Elsevier

Schizophrenia Research

Volume 199, September 2018, Pages 313-318
Schizophrenia Research

Similar psychotic and cognitive profile between ketamine dependence with persistent psychosis and schizophrenia

https://doi.org/10.1016/j.schres.2018.02.049Get rights and content

Abstract

Background

Ketamine has been used to probe the biology of psychosis and cognitive dysfunction in humans. High levels of ketamine abuse are associated with persisting psychosis (KPP) in a minority of users. However, relatively little is known about cognitive function among KPP patients and whether the cognitive impairments associated with KPP resemble those of schizophrenia (SZ).

Methods

We recruited 149 treatment-seeking patients, including nonpsychotic ketamine users (KNP, n = 51), KPP (n = 23), and SZ (n = 75) patients. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychopathology and the Cogstate Brief Battery to assess cognitive function including psychomotor processing speed, attention, working memory, verbal and visual learning and memory, spatial problem solving, and social-emotional cognition.

Results

Ketamine-dependent patients had an extensive history of ketamine use (average duration = 7.1 ± 4.2 years, average consumption = 3.8 ± 2.7 g per day). Although KPP patients used relatively less average ketamine daily dose than KNP patients, KPP patients exhibited significantly greater total PANSS score and subscale scores, while these scores in KPP and SZ patients did not differ significantly. After adjusting for demographic characteristics and antipsychotic dose, KPP and SZ patients showed impairments in spatial problem solving and verbal memory compared to KNP patients, but KPP and SZ patients did not significantly differ from each other.

Conclusion

These data suggest that the symptom profile and cognitive impairments associated with persisting psychosis due to chronic heavy ketamine abuse resemble those of schizophrenia, while KNP patients showed significantly less severe symptom profile and cognitive impairment than KPP and SZ.

Introduction

Ketamine hydrochloride, an uncompetitive N-methyl-d-aspartate glutamate (NMDA) receptor antagonist, is a short-acting general anesthetic for human and veterinary use (White et al., 1982). Recreational ketamine abuse rates increased significantly in many areas of the world over the past two decades (Dillon et al., 2003; Kalsi et al., 2011), particularly in East and South-East Asia (Howland et al., 2011; Joe Laidler, 2005).

Similarity between the cognitive and behavioral effects of ketamine in animals and humans and the signs and symptoms of schizophrenia (SZ) in humans, suggested that abnormalities in NMDA receptor function might contribute to the biology of schizophrenia (Abi-Saab et al., 1998; Javitt et al., 2012; Krystal et al., 2003; Lahti et al., 2001). Among people who chronically abuse ketamine, persisting mild delusional ideation (Morgan et al., 2009, Morgan et al., 2010), sensory disturbances, and other subthreshold psychotic symptoms (Fine and Finestone, 1973; Stone et al., 2014; Tang et al., 2015) are common. Approximately 3% of ketamine abusers develop psychotic symptoms that persist far beyond the period of intoxication, i.e., beyond two hours following drug administration (Abi-Saab et al., 1998; Adler et al., 1998; Kleinloog et al., 2015; Krystal et al., 1994; Liang et al., 2015; Zhang et al., 2014). In individuals with persisting ketamine-induced psychosis to an even greater extent than healthy individuals receiving a single dose of ketamine, their symptom factor structure was similar to that of SZ (Xu et al., 2015).

Cognitive impairments may be an important part of ketamine associated persisting psychosis (KPP). In SZ, independent of its association with psychosis, cognitive dysfunction is an important contributor of functional impairment. Both acute subanesthetic ketamine and individuals recently abstinent from chronic ketamine abuse are associated with cognitive impairments associated with schizophrenia (Morgan and Curran, 2006). Chronic ketamine abusers exhibit semantic and episodic memory impairment (Fletcher and Honey, 2006; Morgan et al., 2004). Ketamine abstainers also had worse performance for verbal fluency than non-ketamine users, but better than current users in source memory task and pattern recognition memory (Morgan et al., 2010). However, cognitive function in KPP has not been well-characterized.

The purpose of the current study was to characterize cognitive function in relation to psychosis symptoms in KPP as compared to non-psychotic ketamine users (KNP) and to SZ. In so doing, this study attempted to determine whether the propensity for psychosis among ketamine abusers was associated with greater cognitive impairments. It also attempted to further explore the similarities between KPP and SZ in relation to hypotheses related to the role of NMDA receptor dysfunction in symptoms and cognitive impairments in these two conditions.

Section snippets

Participants

We recruited treatment-seeking ketamine-dependent inpatients who were admitted to the Department of Addiction Sciences, Taipei City Psychiatric Center (TCPC), Taipei City Hospital and Chang-Gung Memorial Hospital in Taiwan for a detoxification and abstinence treatment program. Patients with SZ were recruited from the inpatient unit of TCPC. The project was approved by the Institutional Review Boards from above hospitals (IRB No TCHIRB-1020529) and the Human Research Protection Program at Yale

Participant description

As shown in Table 1, compared to SZ patients, both KNP and KPP groups were younger and had a lower proportion of female participants. Age of onset of ketamine use did not differ between KNP and KPP groups. The years of education were comparable across the three groups.

The ketamine-dependent patients in this study had abused ketamine chronically (7.1 ± 4.2 years of use) and heavily (3.8 ± 2.7 g and 8.0 ± 6.8 g respectively for average and maximum daily dose). The frequency of ketamine use was 26.1 ± 8.8 

Discussion

The purpose of this study was to determine whether the persisting psychotic symptoms associated with ketamine abuse are associated with cognitive impairments. The principal findings of the current study are: 1) chronic heavy ketamine abusers with persistent psychotic symptoms beyond ketamine discontinuation (KPP) had more severe impairment of verbal memory and spatial problem-solving than those without persistent psychosis (KNP); 2) schizophrenia (SZ) was associated with more severe cognitive

Conflicts of interest

None.

Contributors

Ming-Chyi Huang and Ke Xu designed the study and wrote the protocol. Wan-Ju Cheng and Ming-Chyi Huang were responsible for the bulk of literature review and wrote the first draft of the manuscript. Wan-Ju Chen was responsible for the statistical analysis. Chun-Hsin Chen provided statistical consultancy. Ke Xu, Robert Pietrzak, and John Krystal contributed to data interpretation, discussion, and revision of the manuscript. Chun-Hsin Chen, Chih-Ken Chen, and Ming-Chyi Huang recruited the

Role of the funding source

The funding sources had no involvement in the study design, collection, analysis and interpretation of data, writing of the report or the decision to submit the article for publication.

Acknowledgement

This project is funded by the National Science Council (NSC102-2314-B-182-007), Ministry of Science and Technology (MOST103-2628-B-532-001-MY3, 106-2314-B-532-005-MY3), Taipei City Government (TCH105-01-62-040, 106-01-62-018, and 107-01-62-029), Chang-Gung Memorial Hospital, Keelung (CMRPG2D0261), Taiwan. The work is partially supported by the grant K12 DA000167 from National Institute on Drug Abuse, US, and APA/Merck Early Academic Career Award, US. The authors thank CogState (//www.cogstate.com

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