- Email: [email protected]
Age at initiation of amphetamine use and age at onset of psychosis: The Australian Survey of High Impact Psychosis
Schizophrenia Research 152 (2014) 300–302
Contents lists available at ScienceDirect
Schizophrenia Research journal homepage: www.elsevier.com/locate/schres
Age at initiation of amphetamine use and age at onset of psychosis: The Australian Survey of High Impact Psychosis Brian D. Power a,b,c, Nikos C. Stefanis a,b,⁎, Milan Dragovic a,b, Assen Jablensky a, David Castle d, Vera Morgan a a
School of Psychiatry and Clinical Neurosciences, and Centre for Clinical Research in Neuropsychiatry, University of Western Australia, Australia Clinical Research Centre, North Metropolitan Health Service - Mental Health, WA, Australia Peel and Rockingham Kwinana Mental Health Service, South Metropolitan Area Health Service, Perth, Australia d St. Vincent's Hospital, University of Melbourne, Melbourne, Australia b c
a r t i c l e
i n f o
Article history: Received 2 July 2013 Received in revised form 9 October 2013 Accepted 1 November 2013 Available online 22 November 2013 Keywords: Schizophrenia Causality Cannabis Amphetamine Psychosis
a b s t r a c t Individuals with a psychotic disorder who had a premorbid history of amphetamine use (n = 382) were analyzed in groups according to age of initiation to amphetamine (AIA) and mean number of years of duration of premorbid exposure to amphetamine (DPEA) was calculated. Univariate General Linear Models were used to test for group differences in age at onset of psychotic illness (AOI) and DPEA. Although a temporal direct relationship between AIA and AOI was detected (mean duration 5.3 years), our findings suggested this association was spurious and better explained by a later initiation to amphetamine than to cannabis (by 2–3 years). © 2013 Elsevier B.V. All rights reserved.
1. Introduction Investigating the impact of amphetamine exposure on the brain has proven fruitful for further understanding psychosis aetiology, and is one of the underpinnings of the dopamine sensitization hypothesis of schizophrenia (see Paparelli et al., 2011). Neuroimaging studies report that repeated amphetamine exposure over time in healthy men results in increasing striatal dopamine release (Boileau et al., 2006), and nearly twice as much amphetamine-induced dopamine in the striatum of people with schizophrenia when compared with the brains of healthy controls (Laruelle et al., 1996). Amphetamine use has been associated with increased psychosis risk, and this is enhanced if people have used amphetamine at a younger age or in larger amounts (Farrell et al., 2002; Chen et al., 2003). Furthermore, consumption of illicit substances (such as amphetamine) in addition to cannabis in the prodromal period (in the 12 months prior to the onset of psychosis) has been shown to be associated with an even earlier age at onset in schizophrenia-spectrum
Abbreviations: AIA, age at initiation to amphetamine; AOI, age at onset of illness; DIP, Diagnostic Interview for Psychosis; DPEA, duration of premorbid exposure to amphetamine; SHIP, Survey of High Impact Psychosis. ⁎ Corresponding author at: School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Centre for Clinical Research in Neuropsychiatry, Private Bag No 1, Claremont, WA 6910, Australia. Tel.: +61 8 9347 6429; fax: +61 8 9384 5128. E-mail addresses: [email protected] (B.D. Power), [email protected] (N.C. Stefanis), [email protected] (M. Dragovic), [email protected] (A. Jablensky), [email protected] (D. Castle), [email protected] (V. Morgan). 0920-9964/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.schres.2013.11.003
disorders (Power et al., 2012). Less is known, however, about the impact of amphetamine consumption premorbidly on age at onset of psychosis. We have recently reported a temporal association between age at initiation of cannabis use and age at onset of psychotic illness in 997 participants from the 2010 Australian Survey of High Impact Psychosis (SHIP), with a premorbid exposure to cannabis trend of 7–8 years (Stefanis et al., 2013). In the same large Australian sample of participants with psychotic disorders, we aimed to ascertain how this temporal association is modified, if at all, by age at initiation to amphetamine (AIA). We hypothesized that the consumption of amphetamine in addition to cannabis would exert an additive effect on this temporal association. 2. Experimental/Materials and methods 2.1. Participants Participants were part of the 2010 Survey of High Impact Psychosis (SHIP), which covered seven mental health catchment sites across five Australian States. A two-phase sampling design was utilised (Morgan et al., 2012). In phase 1, all people aged 18–64 living in the catchment sites and in contact with inpatient or community public mental health services, or non-government organisations funded to support people with mental illness were screened for psychosis. In phase 2, the 7955 participants who had screened positive for psychosis in phase 1 were stratified by age and site, and 1825 were randomly selected and interviewed. Participants were ineligible for inclusion in the survey if they had insufficient English, or impaired cognition or communication
B.D. Power et al. / Schizophrenia Research 152 (2014) 300–302
affecting their capacity for informed consent or ability to complete an interview. All participants provided written informed consent; the study was conducted in accordance with the Declaration of Helsinki, and approved by institutional human research ethics committees at each of the seven study sites. 2.2. Measures of diagnoses and substance use Participants were assessed using the Diagnostic Interview for Psychosis (DIP), a standardized semi-structured interview for psychosis (Castle et al., 2006) consisting of the 97 items of the Operational Criteria For Psychosis (OPCRIT) (McGuffin et al., 1991) and utilizing probes derived and adapted from the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry. The OPCRIT diagnostic computer algorithm is used to score the items and classify cases according to ICD-10 or DSM-IV criteria. The criteria applied in this study were ICD10. The DIP also contains a module for enquiring about past substance use, including data on age of first use; the details of this module have been described previously (Stefanis et al., 2013). Participants were designated as substance-users (if they reported daily/almost daily use, use 1–2 days/week, use 2–4 times/month, or use less frequently than once per month) or substance non-users (if they reported no use). A total of 382 participants were designated as amphetamine users.
301
Univariate analysis of variance was used to test for group differences in exposure to amphetamines (time between AIA and AOI). For the entire cohort, the effect of AIA on mean exposure to amphetamines was not significant (F(6,381) = 1.08, p = 0.374), and there was no significant trend observed (F(6,381) = 0.109, p = 0.742). The mean DPEA for the entire SHIP sample was 5.3 (SD = 4.53) years. For the subset of schizophrenia spectrum participants (n = 310), the effect of AIA on mean exposure to amphetamines was not significant (F(6,309) = 0.78, p = 0.31), and again there was no significant trend observed (F(6,309) = 0.009, p = 0.925). The mean DPEA for this subsample was similar, at 5.3 years. For the subset of SHIP participants who used cannabis but did not use amphetamines (n = 630), the mean duration of premorbid exposure to cannabis was 6.87 (SD = 6.34) years. For the subset of schizophrenia spectrum participants who used cannabis but did not use amphetamine (n = 436), the mean duration of premorbid exposure to cannabis was 6.54 (SD = 5.97) years. A paired-samples t-test was conducted to compare mean age of initiation of both cannabis and amphetamines. Comparison showed a significant difference in the mean age of initiation of cannabis (mean = 14.9, SD = 3.2 years) and amphetamines (mean = 18.6, SD = 4.3 years), t(366) = 19.66, r = 0.57, p b 0.001. Fig. 1 shows the time between initiation to drugs (amphetamines vs cannabis) and AOI.
2.3. Definition of age at onset of psychosis
2.4. Statistical analysis Participants were analyzed in seven age groups according to AIA to allow for equal distribution of the sample (ranging from ≤ 15 to 25 + years of age), and mean number of years according to the duration of premorbid exposure to amphetamine (DPEA) was calculated. Univariate General Linear Models were used to test for group differences in AOI and DPEA; analyses were repeated for subsets of the sample, including participants with a schizophrenia-spectrum illness (schizophrenia, schizoaffective disorder, delusional disorder). We then repeated the analyses according to cannabis use (as per Stefanis et al., 2013), but excluded from the analysis those who had used amphetamines (n = 367). We subsequently examined trends in the schizophrenia spectrum sub sample. Finally, a paired-samples t-test was conducted to compare mean age of initiation of cannabis and amphetamines. 3. Results The demographic characteristics of this study sample have been presented previously (Moore et al., 2012; Morgan et al., 2012). Of those who consumed amphetamines prior to onset of illness, almost all had reported also using cannabis (n = 367, or 98.4%). We tested for group differences in AOI between participants in the AIA groups (N = 382); the analysis showed that the effect of AIA prior to onset of illness was significant (F(6,381) = 47.13, p b 0.001), and remained significant after age of participants was used as a covariate (F(7, 381) = 27.39, p b 0.001). This demonstrated that various AIA had distinct AOI. The effect of AIA on AOI also remained significant after family history of schizophrenia or other psychiatric disorders was used as a covariate, (F(8,381) = 26.57, p b 0.001).
4. Discussion When taken together, our findings suggest that the temporal association between age at initiation of cannabis use and age at onset of psychotic illness (with a premorbid exposure to cannabis trend of 7–8 years) (Stefanis et al., 2013) is not modified by amphetamine use. Nonetheless, our findings regarding age at initiation to amphetamine and duration of premorbid exposure to amphetamine in the SHIP cohort require further consideration. For instance, we did observe a direct temporal relationship between age at initiation of amphetamine and age at onset of psychosis. Further, there was a delay of approximately 5 years from initial exposure to amphetamine to the onset of psychosis. Taken on its own, this finding could suggest that the consumption of amphetamine in addition to cannabis may exert an additive toxic effect on individuals on the pathway to developing psychosis, the manifestation of which is delayed for approximately 5 years (regardless of age of initiation). However an alternative and more parsimonious explanation, as supported by our subsequent analysis (e.g., analyzing the subset of SHIP participants who used cannabis but did not use amphetamines), is that the observed association is spurious and better explained by a later initiation to amphetamine than to cannabis (by 2–3 years). Further, numerous other studies have failed to demonstrate an additional effect of polysubstance on age at onset of psychosis (Barnes et al., 2006; Gonzalez-Pinto et al., 2008; Dekker et al., 2012).
Time in years (between initiation to drugs and onset of illness)
AOI was documented to the nearest year, and defined as the earliest age at which medical advice was sought for psychiatric reasons, or at which symptoms began to cause subjective distress or impair functioning. If there were no clear symptoms present to clarify year of onset, or if the participant denied the existence of an illness and no informant was available to provide such data, then age at first hospital admission was used.
10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0
Cannabis Amphetamines
2.0 <=12 13
14
15
16
17
18 19-2122-24 25+
Age of initiation to drugs Fig. 1. Figure showing time between initiation to drugs and onset of illness.
302
B.D. Power et al. / Schizophrenia Research 152 (2014) 300–302
We have, however, recently demonstrated that consumption of illicit substances (such as amphetamine) in addition to cannabis in the 12 months prior to the onset of psychosis is associated with an even earlier age at onset in schizophrenia-spectrum disorders (Power et al., 2012; Stefanis et al., submitted for publication). This might suggest that substances operate via a variety of mechanisms over the life span of the psychotic illness: in the premorbid period, cannabis may influence disease expression in those susceptible individuals, and in the prodromal period, cannabis and other psychotogenic substances may hasten onset of the emerging disease. There are a number of limitations of this study, which include possible recall bias, and the lack of available data on the pattern of substance use of illicit substances until the year prior to illness onset. Further, given the pattern of comorbid use with cannabis, it is not possible to ascertain an independent effect of amphetamine on age at onset of psychosis. Nonetheless, this is one of the largest studies of its kind examining the effects of AIA (in addition to cannabis use) on AOP. Role of funding source The SHIP was funded under contract to the Australian Government Department of Health and Ageing.
Contributors VM, DC and AJ designed the study and wrote the protocol. BP, NS and MD undertook the statistical analysis, and BP wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Conflict of interest The authors have declared that there are no conflicts of interest in relation to the subject of this study.
Acknowledgments SHIP acknowledgement: This publication is based on data collected in the framework of the 2010 Australian National Survey of High Impact Psychosis. The members of the Survey of High Impact Psychosis Study Group are: V. Morgan (National Project Director), A. Jablensky (Chief Scientific Advisor), A. Waterreus (National Project Coordinator), R. Bush, V. Carr, D. Castle, M. Cohen, C. Galletly, C. Harvey, B. Hocking, A. Mackinnon, P. McGorry, J. McGrath, A. Neil, S. Saw, H. Stain. Ethics approvals for the study were obtained from relevant institutional human research ethics committees. The study was funded by the Australian Government Department of Health and Ageing. This report acknowledges the hundreds of mental health professionals who participated in the preparation and conduct of the survey and the many Australians with psychotic disorders who gave their time and whose responses form the basis of this publication.
References Barnes, T.R., Mutsatsa, S.H., Hutton, S.B., Watt, H.C., Joyce, E.M., 2006. Comorbid substance use and age at onset of schizophrenia. Br. J. Psychiatry 188, 237–242. Boileau, I., Dagher, A., Leyton, M., Gunn, R.N., Baker, G.B., Diksic, M., Benkelfat, C., 2006. Modeling sensitization to stimulants in humans. An [11C] Raclopride/Positron Emission Tomography Study in healthy men. Arch. Gen. Psychiatry 63, 1386–1395. Castle, D., Jablensky, A., McGrath, J., Carr, V., Morgan, V., Waterreus, A., Valuri, G., Stain, H., McGuffin, P., Farmer, A., 2006. The diagnostic interview for psychosis (DIP): development, reliability and applications. Psychol. Med. 36, 69–80. Chen, C.K., Lin, S.K., Sham, P.C., Ball, D., Loh, E., Hsiao, C.C., Chiang, Y.L., Ree, S.C., Lee, C.H., Murray, R.M., 2003. Pre-morbid characteristics and co-morbidity of methamphetamine users with and without psychosis. Psychol. Med. 33, 1407–1414. Dekker, N., Meijer, J., Koeter, M., van den Brink, W., van Beveren, N., 2012. Age at onset of non-affective psychosis in relation to cannabis use, other drug use and gender. Psychol. Med. 42, 1903–1911. Farrell, M., Boys, A., Bebbington, P., Brugha, T., Coid, J., Jenkins, R., Lewis, G., Meltzer, H., Marsden, J., Singleton, N., Taylor, C., 2002. Psychosis and drug dependence: results from a national survey of prisoners. Br. J. Psychiatry 181, 393–398. Gonzalez-Pinto, A., Vega, P., Ibanez, B., Mosquera, F., Barbeito, S., Gutierrez, M., Ruiz de Azua, S., Ruiz, I., Vieta, E., 2008. Impact of cannabis and other drugs on age at onset of psychosis. J. Clin. Psychiatry 69, 1210–1216. Laruelle, M., Abi-Dargham, A., van Dyck, C.H., Gil, R., D’Souza, C.D., Erdos, J., McCance, E., Rosenblatt, W., Fingado, C., Zoghbi, S.S., Baldwin, R.M., Seibyl, J.P., Krystal, J.H., Charney, D.S., Innis, R.B., 1996. Single emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic patients. Proc. Natl. Acad. Sci. U. S. A. 93, 9235–9240. McGuffin, P., Farmer, A., Harvey, I., 1991. A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Arch. Gen. Psychiatry 48, 764–770. Moore, E., Mancuso, S.G., Slade, T., Galletly, C., Castle, D.J., 2012. The impact of alcohol and illicit drugs on people with psychosis: the second Australian national survey of psychosis. Aust. N. Z. J. Psychiatry 9, 864–878. Morgan, V.A., Waterreus, A., Jablensky, A., Mackinnon, A., McGrath, J.J., Carr, V., Bush, R., Castle, D., Cohen, M., Harvey, C., Galletly, C., Stain, H., Neill, A.L., McGorry, P., Hocking, B., Shah, S., Saw, S., 2012. People living with psychotic illness in 2010: the second Australian national survey of psychosis. Aust. N. Z. J. Psychiatry 8, 735–752. Paparelli, A., Di Forti, M., Morrison, P.D., Murray, R.M., 2011. Drug-induced psychosis: how to avoid star gazing in schizophrenia research by looking at more obvious sources of light. Front. Behav. Neurosci. 5, 1–9. Power, B.D., Dragovic, M., Jablensky, A., Stefanis, N.C., 2012. Does accumulating exposure to illicit drugs bring forward the age at onset in schizophrenia? Aust. N. Z. J. Psychiatry 47, 51–58. Stefanis, N.C., Dragovic, M., Power, B.D., Jablensky, A., Castle, D., Morgan, V.A., 2013. Age at initiation of cannabis use predicts age at onset of psychosis: the 7- to 8-year trend. Schizophr. Bull. 39, 251–254. Stefanis, N.C., Dragovic, M., Power, B.D., Jablensky, A., Castle, D., Morgan, V.A., 2013. Drug use has differential effect on the age at onset in schizophrenia spectrum vs affective psychotic disorders: the Australian Survey of High Impact Psychosis. Schizophr. Bull. (submitted for publication).
Contents lists available at ScienceDirect
Schizophrenia Research journal homepage: www.elsevier.com/locate/schres
Age at initiation of amphetamine use and age at onset of psychosis: The Australian Survey of High Impact Psychosis Brian D. Power a,b,c, Nikos C. Stefanis a,b,⁎, Milan Dragovic a,b, Assen Jablensky a, David Castle d, Vera Morgan a a
School of Psychiatry and Clinical Neurosciences, and Centre for Clinical Research in Neuropsychiatry, University of Western Australia, Australia Clinical Research Centre, North Metropolitan Health Service - Mental Health, WA, Australia Peel and Rockingham Kwinana Mental Health Service, South Metropolitan Area Health Service, Perth, Australia d St. Vincent's Hospital, University of Melbourne, Melbourne, Australia b c
a r t i c l e
i n f o
Article history: Received 2 July 2013 Received in revised form 9 October 2013 Accepted 1 November 2013 Available online 22 November 2013 Keywords: Schizophrenia Causality Cannabis Amphetamine Psychosis
a b s t r a c t Individuals with a psychotic disorder who had a premorbid history of amphetamine use (n = 382) were analyzed in groups according to age of initiation to amphetamine (AIA) and mean number of years of duration of premorbid exposure to amphetamine (DPEA) was calculated. Univariate General Linear Models were used to test for group differences in age at onset of psychotic illness (AOI) and DPEA. Although a temporal direct relationship between AIA and AOI was detected (mean duration 5.3 years), our findings suggested this association was spurious and better explained by a later initiation to amphetamine than to cannabis (by 2–3 years). © 2013 Elsevier B.V. All rights reserved.
1. Introduction Investigating the impact of amphetamine exposure on the brain has proven fruitful for further understanding psychosis aetiology, and is one of the underpinnings of the dopamine sensitization hypothesis of schizophrenia (see Paparelli et al., 2011). Neuroimaging studies report that repeated amphetamine exposure over time in healthy men results in increasing striatal dopamine release (Boileau et al., 2006), and nearly twice as much amphetamine-induced dopamine in the striatum of people with schizophrenia when compared with the brains of healthy controls (Laruelle et al., 1996). Amphetamine use has been associated with increased psychosis risk, and this is enhanced if people have used amphetamine at a younger age or in larger amounts (Farrell et al., 2002; Chen et al., 2003). Furthermore, consumption of illicit substances (such as amphetamine) in addition to cannabis in the prodromal period (in the 12 months prior to the onset of psychosis) has been shown to be associated with an even earlier age at onset in schizophrenia-spectrum
Abbreviations: AIA, age at initiation to amphetamine; AOI, age at onset of illness; DIP, Diagnostic Interview for Psychosis; DPEA, duration of premorbid exposure to amphetamine; SHIP, Survey of High Impact Psychosis. ⁎ Corresponding author at: School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Centre for Clinical Research in Neuropsychiatry, Private Bag No 1, Claremont, WA 6910, Australia. Tel.: +61 8 9347 6429; fax: +61 8 9384 5128. E-mail addresses: [email protected] (B.D. Power), [email protected] (N.C. Stefanis), [email protected] (M. Dragovic), [email protected] (A. Jablensky), [email protected] (D. Castle), [email protected] (V. Morgan). 0920-9964/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.schres.2013.11.003
disorders (Power et al., 2012). Less is known, however, about the impact of amphetamine consumption premorbidly on age at onset of psychosis. We have recently reported a temporal association between age at initiation of cannabis use and age at onset of psychotic illness in 997 participants from the 2010 Australian Survey of High Impact Psychosis (SHIP), with a premorbid exposure to cannabis trend of 7–8 years (Stefanis et al., 2013). In the same large Australian sample of participants with psychotic disorders, we aimed to ascertain how this temporal association is modified, if at all, by age at initiation to amphetamine (AIA). We hypothesized that the consumption of amphetamine in addition to cannabis would exert an additive effect on this temporal association. 2. Experimental/Materials and methods 2.1. Participants Participants were part of the 2010 Survey of High Impact Psychosis (SHIP), which covered seven mental health catchment sites across five Australian States. A two-phase sampling design was utilised (Morgan et al., 2012). In phase 1, all people aged 18–64 living in the catchment sites and in contact with inpatient or community public mental health services, or non-government organisations funded to support people with mental illness were screened for psychosis. In phase 2, the 7955 participants who had screened positive for psychosis in phase 1 were stratified by age and site, and 1825 were randomly selected and interviewed. Participants were ineligible for inclusion in the survey if they had insufficient English, or impaired cognition or communication
B.D. Power et al. / Schizophrenia Research 152 (2014) 300–302
affecting their capacity for informed consent or ability to complete an interview. All participants provided written informed consent; the study was conducted in accordance with the Declaration of Helsinki, and approved by institutional human research ethics committees at each of the seven study sites. 2.2. Measures of diagnoses and substance use Participants were assessed using the Diagnostic Interview for Psychosis (DIP), a standardized semi-structured interview for psychosis (Castle et al., 2006) consisting of the 97 items of the Operational Criteria For Psychosis (OPCRIT) (McGuffin et al., 1991) and utilizing probes derived and adapted from the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry. The OPCRIT diagnostic computer algorithm is used to score the items and classify cases according to ICD-10 or DSM-IV criteria. The criteria applied in this study were ICD10. The DIP also contains a module for enquiring about past substance use, including data on age of first use; the details of this module have been described previously (Stefanis et al., 2013). Participants were designated as substance-users (if they reported daily/almost daily use, use 1–2 days/week, use 2–4 times/month, or use less frequently than once per month) or substance non-users (if they reported no use). A total of 382 participants were designated as amphetamine users.
301
Univariate analysis of variance was used to test for group differences in exposure to amphetamines (time between AIA and AOI). For the entire cohort, the effect of AIA on mean exposure to amphetamines was not significant (F(6,381) = 1.08, p = 0.374), and there was no significant trend observed (F(6,381) = 0.109, p = 0.742). The mean DPEA for the entire SHIP sample was 5.3 (SD = 4.53) years. For the subset of schizophrenia spectrum participants (n = 310), the effect of AIA on mean exposure to amphetamines was not significant (F(6,309) = 0.78, p = 0.31), and again there was no significant trend observed (F(6,309) = 0.009, p = 0.925). The mean DPEA for this subsample was similar, at 5.3 years. For the subset of SHIP participants who used cannabis but did not use amphetamines (n = 630), the mean duration of premorbid exposure to cannabis was 6.87 (SD = 6.34) years. For the subset of schizophrenia spectrum participants who used cannabis but did not use amphetamine (n = 436), the mean duration of premorbid exposure to cannabis was 6.54 (SD = 5.97) years. A paired-samples t-test was conducted to compare mean age of initiation of both cannabis and amphetamines. Comparison showed a significant difference in the mean age of initiation of cannabis (mean = 14.9, SD = 3.2 years) and amphetamines (mean = 18.6, SD = 4.3 years), t(366) = 19.66, r = 0.57, p b 0.001. Fig. 1 shows the time between initiation to drugs (amphetamines vs cannabis) and AOI.
2.3. Definition of age at onset of psychosis
2.4. Statistical analysis Participants were analyzed in seven age groups according to AIA to allow for equal distribution of the sample (ranging from ≤ 15 to 25 + years of age), and mean number of years according to the duration of premorbid exposure to amphetamine (DPEA) was calculated. Univariate General Linear Models were used to test for group differences in AOI and DPEA; analyses were repeated for subsets of the sample, including participants with a schizophrenia-spectrum illness (schizophrenia, schizoaffective disorder, delusional disorder). We then repeated the analyses according to cannabis use (as per Stefanis et al., 2013), but excluded from the analysis those who had used amphetamines (n = 367). We subsequently examined trends in the schizophrenia spectrum sub sample. Finally, a paired-samples t-test was conducted to compare mean age of initiation of cannabis and amphetamines. 3. Results The demographic characteristics of this study sample have been presented previously (Moore et al., 2012; Morgan et al., 2012). Of those who consumed amphetamines prior to onset of illness, almost all had reported also using cannabis (n = 367, or 98.4%). We tested for group differences in AOI between participants in the AIA groups (N = 382); the analysis showed that the effect of AIA prior to onset of illness was significant (F(6,381) = 47.13, p b 0.001), and remained significant after age of participants was used as a covariate (F(7, 381) = 27.39, p b 0.001). This demonstrated that various AIA had distinct AOI. The effect of AIA on AOI also remained significant after family history of schizophrenia or other psychiatric disorders was used as a covariate, (F(8,381) = 26.57, p b 0.001).
4. Discussion When taken together, our findings suggest that the temporal association between age at initiation of cannabis use and age at onset of psychotic illness (with a premorbid exposure to cannabis trend of 7–8 years) (Stefanis et al., 2013) is not modified by amphetamine use. Nonetheless, our findings regarding age at initiation to amphetamine and duration of premorbid exposure to amphetamine in the SHIP cohort require further consideration. For instance, we did observe a direct temporal relationship between age at initiation of amphetamine and age at onset of psychosis. Further, there was a delay of approximately 5 years from initial exposure to amphetamine to the onset of psychosis. Taken on its own, this finding could suggest that the consumption of amphetamine in addition to cannabis may exert an additive toxic effect on individuals on the pathway to developing psychosis, the manifestation of which is delayed for approximately 5 years (regardless of age of initiation). However an alternative and more parsimonious explanation, as supported by our subsequent analysis (e.g., analyzing the subset of SHIP participants who used cannabis but did not use amphetamines), is that the observed association is spurious and better explained by a later initiation to amphetamine than to cannabis (by 2–3 years). Further, numerous other studies have failed to demonstrate an additional effect of polysubstance on age at onset of psychosis (Barnes et al., 2006; Gonzalez-Pinto et al., 2008; Dekker et al., 2012).
Time in years (between initiation to drugs and onset of illness)
AOI was documented to the nearest year, and defined as the earliest age at which medical advice was sought for psychiatric reasons, or at which symptoms began to cause subjective distress or impair functioning. If there were no clear symptoms present to clarify year of onset, or if the participant denied the existence of an illness and no informant was available to provide such data, then age at first hospital admission was used.
10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0
Cannabis Amphetamines
2.0 <=12 13
14
15
16
17
18 19-2122-24 25+
Age of initiation to drugs Fig. 1. Figure showing time between initiation to drugs and onset of illness.
302
B.D. Power et al. / Schizophrenia Research 152 (2014) 300–302
We have, however, recently demonstrated that consumption of illicit substances (such as amphetamine) in addition to cannabis in the 12 months prior to the onset of psychosis is associated with an even earlier age at onset in schizophrenia-spectrum disorders (Power et al., 2012; Stefanis et al., submitted for publication). This might suggest that substances operate via a variety of mechanisms over the life span of the psychotic illness: in the premorbid period, cannabis may influence disease expression in those susceptible individuals, and in the prodromal period, cannabis and other psychotogenic substances may hasten onset of the emerging disease. There are a number of limitations of this study, which include possible recall bias, and the lack of available data on the pattern of substance use of illicit substances until the year prior to illness onset. Further, given the pattern of comorbid use with cannabis, it is not possible to ascertain an independent effect of amphetamine on age at onset of psychosis. Nonetheless, this is one of the largest studies of its kind examining the effects of AIA (in addition to cannabis use) on AOP. Role of funding source The SHIP was funded under contract to the Australian Government Department of Health and Ageing.
Contributors VM, DC and AJ designed the study and wrote the protocol. BP, NS and MD undertook the statistical analysis, and BP wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Conflict of interest The authors have declared that there are no conflicts of interest in relation to the subject of this study.
Acknowledgments SHIP acknowledgement: This publication is based on data collected in the framework of the 2010 Australian National Survey of High Impact Psychosis. The members of the Survey of High Impact Psychosis Study Group are: V. Morgan (National Project Director), A. Jablensky (Chief Scientific Advisor), A. Waterreus (National Project Coordinator), R. Bush, V. Carr, D. Castle, M. Cohen, C. Galletly, C. Harvey, B. Hocking, A. Mackinnon, P. McGorry, J. McGrath, A. Neil, S. Saw, H. Stain. Ethics approvals for the study were obtained from relevant institutional human research ethics committees. The study was funded by the Australian Government Department of Health and Ageing. This report acknowledges the hundreds of mental health professionals who participated in the preparation and conduct of the survey and the many Australians with psychotic disorders who gave their time and whose responses form the basis of this publication.
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