Secondary Schizophrenia (67 page)

neurotransmitter imbalance

schizophrenia: a randomized

Psychophysiology, 2003.
40
:S17

syndrome. Schizophr Bull, 1990.

placebo-controlled crossover trial.

16
(3):425–32.

Biol Psychiatry, 2003.

246. Behrens M. M., Ali S. S., Dao D.

54
(11):1241–8.

N.,
et al.
Ketamine-induced loss of
255. Brody S. A., Geyer M. A., Large

phenotype of fast-spiking

C. H. Lamotrigine prevents

263. Ahmad S., Fowler L. J., Whitton

interneurons is mediated by

ketamine but not

P. S. Lamotrigine, carbamazepine

NADPH-oxidase. Science, 2007.

amphetamine-induced deficits in

and phenytoin differentially alter

318
(5856):1645–7.

prepulse inhibition in mice.

extracellular levels of

Psychopharmacology (Berl), 2003.

5-hydroxytryptamine, dopamine

247. Jentsch J. D., Elsworth J. D.,

169
(3–4):240–6.

and amino acids. Epilepsy Res,

Redmond D. E.,
et al.

2005.
63
(2–3):141–9.

Phencyclidine increases forebrain

256. Anand A., Charney D. S., Oren D.

monoamine metabolism in rats

A.,
et al.
Attenuation of the

264. Harsing L. G., Gacsalyi I., Szabo

and monkeys: modulation by the

neuropsychiatric effects of

G.,
et al.
The glycine transporter-1

isomers of HA966. J Neurosci,

ketamine with lamotrigine –

inhibitors NFPS and Org 24461: a

1997.
17
(5):1769–75.

support for hyperglutamatergic

pharmacological study.

248. Jentsch J. D., Tran A., Le D.,
et al.

effects of N-methyl-D-aspartate

Pharmacol Biochem Behav, 2003.

Subchronic phencyclidine

receptor antagonists. Arch Gen

74
(4):811–25.

administration reduces

Psychiatry, 2000.
57
(3):270–6.

265. Lane H. Y., Liu Y. C., Huang C. L.,

mesoprefrontal dopamine

257. Large C. H., Webster E. L., Goff

et al.
Sarcosine (N-methylglycine)
utilization and impairs prefrontal

D. C. The potential role of

treatment for acute schizophrenia:

cortical-dependent cognition in

lamotrigine in schizophrenia.

a randomized, double-blind study.

the rat. Neuropsychopharmaco-

Psychopharmacology, 2005.

Biol Psychiatr, 2008.
63
(1):9–12.

logy, 1997.
17
(2):92–9.

181
(3):415–36.

266. Tsai G. C., Lane H. Y., Yang P. C.,

249. Jentsch J. D., Redmond D. E.,

258. Kremer I., Vass A., Gorelik I.,

et al.
Glycine transporter I

167

Elsworth J. D.,
et al.
Enduring

et al.
Placebo-controlled trial of
inhibitor, N-methylglycine

Organic Syndromes of Schizophrenia – Section 3

(Sarcosine), added to

subjects. Psychopharmacology,

schizophrenia, and its cognitive

antipsychotics for the treatment of

2005.
179
(1):303–9.

dysfunction. Pharmacol Biochem

schizophrenia. Biol Psychiatr,

273. Patil S. T., Zhang L., Martenyi F.,

Behav, 1997.
56
(4):797–802.

2004.
55
(5):452–6.

et al.
Activation of mGlu2/3

282. Krystal J. H., D’Souza D. C.,

267. Lane H. Y., Huang C. L., Wu P. L.,

receptors as a new approach to

Mathalon D.,
et al.
NMDA

et al.
Glycine transporter I

treat schizophrenia: a randomized

receptor antagonist effects,

inhibitor, N-methylglycine

Phase 2 clinical trial. Nat Med,

cortical glutamatergic function,

(Sarcosine), added to clozapine

2007.
13
(9):1102–7.

and schizophrenia: toward a

for the treatment of

274. Kim J. S., Kornhuber H. H.,

paradigm shift in medication

schizophrenia. Biol Psychiatr,

Schmidburgk W.,
et al.
Low

development. Psychopharmaco-

2006.
60
(6):645–9.

cerebrospinal-fluid glutamate in

logy, 2003.
169
(3–4):215–33.

268. Neale J. H., Olszewski R. T., Gehl

schizophrenic patients and a new

283. Stone J. M., Morrison P. D.,

L. M.,
et al.
The neurotransmitter
hypothesis on schizophrenia.

Pilowsky L. S. Glutamate and

N-acetylaspartylglutamate in

Neurosci Lett, 1980.
20
(3):379–82.

dopamine dysregulation in

models of pain, ALS, diabetic

schizophrenia – a synthesis

275. Wachtel H., Turski L. Glutamate –

neuropathy, CNS injury and

and selective review.

a new target in schizophrenia.

schizophrenia. Trends Pharmacol

J Psychopharmacol, 2007.

Trends Pharmacol Sci, 1990.

Sci, 2005.
26
(9):477–84.

21
(4):440–52.

11
(6):219–22.

269. Olszewski R. T., Bukhari N., Zhou

284. Jarskog L. F., Glantz L. A.,

276. Farber N. B., Wozniak D. F., Price

J.,
et al.
NAAG peptidase

Gilmore J. H.,
et al.
Apoptotic

M. T.,
et al.
Age-specific

inhibition reduces locomotor

mechanisms in the pathophysio-

neurotoxicity in the rat associated

activity and some stereotypes in

logy of schizophrenia. Prog

with NMDA receptor blockade:

the PCP model of schizophrenia

Neurosychopharmacol Biol

potential relevance to

via group II mGluR. J Neuro,

Psychiatry, 2005.
29
(5):846–58.

schizophrenia? Biol Psychiatr,

2004.
89
(4):876–85.

1995.
38
(12):788–96.

285. Catts V. S., Catts S. V., McGrath J.

270. Olszewski R. T., Wegorzewska M.

J.,
et al.
Apoptosis and

277. Keshavan M. S., Anderson S.,

M., Monteiro A. C.,
et al.

schizophrenia: a pilot study based

Pettegrew J. W. Is schizophrenia

Phencyclidine and dizocilpine

on dermal fibroblast cell lines.

due to excessive synaptic pruning

induced behaviors reduced by

Schizophr Res, 2006.
84
(1):20–8.

in the prefrontal cortex – the

N-acetylaspartylglutamate

Feinberg Hypothesis revisited. J

286. Lipska B. K. Using animal models

peptidase inhibition via

Psychiatr Res, 1994.
28
(3):239–65.

to test a neurodevelopmental

metabotropic glutamate receptors.

hypothesis of schizophrenia.

Biol Psychiatr, 2008.
63
(1):86–91.

278. Glantz L. A., Lewis D. A.

J Psychiatr Neurosci, 2004.

Decreased dendritic spine density

271. Schoepp D. D., Johnson B. G.,

29
(4):282–6.

on prefrontal cortical pyramidal

Wright R. A.,
et al.
LY354740 is a
neurons in schizophrenia. Arch

287. Ozawa K., Hashimoto K.,

potent and highly selective group

Gen Psychiatr, 2000.
57
(1):65–73.

Kishimoto T.,
et al.
Immune

II metabotropic glutamate

activation during pregnancy in

receptor agonist in cells

279. Halberstadt A. L. The

mice leads to dopaminergic

expressing human glutamate

phencyclidine glutamate model

hyperfunction and cognitive

receptors. Neuropharmacology,

of schizophrenia. Clin

impairment in the offspring: a

1997.
36
(1):1–11.

Neuropharmacol, 1995.

neurodevelopmental animal

18
(3):237–49.

272. Krystal J. H., Abi-Saab W., Perry

model of schizophrenia. Biol

E.,
et al.
Preliminary evidence of
280. Tsai G. C., Coyle J. T.

Psychiat, 2006.
59
(6):546–54.

attenuation of the disruptive

Glutamatergic mechanisms in

288. Paylor R., McIlwain K. L.,

effects of the NMDA glutamate

schizophrenia. Ann Rev

McAninch R.,
et al.
Mice deleted

receptor antagonist, ketamine, on

Pharmacol Toxicol, 2002.

for the DiGeorge/velocardiofacial

working memory by pretreatment

42
:165–79.

syndrome region show abnormal

with the group II metabotropic

281. Hirsch S. R., Das I., Garey L. J., et
sensorimotor gating and learning

glutamate receptor agonist,

al. A pivotal role for glutamate in

and memory impairments. Hum

LY354740, in healthy human

the pathogenesis of

Mol Genet, 2001.
10
(23):2645–50.

168

Section 3

Organic syndromes of schizophrenia:

11Schizophreniasecondarytocannabisuse

Wayne Hall and Louisa Degenhardt

Facts box

major psychoactive ingredient in cannabis prepara-r
tions, can produce euphoria, distorted time percep-There are good theoretical reasons why
tion, cognitive and memory impairments
[1, 2, 3].

cannabis may be a contributor to the

Under controlled laboratory conditions, normal vol-development of schizophrenia.

unteers using THC in high doses have reported visual
r
There is compelling evidence that cannabis
and auditory hallucinations, delusional ideas, and
use and psychosis are associated, and the
thought disorder
[4, 5].
Second, a putative clinical
debate is on whether cannabis use is a cause
entity of “cannabis psychosis” has been identified by
of psychosis.

clinical observers in India, Egypt, and the Caribbean,
r
There is strong evidence from longitudinal
regions with a long history of heavy cannabis use
studies that cannabis use may precipitate
[1, 6].

schizophrenia in vulnerable individuals.

A number of possible causal relationships have
r
The vulnerability to cannabis-induced

been suggested between cannabis use and psychosis
psychosis may be genetic, but further

[3].
The first possibility is that cannabis use may pro-research is needed to support the preliminary
duce a specific psychosis de novo. Three variants of
evidence.

this hypothesis can be distinguished: i) that large doses
r

of cannabis may induce a toxic paranoid psychosis
There is also reasonable evidence that

that is analogous to that produced by large doses of
cannabis use exacerbates symptoms of

amphetamine; ii) that heavy cannabis use may pro-psychosis in persons with a psychosis who
duce an acute functional psychosis clinically similar to
continue to use cannabis.

r

paranoid schizophrenia; or iii) that chronic cannabis
The evidence does not rule out the possibility
use may produce a psychotic disorder that persists
that persons with psychosis use cannabis to
beyond the period of intoxication. A second possibil-control some of their symptoms or to
ity is that cannabis use could precipitate an episode of
improve their mood, but the self-medication
schizophrenia in a vulnerable or predisposed individ-hypothesis is unlikely to wholly explain the
ual. A third possibility is that cannabis use may exac-relationship observed between cannabis use
erbate the symptoms of schizophrenia by precipitating
and psychosis.

r

more frequent relapses, or the pharmacological effects
Cannabis may promote psychosis directly

of THC might impair the effectiveness of the neurolep-through the cannabinoid system or indirectly
tic drugs used to treat schizophreniform psychoses.