This action might not be possible to undo. Are you sure you want to continue?
Contents lists available at SciVerse ScienceDirect
journal homepage: www.elsevier.com/locate/schres
Cannabis use and premorbid functioning as predictors of poorer neurocognition in schizophrenia spectrum disorder
P. Andreas Ringen a,⁎, Ingrid Melle a, b, Akiah O. Berg a, b, Ingrid Agartz a, b, c, Olav Spigset d, e, Carmen Simonsen a, Kjetil Sundet a, f, Ole A. Andreassen a, b
KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, N-0424 Oslo, Norway Division of Mental Health and Addiction, Institute for Clinical Medicine, University of Oslo, N-0318 Oslo, Norway Department of Research and Development, Diakonhjemmet Hospital, Box 23, N-0319 Oslo, Norway d Department of Clinical Pharmacology, St. Olav University Hospital, N-7006 Trondheim, Norway e Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, N-7491 Trondheim, Norway f Department of Psychology, University of Oslo, N-0317 Oslo, Norway
a r t i c l e
i n f o
a b s t r a c t
Background: Evidence of associations between neurocognitive function and cannabis use in schizophrenia is inconclusive. However, direct measures of cannabis intake and premorbid function are rarely explored in this context. We investigated the relation between cannabis use, determined by its presence in urine, and neurocognitive functioning in schizophrenia controlling for the potential bias of premorbid functioning. Methods: Naturalistic study of 364 patients with schizophrenia spectrum disorder from catchment areas in Oslo, Norway. Hierarchical multiple regression analyses were used to assess the relationship between cannabis in urine and measures of neurocognitive functioning, with adjustment for confounders, including premorbid functioning. Results: Cannabis was detected in the urine of 21 patients, who had signiﬁcant dysfunction in several neurocognitive domains independent of a current diagnosis of cannabis abuse. However, level of premorbid functioning explained the associations for all measures. Conclusion: Differences in premorbid functioning may explain apparent differences in neurocognitive function between schizophrenia spectrum patients using cannabis or not. The ﬁndings suggest that illness-related traits present early in life can affect both later cannabis use and neurocognition, probably by complex mechanisms. © 2012 Elsevier B.V. All rights reserved.
Article history: Received 23 December 2011 Received in revised form 30 September 2012 Accepted 27 October 2012 Available online 22 November 2012 Keywords: Schizophrenia Cannabis Urine samples Neurocognitive functioning Premorbid functioning
1. Introduction Cannabis is the most prevalent substance of abuse, next to alcohol, in the western world (SAMHSA, 2011), and its use is also common among individuals with psychotic disorders (Green et al., 2007). Substance use is generally related to poorer course and outcome in schizophrenia (Dixon et al., 1991; Linszen et al., 1994; Salyers and Mueser, 2001; Margolese et al., 2004; Lambert et al., 2005; Barak et al., 2008). Longitudinal epidemiological studies have suggested that early exposure to cannabis is related to an increased risk for developing psychosis (Moore et al., 2007), but establishing casual relationships is difﬁcult as reverse causality and interactions with other
⁎ Corresponding author at: KG Jebsen Centre for Psychosis Research - TOP Program, Building 49, Division of Mental Health and Addiction, Oslo University Hospital - Ulleval, Kirkeveien 166, N-0407 Oslo, Norway. Tel.: +47 23 02 73 50; fax: +47 23 02 73 33. E-mail addresses: email@example.com (P.A. Ringen), firstname.lastname@example.org (I. Melle), email@example.com (A.O. Berg), firstname.lastname@example.org (I. Agartz), Olav.Spigset@legemidler.no (O. Spigset), email@example.com (C. Simonsen), firstname.lastname@example.org (K. Sundet), email@example.com (O.A. Andreassen). 0920-9964/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.schres.2012.10.021
environmental and genetic factors cannot be excluded (Minozzi et al., 2010). In experimental studies, the main active constituent of cannabis, Δ9-tetrahydrocannabinol (THC) has been shown to transiently increase symptoms and impair neurocognitive functioning in healthy individuals (D'Souza et al., 2004), with even more pronounced effects in patients with schizophrenia (D'Souza et al., 2005; Morrison et al., 2009). Several cross-sectional clinical studies have, however, found cannabis users with schizophrenia to have less negative symptoms (Dixon et al., 1991; Salyers and Mueser, 2001) and better neurocognitive functioning than non-users (Yucel et al., 2012; Rabin et al., 2011). This apparent inconsistency in ﬁndings may reﬂect the existence of different mechanisms behind associations between cannabis use, symptoms and functional levels in schizophrenia. It is e.g. suggested that schizophrenia patients using cannabis could represent a subgroup with a less severe form of illness (Loberg and Hugdahl, 2009; Yucel et al., 2012). The direct pharmacological effects of THC found in the experimental studies are mediated by cannabinoid receptor activation leading to downstream neuronal changes causing clinical symptoms and cognitive dysfunction (D'Souza et al., 2005). However, the underlying psychopathology of the associations revealed in clinical studies may be other than direct
consecutively selected and thoroughly described sample of patients with schizophrenia from a catchment area based hospital setting. cannabis (and its metabolites) is cleared from urine within a few days after a single intake. and be willing and able to give informed consent.. since schizophrenia is a broad clinical syndrome with a complex etiology and several mutually interacting risk factors. USA) and liquid chromatography-mass spectrometry (LC-MS) (Bagoien et al. Poor premorbid functioning is associated with a more severe course of schizophrenia. to have a DSM-IV diagnosis of schizophrenia. This number represents the available data in the most recent updating of the on-going inclusions in the TOP database in April 2012. subjects with schizophreniform disorder 30 (8. 2009). allowing for a high degree of representativity for participating patients. 2. Patients were recruited consecutively from in. Although the validity of self-reports of illicit drug use is generally reported to be acceptable.8%) of the patients this condition was current (not in full remission).P. 2. and lack of control for susceptibility traits. Ringen et al. psychiatric residents or clinical psychologists)..7%). Prevalence of current abuse/addiction was 38 (10. Investigation of the possible role for susceptibility traits is of special interest.. see Ringen et al. Data on the ﬁrst 364 consecutively recruited patients with valid urine tests and complete data sets on relevant outcome variables are included in the current analyses. occupational status. 57 patients had a lifetime DSM-IV diagnosis of cannabis abuse or addiction (15. 2009). a diagnosis of current abuse or addiction is associated with long-term use and not necessarily with current. Cannabinoids can be easily measured in urine and is a robust evidence of cannabis use. 2) Long-term cannabis intake or poor premorbid function inﬂuence these relationships. and in this period the person may be totally abstinent.77.4.6). failure to account for other types of substance use.2. For details.4%) for stimulants (amphetamines. Assessment of premorbid functioning is therefore of importance in the study of overlapping psychopathological factors leading to cannabis intake and outcome in schizophrenia. Subjects with schizophrenia counted 278 (76. (2008). 1998).. cocaine or ecstasy). duration and individual metabolic factors (Lowe et al.4%). Materials and methods 2. 1982). Full remission is not achieved until after 12 months without fulﬁlling criteria. / Schizophrenia Research 143 (2013) 84–89 85 pharmacological effects. including neurocognition (Ho et al. It may however remain traceable in urine for several weeks after a period of chronic daily exposure. All interviewers participated in regularly diagnostic consensus meetings led by a clinically and scientiﬁcally well experienced supervisor.3. and 43. Exclusion criteria were the presence of a diagnosis of developmental disorder. Furthermore. among others. modules A-E. Overview The study was part of the Thematically Organized Psychosis (TOP) Study. Assessments of diagnosis Diagnosis was established using the Structural Clinical Instrument of Diagnosis for DSM-IV axis I disorders (SCID – I). There were no other treatment organizations serving these areas. The following hypotheses were postulated for the study: 1) Recent cannabis intake as determined by urine analyses is associated with altered cognitive functioning in patients with schizophrenia. The current study aimed at investigating the relationship between objective urine measures of cannabis use. Emphasis was put on recruiting all patients regardless of level of involvement in their respective treatment programs. all raters ﬁnished a training course in SCID assessment based on the training program at the UCLA (Ventura et al.4%) for alcohol and 16 (4. be due to methodological problems. including enzyme immunoassay (CEDIA. see Ringen et al. 2004). type of . covering a catchment area of 485 000 inhabitants. neurocognition and premorbid functioning in a large. Diagnosis of abuse/addiction of any substance was established using the SCID-E module. such as bias in sample recruitment. Fremont..and outpatient psychiatric units.2 years (SD = 9. Assessments of substance use Urine samples for drugs of abuse were collected in the morning the same day as the neuropsychological testing took place. 2011). symptoms and functioning Premorbid functioning was assessed by the Premorbid Adjustment Scale (PAS) (Cannon-Spoor et al. there are several limitations to self-reports compared to objective markers of use (Del Boca and Noll. To be eligible for inclusion in the present part of the study the patients had to be between 18 and 65 years. High scores on the PAS signify poor functioning. patterns of use need some time to evolve in order to cause substantially reduced functioning as required in the criteria. years of education. Thus. However. suboptimal methods for determining cannabis use.. The childhood age intervals were used in order to have a uniform premorbid measure for all participants. PAS scores were divided into premorbid academic and social functioning according to premorbid age intervals (Larsen et al. 2. The reliability of diagnoses has been assessed to be high. with a Kappa value of 0. For further details. Cut-off levels were in the range 20-40 ng/mL for the THC metabolite THC-carboxylic acid (THC-COOH). Deﬁnitions of use thus differ between studies. Recruitment to the current part of the study was carried out from 2004 until 2011 from the three major hospitals in Oslo. and this measure is often used as a susceptibility trait and a proxy for a more severe form of the disorder. The notion that schizophrenia patients using cannabis represent a subgroup with a different severity is difﬁcult to explore.4%). A mere presence of cannabis in urine is therefore not necessarily evidence for a very recent intake of cannabis use.A. The clinical studies have determined cannabis exposure according to self-reported use over a deﬁned level (quantity. Data were collected about ethnicity (European versus not European). or according to ICD or DSM diagnostic criteria. (2008). 2007). schizophreniform disorder or schizoaffective disorder. The diagnostic categories of abuse or addiction in DSM-IV are broad entities. assessment of premorbid functioning could be of help to explore if premorbid factors may be associated with both cannabis use and clinical sub-groups of schizophrenia. Mean age was 31. serious brain damage or not speaking Norwegian. Microgenics Corporation. In addition. duration. 2. depending on dose. frequency.. The TOP study is approved by the Regional Committee for Medical Research Ethics and the Norwegian Data Inspectorate. recency/abstinence).1. including overlapping neurobiological substrates for psychosis and cannabis use. All assessments were conducted by trained clinicians working as research fellows (psychiatrists.1% (N = 157) were female. in 43 (11. In general. 2000). CA. and effects of cannabis exposure on brain maturation (Murray et al. as there is evidence pointing to gene-environment interactions between cannabis and schizophrenia symptoms. marital/civil status. Norway (Ringen et al. Standard methods for the detection of illegal substances in urine were used. For the amphetamines and ecstasy the maximum cut-off level was 500 ng/mL whereas for cocaine it was 150 ng/mL. Assessment of sociodemographic characteristic. 2008). Norway. Information on daily tobacco use was recorded.. The inconsistencies in the literature could also. This recruitment design has shown to give the subjects a high degree of representativity with the general schizophrenia population in the city of Oslo.2%) and subjects with schizoaffective disorder 56 (15.
2. Tests from domains previously found to be sensitive to dysfunction in groups with cannabis use.3.1. Higher scores on the neuropsychological tests signify better performance on all tests except for the D-KEFS interference tests where higher scores signify poorer performance. 2010) in which pairs of numbers are presented on a computer screen.5. Below follows a step-by step description of the procedure. fewer years of education and more often a diagnosis of abuse or addiction. All correlations indicated more negative conditions . Subjects who were positive for cannabis in urine had signiﬁcantly lower premorbid academic functioning. 2. A hierarchical stepwise approach was selected in order to discern the effects of the different variables in the associations. 2. The inter-rater reliability of the symptom assessments in the TOP study have been shown to be good with an Intraclass Coefﬁcient (ICC)(Shrout and Fleiss. range 0-33). General cognitive functioning / Current IQ was assessed with the Wechsler Abbreviated Scale of Intelligence (WASI) (Wechsler. from the Wechsler Adult Intelligence Scale (WAIS-III) (Wechsler. Symptoms and functioning levels are reported here for better description of the sample only and are not intended for testing of hypotheses. Symbols must be ﬁlled in manually in a form according to a number-key. Working memory We used the 2-back version of the Bergen n-back task (Haatveit et al.82 and GAF of 0.5. 2003). Since differences in group sizes were large. 2008).A. all tests are standard tests in validated translations (Simonsen et al.. Gender and age were chosen as a priori independent variables and entered as the ﬁrst step.6. neuropsychological variables and clinical and sociodemographic variables are shown in Table 3.5. 2004) the total number of words repeated immediately after ﬁve reading trials of a list of 16 words was used as a measure of verbal memory (List A). Bivariate associations Pearson correlations were used to assess bivariate associations between cannabis in urine. Domains: 2. Executive functioning / interference control From the third trial in the Color–Word Interference Test. Psychomotor speed The Digit Symbol test from Wechsler Adult Intelligence Scale (WAIS-III) (Wechsler. Verbal memory From the California Verbal Learning Task (CVLT-II) (Delis et al. Evaluation of the effect of possible confounders A series of multiple linear regression analyses was used to evaluate the possible confounders of the signiﬁcant associations in the group comparisons between cannabis in urine and the neurocognitive variables. Results Cannabis was found in the urine in 21 patients (5. One variable without normal distribution (“interference control”) was analyzed with a non-parametrical test and logarithmically transformed to achieve a normal distribution of the values used in correlation and regression analyses. 2.8%).6.86 (Ringen et al.2. Normal distribution for continuous variables was assessed based on histograms and normal probability plots. 2. Signiﬁcant correlations between cannabis in urine.. using the split version of GAF (Pedersen et al.. 2007). 3.6. We used the sensitivity index d-prime to gather information regarding how a participant is able to discriminate targets from non-targets as a measure of working memory.. The score is the number of symbols correctly ﬁlled in within a time limit. Group differences in neuropsychological test results are shown in Table 2. dichotomous variables were analyzed with Chi-square tests/Fisher exact tests when cell counts allowed (> 5).1. Statistical procedures All analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 19. A positive urine test for cannabis was signiﬁcantly associated with poorer scores on measures for digit span forwards (attention). and the participant is instructed to press a key whenever the pair of numbers corresponds to the pair of numbers presented two trials before. Neurocognitive assessment A comprehensive neuropsychological test battery was administered to all participants by trained assessment personnel (psychologists trained by a specialist in clinical neuropsychology). and were entered in the model in separate intermediate steps. d-prime (working memory) and interference control (executive functioning) (Table 2).. part of the Delis Kaplan Executive Functioning System (D-KEFS)(Delis et al. Statistical signiﬁcance was determined using the . The sample size in the cannabis positive group with current use of antipsychotics (n = 16) was too small to analyze differences with regard to type.4. 1979) for PANSS positive symptoms of 0. 2005).. The neurocognitive variables were chosen as dependent variables and cannabis in urine was entered as independent variable in the last step.0.. Group comparisons T-tests were used to compare the cannabis-positive urine and the cannabis-negative urine groups on continuous variables.86 P. The session consists of 100 pairs divided on 20 target pairs and 80 non-target pairs. These measures were recorded within a few weeks from the urine tests and the neuropsychological evaluations (median 12.2.5. All subjects showed adequate neuropsychological test effort as indicated by the forced recognition trial of the California Verbal Learning Task (CVLT-II) (Delis et al. clinical and sociodemographic variables found to be signiﬁcantly associated with cannabis in urine and the neuropsychological test results. 2. premorbid academic functioning and a ﬁnding of amphetamines and/or cocaine in urine. 2. The measures used were the Global Assessment of Functioning Scale (GAF).5. Ringen et al. equal variances were not assumed for the t-tests.6. These variables included a current DSM-IV diagnosis of cannabis abuse and/or addiction. duration of illness and current psychopharmacological medication.05 level and 2-tailed tests of signiﬁcance. 2003) was used as a measure of psychomotor speed. the time taken to name the color of the ink on a list of written color names incongruent with the color of the ink was used to measure interference control. 1987).5 days. 2. 2007) and the Positive and Negative Symptoms Scale (PANSS) (Kay et al. dosage and duration of use (Table 1).. The other independent variables were chosen independently for each dependent variable if signiﬁcantly associated (p b . 2004).5. 2009). bipolar disorder and/or schizophrenia were included.05) with both the dependent variable and the presence of cannabis in urine in the bivariate analyses. the maximum number of digits repeated in the same order as presented was used as a measure of focused attention. Attention With the Digit Span Test (forward version).3. / Schizophrenia Research 143 (2013) 84–89 health care (inpatient or outpatient).5. 2. Group comparisons of demographic and clinical characteristics according to presence of cannabis in urine or not are shown in Table 1.
7 3. increase the risk for substance/cannabis use in line with the self-medication hypothesis.359 .g.2 81. *Variable without normal distribution: median and range (min–max). these associations were no longer statistically signiﬁcant and premorbid functioning was instead highly signiﬁcantly associated with the neuropsychological test results. 2007).3 14.2 N 6 6 13 17 15 3 3 2 10 1 3 16 Positive for cannabis in urine N = 21 N 21 18 19 19 19 20 17 19 20 20 21 Mean 28.5 10. Both mechanisms related to brain maturation and direct pharmacological effects may still be involved (Murray et al. equal variances not assumed. the d-prime test and the interference control test (Table 4a). However.5 SD 9.3 4..1 1. Adding independent t-tests. amphetamine.9 86.5 8.8 5.. but gives limitations to statistical power and reduced possibilities to explore subgroups within our sample. verbal learning. Mann–Whitney U-test.7 7. However. Such deﬁcits could. . the results obtained after entering premorbid functioning in the regressions might also be cases of statistical interference. Rabin et al. which in turn could affect neurocognition. where reported use of cannabis is found to be associated with better functioning and less symptoms (Yucel et al.. 3 Cocaine.05).8 14. Table 2 Neuropsychological measures in 364 patients with schizophrenia according to cannabis in urine or not. In this view.7 1. Discussion The main ﬁnding of the present study was that presence of cannabis in urine was not associated with levels of neurocognitive functioning after adjusting for premorbid functioning.0 12. as none of the previous studies controlled for premorbid functioning.4 1..3 76.6 2. in turn.3 9.4 1. through an interaction with perceived stress..4 5.465 . The cross-sectional design does not enable conclusions about cause and effect. a more severe form of the disorder could independently lead to both higher risks of an extensive cannabis intake and of poorer cognitive outcome. 2005).6 4.9 Positive for cannabis in urine N = 21 N 21 21 16 21 21 Mean 55.0 71. They however differ from group comparisons of clinical studies with cannabis use deﬁned by interview.1 2.135 .091 87 while cannabis in urine no longer had a signiﬁcant contribution to any of these measures (Table 4b). The current results are difﬁcult to compare directly with previous ﬁndings.7 2.1 1.5 p .7 98.611 . our ﬁndings do not support a direct effect of cannabis on neurocognitive measures. Due to the high association between premorbid functioning and current cannabis use.2 2.954 .1 2. Differences in study populations.4 0. and Fisher exact tests (levels of signiﬁcance below the 0.9 15.001 ⁎ ⁎ .6 2. 2 Wechsler Abbreviated Scale of Intelligence.6 72.7 16. / Schizophrenia Research 143 (2013) 84–89 Table 1 Demographic and clinical characteristics of 364 patients with schizophrenia spectrum disorder according to a ﬁnding of cannabis in urine or not.6 2. 2005). methamphetamine or ecstasy. Full IQ.3 SD 21.4 p 0.491 .05 level in bold).2 6. list A 341 343 273 342 343 Mean 56. ⁎ Too small numbers in cells for Fisher tests. The ﬁrst series of hierarchical multiple regression analyses indicated that ﬁnding cannabis in urine contributed signiﬁcantly to the variance in current levels of the Digit Span forward test.1 7. signiﬁcant differences in bold (p values ≤ 0. and hence also differences in the representation of possible sub-groups. The comparisons between the urine cannabis positive and negative groups are in line with previous reports from experimental studies showing that intake of cannabis causes transient clinical deterioration (D'Souza et al.3 5.2 73..0 17.126 t-tests.4 14. It could also be that poor premorbid functioning in schizophrenia represents a more serious form of the disorder.0 48.2 36-321 16.2 5.4 3. and it could be that we are dealing with different co-existent clinical sub-groups.0 1. it is of interest that cannabis in urine explained the association between a diagnosis of cannabis abuse or addiction and neurocognition in the analyses. The current study has some limitations.006 . A possible alternative interpretation could be that poor premorbid functioning in schizophrenia instead was associated with increased vulnerability for adverse effects of cannabis on neurocognition.5 9.P.584 ⁎ ⁎ ⁎ b . Negative for cannabis in urine N = 343 N Age (years) Premorbid academic functioning1 Premorbid social functioning1 Age of onset of psychosis Duration of untreated psychosis (years) Age of onset of cannabis use Number of psychotic episodes Duration of illness Number of alcohol units consumed past 14 days Years of education Full IQ 2 N Female Ethnic non-European Education in Norway Outpatients Schizophrenia Schizophreniform disorder Schizoaffective disorder Alcohol abuse (current) Cannabis abuse (current) Stimulant3 abuse (current) Stimulants3 in urine Current use of antipsychotics 151 60 254 252 263 27 53 36 33 15 3 296 343 307 311 335 322 313 154 337 339 339 336 Mean 31. 4 subtests. The small sample size of the cannabis-positive group is a result of the naturalistic design.3 11.3 1. Thus. Alternatively.0 1. 4.6 61.8 81.104 . as the underlying mechanisms of cannabis use and psychosis are not known.2 SD 7.5 17.0 72.6 4. The results of the hierarchical multiple regression analyses controlling for the variables with signiﬁcant bivariate associations to cannabis in urine are shown in Tables 4a–4b. in a model for comorbidity by Chamber and colleagues (Chambers et al.1 1.3 6.990 .0 18. This would be an interpretation in accordance with the ﬁndings of pharmacological effects of THC on neurocognition as reported by D'Souza and colleagues (D'Souza et al.7 76. this turned out to have a statistically highly signiﬁcant contribution.9 % 28.4 7.7 2. after introducing premorbid functioning in the regression models.5 47. and several were statistically signiﬁcant associated with cannabis in urine also after controlling for a current diagnosis of cannabis abuse and/or addiction. in the group with cannabis in urine.182 . when adding premorbid academic functioning to the model in the second series of regression analyses. including neurocognitive deﬁcits.4 4. 2001).821 . 2012.9 2. We found nominally poorer scores for every neurocognitive measure in the cannabis positive group.A.2 16.5 % 44. as suggested e.3 24.0 42.6 12. 1 Premorbid assessment of functioning (PAS).910 0. These interpretations are somewhat in opposition to the previously discussed hypothesis that cannabis-using patients represent a subgroup with a less severe form of the disorder. but do neither rule this out.1 SD 15.7 1.2 7. However.3 1.6 24.015 0. 2011).7 1.2 5.031 0. Several neurocognitive measures correlated signiﬁcantly with the same background variables as cannabis in urine (Table 3). Negative for cannabis in urine N= 345 N Digit Symbol Coding Digit Span forward Working memory.194 p .014 .095 . Ringen et al.3 91. none of the parameters related to severity of the course of illness showed any association with cannabis in urine in the current study. d prime Interference control* CVLT. This is intriguing. might account for some of the differences of the current ﬁndings compared to earlier studies.010 0. There may be several explanations to the current ﬁndings.669 .6 31. Poor premorbid functioning could be a susceptibility trait for later cannabis use.8 34-197 10.4 18.
011 − .032 dependency 3 .727 THC-COOH in urine 12.A. sociodemographic factors and neuropsychological variables in 364 patients with schizophrenia spectrum disorder.220 Executive functioning.314 − .050 urine 3.093 − 1.000 − .664 Age Female gender 2 .142 − .152 .271 .286 Cannabis abuse/ .237 − .245 − .119 − .589 . Block model summary for each step Block No. Variable R2 Change Contribution of separate variables for last step t P value 95% CI of B lower 5.182 .838 .044 . Interference control Constant … … 50.926 Age .970 .208 − .119 − 2. Only signiﬁcant associations shown (p values ≤ 0.198 − 3.352 .058 − 1.107 − .450 .025 7. However.270 Executive functioning.136 .010 3.255 .035 4. / Schizophrenia Research 143 (2013) 84–89 Table 3 Bivariate correlations (Pearson's R) between substance use. cannabidiol.028 Working memory.170 urine 3.044 4.222 .013 3.305 Contribution of separate variables for last step t P 95% CI of B value lower upper 24.242 − .311 − .029 − .011 Stimulants in urine 3 . variables to the regression model reduces power and increases risk for type II errors.130 .752 24.404 . Premorbid: Premorbid academic functioning (PAS).004 1.163 − 2.017 2 .146 − .006 1.014 .006 − 1.495 − .026 .000 .105 1.517 .009 − .607 .569 .288 .069 4.035 2.123 − 2. Digit span forward Constant … 1 .899 − .537 Cannabis abuse/ dependency 3 .843 3.824 . i.536 Cannabis abuse/ dependency 3 . N-back/d-prime Constant … … 1 .083 Age Female gender 2 .284 − .672 .053 − 1.155 − .000 1 . 2010).058 − 1.000 − .051 Premorbid functioning 4 .132 − . d prime Interference control* Verbal learning. comparison Table 4b Results of regressions controlling for premorbid functioning.008 − .289 − . Cannabis in urine Cannabis in urine Digit Symbol Coding Digit Span forward Working memory.772 − . Block model summary for each step Block No.014 .980 . Interference control Constant … … 58. *log-transformed.031 .021 − .927 − .115 . The urine measurement can be used to determine intake by very high degree of certainty. Variable R2 F Beta Change Change forward … … .002 ..05).000 − .865 − .786 Premorbid .328 − 1.254 .000 1 .270 .013 5.375 .233 .023 7.000 − .005 − .685 .237 .880 THC-COOH in .691 . However.021 6.080 − 1.008 . Although we have argued that the study sample has a high degree of representativity.019 − . but lack speciﬁc information concerning the time passed since the intake took place and the amount of cannabis consumed.010 dependency 3 .380 .146 2.006 .898 − .274 − .166 . as our ﬁndings are based on comparisons of patients with cannabis in urine or not from the same region.900 Cannabis abuse/ .277 .092 − 1.033 Premorbid functioning 4 .892 .090 Working memory.003 THC-COOH in urine … .164 − . which is suggested to have antipsychotic properties (Bhattacharyya et al.306 − .017 .058 − .002 .959 4.033 9.181 Attention.138 − .266 − .037 − .227 − 3.025 7.543 − . Cannabis in urine: THC-COOH in urine.g.841 − .711 .714 .064 5.032 5.171 . the general representativity of the sample may be discussed as we cannot rule out any speciﬁc regional bias in the Oslo region.121 .071 − 1.127 − 2.711 upper 6.148 2 .028 THC-COOH in urine 12.038 − .123 2. .129 .: DSM-IV Diagnosis of cannabis abuse or addiction.008 − .462 .115 .047 − .202 17.184 − . the sensitivity and speciﬁcity are considered adequate for the scope of this paper and as long as the main ﬁndings are based on relative results.128 Age Female gender Ethnicity Premorbid .005 Age Female gender 2 .098 − 1.251 .814 .460 .848 .008 − .028 4.243 − .091 .005 Female gender − .200 .169 − 2.888 .245 − .000 − . CVLT list A X − .770 .88 P.961 .231 − . The measurements also lack information of other constituents of the cannabis than THC as e.151 .579 − .397 3.001 − . Cannabis abuse/dep.842 .145 3.002 − .364 F Beta Change Table 4a Results of regressions without controlling for premorbid functioning.232 .010 4.078 1. we argue that it is highly unlikely that there are some geographical factors that speciﬁcally interact with this effect.212 − .184 − . Ringen et al.027 10.024 4.001 . The urine measurements were performed at different labs and with different methods.224 − .010 Age .099 − .012 functioning 4 THC-COOH in .007 .000 1.136 − .e.124 Pearson correlation coefﬁcients.216 Cannabis abuse/dep.034 − .053 − . N-back/d-prime Constant … … 1 .017 − .366 .009 .158 2.140 2.159 − .028 − 1.064 − 1.222 − 3.934 − . Digit span Constant 1 Age Female gender 2 Stimulants in urine 3 THC-COOH in urine Attention.780 .092 − .005 Female gender − .140 2.177 Stimulants in urine .246 − .264 6.980 .229 .016 .285 − .
. The positive and negative syndrome scale (PANSS) for schizophrenia. Bull. 470–484. Gueorguieva.. R. Wood. D. Shaner. Friis... B. Y. Ringen's work is funded by the Division of Mental Health and Addiction. Moore. Bull.. Bhattacharyya. Opler. Ringen has served as a consultant for Eli Lilly and received speakers' honoraria from Lundbeck. Norway. Differences in prevalence and patterns of substance use in schizophrenia and bipolar disorder. L. Weiser. O' Carroll..A.. J. T. Spigset and Sundet contributed to the design of the study. 885–895. M. Schizophr.H. M.D. U. Hagtvet. Simonsen. Clin. Res. Malchy. psychosis. Tunstall. K... Psychiatry 164.F. Opjordsmoen. 2001. S. E. Am. Krystal..D. S. Psychiatry Res. Acta Psychiatr. Stone. M. Kramer. Barak. Wechsler Abbreviated Scale of Intelligence (WASI).R. Fusar-Poli..V.. T.. S.A. Chambers. Cadet. E. R... J.A.. 109–123.. McGorry. Greenﬁeld.. Melle.E. Baruch. 1998. J.. Furthermore.. A. Cooper.J.V. Andreassen.. Jonsdottir.. bi-Saab. Margolese. psychopathology. Johannessen.D. D. S. S.. Soto... 2005. Bull. Scand. premorbid functioning was controlled for. Wade. L... T.. Psychiatr. D. B. Takagi. Barnes. 316–330..I. P.. Measurement of premorbid adjustment in chronic schizophrenia. .. Pantelis. Lingford-Hughes. important bias is unlikely.. Psychiatry 48. Fornito.O. 112. Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition. C.. P.. Melle. Schizophr. Hugdahl. Green. Biol. Z. D.. L. 163–173... Engh. Kapur. McGuire.. Forselius-Bielen. Lenior.C. Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deﬁcits in schizophrenia. 273–279. 2004. L.A. A.F. Psychopharmacol. D.. M..M. We found that an apparent association with recent cannabis intake and poorer neurocognition was explained by the level of premorbid academic functioning. Crippa. Cannabis. 105. T. 2008.H. A. 8.J. Neuropsychol..H. Psychiatry 155. Gueorguieva. S. Rabin. J... George. A.A. 66–75... mood and cognitive functioning. Ringen. 167153 and 164778/V50) and South-East Norway Health Authority (No. Zakzanis. D.J. Engh. Del Boca. Oslo University Hospital. S. Res. Self.T. Shaw. Macdougall. Sweeney. 42. Brewer..A.. Mintz. Harary. 2004. Birkenaes. E.C. Social functioning. Psychol.A. 2012. Role of funding source The funding sources had no involvement in the authors' work.. Larsen. 71–83.K.. 2009. F..H. J.. The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample. Wechsler... Pearson Assessment... Loberg. T.. Naber. K. J.. Exp. Potkin. Schizophr.J..C. Neurosci.. 73–83. 248–254. 2001. Neuropsychopharmacology 29. P. Schizophr. Simonsen and Spigset designed the study..H... 2007) have previously been shown to be valid in this patient group. Sundet.A. J. Suicide attempts of schizophrenia patients: A case-controlled study in tertiary care... Negrete.. P.D... Schizophr. N.. GSK.M. Herning.. Yuen.. O... A.. J.C. Addiction 95 (Suppl. Dingemans..R..K.L. Morrison. P. Neurosci. G..D. Opposite effects of delta-9tetrahydrocannabinol and cannabidiol on human brain function and psychopathology.D. More studies of cannabis use in representative patient samples from different regions and preferably with a longitudinal perspective are warranted to clarify the underlying mechanisms of the current ﬁndings. 39.K. Andreassen..E. S. A... G. Bora. Vaskinn. R. F. 13. Stockholm. Drug Alcohol Rev. P. Atakan.H... Haatveit. D. Lowe. 1991. 111–116. Dr. R. S. P. / Schizophrenia Research 143 (2013) 84–89 89 between patients with positive and negative urine. Faerden.G. Ringen et al. Pearson Assessment.K. R.. 97... Melle.. G. Melle and Ringen did the statistical analysis. P. 304–317. P. R. A neurobiological basis for substance abuse comorbidity in schizophrenia. To the best of our knowledge this is the ﬁrst study to assess the association between cannabis in urine and neurocognitive variables in a naturalistic clinical sample of patients with schizophrenia. Solowij. 420–428.M. Melle. 2010. Lancet 370. The impact of substance use disorders on clinical outcome in 643 patients with ﬁrst-episode psychosis. R.. 157–166. Simonsen. W. Cooper. 2008. 108–115. Drug Alcohol Depend.. Fiszbein. 1979. Front. S. Nat. Ringen. Minozzi.... T. Delis.P. Melle and Andreassen wrote the ﬁrst draft of the manuscript.. 3.. 2009. Fleiss. P.. however both self-reports of substance use (Weiss et al. 29.. V... Noordsy. Stockholm. Friis. B. Rockville (MD).. Shrout.. Jonsdottir. 37 (1).. Haahr. A... Morrison. Cotton. 2005. K..L. Compr. 261–276. N. Birkenaes. A. 1998) and PAS data (Brill et al. T. Amato.. Reichenberg. Murray. C. S. Ammerman. Bull. L.US Department of Health and Mental Services. A. 2011.A. O.. Schizophr. 2004. Dixon.. V..T..L. 2004..A. P.147787... Acknowledgements The study is part of the Thematically Organized Psychosis (TOP) study and has been funded by grants from the Research Council of Norway (No.E. 1982.. S. 594–608. S. Psychiatry 51. Arch.. Linszen. All authors contributed to and have approved the ﬁnal manuscript. An overview of systematic reviews on cannabis and psychosis: discussing apparently conﬂicting results. Psychol... 2007. E. Andreassen. 2007. Wassink. Haas. P. 2007. The validity of several of the neuropsychological tests is associated with the language skills of the subjects. Achiron. H... the mind and society: the hash realities. B. Abraham. 2011. Y. Holt. A.. 128.. D'Souza. Extended urinary [Delta]9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure. D. Opjordsmoen. R.E. J. Lundbeck. Sundet. Martin-Santos. 141–148. J.A.. 24–32. Ringen. and Ringen... Yucel. Allen. Perry.A.. Gen. Opjordsmoen. Norwegian manual supplement. O. J. J. Br. 2005.. Am. Ziebell. M.A. Accuracy of self-reported premorbid functioning in schizophrenia. 38 (9). Drug and alcohol use among patients with schizophrenia and related psychoses: levels and consequences. D. M..M. R. Pearson Assessment. S. Ober. E. Kaplan. Res.. S. Gill. K..P. 2011. Delis. C. 2000. Brill. Zahlsen.A. Conus. Contributors Agartz. D.P. Schizophr. S. Cannabis use and cognition in schizophrenia.. 1998. Kaplan. Zuardi.. Borgwardt. C. Hugdahl.B. Kramer. 1987. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis.T. 103–108. C. A.M. J.R. Mueser. Frances. Schimmelmann. Cannabis abuse and the course of recent-onset schizophrenic disorders. Lubman.M. Drake. J.. 2007.M. G. Kay. K. E. References Bagoien. 822–826... I. 1241–1249. R... Schizophr.M. J. Berg. 1–10.. D. R.J. Murray. Bull. Tempier. Wechsler Adult Intelligence Scale.B. Weiden. 319–328. M. 764–774. J. Ventura..H. McKeown... The Delis-Kaplan Executive Function System (DKEFS). A. and addiction. M.. W. M. Rabinowitz. A. Murray. Seal. Psychiatry 148. Am.. Res.. T... Perucci. M. Davidson. Larsen. Norwegian manual supplement.123/2004). 8. P. McGorry.W.. (12-10-2011).. Vecchi. We did not ﬁnd cannabis to be associated with any beneﬁcial factors. Stockholm. Ringen.. 67. P. Y. Wechsler. P..M. Madonick. Vaglum.M. Mehta.I. Bargagli.C.. E. R... S. Doersch. Friis. G. Validity of substance use self-reports in dually diagnosed outpatients.M... Stockholm. P. Karterud. I. Melle. J. Janssen and BMS. T. Brunette. Nosarti. T. Ofﬁce of Applied Studies (OAS). J.. D'Souza. Conﬂicts of interest Dr. 224–230. Psychiatry 50. Salyers.. Noll. Braley. Truth or consequences: the validity of self-report data in health services research on addictions. Psychol.. N. Rev. F..W.. A. Giampietro.. Schizophrenia and cooccurring substance use disorder. Psychiatry 57.. Biol. J.K. Psychiatry 185. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. P.A. Nesvag.D. Res.. USA .. Aamo.... Zois. Krystal. Kapur.. Krystal. Melle.. Lagerberg.P. second edition (CVLT-II). M. 2009. Hum.. 2010. 1558–1572.G. Evaluation of a urine on-site drugs of abuse screening test in patients admitted to a psychiatric emergency unit. G.. T. Schizophr. I.. 48. third edition (WAIS-III). 2003. This suggests the presence of clinical sub-groups and complex and overlapping multifactorial psychopathological mechanisms. 53. Davoli. Aizenberg. D. although the current tests have been selected to minimize this kind of unwanted bias. Substance Abuse and Mental Health Services Administration (SAMHSA). D. L. S. 3). M. Morken.I.. Najavits.... Med. Jones. Rund. 88–94. N. Reports on speciﬁc drugs. S.F.... 2010. Clin. Darwin. R. K. Andreasen.. Pearson Assessment.. 2007. J.. Henquet..W.B. H. J. 1607–1616.M. D. Training and quality assurance with the Structured Clinical Interview for DSM-IV (SCID-I/P). J... Powell. Intraclass correlations: uses in assessing rater reliability. The effects of cannabis use on neurocognition in schizophrenia: A meta-analysis.K. Med. S.. H. J. Generalizability studies of the Global Assessment of Functioning-Split version. Oslo. S347–S360.. The validity of d prime as a working memory index: results from the "Bergen n-back task"..F. D. The other authors report no competing interests. Dr.. California Verbal Learning Test. Historic variables are based on retrospective self-reports and are thus less reliable than would have been the case with a longitudinal study... A. 2009. Norwegian manual supplement. Y. Wyner. 29. J. Lubin.. Liberman.B.. J. A. R. 79. M. K. D. Andreassen. Di. Premorbid adjustment in ﬁrstepisode non-affective psychosis: distinct patterns of pre-onset course. I.. Green.R. Wu. J... Wyatt. Cannon-Spoor..C.. 127–128... 2007. S. B. G. Weiss.A... Huestis. Winton-Brown.A. K. Neuropsychopharmacology 35. Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group.. Andreassen.. T. M. G. R. McGlashan.. Drug abuse in schizophrenic patients: clinical correlates and reasons for use.. Pedersen. Ueland. Res.. K. Lambert.. J. Burke. O. 2011.. 402–408. The funding sources had no involvement in the authors' work.J. 1994.. Moritz. D. Ho. Braley.. H. Lewis.A. T.. SAMHSA. H.A. Norwegian manual supplement. Ringen managed the literature searches. Faerden. W. C.H. T. Morrison. K. Zammit.D. 128.. R. The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis. and medication side effects in relation to substance use and abuse in schizophrenia. Lee. Andreassen has received speakers honoraria from Eli Lilly. S. 86. Spigset. Lubman... Conus. S.C. 38 (2)..
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue listening from where you left off, or restart the preview.