Khat use and occurrence of psychotic symptoms in the general male population in Southwestern Ethiopia: evidence for sensitization by traumatic experiences
Authors: Kristina Adorjan, Michael Odenwald, Marina Widmann, Markos Tesfaye, Fasil Tessema, Stefan Toennes, Sultan Suleman, Sergi Papiol, Matiwos Soboka, Zeleke Mekonnen, Brigitte Rockstroh, Marcella Rietschel, Oliver Pogarell, Ezra Susser, Thomas G. Schulze
Journal: World Psychiatry (2017)

Khat trees are native to East Africa and the Arabian peninsula. Their leaves contain amphetamine-like alkaloids such as cathinone, cathine and norephedrine, and are chewed for their stimulating and euphorigenic effects1. Khat use varies by season: in the dry season, there is limited availability and market prices are high; in the rainy season, the opposite is true. Excessive use is associated with dependence and khat-induced psychosis2. In collaboration with the Gilgel Gibe Field Research Center of Jimma University, in Southwestern Ethiopia, we studied khat use and khat-induced psychotic symptoms in 1,100 men aged 18 to 40 years (mean 28.4 ± 6.6), randomly selected from the center's population registry. Trained raters interviewed participants at two subsequent time points, i.e. during the dry season (T1; N=853) and during the rainy season, nine months later (T2; N=695). They explored khat use during the past 7 days using the Timeline Followback Method Assessment. Psychotic symptoms experienced during the past 6 months were assessed by four items from the Composite International Diagnostic Interview (CIDI) selected on the basis of previous studies3. Khat-induced psychotic symptoms were defined as being present during or up to 6 hours after consumption and assessed with supplementary questions3. Potentially traumatic experiences (e.g., assault or life-threatening injury) during the period up to T1 or since T1 were explored by an adapted version of the Life Events Checklist for DSM-5 (LEC-5)4. A cut-off of four experiences was fixed by median split. Urine samples were collected to analyze khat alkaloids through immunoassay tests for amphetamine. Khat use in the past 7 days was reported by 599 individuals (70.2%) at T1, and 565 (81.3%) at T2. The 6-month prevalence of khat-induced psychotic symptoms was 7.9% at T1 and 12.8% at T2. At T2, we found 225 individuals with a positive immunoassay test. In these subjects, the rate of khat-induced psychotic symptoms was 26.6% among those with a history of four or more past traumatic experiences (N=124) and 14.0% among those with a history of less than four of those experiences (N=121) (p=0.015). This result could not be explained by higher khat use among the high trauma group (p>0.081 for all use indicators in the last 7 days among people with high vs. low trauma load). We also observed that recent trauma exposure was associated with elevated presence of khat-induced psychotic symptoms in individuals with low trauma exposure during the period up to T1 (with recent trauma: 28%; without recent trauma: 12%; p=0.009). Among individuals with high trauma exposure during that period, additional recent trauma did not have this effect (with recent trauma: 25%; without recent trauma: 26%; p=0.933). Our findings suggest that, in the general male population of an African country, traumatic experiences can sensitize to the effects of a psychomimetic substance. This is in line with the behavioral sensitization paradigm, which suggests that repeated administration of amphetamines or exposure to stress can cause sensitization of dopamine neurons and consequently a higher dopamine release in response to subsequent stress or amphetamine, which facilitates the development of psychotic symptoms5-7. Kristina Adorjan1-3, Michael Odenwald4,5, Marina Widmann4,5, Markos Tesfaye6, Fasil Tessema6, Stefan Toennes7, Sultan Suleman6, Sergi Papiol1, Matiwos Soboka6, Zeleke Mekonnen6, Brigitte Rockstroh4,5, Marcella Rietschel8, Oliver Pogarell2, Ezra Susser9,10, Thomas G. Schulze1 1Institute of Psychiatric Phenomics and Genomics, Medical Center of University of Munich, Munich, Germany; 2Department of Psychiatry and Psychotherapy, Medical Center of University of Munich, Munich, Germany; 3Center for International Health, University of Munich, Munich, Germany; 4University of Konstanz, Konstanz, Germany; 5vivo international e.V., Germany; 6Jimma University, Jimma, Ethiopia; 7Goethe University, Frankfurt am Main, Germany; 8Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany; 9Mailman School of Public Health, Columbia University, New York, NY, USA; 10New York State Psychiatric Institute, New York, NY, USA The authors acknowledge support by the Dr. Lisa Oehler Foundation, Kassel, Germany. The first two as well as the last two authors contributed equally to this work.