NNF Årsmøtekonferanse

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1 U N I V E R S I T Y O F B E R G E N Department of Biological and Medical Psychology Cannabis use in non-affective psychoses: Relationship to age at onset, cognitive functioning and social cognition NNF Årsmøtekonferanse

2 High vulnerability (e.g. COMTVal/Val) Disrupted neurodevelopmental processes Ongoing cannabis use Schizophrenia like psychosis Poor outcome Low vulnerability (e.g. COMTVal/Val) Early initiation/lifelong cannabis use Early AO Normal cognition +symptoms - symptoms Subclinical «symptoms» CU stops Good outcome Good outcome Asymptomatic Pathway to psychosis in early initiated lifelong cannabis users

3 How to study vulnerability in non-affective psychosis Family history of psychosis Cognition Social cognition Endophenotype quantitative trait like deficits Cannabis use is considered an environmental factor that can increase the risk for developing a psychotic disorder Recent use of cannabis/life-time use

4 Cannabis THC and CBD often work in opposition THC delta-(9)-tetrahydrocannabinol Euphoria Anxiety Psychosis Transient cognitive impairment Hunger Recreational drug users ~70 cannabinoids CBD cannabidiol No euphoria Anti-anxiety Anti-psychotic No cognitive deficits Drug companies D'Souza, D. C., et al. (2005) Delta-9-tetrahydrocannabinol effects in schizophrenia: implications for cognition, psychosis, and addiction. Biological Psychiatry 57, Freeman, T. P., & Winstock, A. R. (2015). Examining the profile of high-potency cannabis and its association with severity of cannabis dependence. Psychological Medicine, 45(15),

5 Cannabis use in non-affective psychoses: Relationship to age at onset, cognitive functioning and social cognition Academic unit Helle, S., Gjestad, R., Johnsen, E., Kroken, R. A., Jørgensen, H. A., Løberg, E.-M. (2014). Cognitive changes in patients with acute phase psychosis- Effects of illicit drug use. Psychiatry Research, 220(3), doi: /j.psychres Helle, S., Ringen, P. A., Melle, I., Larsen, T. K., Gjestad, R., Johnsen, E., Lagerberg, T. V., Andreassen, O. A., Kroken, R. A., Joa, I, Hegelstad, W.T.V., Løberg, E.-M. (2016). Cannabis use is associated with 3 years earlier onset of schizophrenia spectrum disorder in a naturalistic, multisite sample (N=1119). Schizophrenia Research,170, (1), doi: /j.schres Helle, S., Løberg, E-M, Gjestad, R., Lysaker, P. (submitted). The positive link between neurocognition and cannabis use is not explained by superior social cognition. Journal of the International Neuropsychological Society

6 Recruitment from different research sites Bergen Psychosis Project ( ) Study 1 The Thematically Organized Psychosis ( ), Oslo Early Treatment and Intervention in Psychosis ( ), Stavanger Bergen Psychosis Project 2 ( ) Neurocognition of Schizophrenia ( ), Bergen Study 2 Metacognition study ( ), Indiana Study 3

7 Paper 1

8 Some of the most frequently used illicit substances, cannabis and stimulants, may induce transient positive psychotic symptoms and cognitive alterations Illicit drug use may have a more temporary influence on cognition, generating a short-term cognitive and psychotic breakdown

9 Aim: to compare cognitive changes in patients with non-affective psychosis with and without illicit drug use after an acute psychotic episode Hypothesis: non-affective psychosis with illicit drug use would show more cognitive improvement from time of admission to a psychiatric emergency ward to time of discharge from the acute ward or after 6 weeks at the latest

10 Admission 4-6 weeks Discharge n=123 n= 67 The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) The Positive and Negative Syndrome Scale (PANSS)

11 Substance use at baseline cannabis; n = 31 (all) Lifetime cannabis use from clinical records Urine samples stimulants; n = 6 stimulants, sedatives, hypnotica, anxiolytica; n = 3 stimulants and opiates; n = 2 stimulants, sedatives, hypnotica, anxiolytica, opiates; n = 1

12 Mean (SD) Demographic, clinical and cognitive characteristics BASELINE Drugn= 92 Drug+ n=31 FOLLOW-UP Drugn=52 Drug+ n=15 Men % 62.0 % 83.9 % * 63.4 % 81.2 % Age (12.82) (6.11)* (13.40) 25.80(5.66)*** Education (years) Medication (DDD) PANSS (3.10) (2.86) (2.97) (3.50) 1.16 (0.56).94 (0.47) Positive scale (3.92) (5.38) (4.32) (4.47) Negative scale (7.39) (8.67) (6.38) (7.27) Gen. psychopath (6.05) (7.19) (7.03) (3.02) Total (12.36) (16.29) (15.20) (9.58) RBANS total (9.98) (8.81) (7.45) (8.68) Significant at the p <.0.05 level, ** p < 0.00

13 Cognition Academic unit Change in cognition Time (Group x Age interaction: b = -0.29, P < 0.05).

14 Summary, study 1 As hypothesized, the psychosis group with illicit drug use showed the largest increase in performance on the global measure of cognitive functioning from baseline to follow-up, especially among the youngest patients in this group.

15 Paper 2

16 The main aims of this study were to: 1) examine the relationship between substance use and age at onset, in addition to the influence of possible confounders, in schizophrenia spectrum disorders, 2) examine the effect of specific substance use, such as cannabis, stimulants, cocaine, opiates and hallucinogens, on this relationship.

17 Substance use Interviews lifetime use of substance Urine samples Clinical Drug Use Scale (DUS) and Clinical Alcohol Use Scale (AUS)

18 Significant at the * p <.0.05 level, ** p < 0.00 Mean (SD) Demographic and clinical characteristics 492 (44.4%) 627 (56.0%) ** Men % 263 (53.5%) 425 (67.8%) ** Family history of psychosis Abstinent group n (%) Substance group n (%) 91 (20.7%) 101 (17.3%) Age 32.3 (11.2) 28.3 (8.3) ** Education (years) 12.9 (3.0) 12.0 (2.6) ** Age at onset 25.9 (9.7) 23.0 (7.1) ** PANSS Positive scale 15.6 (5.5) 15.9 (5.3) Negative scale 15.1 (6.3) 15.6 (6.4) Gen. psychopath (8.3) 32.5 (8.2) * Total 62.4 (16.4) 64.2 (16.4)

19 Results Bivariate analysis showed that the Substance group had an earlier mean age at onset (M = 23.0; SD 7.1) compared to the Abstinent group, 25.9 (SD 9.7). Thus, the patients with substance use had a 2.9 year earlier onset than the patients without substance use

20 Paper 3 The positive link between neurocognition and cannabis use is not explained by superior social cognition Siri Hellea,b*, Else-Marie Løberga,c,d, Rolf Gjestada, Paul H. Lysakere,f,

21 The aims of the study replicate the previous relationship between neurocognitive functioning and a longer duration of cannabis use in patients with schizophrenia test whether social cognition explains the potential relationship between duration of cannabis use and neurocognition

22 Delis-Kaplan Executive Function System (D-KEFS) Delis, Kaplan & Kramer, 2000 Clark et al. (2010): inhibition/set shifting and mental flexibility by using D-KEFS in patients with schizophrenia Mental flexibility: the ability to form and reform ideas about how different stimuli can be related to one another in a goal directed manner Word Context Test (total consecutively correct scaled score), Sorting Test Condition 1 (confirmed correct sorts scaled score), Twenty Questions Test (total weighted achievement scaled score), Proverb Test Condition 1 (total achievement free inquiry scaled score)

23 Theory of Mind: Eyes Test Hinting Test Social cognition measures Affect recognition: Bell-Lysaker Emotion Recognition Task (BLERT)

24 Mean (SD) Demographic clinical characteristics N = 87 Item n (%) Men % 75 (86.2%) Mean (SD) Age (8.34) Education (years) (1.72) Age at first hospitalization PANSS (12.21) Positive sub-scale (4.42) Negative sub-scale (5.55) Excitement sub-scale 7.67 (2.50) Depressive sub-scale (3.97) Cognitive sub-scale (4.43)

25 N = 87 Lifetime substance use (months): Alcohol (152.20) Cannabis (99.36) Cocaine (61.05) Hallucinogens 8.29 (46.67) Amphetamine 2.31 (9.19) Heroin 1.51 (5.77) Methadone 1.01 (5.88) Opiate (other) 1.06 (6.01) Sedatives (other) 0.91 (5.75) Barbiturates 0.51 (2.46)

26 Bivariate (one-tailed) significant correlations between measures of executive functioning, social cognition and substance use Academic unit Item Cogn: Flex 2. Cogn: Inhibition 3. Social Cogn: Hinting 4. Social Cogn : Affect Recogn 5. Social Cogn: Eyes 6. Cannabis Use 7. Illicit Substance Use 1,591**,424**,578**,379**,220* 1,341**,453**,404** 1,384**,260*,190* 1,494** 1,193* 1,454**,372** 1 8. Alcohol Use *p<.05, **p<

27 Results Academic unit The Structural model of the direct and indirect relations between predictor variables and the cannabis outcome variable Cannabis use was significantly and positively related to Mental Flexibility and negatively related to BLERT (audio-visual affect recognition task designed to evaluate a person s ability to discriminate between seven affect states Social cognition).

28 Summary of findings Study 1: The psychosis group with illicit drug use showed the largest increase in performance on the global measure of cognitive functioning from baseline to follow-up, especially among the youngest patients in this group. Study 2: Use of cannabis was associated with a 3 years earlier age at onset of psychotic symptoms. No other illegal substance was related to earlier age at onset Study 3: Better neurocognition, i.e. a higher mental flexibility score, was related to longer duration of cannabis use, when adjusting for social cognition measures.

29 Thank you for attention! Academic unit