;21(4):440-452.
Stone JM. Imaging the glutamate system in humans: Relevance to drug discovery for
schizophrenia. Curr Pharm Des 2009;15:2594-1602.
Stone MH. History of schizophrenia and its antecedents. In: Textbook of Schizophrenia.
Lieberman JA, Stroup TS, Perkins DO, eds. American Psychiatric Publishing,
Washington DC, 2006.
Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a
meta-analysis of twin studies. Arch Gen Psychiatry 2003;60:1187-1192.
Susser ES, Lin SP. Schizophrenia after prenatal exposure to the Dutch Hunger Winter of
1944-1945. Arch Gen Psychiatry 1992;49:983-998.
Tanapat P, Hastings NB, Reeves AJ, Gould E. Estrogen stimulates a transient increase in
the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci
1999;19:5792-5801.
Tandon R, DeQuardo JR, Taylor SF, et al. Phasic and enduring negative symptoms in
schizophrenia: biological markers and relationship to outcome. Schizophr Res
2000;45(3):191-201.

105

Tandon R, Keshavan MS, Nasrallah HA. Schizophrenia, Just the Facts:What we know
in 2008. 2.Epidemiology and etiology. Schizophr Res 2008;102:1-18.
Tandon R, Nasrallah HA, Keshavan MS. Schizophrenia, just the facts 4. Clinical
features and conceptualization. Schizophr Res 2009;110:1-23.
Thara R, Henrietta M, Joseph A, et al. Ten-year course of schizophrenia-the Mandras
longitudinal study. Acta Psychiatr Scand 1994;90:329-336.
Toga AW, Thomson PM, Sowell ER. Mapping brain maturation. Trends Neurosci
2006;29(3):148-159.
Torrey EF, Rawlings R, Waldman IN. Schizophrenic births and viral diseases in two
states. Schizophr Res 1988;1:73-77.
Torrey EF, Miller J. The invisible plague: The rise of mental illness from 1750 to present.
Rutgers University Press, New Brunswick NJ, 2001.
Tosato S, Dazzan P. The psychopathology of schizophrenia and the presence of
neurological soft signs: a review. Curr Opin Psychiatry 2005;18:285-288.
Tsuang MT, Stone WS, Glatt SJ, Faraone SV. Schizophrenia Spectrum: Pathology and
Treatment. In: Comprehensive Textbook of Psychiatry, 8th ed. Sadock BJ, Sadock VA,
eds. Lippinkott Williams & Wilkins, Philadelphia, 2005.
Ungvari GS, Goggins W, Leung SK, Gerevish J. Schizophrenia with prominent catatonic
features(catatonic schizophrenia) II. Factor analysis of the catatonic syndrome. Prog
Neuropsychopharmacol Biol Psychiatry 2007;31:462-468.
Usall J, Haro JM, Ochoa S, et al. Influence of gender on social outcome in schizophrenia.
Acta Psychiatr Scand 2002;106:337-342.
Veling W, Susser E, van Os, et al. Ethnic density of neighborhoods and incidence of
psychotic disorders among immigrants. Am J Psychiatry 2008;165:66-73.
Vita A, De Peri L, Silenzi C, Dieci M. Brain morphology in first-episode schizophrenia:
systematic review and meta-analysis of quantitative magnetic resonance imaging studies.
Schizophr Res 2006;82:75-88.
Vollema MG, Van den Bosch RJ. The multidimensionality of schizotypy. Schizophr Bull
1995;21(1):19-31.
Whalley HC, Harris JC, Lawrie SM. The neurobiological underpinnings of risk and
conversion in relatives of patients with schizophrenia. Int Rev Psychiatry 2007;19(4):38397.
Whalley HC, Steele JD, Mukherjee P, Romaniuk L, McIntosh AM, Hall J, Lawrie SM.
Connecting the brain and new drug targets for schizophrenia. Curr Pharm Des
2009;15:2615-2631.

106

Woods SW, Breier A, Zipurski RB, et al. Randomized trial of olanzapine versus placebo
in the symptomatic acute treatment of the schizophrenic prodrome. Biol Psychiatry
2003;54:453-464.
World Health Organization. The ICD-10 Classification of Mental and Behavioural
Disorders: Diagnostic Criteria for Research. Geneva: World Health Organization; 1992.
Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET. Metaanalysis of regional brain volumes in schizophrenia. Am J Psychiatry 2000;157:16-25.
Yasuda Y, Hashimoto R, Ohi K, et al. Impact on schizotypal personality trait of a
genome-wide supported psychosis variant of the ZNF804A gene. Neurosci Lett
2011;495(3):216-220.
Yung AR, McGorry PD, McFarlane CA, et al. Monitoring and care of young people at
incipient risk of psychosis. Schizophr Bull 1996;22:283-303.
Yung AR, Phillips LJ, McGorry PD, et al. Prediction of psychosis: a step towards
indicated prevention of schizophrenia. Br J Psychiatry 1998;172(33):14-20.
Yung AR, Philips LJ, Yuen HP, et al. Psychosis prediction: 12-month follow up of a
high-risk(prodromal) group. Schizophr Res 2003;60:21-32.
Yung AR, Philips LJ, Yuen HP, et al. Risk factors for psychosis in an ultra-high-risk
group: psychopathology and clinical features. Schizophr Res 2004;67:131-142.
Ziedonis DM, George TP. Smoking and nicotine use. Schizophr Bull 1997;23:247-254.
Zimmerman M, Coryell W. DSM-III personality disorder diagnoses in a nonpatient
sample: demographic correlates and comorbidity. Arch Gen Psychiatry 1989;46:682-689.
Zornberg GL, Buka SL, Tsuang MT. Hypoxic-ischemic-related fetal/neonatal
complications and risk of schizophrenia and other nonaffective psychoses: a 19-year
longitudinal study. Am J Psychiatry 2000;157:196-202.

107