Substance Use in Adolescence and Psychosis

ANRV407-CP06-13

ARI

19 December 2009

5:15

V I E W

A

N

I N

C E

S

R

E

D V A

Review in Advance first posted online on January 4, 2010. (Changes may still occur before final publication online and in print.)

Annu. Rev. Clin. Psychol. 2010.6. Downloaded from arjournals.annualreviews.org by University of Wollongong on 03/17/10. For personal use only.

Substance Use in Adolescence and Psychosis: Clarifying the Relationship Emma Barkus and Robin M. Murray Institute of Psychiatry, King’s College London, De Crespigny Park, SE58A4 London, United Kingdom; email: [email protected], [email protected]

Annu. Rev. Clin. Psychol. 2010. 6:13.1–13.25

Key Words

The Annual Review of Clinical Psychology is online at clinpsy.annualreviews.org

cannabis, alcohol, stimulants, personality, psychosis, schizophrenia

This article’s doi: 10.1146/annurev.clinpsy.121208.131220 c 2010 by Annual Reviews. Copyright All rights reserved 1548-5943/10/0427-0001$20.00

Abstract Adolescence is a time of exploration of the self, and this exploration may involve the use of alcohol and drugs. Sadly, for some, adolescence also marks the first signs of a psychosis. The temporal proximity between the onset of substance use and of psychosis has been the cause of much debate. Here we review the association of alcohol, cannabis, stimulants, and other drugs with psychosis, and we conclude that the use of cannabis and the amphetamines significantly contributes to the risk of psychosis.

13.1

Changes may still occur before final publication online and in print.

ANRV407-CP06-13

ARI

19 December 2009

5:15

Contents


INTRODUCTION . . . . . . . . . . . . . . . . . . 13.2 ARE THE RATES OF SUBSTANCE USE HIGHER IN THOSE WITH PSYCHOSIS THAN IN THE GENERAL POPULATION? . . . . . . 13.2 WHAT IS THE DIRECTION OF THE RELATIONSHIP BETWEEN SUBSTANCE USE AND PSYCHOSIS? . . . . . . . . . . . . . . . 13.4 Alcohol Use . . . . . . . . . . . . . . . . . . . . . . . 13.4 Cannabis Use . . . . . . . . . . . . . . . . . . . . . . 13.4 Stimulants . . . . . . . . . . . . . . . . . . . . . . . . . 13.5 Substances Acting on Glutamate . . . . 13.6 PSYCHOSIS ENDOPHENOTYPES AND THE EFFECTS OF SUBSTANCE USE . . . . . . . . . . . . . . . . 13.7 ARE RISK FACTORS FOR SUBSTANCE USE THE SAME IN THOSE WITH PSYCHOSIS AS IN THE GENERAL POPULATION? . . . . . . . . . . . . . . . . . .13.11 SUBSTANCE USE AND THE PRODROME FOR PSYCHOSIS . .13.12 SUBSTANCE USE AND THE NATURE AND OUTCOME OF PSYCHOSIS . . . . . . . . . . . . . . . . . .13.12 COGNITION IN PATIENTS WHO DO AND DO NOT USE SUBSTANCES . . . . . . . . . . . . . .13.13 CONCLUSIONS . . . . . . . . . . . . . . . . . . . .13.14

INTRODUCTION

V I E

ARE THE RATES OF SUBSTANCE USE HIGHER IN THOSE WITH PSYCHOSIS THAN IN THE GENERAL POPULATION? The risk of substance use in patients with schizophrenia was reported to be 4.6 times that of the general population in the United States (Regier et al. 1990). A large study of patients suffering their first episode of psychosis in

W

R

E

Adolescence marks a period of rapid change in an individual, not only biologically but also psychologically and socially. Individuals may try on different personas in order to explore their own personality and beliefs. Part of this process may include the use of recreational substances such as alcohol, cannabis, and other illegal recreational drugs. Indeed, it seems that within Western societies, particularly in Europe, the use of alcohol and cannabis are so

widespread that their use has almost become a rite of passage for teenagers and an accepted part of adolescent and student culture (e.g., Watson et al. 2000). However, for a minority, adolescence and early adulthood also mark the emergence of mental health difficulties. Here we focus on psychotic disorders; these are a group of illnesses marked by the presence of unusual belief systems which do not conform to societal norms (delusions), hallucinations (particularly auditory), and disorders of thought and cognition. These difficulties can coexist with marked depressive or manic (affective) symptoms. The pattern of symptoms expressed leads to a variety of diagnostic labels: schizophrenia, schizophreniform psychosis, schizoaffective disorder, and psychotic disorder not specified. Already the reader will have noted that both substance use, on the one hand and the first signs of psychosis, on the other, commonly begin in late adolescence and early adult life. Whether their co-occurrence is more than just chance has attracted much attention and is the subject of the current review. We employ the term “substance use” to refer to recreational use and use it to include alcohol as well as illegal recreational drugs; the terms “dependency” and “abuse” are only used when the articles cited differentiate between these specifically defined problems. The definitions of dependency and abuse according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (Am. Psychiatr. Assoc. 2000), are presented in Table 1.

S 13.2

·

Murray

I N

A

C

E

Barkus

D V A N


19 December 2009

5:15

Australia found that 74% of patients had a lifetime prevalence of a substance use disorder, and 62% presented with current substance use disorders at baseline (Lambert et al. 2005). Many other studies also acknowledge that rates of substance use are higher in patients with psychotic disorder both at onset and in those who have had psychotic disorders for a longer period of time (e.g., Barnett et al. 2007). The environment in which studies are performed needs to be considered when assessing elevated substance use in psychotic patients (e.g., Coulston et al. 2007). For instance, drug use is associated with increased relapse and hospitalization. Therefore, studies conducted on inpatient rather than community samples are likely to select patients in whom drug use may be especially common due to the worse course of psychosis in those who use drugs. One must also realize that the type of drugs used by psychotic patients will reflect to a considerable extent those used by the general population since patients are subject to the same social influences as the rest of the population. Such social influences determine which substances are “trendy” at a point in time, and this will influence the drugs available to patients. Alcohol is abused commonly by patients with psychosis and by the nonpsychotic population, but certain classes of substance are more frequently abused by patients with psychosis. For instance stimulants, such as amphetamine, as well as cannabis and nicotine, appear to be especially likely to be used by patients with psychotic disorders (e.g., Addington & Addington 2001, Kavanagh et al. 2004, Lambert et al. 2005). In Norway, Ringen et al. (2008) reported rates of amphetamine and cocaine use in patients with psychotic disorders that exceeded those reported in the general population by 160%. However, other drugs, such as heroin or morphine, are not reported to be used more heavily by patients with schizophrenia. Part of the explanation may be the relatively low rates of use of such drugs in the general population and therefore lack of access. Alternatively, it may be that some but not all illicit drugs

Table 1 Substance use and substance dependency in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (Am. Psychiatr. Assoc. 1994) Dependence—at least three of: Tolerance Withdrawal Increased use Cut down use Time dedicated to substance Give up alternatives Continued use despite physical/ psychological harm Abuse—at least one of: Failing responsibilities Dangerous use Contact with legal services as a result of substance Problems with friends and family

have pharmacological characteristics that may explain the association between their use and psychosis. For example, substances such as amphetamine, cannabis, and phencyclidine (PCP) have been reported to lead to psychotic-like experiences in the experimental situation. This has been taken as evidence that these substances lead to changes in neurotransmitter levels that mimic the alterations that occur in idiopathic psychosis. There is substantial literature concerned with the use of nicotine in patients with schizophrenia. Almost all studies suggest there are higher rates of smoking in patients with schizophrenia compared to the general population (e.g., Ripoll et al. 2004, Roick et al. 2007), with some reports of a similar pattern in relatives of patients with schizophrenia (e.g., Smith et al. 2008) and in those who are psychosis prone (e.g., Esterberg et al. 2007). It has been proposed that nicotine may be used in excess in these groups because of its cognitive enhancing qualities (e.g., Levin et al. 2006, Ripoll et al. 2004). However, given the attention that nicotine has already received in the literature and the fact that nicotine does not induce psychotic symptoms, we do not consider it further in this review.

E

V I E

W

S

www.annualreviews.org • Substance Use in Adolescence and Psychosis

13.3

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

5:15

WHAT IS THE DIRECTION OF THE RELATIONSHIP BETWEEN SUBSTANCE USE AND PSYCHOSIS?


There are at least four possible explanations for an excess use of substances in those with psychosis: (a) substance use can cause psychosis; (b) there are common risk factors for both; (c) the development of psychosis makes the development of substance use more likely; and (d ) having both mental health difficulties and substance use problems makes it more likely that an individual will come to treatment for one and therefore the other may be more likely to be detected. We discuss the evidence for these, with a particular emphasis on whether substance use can contribute to the onset of psychosis.

Alcohol Use

V I E

W

R

E

In many studies, the use of alcohol and drugs is combined under the term “substance use,” but some studies do report separate rates. In Sweden, the sale of alcohol is highly controlled; in patients with schizophrenia, alcohol consumption exceeds that reported for the general population (Cantor-Graae et al. 2001). An elevated level of alcohol use in patients with schizophrenia is also reported in other studies (Sevy et al. 2001, van Mastrigt et al. 2004). However, in an Australian first episode study, an alcohol-only disorder was one of the least frequently reported disorders (Lambert et al. 2005). Roick et al. (2007) reported lower rates of daily alcohol use in German patients with schizophrenia compared to the general population; additionally, in comparison with the general population sample, a larger proportion of patients did not drink at all. Lower rates of alcohol consumption by in-patients with severe mental health problems compared with general population rates have also been reported in the United Kingdom (Bernadt et al. 1984) and in community patients with schizophrenia compared to the general population (Brown et al. 1999).

S 13.4

·

Cannabis Use Cannabis is the most frequently used illicit drug in the world both in the general population (United Nations Report 2008) and among patients with psychotic disorders (e.g., Kavanagh et al. 2004, Mueser et al. 1990). When considering the relationship between cannabis use and psychosis, the usual difficulties exist in

Murray

I N

A

C

E

Barkus

Alcohol is much more freely available and its use more socially acceptable than that of other substances. There is little evidence to implicate alcohol in initiating the onset of schizophrenia, but as its use is often associated with that of other substances, it is difficult to totally rule it out as a mediating variable in the onset of psychotic symptoms (e.g., Baeza et al. 2009). In the general U.K. adult population, alcohol is associated with a twofold-increased risk for psychotic symptoms, even after controlling for other factors such as drug use ( Johns et al. 2004). Of course, long-term heavy alcohol use can lead to brain damage (such as Korsakov’s syndrome) that can produce psychotic symptoms. However, these symptoms tend to have the hallmarks of organic psychosis, being characterized by visual hallucinations and prominent cognitive difficulties. Heavy use of alcohol at an early age may lead to changes in the brain that are reflected in alterations in cognitive performance (e.g., White & Swartzwelder 2004). But alcohol-related psychotic symptoms tend to occur in those past the traditional younger risk period for the onset of psychosis. Hambrecht & Häfner (1996) reported that heavy alcohol use followed rather than preceded the first signs of psychosis and pointed to alcohol being used for self-medication rather than causing the onset of psychotic symptoms. Other reports indicate that patients may use alcohol to alleviate negative symptoms and encourage social interactions (e.g., Hambrecht & Häfner 1996, Salyers & Mueser 2001); the latter would not be surprising since this is one of the main reasons for drinking in the general population.

D V A N


19 December 2009

5:15

interpreting the literature: Are those who are psychosis prone more likely to use cannabis or, regardless of underlying predisposition, can cannabis use cause or precipitate psychotic symptoms (e.g., Barkus et al. 2006, Degenhardt & Hall 2001, McGuire et al. 1995, van Os et al. 2002)? There is no dispute that patients with established psychosis who continue to use cannabis have a worse prognosis than those who stop (e.g., Grech et al. 2005, Kovasznay et al. 1997, Linszen & van Amelsvoort 2007). Neither is there any dispute that administration of -9-THC, the major psychoactive compound in cannabis, produces a transient psychosis-like state in healthy volunteers (D’Souza et al. 2004, Morrison et al. 2009) and can also exacerbate psychotic symptoms in patients with schizophrenia, despite them being clinically stable and medicated at the time (D’Souza et al. 2005). Evidence from longitudinal epidemiological studies of general population samples indicates that cannabis use is associated with elevated risk of subsequent psychotic symptoms and illnesses including schizophrenia (Andreassen et al. 1987, Arseneault et al. 2002, van Os et al. 2002, Zammit et al. 2002). Two recent metaanalyses (Henquet et al. 2005, Moore et al. 2007) conclude that cannabis use is a contributory cause of psychotic illness. It has been suggested that those who have a vulnerability to psychosis (individuals who are psychosis prone or express high levels of schizotypy) are more likely to have psychotic-like experiences in the immediate high after smoking cannabis (Barkus et al. 2006, Barkus & Lewis 2008, Henquet et al. 2006, Stirling et al. 2008, Verdoux et al. 2003). There are also some suggestions that cannabis use in early adolescence, before the age of 15 years, may have the most significant impact on the risk for future development of a psychotic disorder (Arseneault et al. 2002). Prior to the age of 15, many neurobiological and hormonal changes are taking place. Cannabis use in this time of rapid biological change may be more likely to lead to

alterations in neurobiology that increase psychosis risk (e.g., Adriani & Laviola 2004, Viveros et al. 2005). Of course, given the high rates of cannabis use in the general population, the incidence of psychotic disorders would be much higher if cannabis use alone caused psychosis. Rather, it is suggested that cannabis use interacts with other risk factors for psychosis, such as genetic vulnerability, and other environmental factors, such as obstetric insults and various social adversities, to contribute toward psychosis onset (Arseneault et al. 2004, Fergusson et al. 2006, Henquet et al. 2008, Semple et al. 2005).

Stimulants Curran et al. (2004) reviewed experimental and longitudinal studies concerned with stimulants and concluded there was evidence (a) that their use could lead to a transient psychotic state and exacerbate psychotic symptoms in medicated patients with schizophrenia (regardless of medication status), and (b) that individuals may become sensitized to the psychotomimetic effects of stimulants. Connell’s (1958) monograph provided evidence suggesting chronic use of amphetamine can induce a state that mimics paranoid schizophrenia. The ability of amphetamine to induce psychotic symptoms has also been shown in experimental studies (e.g., Featherstone et al. 2007, Hermens et al. 2009). Amphetamine increases striatal dopamine release in healthy volunteers, and patients with schizophrenia are more sensitive to these effects (e.g., Laruelle & Abi-Dargham 1999, Laruelle et al. 1996, Martinez et al. 2003). There is also limited evidence from longitudinal studies for amphetamine use predicting the onset of psychosis later in life (Andreassen et al. 1987, Zammit et al. 2002). However, given the relatively low rates of amphetamine use in the general population, it is difficult to determine the risk for psychotic disorders attributable to amphetamine use. Methamphetamine is a more potent form of amphetamine, and like amphetamine, it is

E

V I E

W

S


13.5

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

used recreationally. Its use has been epidemic in Pacific countries such as Japan, Taiwan, and Thailand for many years (e.g., Ujike & Sato 2004). In the past decade, it has spread to the west coast of North America and is slowly moving east (Caulkins 2003, Jacobs 2002, Morgan 1998, Rawson et al. 2002), particularly in the homosexual community (Freese et al. 2002, Morgan & Beck 1997). Rates of methamphetamine dependency in the U.S. general population, aged 12 years and above, increased dramatically between 2002 and 2004 (NSDUH Report 2005). Its use can induce a psychotic state, and chronic use can lead to a picture almost identical to that of paranoid schizophrenia (Chen et al. 2003, 2005; McKetin et al. 2006). However, again there is evidence that the risk of psychotic illness is particularly high in those with a family history of the disorder and/or pre-existing schizoid and schizotypal personality (Chen et al. 2003, 2005). In recreational use, cocaine induces a confident and euphoric state. However, this can be accompanied by agitation that leads to paranoia; persistent use can lead to more florid psychotic symptoms (Mahoney et al. 2008). Although cocaine has been reported to be used in excess in some studies of patients with schizophrenia (e.g., Ringen et al. 2008), the Swedish Army study failed to find evidence that cocaine use confers a risk for the development of a chronic psychotic disorder (Andreassen et al. 1987, Zammit et al. 2002). Khat is a plant substance that has been used primarily in Africa and Arabian countries, although it is now also used in the United Kingdom and elsewhere by migrant workers. Khat contains an amphetamine-like substance (see Feyissa & Kelly 2008 for a review). Odenwald (2007) has reviewed evidence for its relationship with psychotic disorders. Although there were very few systematic studies, Odenwald felt there was sufficient evidence to suggest it can induce transient psychotic episodes and that those with an underlying predisposition to psychosis are more vulnerable to these effects. Ecstasy has a primary effect on serotonin but also interacts with the dopamine system (e.g.,


V I E

W

R

E

5:15

S 13.6

·

Substances Acting on Glutamate In acute studies, ketamine is said to produce positive as well as negative symptoms of psychosis (e.g., Curran & Morgan 2000, Muetzelfeldt et al. 2008, Pomarol-Clotet et al. 2006), and these effects have been used to support a glutamatergic model of psychosis (e.g., Deakin et al. 2008, Stone et al. 2008). A number of studies have reported on the use of ketamine as a recreational drug, but to date there are no follow-up studies examining the risk of developing a psychotic disorder after recreational ketamine use. This may be owing to the relatively low rates of ketamine use in the general population, but the lack of such studies does seem an oversight given the frequency with which ketamine is cited as an experimental model of psychosis. Phencyclidine (PCP) was a popular recreational drug in certain parts of the United States during the 1980s and early 1990s, but it is not frequently taken today. However, PCP is frequently used as an animal model of psychosis and is thought to represent a model of the glutamatergic alterations that may take place prior to the onset of a psychotic disorder (e.g., Jentsch & Roth 1999, Mouri et al. 2007). In humans, PCP can induce a transient psychotic disorder that responds well to typical antipsychotic treatment (Carls & Ruehter 2006). In their summary of the effects of PCP, Jentsch & Roth (1999) consider that repeated (rather than acute) administrations of PCP produce a more accurate

Murray

I N

A

C

E

Barkus

Steele et al. 1994). Reports have indicated that ecstasy can lead to psychotic symptoms either transiently or perhaps contributing to the onset of a psychotic disorder (e.g., McGuire & Fahy 1991, McGuire et al. 1994). However, given the small number of reported cases, this must be a rare event considering its widespread use in the rave and dance culture of the 1990s. A few reports suggest that the negative effects of ecstasy use on cognitive performance may be dependent upon the age of age exposure; i.e., use at a younger age is associated with worse outcome (Broening et al. 1994).

D V A N


19 December 2009

5:15

behavioral and neurobiological model of psychosis.

Interest in establishing markers that are present prior to the onset of psychosis and that may be targets for treatment has increased recent work that attempts to identify objectively measurable risk markers for psychosis. The complexity of the genetic predisposition to psychiatric disorders has also led to resurgence in identifying endophenotypes. Endophenotypes are linked with the underlying vulnerability for the psychiatric condition and are generally thought to be nearer the action of genes than of symptoms. Gottesman & Gould (2003) have established criteria for an endophenotype. It should (a) cooccur with the illness in the general population; (b) co-occur with the illness within families; (c) be heritable; (d ) be present regardless of fluctuations in illness; and (e) be present in higher rates in relatives of those with the illness. These criteria demonstrate the biological proximity between the endophenotype and illness; however, for an endophenotype to be a useful model for psychosis, it should also be exacerbated by environmental factors similar to those reported in patients (Gould & Gottesman 2006). For psychosis, endophenotypes include cognitive or information-processing deficits that coexist with the disorder. A number of cognitive deficits can be considered endophenotypes for psychosis. The advantage of a focus on task performance is that translational models from animals to humans can be used to examine the relationship between substance use and psychosis endophenotypes, and, of course, in animal studies there is more accurate quantification of exposure to the substance. Table 2 summarizes acute and subacute/chronic studies for recreational drugs for three relevant endophenotypes. Spatial working memory, delayed memory, and working memory have sufficient supporting evidence to be considered endophenotypes

E

V I E

W

R


PSYCHOSIS ENDOPHENOTYPES AND THE EFFECTS OF SUBSTANCE USE

for psychosis. Patients with schizophrenia have impaired performance in these domains (Driesen et al. 2008, Van Snellenberg 2009), as do their relatives (Conklin et al. 2000, Park et al. 1995), those from the general population who express schizotypy (Saperstein et al. 2006), and prodromal or at-risk mental state (ARMS) patients (e.g., O’Connor et al. 2009, Smith et al. 2006). One study has suggested that schizotypal traits in relatives of patients with schizophrenia mediate proneness to cognitive deficits in the domain of memory (Diwadkar et al. 2006). Working memory performance has also been related to the Val158Met polymorphism on the gene encoding for COMT. This enzyme is involved in the breakdown of dopamine, which has particular significance for the efficiency of prefrontal cortex functioning. This gene has been found to modulate working memory performance in patients, relatives, and healthy volunteers (Diaz-Asper et al. 2008) and is related to the blood-oxygen-level-dependent signal (measured with functional magnetic resonance imaging) in the prefrontal cortex during a working memory task (e.g., Egan et al. 2001, Sambataro et al. 2009). Both spatial and standard working memory may be sensitive to biological vulnerability for psychosis and substance use since they involve widely distributed brain regions (e.g., Henseler et al. 2009). Animal and human studies show that certain substances of abuse administered both acutely and chronically have an impact on performance in spatial and standard working memory. Substance use has also been reported to modulate the neural underpinnings of memory tasks (e.g., Moeller et al. 2004, Padula et al. 2007, Schweinsburg et al. 2008). Given that alcohol and other substance use has been associated with decrements in memory, it is difficult to hypothesize that particular neurochemical imbalances or brain areas are sensitive to environmental insult in the form of substance use. For example, low-dose administration of 3,4methylenedioxymethamphetamine (ecstasy) leads to detriments to memory performance and increased anxiety in the absence of depletion in serotonin levels or long-term neurotoxic

S


13.7

I N

E

ARI

A


C

ANRV407-CP06-13

D V A N

S

I N

E

E

A

C

R

V I E

13.8

Barkus

·

Murray

D V A N


Chronic/subacute dosing

Working and delayed memory Human studies Acute


Animal studies Acute

Groth-Marnat et al. (2007) Rosselli et al. (2001)

–

– McKetin & Mattick (1997) Rapeli et al. (2005)

–

Santucci et al. (2004)

Santucci (2008)

Morgan et al. (2009)

Lofwall et al. (2006)

Krystal et al. (2005)

Pitsikas & Boultadakis (2009) Enomoto & Floresco (2009)

–

Mattay et al. (2000)

Mandillo et al. (2003) Aultman & Moghaddam (2001)

Pitsikas et al. (2008)

Morgan et al. (2009)

Rowland et al. (2005)

–

– Hoff et al. (1996)

– Ornstein et al. (2000) –

Blokland et al. (1998)

–

–

Ketamine

Bhattachary & Powell (2001)

–

–

–

Kuypers & Ramaekers (2005) Dunmont et al. (2008) Rogers et al. (2009)

Able et al. (2006)

Chen et al. (2005)

–

Braida et al. (2002)

Montgomery & Fisk (2008)

Fox et al. (2002)

Kuypers & Ramaekers (2007)

Ecstasy (MDMA)

–

Mandillo et al. (2003) Li et al. (2003)

Rupniak et al. (1991)

Boyce et al. (1991)

–

– –

–

Phencyclidine

D’Souza et al. (2004) Morrison et al. (2009) Schweinsburg et al. (2008) Harvey et al. (2007)

Mishima et al. (2001) Robinson et al. (2007) Fadda et al. (2004)

Schweinsburg et al. (2008) Harvey et al. (2007)

Weinstein et al. (2008)

Canabis/CB1 agonists

19 December 2009


Spatial working memory Human studies Acute

W Cocaine

ARI

Amphetamine

Table 2 The effects of a number of substances on spatial working memory, standard working memory, and prepulse inhibition. References cited describe the detrimental effects of the substance on the endophenotype in animals and humans∗


ANRV407-CP06-13 5:15

E

I N


R

Mansbach et al. (1988)

Hijzen et al. (1991)

Martinez et al. (1999a) Byrnes & Hammer (2000)

Martinez et al. (1999a) Doherty et al. (2008)

–

–

Mansbach et al. (1988) Bakshi et al. (1995)

–

–

Johansson et al. (1995) De Bruin et al. (1999) Chan et al. (2008)

–

–

Note: This list is not exhaustive but rather represents tasks with available evidence for both humans and animals.

E

A

C

S


∗




Liechti et al. (2001) –

–

Krueger et al. (2009)

– –

–

Pitsikas & Boultadakis (2009)

George et al. (2008)

Kumari et al. (1998) Hutchison & Swift (1999) –

Castner et al. (2005)

–

–

–

Dulawa & Geyer (2000) –

Geyer et al. (1984) Martinez et al. (1999b) –

Kehne et al. (1999)

–

Heekeren et al. (2004)

– –

Morley et al. (2001)

Piper (2007)

–

Trigo et al. (2008)

Geyer et al. (2001)

–

–

– –

Jentsch et al. (2000)

Baron & Wenger (2001) Hudzik & Wenger (1993) Jentsch et al. (1997)

Malone & Taylor (2006) Wegener & Koch (2009) –

Nagai et al. (2006)

Scholes & Martin-Iverson (2009) Kedzior & Martin-Iverson (2006)

– –

Da & Takahashi (2002) Wegener & Koch (2009) Hampson et al. (2003)

Varvel et al. (2005)

19 December 2009

Prepulse inhibition Human studies Acute


Beatty & Rush (1983)

ARI



ANRV407-CP06-13 5:15

V I E

W

13.9

D V A N

ANRV407-CP06-13

ARI

19 December 2009

effects (Baumann et al. 2007). This suggests that other monoamines are related to the cognitive and behavioral alterations associated with ecstasy use (Clemens et al. 2007). Prepulse inhibition (PPI) is an informationprocessing measure that is considered an endophenotype for psychosis; it is measureable in both animals and humans. PPI is the attenuation of the startle response with a preceding nonstartling stimuli. An eye blink is usually measured as a startle response in humans, and it is considered a physiologically basic reflex. PPI is thought to operate as a sensory gating mechanism to help to determine what stimuli in the environment can be ignored. PPI deficits are reported in patients with schizophrenia (e.g., Braff et al. 2001, Kumari et al. 2000, Weike et al. 2000), relatives of patients with psychosis (Cadenhead et al. 2000), patients with schizotypal personality disorder (Cadenhead et al. 1993), and psychometrically defined schizotypes (e.g., Perlstein et al. 1989, Simons & Giardina 1992). Disrupted PPI is also associated with other psychiatric and neurological disorders, such as obsessive-compulsive disorder (Swerdlow et al. 1993) and Tourette’s syndrome (Swerdlow et al. 2001), suggesting that PPI deficits may not have specificity for psychosis. However, an extensive animal literature on PPI and substances of abuse justifies its inclusion in this review. From Table 2, it can be seen that most drugs of abuse lead to deficits in PPI. However, there are one or two exceptions. Ecstasy is a drug that shows cross-species differences in its effects on PPI. In humans, administration of the drug tends to lead to increased PPI, whereas disruption of PPI is reported at comparable doses in rats (e.g., Vollenweider et al. 1999). This difference is thought to be due to the effects of ecstasy at the subtypes of serotonin receptors (e.g., Liechti et al. 2001). These data highlight the potential restrictions of cross-species translation in drug effects, whereby physiological differences lead to contradictory results in behavioral outcomes. However, it is interesting to note that ecstasy produces robust deficits in working memory, implying that the


V I E

W

R

E

5:15

S 13.10

·

Murray

I N

A

C

E

Barkus

neurobiological and physiological mechanisms underpinning PPI and working memory are indeed very different. Acute human studies using cocaine and PCP are seldom possible at this time owing to restrictions imposed by ethical committees. Furthermore, recreational PCP users are understudied. The number of studies exploring the effects of these drugs chronically reflects the recreational use of these drugs in society: The degree of perceived problem use of a drug has driven the amount of research performed to examine its deleterious effects. Additionally, in animal studies, modeling of chronic dosing of a substance occurs neo- or prenatally, which does not correspond well to the effects of recreational drug use in humans. Many of the areas and substances outlined in Table 2 have references that report no effect of the substance on cognitive performance or subtle differences in other cognitive domains other than those discussed here (e.g., Abel et al. 2003, Bortolato et al. 2005, Colzato et al. 2009, Del Olmo et al. 2007, Ehrhardt et al. 1999, Oranje et al. 2002). These contradictory results could be attributed to methodological differences (such as the strain of animal used or task difficulty) or reflect the complexities in the interplay between ingested substances and individual differences in neurophysiology. One substance of use that reflects these complexities is amphetamine. Mattay et al. (2000) reported that the effects of acute administration of amphetamine on cognition were mediated by the COMT Val158Met polymorphism, with only those carrying the gene for the low-activity enzyme (Met) showing cognitive deficits following amphetamine administration; the other participants showed an improvement in cognitive performance following amphetamine administration. It has been hypothesized that dopamine turnover in the prefrontal cortex mediates working-memory performance by determining the efficiency of the response in the prefrontal cortex. This leads to an inverted-U response, whereby individuals have a resting-state high- or low-efficiency prefrontal response (according to their COMT Val158Met genotype), and the administration

D V A N


19 December 2009

5:15

of dopaminergic antagonists will “push” them into a new position around the inverted U. This role of the prefrontal cortex has been supported by functional magnetic resonance imaging studies using working-memory tasks (e.g., Mattay et al. 2003, Tipper et al. 2005). Other studies have replicated the positive effects of amphetamine on cognitive performance in patients with schizophrenia (Barch & Carter 2005), those with schizotypal personality (Kirrane et al. 2000), and healthy volunteers (e.g., Zeeuws & Soetens 2007). However, the situation may be further complicated by the doses of amphetamine given: Arnsten (2006) suggests that the amphetamine-related improvements in cognitive performance may only occur at lower doses. Given that the studies reporting data on chronic or longer-term recreational use of amphetamine summarized in Table 2 report detrimental effects on cognitive performance, it is likely that continued exposure to the drug affects the dopamine system in a negative fashion. Additionally, given the dynamic nature of neurotransmitter systems, it is possible that continued exposure to amphetamines may lead to establishment of a new baseline of dopamine activity. Examining the effects of substances on endophenotypes for psychosis in healthy volunteers may help to elucidate the neurobiological effects of substance use on cognition, but this has limited value for determining the effects of these substances on a psychosis-prone brain. Extensive literature suggests that those who are prone to psychosis have structural and neurochemical differences that differentiate them from healthy volunteers. Chambers et al. (2001) suggest that in psychosis, the breakdown in connectivity between the prefrontal cortex and hippocampus leads to dysregulation of neurotransmitter input and outputs from the nuclear accumbens. The outcome of this dysregulation is a hypersensitivity to dopamine release and decreased behavioral inhibitory responses. This may increase the rewarding properties of drugs of abuse and help to explain why substance use is associated with psychosis. Although this hypothesis explains why patients with psychosis

are more sensitive to the effects of alcohol and cannabis (e.g., D’Souza et al. 2005), it does not explain why substance use is present in some but not all patients with psychosis, since Chambers et al. (2001) view this mechanism as being ubiquitously associated with psychosis risk.

ARE RISK FACTORS FOR SUBSTANCE USE THE SAME IN THOSE WITH PSYCHOSIS AS IN THE GENERAL POPULATION? Demographic variables associated with substance use in patients with psychotic disorders and in the general population include male gender and young age (e.g., Addington & Addington 2007, Barnett et al. 2007). Family discord is associated with the initiation of substance use in adolescents (e.g., Pedersen 1990) and is common in the families of people with schizophrenia, but of course the latter may be a consequence of the illness. Given that traits such as impulsivity are known to predict substance use in the general population, it is possible that these personality traits operate in a similar manner in those at risk for psychosis (e.g., Adams et al. 2003, Dervaux et al. 2001, Schmid et al. 2007). Furthermore, the expression of some personality traits, such as schizotypy, may be a premorbid expression of an individual’s vulnerability toward developing both a substance use disorder and psychosis. Schizotypy comprises attenuated psychotic symptoms including positive symptoms, such as unusual belief systems and perceptual experiences, and negative symptoms in the form of social withdrawal, anxiety, and depression (Raine 2006). Cannabis has received the greatest attention in the schizotypy literature. Some studies suggest that cannabis use elevates schizotypal characteristics (Bailey & Swallow 2004; Dumas et al. 2002; Mass et al. 2001; Nunn et al. 2001; Schiffman et al. 2005; Skosnik et al. 2001, 2006, 2007; Stefanis et al. 2004), but not all studies have found this association (e.g., Barkus et al. 2006; see Earleywine 2006 for a cautionary note). However, Van Os and colleagues (2002)

E

V I E

W

S


13.11

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

5:15

reported that cannabis use per se increases the likelihood of experiencing psychotic symptoms, with a stronger effect in those with psychosis proneness at the baseline; i.e., the latter may be more sensitive to its effects (see also Barkus et al. 2006, Henquet et al. 2006, Verdoux et al. 2003).

SUBSTANCE USE AND THE PRODROME FOR PSYCHOSIS


There has been much recent interest in identifying those likely to develop psychosis. The most significant aspects of the so-called prodrome for psychosis are deterioration in functioning, psychotic-like experiences, and expression of genetic liability, in the form of family history or schizotypal traits (Yung & McGorry 1996). Phillips et al. (2002) noted that reported rates of cannabis use were low in those attending a prodromal clinic compared to other services. but they were still significantly higher than those reported for the general Australian population. In the 12 months prior to the onset of psychosis, 18% of their sample met the criteria for cannabis dependency, 22% used cannabis once a month or more, and 13% used it less than once a month. These rates were similar to lifetime use, indicating there had been no change in cannabis usage. In the Calgary Early Psychosis Service, Addington & Addington (2007) reported that 51.7% of patients met criteria for a substance use disorder: 33% were cannabis related and 35% were alcohol related. Phillips et al. (2002) found that of those who made the transition to frank psychosis within a year, 37% were cannabis users compared to 29% noncannabis users; this difference did not reach statistical significance. However, in a study from the United States, those who had cannabis dependency or abuse were significantly more likely to make a transition into a psychotic disorder within twelve months (Kristensen & Cadenhead 2007). Hambrecht & Häfner (1996) attempted to tease apart the temporal relationship between the first signs and symptoms of psychosis (these could be comparable to a prodrome). In 28% of their sample, drug abuse occurred at least a year before the

V I E

W

R

E

S 13.12

·

SUBSTANCE USE AND THE NATURE AND OUTCOME OF PSYCHOSIS A number of studies have reported that age of first use of cannabis, cocaine, ecstasy, and amphetamine is significantly associated with age of onset of first psychotic symptoms (Addington & Addington 2007, Andreassen et al. 1987, ¨ Arendt et al. 2005, Barnett et al. 2007, Buhler et al. 2002, Cantwell et al. 2000, van Mastrigt et al. 2004, Zammit et al. 2002). Barnes et al. (2006) suggest that this effect is particularly related to cannabis use. However, not all studies report this association (e.g., Cantor-Graae et al. 2001, Sevy et al. 2001). Clinical psychiatrists have been much preoccupied with the distinction between substanceinduced psychosis and idiopathic schizophrenia. In reality, the former often progresses into the latter, with certain individuals more likely to make this step. Caton et al. (2007) followed up individuals diagnosed with substanceinduced psychosis. Twelve months later, 25% had received a diagnosis of primary psychoses. Those who made a transition to a primary psychotic disorder were more likely to have a family history of mental health problems, poorer premorbid adjustment, and less awareness of psychotic symptoms. Arendt et al. (2005) focused on 535 patients initially presenting with a cannabis-induced psychotic disorder. Within three years, 44.5% went on to be diagnosed with a schizophrenia-spectrum disorder. Mathias et al. (2008) summarize the literature to date. Variables that distinguished substanceinduced psychosis from primary psychosis were

Murray

I N

A

C

E

Barkus

onset of the first signs of schizophrenia, for 35% both occurred at a similar time, and for 38% the symptoms of schizophrenia occurred before drug abuse. Cannon et al. (2008) reported that in their North American sample, history of any substance abuse was predictive of those who made a transition to psychosis in a 30-month follow-up, but substance use had poor sensitivity to discriminate converters to psychosis from nonconverters.

D V A N


19 December 2009

5:15

presence of visual hallucinations, insight into cause of symptoms, better premorbid functioning, older age of symptom onset, and no family history of mental health difficulties. Another issue of great import to clinicians is whether individuals stop their drug use after being diagnosed with psychosis. Addington & Addington (2007) reported that in an early psychosis service, 51.7% of patients met criteria for abuse/dependency at baseline, but at 12month follow-up, this had dropped to 32.5%, a significant decrease. Three other studies have reported that after treatment, many patients show a substantial decrease in substance use (Addington & Addington 2001, Lambert et al. 2005, Sorbara et al. 2003). One study reported that 15 months after the onset of psychosis, one in five patients had stopped using any substances; those who continued substance use did not increase their use, and no patients initiated substance use (Wade et al. 2006). If psychotic patients are diagnosed with substance dependency rather than just use, they are more likely to be still using seven years later (Bartels et al. 1995). Lambert et al. (2005) reported that approximately one-quarter of their sample continued to meet the criteria for substance use disorder throughout treatment, with the majority using at the same rates established prior to the onset of treatment. There have been many reports that substance use by psychotic patients leads to increased hospitalization and remission (Cleghorn et al. 1991, Drake et al. 1989, Gerding et al. 1999, Lambert et al. 2005, LeDuc & Mittleman 1995, Møller & Linaker 2004), although a few studies have not found this (Mueser et al. 1990, 2000). Patients with psychosis who use substances have a poorer response to treatment (Cantor-Graae et al. 2001, Kavanagh et al. 2004) and a worse outcome, and, as noted above, those who continue to use cannabis have a worse clinical prognosis than do those who stop (e.g., Grech et al. 2005, Kovasznay et al. 1997, Linszen & van Amelsvoort 2007). An integrated treatment approach, using both pharmacological and psychological interventions, is necessary to manage

symptoms in patients with psychosis and substance use dependency (Drake et al. 2001, Hjorthøj et al. 2009). However, psychological interventions can only be engaged in changing behaviors, which occurs when the patient realizes his drug use needs to be addressed and expresses the readiness and motivation to change.

COGNITION IN PATIENTS WHO DO AND DO NOT USE SUBSTANCES The existing literature on cognitive performance in psychotic patients who do use substances compared to those who do not has produced mixed results. Some studies report relatively intact (or better) cognition in substance-using patients with psychosis ¨ et al. 2007, Kumra et al. ( Jockers-Scherubl 2005, Sevy et al. 2007, Stirling et al. 2005), whereas others report that those who do not use substances fair better (Allen et al. 1999, Liraud & Verdoux 2002, Manning et al. 2007, Pencer & Addington 2003, Serper et al. 2000). Many of these studies are confounded by differences in antipsychotic exposure, duration of illness, and age of onset. Additionally, the length of time patients have used the substance may have an effect on the results; for example, the effects of heavy alcohol use may only be evident in older participants (Mohamed et al. 2006). Comorbid cannabis use leads to the largest diversity in the findings (e.g., Coulston et al. 2007). Some evidence indicates that cannabidiol, one constituent of cannabis, is a cognitive enhancer (e.g., Bhattacharyya et al. 2009), and early data suggest that it may be neuroprotective against insults as severe as hypoxic-ischemia (Alverez et al. 2008). However, further research is necessary to isolate which cannabinoids may have a positive effect on cognition. Some authors suggest that those who develop psychosis after using cannabis or other illicit substances represent a distinct subgroup of patients who may have better long-term preservation in their cognitive capacity because their psychotic disorder has been more driven by environmental factors (i.e.,

E

V I E

W

S


13.13

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

5:15

substance use) than endogenous factors (i.e., genetic vulnerability and/or neurodevelopmental impairment).

CONCLUSIONS


The use of recreational drugs varies with geographic location and social fashions, and the risk factors that increase the likelihood of initiation and maintenance of substance use in patients with psychotic disorders mirror those reported in the general population. However, we do not fully understand why some people can use recreational drugs without significant adverse effects while others develop psychosis. Among possible mediating factors are schizotypy or psychosis proneness. Thus, the experiences that people have when using recreational drugs may reflect an underlying vulnerability to a psychotic disorder. However, the value of these initial drug-induced experiences in predicting the onset of psychotic disorders is yet to be established. Whether substance use causes the onset of psychosis is still debated. Clearly, the answer depends on the particular substance being used. For example, in the majority of

people who develop psychosis in the context of abuse of amphetamines, once the substance is withdrawn and the psychotic episode is treated, the psychotic symptoms cease in the absence of further use. However, in a minority, the psychosis continues or abates and then returns, and the picture changes to unrelenting psychotic disorder. The variables that differentiate those who go on to develop a persistent psychotic disorder after a substance-induced episode include family history of mental health problems and psychosis-prone personality (Chen et al. 2003, 2005). There has been a recent emphasis on cannabis use in both the epidemiological and clinical literature. There is now a widespread acceptance among psychiatrists that heavy use of cannabis increases the risk of psychosis, and continued uses worsens the outcome. However, future research needs to address the mechanisms underlying the epidemiological findings. In addition, further research is needed on the differing risks associated with the use of different illicit substances. Given the varying neurobiological effects of these substances, it seems unlikely that they will influence psychosis in the same manner.

DISCLOSURE STATEMENT The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review.

ACKNOWLEDGMENT EB would like to acknowledge the support of a NARSAD Young Investigator Award.

LITERATURE CITED

V I E

W

R

E

Abel KM, Allin MP, Hemsley DR, Geyer MA. 2003. Low dose ketamine increases prepulse inhibition in healthy men. Neuropharmacology 44(6):729–37 Able JA, Gudelsky GA, Vorhees CV, Williams MT. 2006. 3,4-Methylenedioxymethamphetamine in adult rats produces deficits in path integration and spatial reference memory. Biol. Psychiatry 59(12):1219–26 Adams JB, Heath AJ, Young SE, Hewitt JK, Corley RP, et al. 2003. Relationships between personality and preferred substance and motivations for use among adolescent substance abusers. Am. J. Drug Alcohol Abuse 29(3):691–712 Addington J, Addington D. 2001. Impact of early psychosis program on substance use. Psychiatr. Rehabil. J. 25:60–67

S 13.14

·

Murray

I N

A

C

E

Barkus

D V A N


19 December 2009

5:15

Addington J, Addington D. 2007. Patterns, predictions and impact of substance use in early psychosis: a longitudinal study. Acta Psychiatr. Scand. 115:304–9 Adriani W, Laviola G. 2004. Windows of vulnerability to psychopathology and therapeutic strategy in the adolescent rodent model. Behav. Pharmacol. 15:341–52 Allen DN, Goldstein G, Aldarondo F. 1999. Neurocognitive dysfunction in patients diagnosed with schizophrenia and alcoholism. Neuropsychology 13:62–68 Alverez FJ, Lafuente H, Rey-Santano MC, Mielgo VE, Gastiasoro E, et al. 2008. Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets. Pediatr. Res. 64(6):653–58 Am. Psychiatr. Assoc. 1994. Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: Am. Psychiatr. Assoc. 4th ed. Andreassen S, Allebeck P, Engstrom A, Rydberg U. 1987. Cannabis and schizophrenia: a longitudinal study of Swedish conscripts. Lancet 8574:1483–85 Arendt M, Rosenberg R, Foldager L, Perto G, Munk-Jørgensen P. 2005. Cannabis-induced psychosis and subsequent schizophrenia spectrum disorders: follow-up study of 535 incident cases. Br. J. Psychiatry 187:510–15 Arnsten AF. 2006. Stimulants: therapeutic actions in ADHD. Neuropsychopharmacology 31(11):2376–83 Arseneault L, Cannon M, Poulton R. 2002. Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 325:1212–13 Arseneault L, Cannon M, Witton J, Murray RM. 2004. Casual association between cannabis and psychosis: examination of the evidence. Br. J. Psychiatry 184:110–17 Aultman JM, Moghaddam B. 2001. Distinct contributions of glutamate and dopamine receptors to temporal aspects of rodent working memory using a clinically relevant task. Psychopharmacology (Berl.) 153(3):353–64 Baeza I, Graell M, Moreno D, Castro-Fornieles J, Parellada M, et al. 2009. Cannabis use in children and adolescents with first episode psychosis: influence on psychopathology and short-term outcome (CAFEPS study). Schizophr. Res. 113(2–3):129–37 Bailey EL, Swallow BL. 2004. The relationship between cannabis use and schizotypal symptoms. Eur. Psychiatry 19(2):113–14 Bakshi VP, Geyer MA, Taaid N, Swerdlow NR. 1995. A comparison of the effects of amphetamine, strychnine and caffeine on prepulse inhibition and latent inhibition. Behav. Pharmacol. 6:801–9 Barch DM, Carter CS. 2005. Amphetamine improves cognitive function in medicated individuals with schizophrenia and in healthy volunteers. Schizophr. Res. 77(1):43–58 Barkus EJ, Lewis S. 2008. Schizotypy and psychosis-like experiences from recreational cannabis in a nonclinical sample. Psych. Med. 38(9):1267–76 Barkus EJ, Stirling J, Hopkins RS, Lewis S. 2006. Cannabis-induced psychosis-like experiences are associated with high schizotypy. Psychopathology 39(4):175–78 Barnes TRE, Mutsatsa SH, Hutton SB, Watt HC, Joyce EM. 2006. Comorbid substance use and age at onset of schizophrenia. Br. J. Psychiatry 188:237–42 Barnett JH, Werners U, Secher SM, Hill KE, Brazil R, et al. 2007. Substance use in a population-based clinic sample of people with first-episode psychosis. Br. J. Psychiatry 190:515–20 Baron SP, Wenger GR. 2001. Effects of drugs of abuse on response accuracy and bias under a delayed matching-to-sample procedure in squirrel monkeys. Behav. Pharmacol. 12:247–56 Bartels SJ, Drake RE, Wallach MA. 1995. Long-term course of substance use disorders among patients with severe mental illness. Psychiatr. Serv. 46:248–51 Baumann MH, Wang X, Rothman RB. 2007. 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings. Psychopharmacology 189(4):407–24 Beatty WW, Rush JR. 1983. Retention deficit after d-amphetamine treatment: memory defect or performance change? Behav. Neural. Biol. 37:265–75 Bernadt MW, Mumford J, Murray RM. 1984. A discriminant-function analysis of screening tests for excessive drinking and alcoholism. J. Stud. Alcohol 45(1):81–86 Bhattachary S, Powell JH. 2001. Recreational use of 3,4-methylenedioxymethamphetamine (MDMA) or “ecstasy”: evidence for cognitive impairment. Psychol. Med. 31(4):647–58

E

V I E

W

S


13.15

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, et al. 2009. Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. Epub ahead of print Blokland A, Honig W, Prickaerts J. 1998. Effects of haloperidol and d-amphetamine on working and reference memory performance in a spatial cone field task. Behav. Pharmacol. 9:429–36 Bortolato M, Aru GN, Frau R, Orru` M, Luckey GC, et al. 2005. The CB receptor agonist WIN 55212-2 fails to elicit disruption of prepulse inhibition of the startle in Sprague-Dawley rats. Psychopharmacology (Berl.) 177(3):264–71 Boyce S, Rupniak NM, Steventon MJ, Cook G, Iversen SD. 1991. Psychomotor activity and cognitive disruption attributable to NMDA, but not sigma, interactions in primates. Behav. Brain Res. 42:115–21 Braff DL, Geyer MA, Light GA, Sprock J, Perry W, et al. 2001. Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophr. Res. 49:173–80 Braida D, Pozzi M, Cavallini R, Sala M. 2002. 3,4 Methylenedioxymethamphetamine (ecstasy) impairs eightarm radial maze performance and arm entry pattern in rats. Behav. Neurosci. 116(2):298–304 Broening HW, Bacon L, Slikker W Jr. 1994. Age modulates the long-term but not the acute effects of the serotonergic neurotoxicant 3,4-methylenedioxymethamphetamine. J. Pharmacol. Exp. Ther. 271(1):285– 93 Brown S, Birtwistle J, Roe L, Thompson C. 1999. The unhealthy lifestyle of people with schizophrenia. Psychol. Med. 29:697–701 ¨ ¨ Buhler B, Hambrecht M, Loffler W, an der Heiden W, Häfner H. 2002. Precipitation and determination of the onset and course of schizophrenia by substance abuse—a retrospective and prospective study of 232 population-based first illness episodes. Schizophr. Res. 54:243–51 Byrnes JJ, Hammer RP. 2000. The disruptive effects of cocaine on prepulse inhibition is prevented by repeated administration in rats. Neuropsychopharmacology 22:551–54 Cadenhead KS, Geyer MA, Braff DL. 1993. Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder. Am. J. Psychiatry 150:1862–67 Cadenhead KS, Swerdlow NR, Shafer KM, Diaz M, Braff DL. 2000. Modulation of the startle response and startle laterality in relatives of schizophrenia patients and schizotypal personality disordered subjects: evidence of inhibitory deficits. Am. J. Psychiatry 157:1660–68 Cannon TD, Cadenhead K, Cornblatt B, Woods SW, Addington J, et al. 2008. Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Arch. Gen. Psychiatry 65(1):28–37 Cantor-Graae E, Nordstrom LG, McNeil TF. 2001. Substance abuse in schizophrenia: a review of the literature and a study of correlates in Sweden. Schizophr. Res. 48:69–82 Cantwell R, Brewin J, Glazebrook C, et al. 2000. Prevalence of substance misuse in first episode psychosis. Br. J. Psychiatry 174:150–53 Carls KA, Ruehter VL. 2006. An evaluation of phencyclidine (PCP) psychosis: a retrospective analysis at a state facility. Am. J. Drug Alcohol Abuse 32:673–78 Castner SA, Vosler PS, Goldman-Rakic PS. 2005. Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex. Biol. Psychiatry 57(7):743–51 Caton CL, Hasin DS, Shrout PE, Drake RE, Dominguez B, et al. 2007. Stability of early-phase primary psychotic disorders with concurrent substance use and substance-induced psychosis. Br. J. Psychiatry 190:105–11 Caulkins J. 2003. Methamphetamine epidemics: an empirical overview. Law Enforcement Exec. Forum 3:17–42 Chambers RA, Krystal JH, Self DW. 2001. A neurobiological basis for substance abuse comorbidity in schizophrenia. Biol. Psychiatry 50:71–83 Chan MH, Chiu PH, Sou JH, Chen HH. 2008. Attenuation of ketamine-evoked behavioral responses by mGluR5 positive modulators in mice. Psychopharmacology 198(1):141–48 Chen C-K, Lin S-K, Sham PC, Ball D, Loh el-W, et al. 2003. Pre-morbid characteristics and comorbidity of methamphetamine users with and without psychosis. Psychol. Med. 33:1407–14 Chen CK, Lin SK, Sham PC, Ball D, Loh el-W, Murray RM. 2005. Morbid risk for psychiatric disorder among the relatives of methamphetamine users with and without psychosis. Am. J. Med. Genet. 136:87–91 Cleghorn JM, Kaplan RD, Szechtman B, Szechtman H, Brown GM, et al. 1991. Substance abuse and schizophrenia: effects on symptoms but not on neurocognitive function. J. Clin. Psychiatry 52:26–30


V I E

W

R

E

5:15

S 13.16

·

Murray

I N

A

C

E

Barkus

D V A N


19 December 2009

5:15

Clemens KJ, McGregor IS, Hunt GE, Cornish JL. 2007. MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical research. Drug Alcohol Rev. 26(1):9–15 Colzato LS, Huizinga M, Hommel B. 2009. Recreational cocaine polydrug use impairs cognitive flexibility but not working memory. Psychopharmacology (Berl.). Epub ahead of print Conklin HM, Curtis CE, Katsanis J, Iacono WG. 2000. Verbal working memory impairment in schizophrenia patients and their first degree relatives: evidence from the Digit Span Task. Am. J. Psychiatry 157:275–77 Connell P. 1958. Amphetamine Psychosis. London: Maudsley Monograph, No. 5. London: Chapman & Hall Coulston CM, Perdices M, Tennant CC. 2007. The neuropsychology of cannabis and other substance use in schizophrenia: review of the literature and critical evaluation of methodological issues. Aust. N. Z. J. Psychiatry 41:869–84 Curran C, Byrappa N, McBride A. 2004. Stimulant psychosis: systematic review. Br. J. Psychiatry 185:196–204 Curran HV, Morgan C. 2000. Cognitive, dissociative and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later. Addiction 95(4):575–90 Da S, Takahashi RN. 2002. SR 141716A prevents delta 9-tetrahydrocannabinol-induced spatial learning deficit in a Morris-type water maze in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 26(2):321–25 Deakin JF, Lees J, McKie S, Hallak JE, Williams SR, Dursun SM. 2008. Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Arch. Gen. Psychiatry 65(2):154–64 De Bruin NMWJ, Ellenbroek BA, Cools AR, Coenen AML, Van Luijtelaar ELJM. 1999. Differential effects of ketamine on gating of auditory evoked potentials and prepulse inhibition in rats. Psychopharmacology 142:9–17 Degenhardt L, Hall W. 2001. The association between psychosis and problematical drug use among Australian adults: findings from the National Survey of Mental Health and Well-Being. Psychol. Med. 31:659–68 Del Olmo N, Higuera-Matas A, Miguéns M, Garc´ıa-Lecumberri C, Ambrosio E. 2007. Cocaine selfadministration improves performance in a highly demanding water maze task. Psychopharmacology (Berl.) 195(1):19–25 Dervaux A, Baylé FJ, Laqueille X, Bourdel MC, Le Borgne MH, et al. 2001. Is substance abuse in schizophrenia related to impulsivity, sensation seeking, or anhedonia? Am. J. Psychiatry 158(3):492–94 Diaz-Asper CM, Goldberg TE, Kolachana BS, Straub RE, Egan MF, Weinberger DR. 2008. Genetic variation in catechol-O-methyltransferase: effects on working memory in schizophrenic patients, their siblings, and healthy controls. Biol. Psychiatry 63(1):72–79 Diwadkar VA, Montrose DM, Dworakowski D, Sweeney JA, Keshavan MS. 2006. Genetically predisposed offspring with schizotypal features: an ultra high-risk group for schizophrenia? Prog. Neuropsychopharmacol. Biol. Psychiatry 30(2):230–38 Doherty JM, Masten VL, Powell SB, Ralph RJ, Klamer D, et al. 2008. Contributions of dopamine D1, D2, and D3 receptor subtypes to the disruptive effects of cocaine on prepulse inhibition in mice. Neuropsychopharmacology 33(11):2648–56 Drake RE, Essock SM, Shaner A, Carey KB, Minkoff K, et al. 2001. Implementing dual diagnosis services for clients with severe mental illness. Psychiatr. Serv. 52:469–76 Drake RE, Osher FC, Wallach MA. 1989. Alcohol use and abuse in schizophrenia: a prospective community study. J. Nerv. Ment. Dis. 177:408–14 Driesen NR, Leung HC, Calhoun VD, Constable RT, Gueorguieva R, et al. 2008. Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence. Biol. Psychiatry 64(12):1026–34 D’Souza DC, Abi-Saab WM, Madonick S, Forselius-Bielen K, Doersch A, et al. 2005. Delta-9tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis and addiction. Biol. Psychiatry 57:594–608 D’Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT. 2004. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 29:1558–72 Dulawa SC, Geyer MA. 2000. Effects of strain and serotonergic agents on prepulse inhibition and habituation in mice. Neuropharmacology 39(11):2170–79

E

V I E

W

S


13.17

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

Dumas P, Saoud M, Bouafia S, Gutknecht C, Ecochard R, et al. 2002. Cannabis use correlates with schizotypal personality traits in healthy students. Psychiatry Res. 109(1):27–35 Dumont GJ, Wezenberg E, Valkenberg MM, de Jong CA, Buitelaar JK, et al. 2008. Acute neuropsychological effects of MDMA and ethanol (co)administration in healthy volunteers. Psychopharmacology (Berl.) 197(3):465–74 Earleywine M. 2006. Schizotypy, marijuana, and differential item functioning. Hum. Psychopharmacol. 21(7):455–61 Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, et al. 2001. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl. Acad. Sci. USA 98:6917–22 Ehrhardt J, Sabel BA, Schroeder U. 1999. Subchronically applied phencyclidine fails to disrupt prepulse inhibition in rats. Eur. Neuropsychopharmacol. 10:69–74 Enomoto T, Floresco SB. 2009. Disruptions in spatial working memory, but not short-term memory, induced by repeated ketamine exposure. Prog. Neuropsychopharmacol. Biol. Psychiatry 33(4):668–75 Esterberg ML, Jones EM, Compton MT, Walker EF. 2007. Nicotine consumption and schizotypy in firstdegree relatives of individuals with schizophrenia and nonpsychiatric controls. Schizophr. Res. 97(1–3):6–13 Fadda P, Robinson L, Fratta W, Pertwee RG, Riedel G. 2004. Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats. Neuropharmacology 47(8):1170–79 Featherstone RE, Kapur S, Fletcher PJ. 2007. The amphetamine-induced sensitized state as a model of schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 31(8):1556–71 Fergusson DM, Poulton R, Smith PF, Boden JM. 2006. Cannabis and psychosis. BMJ 332(7534):172–75 Feyissa AM, Kelly JP. 2008. A review of the neuropharmacological properties of khat. Prog. Neuropsychopharmacol. Biol. Psychiatry 32(5):1147–66 Fox HC, McLean A, Turner JJ, Parrott AC, Rogers R, Sahakian BJ. 2002. Neuropsychological evidence of a relatively selective profile of temporal dysfunction in drug-free MDMA (“ecstasy”) polydrug users. Psychopharmacology (Berl.) 162(2):203–14 Freese TE, Miotto K, Reback CJ. 2002. The effects and consequences of selected club drugs. J. Subst. Abuse Treat. 23:151–56 George O, Mandyam CD, Wee S, Koob GF. 2008. Extended access to cocaine self-administration produces long-lasting prefrontal cortex-dependent working memory impairments. Neuropsychopharmacology 33(10):2474–82 Gerding LB, Labbate LA, Measom MO, Santos AB, Arana GW. 1999. Alcohol dependence and hospitalization in schizophrenia. Schizophr. Res. 38:71–75 Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR. 2001. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156:117– 54 Geyer MA, Segal DS, Greenberg BD. 1984. Increased startle responding in rats treated with phencyclidine. Neurobehav. Toxicol. Teratol. 6:1–4 Gottesman II, Gould TD. 2003. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160(4):636–45 Gould TD, Gottesman II. 2006. Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav. 5(2):113–19 Grech A, Van Os J, Jones PB, Lewis SW, Murray RM. 2005. Cannabis use and outcome of recent onset psychosis. Eur. Psychiatry 20(4):349–53 Groth-Marnat G, Howchar H, Marsh A. 2007. Memory performance in abstinent 3,4methylenedioxymethamphetamine (MDMA, “ecstasy”) users. Percept. Mot. Skills 104(1):43–55 Hambrecht M, Häfner H. 1996. Substance abuse and the onset of schizophrenia. Biol. Psychiatry 40:1155–63 Hampson RE, Simeral JD, Kelly EJ, Deadwyler SA. 2003. Tolerance to the memory disruptive effects of cannabinoids involves adaptation by hippocampal neurons. Hippocampus 13(5):543–56 Harvey MA, Sellman JD, Porter RJ, Frampton CM. 2007. The relationship between nonacute adolescent cannabis use and cognition. Drug Alcohol Rev. 26(3):309–19 Heekeren K, Daumann J, Geyer MA, Gouzoulis-Mayfrank E. 2004. Plasticity of the acoustic startle reflex in currently abstinent ecstasy (MDMA) users. Psychopharmacology (Berl.) 173(3–4):418–24


V I E

W

R

E

5:15

S 13.18

·

Murray

I N

A

C

E

Barkus

D V A N


19 December 2009

5:15

Henquet C, Di Forti M, Morrison P, Kuepper R, Murray RM. 2008. Gene-environment interplay between cannabis and psychosis. Schizophr. Bull. 34(6):1111–21 Henquet C, Murray R, Linszen D, van Os J. 2005. The environment and schizophrenia: the role of cannabis use. Schizophr. Bull. 31(3):608–12 Henquet C, Rosa A, Krabbendam L, Papiol S, Fananás L, et al. 2006. An experimental study of catechol-omethyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31(12):2748–57 Henseler I, Falkai P, Gruber O. 2009. A systematic fMRI investigation of the brain systems subserving different working memory components in schizophrenia. Eur. J. Neurosci. 30(4):693–702 Hermens DF, Lubman DI, Ward PB, Naismith SL, Hickie IB. 2009. Amphetamine psychosis: a model for studying the onset and course of psychosis. Med. J. Aust. 190(4 Suppl.):S22–25 Hijzen TH, Broersen LM, Slangen JL. 1991. Effects of subchronic d-amphetamine on prepulse and gap inhibition of the acoustic startle reflex in rats. Biol. Psychiatry 29:1119–28 Hjorthøj C, Fohlmann A, Nordentoft M. 2009. Treatment of cannabis use disorders in people with schizophrenia spectrum disorders—a systematic review. Addict. Behav. 34(6–7):520–25 Hoff AL, Riordan H, Morris L, Cestaro V, Wieneke M, et al. 1996. Effects of crack cocaine on neurocognitive function. Psychiatry Res. 60(2–3):167–76 Hudzik TJ, Wenger GR. 1993. Effects of drugs of abuse and cholinergic agents on delayed matching-to-sample responding in squirrel monkey. J. Pharmacol. Exp. Ther. 265:120–27 Hutchison KE, Swift R. 1999. Effect of d-amphetamine on prepulse inhibition of the startle reflex in humans. Psychopharmacology 143:394–400 Jacobs A. 2002. In clubs, a potent drug stirs fear of an epidemic. N.Y. Times Jan. 29, p. B1 Jentsch JD, Roth RH. 1999. The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 20(3):201–25 Jentsch JD, Roth RH, Taylor JR. 2000. Object retrieval/detour deficits in monkeys produced by prior subchronic phencyclidine administration: evidence for cognitive impulsivity. Biol. Psychiatry 48:415–24 Jentsch JD, Tran A, Le D, Youngren KD, Roth RH. 1997. Subchronic phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal-cortical dependent cognition in the rat. Neuropsychopharmacology 17:92–99 ¨ MC, Wolf T, Radzei N, Schlattmann P, Rentzsch J. 2007. Cannabis use induces differJockers-Scherubl ent cognitive changes in schizophrenic patients and healthy controls. Prog. Neuropsychopharmacol. Biol. Psychiatry 31:1054–63 Johansson C, Jackson DM, Zhang J, Svensson L. 1995. Prepulse inhibition of acoustic startle, a measure of sensorimotor gating: effects of antipsychotics and other agents in rats. Pharmacol. Biochem. Behav. 52:649–54 Johns LC, Cannon M, Singleton N, Murray RM, Farrell M, et al. 2004. Prevalence and correlates of selfreported psychotic symptoms in the British population. Br. J. Psychiatry 185:298–305 Kavanagh DJ, Waghorn G, Jenner L, Chant DC, Carr V, et al. 2004. Demographic and clinical correlates of comorbid substance use disorders in psychosis: multivariate analyses from an epidemiology sample. Schizophr. Res. 66:115–24 Kedzior KK, Martin-Iverson MT. 2006. Chronic cannabis use is associated with attention-modulated reduction in prepulse inhibition of the startle reflex in healthy humans. J. Psychopharmacol. 20(4):471–84 Kehne JH, Padich RA, McCloskey TC, Taylor VL, Schmidt CJ. 1996. 5-HT modulation of auditory and visual sensorimotor gating: I. Effects of 5-HT releasers on sound and light prepulse inhibition in Wistar rats. Psychopharmacology (Berl.) 124(1–2):95–106 Kirrane RM, Mitropoulou V, Nunn M, New AS, Harvey PD, et al. 2000. Effects of amphetamine on visuospatial working memory performance in schizophrenia spectrum personality disorder. Neuropsychopharmacology 22(1):14–18 Kovasznay B, Fleischer J, Tanenberg-Karat M, Jandorf L, Miller D, Bromet E. 1997. Substance use disorder and the early course of illness in schizophrenia and affective psychosis. Schizophr. Bull. 23(2):195–201 Kristensen K, Cadenhead KS. 2007. Cannabis abuse and risk for psychosis in a prodromal sample. Psychiatry Res. 151(1–2):151–54

E

V I E

W

S


13.19

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

Krueger DD, Howell JL, Oo H, Olausson P, Taylor JR, Nairn AC. 2009. Prior chronic cocaine exposure in mice induces persistent alterations in cognitive function. Behav. Pharmacol. Epub ahead of print Krystal JH, Perry EB Jr, Gueorguieva R, Belger A, Madonick SH, et al. 2005. Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch. Gen. Psychiatry 62(9):985–94 Kumari V, Mulligan OF, Cotter PA, Poon L, Toone BK, et al. 1998. Effects of single oral administrations of haloperidol and d-amphetamine on prepulse inhibition of the acoustic startle reflex in healthy male volunteers. Behav. Pharmacol. 9:567–76 Kumari V, Soni W, Mathew VM, Sharma T. 2000. Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication. Arch. Gen. Psychiatry 57:609–14 Kumra S, Thaden E, DeThomas C, Kranzler H. 2005. Correlates of substance abuse in adolescents with treatment refractory schizophrenia and schizoaffective disorder. Schizophr. Res. 73:369–71 Kuypers KP, Ramaekers JG. 2005. Transient memory impairment after acute dose of 75 mg 3,4-methylenedioxymethamphetamine. J. Psychopharmacol. 19(6):633–39 Kuypers KP, Ramaekers JG. 2007. Acute dose of MDMA (75 mg) impairs spatial memory for location but leaves contextual processing of visuospatial information unaffected. Psychopharmacology (Berl.) 189(4):557–63 Lambert M, Conus P, Lubman DI, Wade D, Yuen H, et al. 2005. The impact of substance use disorders on clinical outcome in 643 patients with first-episode psychosis. Acta Psychiatr. Scand. 112:141–48 Laruelle M, Abi-Dargham A. 1999. Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J. Psychopharmacol. 13(4):358–71 Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D’Souza CD, et al. 1996. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc. Natl. Acad. Sci. USA 93(17):9235–40 LeDuc PA, Mittleman G. 1995. Schizophrenia and psychostimulant abuse: a review and reanalysis of clinical evidence. Psycopharmacology (Berl.) 121:407–27 Levin ED, McClernon FJ, Rezvani AH. 2006. Nicotinic effects on cognitive function: behavioural characterization, pharmacological specification, and anatomic localization. Psychopharmacology (Berl.) 184(3–4):523–39 Li Z, Kim CH, Ichikawa J, Meltzer HY. 2003. Effect of repeated administration of phencyclidine on spatial performance in an eight-arm radial maze with delay in rats and mice. Pharmacol. Biochem. Behav. 75:335–40 Liechti ME, Geyer MA, Hell D, Vollenweider FX. 2001. Effects of MDMA (ecstasy) on prepulse inhibition and habituation of startle in humans after pretreatment with citalopram, haloperidol, or ketanserin. Neuropsychopharmacology 24(3):240–52 Linszen D, van Amelsvoort T. 2007. Cannabis and psychosis: an update on course and biological plausible mechanisms. Curr. Opin. Psychiatry 20:116–20 Liraud F, Verdoux H. 2002. Effect of comorbid substance use on neuropsychological performance in subjects with psychotic or mood disorders. Encephale 28:160–68 Lofwall MR, Griffiths RR, Mintzer MZ. 2006. Cognitive and subjective acute dose effects of intramuscular ketamine in healthy adults. Exp. Clin. Psychopharmacol. 14(4):439–49 Mahoney JJ 3rd, Kalechstein AD, De La Garza R 2nd, Newton TF. 2008. Presence and persistence of psychotic symptoms in cocaine- versus methamphetamine-dependent participants. Am. J. Addict. 17(2):83–98 Malone DT, Taylor DA. 2006. The effect of Delta9-tetrahydrocannabinol on sensorimotor gating in socially isolated rats. Behav. Brain Res. 166(1):101–9 Mandillo S, Rinaldi A, Oliverio A, Mele A. 2003. Repeated administration of phencyclidine, amphetamine and MK-801 selectively impairs spatial learning in mice: a possible model of psychotomimetic drug-induced cognitive deficits. Behav. Pharmacol. 14(7):533–44 Manning V, Wanigaratne S, Best D, Strathdee G, Schrover I, Gossop M. 2007. Screening for cognitive functioning in psychiatric outpatients with schizophrenia, alcohol dependence, and dual diagnosis. Schizophr. Res. 91:151–58 Mansbach RS, Geyer MA, Braff DL. 1988. Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 94:507–14 Martinez D, Slifstein M, Broft A, Mawlawi O, Hwang DR, et al. 2003. Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. J. Cereb. Blood Flow Metab. 23(3):285–300


V I E

W

R

E

5:15

S 13.20

·

Murray

I N

A

C

E

Barkus

D V A N


19 December 2009

5:15

Martinez ZA, Ellison GD, Geyer MA, Swerdlow NR. 1999a. Effects of sustained cocaine exposure on sensorimotor gating of startle in rats. Psychopharmacology (Berl.) 142(3):253–60 Martinez ZA, Ellison GD, Geyer MA, Swerdlow NR. 1999b. Effects of sustained phencyclidine exposure on sensorimotor gating of startle in rats. Neuropsychopharmacology 21:28–39 Mass R, Bardong C, Kindl K, Dahme B. 2001. Relationship between cannabis use, schizotypal traits, and cognitive function in healthy subjects. Psychopathology 34(4):209–14 Mathias S, Lubman DI, Hides L. 2008. Substance-induced psychosis: a diagnostic conundrum. J. Clin. Psychiatry 69(3):358–67 Mattay VS, Callicott JH, Bertolino A, Heaton I, Frank JA, et al. 2000. Effects of dextroamphetamine on cognitive performance and cortical activation. Neuroimage 12(3):268–75 Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, et al. 2003. Catechol O-methyltransferase val158met genotype and individual variation in the brain response to amphetamine. Proc. Natl. Acad. Sci. USA 100(10):6186–91 McGuire P, Fahy T. 1991. Chronic paranoid psychosis after misuse of MDMA (“ecstasy”). BMJ 302:697 McGuire PK, Cope H, Fahy TA. 1994. Diversity of psychopathology associated with the use of 3,4methylenedioxymethamphetamine (“ecstasy”). Br. J. Psychiatry 165:391–95 McGuire PK, Jones P, Harvey I, Williams M, McGuffi NP, Murray RM. 1995. Morbid risk of schizophrenia for relatives of patients with cannabis associated psychosis. Schizophr. Res. 15:277–81 McKetin R, Mattick RP. 1997. Attention and memory in illicit amphetamine users. Drug Alcohol Depend. 48(3):235–42 McKetin R, McLaren J, Lubman D, Hides L. 2006. The prevalence of psychotic symptoms among methamphetamine users. Addiction 101(10):1473–78 Mishima K, Egashira N, Hirosawa N, Fujii M, Matsumoto Y, et al. 2001. Characteristics of learning and memory impairment induced by delta9-tetrahydrocannabinol in rats. Jpn. J. Pharmacol. 87(4):297–308 Moeller FG, Steinberg JL, Dougherty DM, Narayana PA, Kramer LA, Renshaw PF. 2004. Functional MRI study of working memory in MDMA users. Psychopharmacology (Berl.) 177(1–2):185–94 Mohamed S, Bondi M, Kasckow JW, Golshan S, Jeste DV. 2006. Neurocognitive functioning in dually diagnosed middle aged and elderly patients with alcoholism and schizophrenia. Int. J. Geriatr. Psychiatry 21:711–18 Møller T, Linaker OM. 2004. Symptoms and lifetime treatment experiences in psychotic patients with and without substance abuse. Nord. J. Psychiatry 58:237–42 Montgomery C, Fisk JE. 2008. Ecstasy-related deficits in the updating component of executive processes. Hum. Psychopharmacol. 23(6):495–511 Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, et al. 2007. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 370(9584):319–28 Morgan CJ, Muetzelfeldt L, Curran HV. 2009. Ketamine use, cognition and psychological wellbeing: a comparison of frequent, infrequent and ex-users with polydrug and nonusing controls. Addiction 104(1):77–87 Morgan MJ. 1998. Recreational use of “ecstasy” (MDMA) is associated with elevated impulsivity. Neuropsychopharmacology 19:252–64 Morgan P, Beck J. 1997. The legacy and the paradox: hidden contexts of methamphetamine use in the United States. In Amphetamine Misuse: International Perspectives on Current Trends, ed. H Klee, pp. 135–62. Amsterdam: Harwood Acad. Morley KC, Gallate JE, Hunt GE, Mallet PE, McGregor IS. 2001. Increased anxiety and impaired memory in rats 3 months after administration of 3,4-methylenedioxymethamphetamine (“ecstasy”). Eur. J. Pharmacol. 433:91–99 Morrison PD, Zois V, McKeown DA, Lee TD, Holt DW, et al. 2009. The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol. Med. 39(10):1607–16 Mouri A, Noba Y, Enomoto T, Nabeshima T. 2007. Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochem. Int. 51:173–84 Mueser KT, Yarnold PR, Levinson DF, Singh H, Bellack AS, et al. 1990. Prevalence of substance abuse in schizophrenia: demographic and clinical correlates. Schizophr. Bull. 16:31–56

E

V I E

W

S


13.21

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

Mueser KT, Yarnold PR, Rosenberg SD, Swett C Jr, Miles KM, et al. 2000. Substance use disorder in hospitalized severely mentally ill psychiatric patients: prevalence, correlates, and subgroups. Schizophr. Bull. 26:179–92 Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJ, Curran HV. 2008. Journey through the K-hole: phenomenological aspects of ketamine use. Drug Alcohol Depend. 95(3):219–29 Nagai H, Egashira N, Sano K, Ogata A, Mizuki A, et al. 2006. Antipsychotics improve Delta9tetrahydrocannabinol-induced impairment of the prepulse inhibition of the startle reflex in mice. Pharmacol. Biochem. Behav. 84(2):330–36 NSDUH: National Survey on Drug Use and Health. 2005. www.oas.samhsa.gov/nsduh.htm Nunn JA, Rizza F, Peters ER. 2001. The incidence of schizotypy among cannabis and alcohol users. J. Nerv. Ment. Dis. 189(11):741–48 O’ Connor M, Harris JM, McIntosh AM, Owens DG, Lawrie SM, Johnstone EC. 2009. Specific cognitive deficits in a group at genetic high risk of schizophrenia. Psychol. Med. 39(10):1649–55 Odenwald M. 2007. Chronic khat use and psychotic disorders: a review of the literature and future prospects. Sucht 53(1):9–22 Oranje B, Gispen-de Wied CC, Verbaten MN, Kahn RS. 2002. Modulating sensory gating in healthy volunteers: the effects of ketamine and haloperidol. Biol. Psychiatry 52(9):887–95 Ornstein TJ, Iddon JL, Baldacchino AM, Sahakian BJ, London M, et al. 2000. Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology 23(2):113–26 Padula CB, Schweinsburg AD, Tapert SF. 2007. Spatial working memory performance and fMRI activation interaction in abstinent adolescent marijuana users. Psychol. Addict. Behav. 21(4):478–87 Park S, Holzman PS, Goldman-Rakic PS. 1995. Spatial working memory deficits in the relatives of schizophrenic patients. Arch. Gen. Psychiatry 52:821–28 Pedersen W. 1990. Adolescents initiating cannabis use: cultural opposition or poor mental health. J. Adolesc. 13:327–39 Pencer A, Addington J. 2003. Substance use and cognition in early psychosis. J. Psychiatry Neurosci. 28:48–54 Perlstein WM, Fiorito E, Simons RF, Graham FK. 1989. Pre-stimulation effects on reflex blink and evoked potentials in normal and schizotypal subjects. Psychophysiology 26(Suppl.):S48 (Abstr.) Phillips LJ, Curry C, Yung AR, Pan Yuen H, Adlard S, McGorry PD. 2002. Cannabis use is not associated with the development of psychosis in “ultra” high-risk group. Aust. N. Z. J. Psychiatry 36:800–6 Piper BJ. 2007. A developmental comparison of the neurobehavioral effects of ecstasy (MDMA). Neurotoxicol. Teratol. 29(2):288–300 Pitsikas N, Boultadakis A. 2009. Pre-training administration of anesthetic ketamine differentially affects rats’ spatial and nonspatial recognition memory. Neuropharmacology 57(1):1–7 Pitsikas N, Boultadakis A, Sakellaridis N. 2008. Effects of subanesthetic doses of ketamine on rats’ spatial and nonspatial recognition memory. Neuroscience 154(2):454–60 Pomarol-Clotet E, Honey GD, Murray GK, Corlett PR, Absalom AR, et al. 2006. Psychological effects of ketamine in healthy volunteers. Phenomenological study. Br. J. Psychiatry 189:173–79 Raine A. 2006. Schizotypal personality: neurodevelopmental and psychosocial trajectories. Annu. Rev. Clin. Psychol. 2:291–326 ¨ Rapeli P, Kivisaari R, Kähkonen S, Puuskari V, Autti T, Kalska H. 2005. Do individuals with former amphetamine dependence have cognitive deficits? Nord. J. Psychiatry 59(4):293–97 Rawson RA, Anglin MD, Ling W. 2002. Will the methamphetamine problem go away? J. Addict. Dis. 21:5–19 Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, et al. 1990. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiology Catchment Area (ECA) study. J. Am. Med. Assoc. 264:2511–18 Ringen PA, Melle I, Birkenæs AB, Engh JA, Færden A, et al. 2008. Illicit drug use in patients with psychotic disorders compared with that in the general population: a cross-sectional study. Acta Psychiatr. Scand. 117:133–38 Ripoll N, Bronnec M, Bourin M. 2004. Nicotinic receptors and schizophrenia. Curr. Med. Res. Opin. 20(7):1057–74


V I E

W

R

E

5:15

S 13.22

·

Murray

I N

A

C

E

Barkus

D V A N


19 December 2009

5:15

Robinson L, Goonawardena AV, Pertwee RG, Hampson RE, Riedel G. 2007. The synthetic cannabinoid HU210 induces spatial memory deficits and suppresses hippocampal firing rate in rats. Br. J. Pharmacol. 151(5):688–700 Rogers G, Elston J, Garside R, Roome C, Taylor R, et al. 2009. The harmful health effects of recreational ecstasy: a systematic review of observational evidence. Health Technol. Assess. 13(6):iii–iv, ix–xii, 1–315 Roick C, Fritz-Wieacker A, Matschinger H, Heider D, Schindler J, et al. 2007. Health habits of patients with schizophrenia. Soc. Psychiatry Psychiatr. Epidemiol. 42(4):268–76 Rosselli M, Ardila A, Lubomski M, Murray S, King K. 2001. Personality profile and neuropsychological test performance in chronic cocaine-abusers. Int. J. Neurosci. 110(1–2):55–72 Rowland LM, Astur RS, Jung RE, Bustillo JR, Lauriello J, Yeo RA. 2005. Selective cognitive impairments associated with NMDA receptor blockade in humans. Neuropsychopharmacology 30(3):633–39 Rupniak NM, Samson NA, Steventon MJ, Iversen SD. 1991. Induction of cognitive impairment by scopolamine and noncholinergic agents in rhesus monkeys. Life Sci. 48:893–99 Salyers MP, Mueser KT. 2001. Social functioning, psychopathology, and medication side effects in relation to substance use and abuse in schizophrenia. Schizophr. Res. 48(1):109–23 Sambataro F, Reed JD, Murty VP, Das S, Tan HY, et al. 2009. Catechol-O-methyltransferase valine(158)methionine polymorphism modulates brain networks underlying working memory across adulthood. Biol. Psychiatry 66(6):540–48 Santucci AC. 2008. Adolescent cocaine residually impairs working memory and enhances fear memory in rats. Exp. Clin. Psychopharmacol. 16(1):77–85 Santucci AC, Capodilupo S, Bernstein J, Gomez-Ramirez M, Milefsky R, Mitchell H. 2004. Cocaine in adolescent rats produces residual memory impairments that are reversible with time. Neurotoxicol. Teratol. 26(5):651–61 Saperstein AM, Fuller RL, Avila MT, Adami H, McMahon RP, et al. 2006. Spatial working memory as a cognitive endophenotype of schizophrenia: assessing risk for pathophysiological dysfunction. Schizophr. Bull. 32(3):498–506 Schiffman J, Nakamura B, Earleywine M, LaBrie J. 2005. Symptoms of schizotypy precede cannabis use. Psychiatry Res. 134(1):37–42 Schmid B, Hohm E, Blomeyer D, Zimmermann US, Schmidt MH, et al. 2007. Concurrent alcohol and tobacco use during early adolescence characterizes a group at risk. Alcohol 42(3):219–25 Scholes KE, Martin-Iverson MT. 2009. Alterations to prepulse inhibition (PPI) in chronic cannabis users are secondary to sustained attention deficits. Psychopharmacology (Berl.). Epub ahead of print Schweinsburg AD, Nagel BJ, Schweinsburg BC, Park A, Theilmann RJ, Tapert SF. 2008. Abstinent adolescent marijuana users show altered fMRI response during spatial working memory. Psychiatry Res. 163(1):40–51 Semple DM, McIntosh AM, Lawrie SM. 2005. Cannabis as a risk factor for psychosis: systematic review. J. Psychopharmacol. 19(2):187–94 Serper MR, Bergman A, Copersino ML, Chou JCY, Richarme D, Cancro R. 2000. Learning and memory impairment in cocaine-dependent and comorbid schizophrenic patients. Psychiatr. Res. 93:21–32 Sevy S, Burdick KE, Visweswaraiah H, Abdelmessih S, Lukin M, et al. 2007. Iowa Gambling Task in schizophrenia: a review and new data in patients with schizophrenia and co-occurring cannabis use disorders. Schizophr. Res. 92(1-3):74–84 Sevy S, Robinson D, Solloway S, Alvir JM, Woerner MG, et al. 2001. Correlates of substance misuse in patients with first episode schizophrenia and schizoaffective disorder. Acta Psychiatr. Scand. 104:367–74 Simons RF, Giardina BD. 1992. Reflex modification in psychosis-prone young adults. Psychophysiology 29:8–16 Skosnik PD, Krishnan GP, Aydt EE, Kuhlenshmidt HA, O’Donnell BF. 2006. Psychophysiological evidence of altered neural synchronization in cannabis use: relationship to schizotypy. Am. J. Psychiatry 163(10):1798– 805 Skosnik PD, Park S, Dobbs L, Gardner WL. 2008. Affect processing and positive syndrome schizotypy in cannabis users. Psychiatry Res. 157(1–3):279–82 Skosnik PD, Spatz-Glenn L, Park S. 2001. Cannabis use is associated with schizotypy and attentional disinhibition. Schizophr. Res. 48(1):83–92 Smith CW, Park S, Cornblatt B. 2006. Spatial working memory deficits in adolescents at clinical high risk for schizophrenia. Schizophr. Res. 81(2–3):211–15

E

V I E

W

S


13.23

E

I N

A


C

ARI

R


ANRV407-CP06-13

D V A N

ANRV407-CP06-13

ARI

19 December 2009

Smith MJ, Barch DM, Wolf TJ, Mamah D, Csernansky JG. 2008. Elevated rates of substance use disorders in nonpsychotic siblings of individuals with schizophrenia. Schizophr. Res. 106:294–99 Sorbara F, Liraud F, Assens F, Abalan F, Verdoux H, et al. 2003. Substance use and the early course of psychosis: a 2-year follow-up of first admitted subjects. Eur. Psychiatr. 18:133–36 Steele TD, McCann UD, Ricaurte GA. 1994. 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”): pharmacology and toxicology in animals and humans. Addiction 89(5):539–51 Stefanis NC, Delespaul P, Henquet C, Bakoula C, Stefanis CN, et al. 2004. Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction 99(10):1333–41 Stirling J, Barkus EJ, Nabosi L, Irshad S, Roemer G, et al. 2008. Cannabis-induced psychotic-like experiences are predicted by high schizotypy. Confirmation of preliminary results in a large cohort. Psychopathology 41(6):371–78 Stirling J, Lewis S, Hopkins R, White C. 2005. Cannabis use prior to first onset psychosis predicts spared neurocognition at 10-year follow-up. Schizophr. Res. 75:135–37 Stone JM, Erlandsson K, Arstad E, Squassante L, Teneggi V, et al. 2008. Relationship between ketamineinduced psychotic symptoms and NMDA receptor occupancy: a [(123)I]CNS-1261 SPET study. Psychopharmacology 197(3):401–8 Swerdlow NR, Benbow CH, Zisook S, Geyer MA, Braff DL. 1993. A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol. Psychiatry 33:298–301 Swerdlow NR, Karban B, Ploum Y, Sharp R, Geyer MA, Eastvold A. 2001. Tactile prepuff inhibition of startle in children with Tourette’s syndrome: in search of a “fMRI-friendly” startle paradigm. Biol. Psychiatry 50:578–85 Tipper CM, Cairo TA, Woodward TS, Phillips AG, Liddle PF, Ngan ET. 2005. Processing efficiency of a verbal working memory system is modulated by amphetamine: an fMRI investigation. Psychopharmacology 180(4):634–43 Trigo JM, Cabrero-Castel A, Berrendero F, Maldonado R, Robledo P. 2008. MDMA modifies active avoidance learning and recall in mice. Psychopharmacology (Berl.) 197(3):391–400 Ujike H, Sato M. 2004. Clinical features of sensitization to methamphetamine observed in patients with methamphetamine dependence and psychosis. Ann. N.Y. Acad. Sci. 1025:279–87 United Nations Report. 2008. World Drugs Report 2008. Vienna, Austria: U.N. Office Drugs Crime van Mastrigt S, Addington J, Addington D. 2004. Substance misuse at presentation to an early psychosis program. Soc. Psychiatry Psychiatr. Epidemiol. 39:69–72 van Os J, Bak M, Hanssen M, Bijl RV, de Graaf R, Verdoux H. 2002. Cannabis use and psychosis: a longitudinal population-based study. Am. J. Epidemiol. 156:319–27 Van Snellenberg JX. 2009. Working memory and long-term memory deficits in schizophrenia: Is there a common substrate? Psychiatry Res. 174(2):89–96 Varvel SA, Anum E, Niyuhire F, Wise LE, Lichtman AH. 2005. Delta(9)-THC-induced cognitive deficits in mice are reversed by the GABA(A) antagonist bicuculline. Psychopharmacology (Berl.) 178(2–3):317–27 Verdoux H, Sorbara F, Gindre C, Swendsen JD, van Os J. 2003. Cannabis use and dimensions of psychosis in a nonclinical population of female subjects. Schizophr. Res. 59(1):77–84 Viveros MP, Llorente R, Moreno E, Marco EM. 2005. Behavioural and neuroendocrine effects of cannabinoids in critical developmental periods. Behav. Pharmacol. 16(5–6):353–62 Vollenweider FX, Remensberger S, Hell D, Geyer MA. 1999. Opposite effects of 3,4methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus healthy humans. Psychopharmacology 143:365–72 Wade D, Harrigan S, Edwards J, Burgess PM, Whelan G, et al. 2006. Course of substance misuse and daily tobacco use in first-episode psychosis. Schizophr. Res. 81:145–50 Watson SJ, Benson JA, Joy JE. 2000. Marijuana and medicine: assessing the science base. A summary of the 1999 Institute of Medicine report. Arch. Gen. Psychiatry 57:547–52 Wegener N, Koch M. 2009. Behavioural disturbances and altered Fos protein expression in adult rats after chronic pubertal cannabinoid treatment. Brain Res. 1253:81–91 Weike AI, Bauer U, Hamm AO. 2000. Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients. Biol. Psychiatry 47:61–70


V I E

W

R

E

5:15

S 13.24

·

Murray

I N

A

C

E

Barkus

D V A N


ANRV407-CP06-13

ARI

19 December 2009

5:15


Weinstein A, Brickner O, Lerman H, Greemland M, Bloch M, et al. 2008. A study investigating the acute doseresponse effects of 13 mg and 17 mg Delta 9-tetrahydrocannabinol on cognitive-motor skills, subjective and autonomic measures in regular users of marijuana. J. Psychopharmacol. 22(4):441–51 White AM, Swartzwelder HS. 2004. Hippocampal function during adolescence: a unique target of ethanol effects. Ann. N. Y. Acad. Sci. 1021:206–20 Yung AR, McGorry PD. 1996. The prodromal phase of first-episode psychosis: past and current conceptualizations. Schizophr. Bull. 22(2):353–70 Zammit S, Allebeck P, Andreasson S, Lundber I, Lewis G. 2002. Self-report cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ 325:1199 Zeeuws I, Soetens E. 2007. Verbal memory performance improved via an acute administration of D-amphetamine. Hum. Psychopharmacol. 22(5):279–87

V I E

W

R

E

S


13.25


C

E

I N

A

D V A N