Heroin; Diacetylmorphine; Functional magnetic resonance imaging (fMRI); Stress; Heroin dependence; Personality disorder; functional magnetic resonance imagin
Andre Schmidt Niklaus Denier Undine Lang Stefan Borgwardt Marc Walter (2015), Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution, in Transl Psychiatry
, 24(5), 533.
Schmidt André Walter Marc ... Borgwardt S (2015), Normalizing effect of heroin maintenance treatment on stress-induced brain connectivity, in Brain
, 138(1), 217-228.
Marc Walter (2015), Orbitofrontal response to drug-related stimuli after heroin administration., in Addiction Biology
, 20(3), 570-579.
Andre Schmidt Marc Walter (2014), Altered prefrontal connectivity after acute heroin administration during cognitive control, in The International Journal of Neuropsychopharmacology
, 17(9), 1375-1385.
Marc Walter (2013), Acute effects of intravenous diacetylmorphine on the hypothalamic-pituitary-adrenal axis response, in J Clin Psychopharmacol
, 33(2), 193-198.
Denier Niklaus, Schmidt André, Gerber Hana, Riecher-Rössler Anita, Wiesbeck Gerhard, Huber Christian, Lang Undine E, Radue Ernst-Wilhelm, Walter Marc, Borgwardt Stefan (2013), Association of frontal gray matter volume and cerebral perfusion in heroin addiction: a multimodal neuroimaging study., in Front. Psychiatry
Schmidt André, Walter Marc, Gerber Hana, Schmid Otto, Smieskova Renata, Bendfeldt Kerstin, Wiesbeck Gerhard A., Riecher-Rössler Anita, Lang Undine E., Rubia Katya, McGuire Philip, Borgwardt Stefan (2013), Inferior Frontal Cortex Modulation with an Acute Dose of Heroin During Cognitive Control, in Neuropsychopharmacology
, 38(11), 2231-2239.
Denier Niklaus, Gerber Hana, Vogel Marc, Klarhöfer Markus, Riecher-Rössler Anita, Wiesbeck Gerhard A, Lang Undine E, Borgwardt Stefan, Walter Marc (2013), Reduction in cerebral perfusion after heroin administration: a resting state arterial spin labeling study, in PLoS One
Gerber Hana, Borgwardt Stefan J., Schmid Otto, Gerhard Urs, Joechle Wolfgang, Riecher- Rössler Anita, Wiesbeck Gerhard A, Walter Marc (2012), The impact of diacetylmorphine on hypothalamic-pituitary-adrenal axis activity and heroin craving in heroin dependence, in European Addiction Research
, 18(3), 116-123.
Gerber Hana, Borgwardt Stefan J., Gerhard Urs, Riecher-Rössler Anita, Wiesbeck Gerhard A., Walter Marc (2011), Stress und Stressreaktivität bei der Opioidabhängigkeit – ein Überblick, in Schweizer Archiv für Neurologie und Psychiatrie
, 162(6), 239-245.
Walter Marc, Wiesbeck Gerhard A., Riecher-Rössler Anita, Borgwardt Stefan J. (2010), Neural effects of heroin – relation to anxiety stress, in Progress in Neuro-Psychopharmacology & Biological Psychiatry
, 34(5), 816-817.
Blum Julia, Gerber Hana, Gerhard Urs, Schmid Otto, Petitjean Sylvie, Riecher-Rössler Anita, Wiesbeck Gerhard A., Borgwardt Stefan J., Walter Marc, Acute effects of heroin on emotions in heroin-dependent patients, in American Journal on Addictions
Schmidt André, Borgwardt Stefan, Gerber Hana, Wiesbeck Gerhard A, Schmid Otto, Riecher-Rössler Anita, Smieskova Renata, Lang Undine E, Walter Marc, Acute Effects of Heroin on Negative Emotional Processing: Relation of Amygdala Activity and Stress-Related Responses, in Biol Psychiatry
Seifert C Walter Marc, Reduced volume of the nucleus accumbens in heroin addiction., in Eur Arch Psychiatry Clin Neurosci
1. SummaryBackground: Heroin dependence (HD) is a chronic relapsing brain disorder that is defined by a compulsion to seek and use heroin, and a loss of control in limiting intake. Stress is a key factor for relapse in heroin-dependent patients. The prescription of diacetylmorphine (heroin) itself for maintenance has become an established treatment in several European countries. However, the neurobiological effects of diacetylmorphine (DAM) on brain function and stress response have not been studied so far. Imaging the acute effects of DAM administration during stress stimuli would elucidate the neurocircuitry and neurobiology of substance use in patients with HD. Working hypothesis: We expect that DAM attenuates the engagement of brain regions involved in response inhibition (prefrontal and anterior cingulate cortex), emotional processing (amygdala) and working memory (frontal and mediotemporal cortex). Additionally, we hypothesize that DAM reduces stress response (cortisol, heart rate, skin conductance) to emotional and cognitive stimuli, especially in patients with HD and concomitant borderline personality disorder traits. Specific aims: To investigate the effect of DAM on brain using functional magnetic resonance imaging (fMRI), coupled with measurements of cortisol concentrations and neurophysiological stress parameters during the presentation of emotional and cognitive stimuli in patients with HD. Methods: Thirty heroin-dependent patients on stable heroin maintenance will be examined in a randomized placebo-controlled crossover design. They will be compared with 30 heroin-dependent age- and gender-matched but otherwise healthy volunteers receiving saline. The heroin-dependent patients will administer either their individual dose of prescribed DAM dose or saline through an indwelling intravenous line. Afterwards they will complete four experimental paradigms testing response inhibition, emotional processing and working memory while brain responses are measured with fMRI. Before and after the fMRI investigation cortisol samples, DAM blood levels, neurophysiological and psychological stress parameters, such as skin conductance, heart rate, anxiety, anger, and heroin craving will be measured. Expected value of the proposed project: DAM effects on brain function and stress will advance our understanding of the mechanisms underlying HD. It is the first neuroimaging study investigating the neural basis of HD after intravenous DAM administration in humans. Determining the neurofunctional and neurophysiological basis of heroin dependence may facilitate clinical diagnosis and improve clinical interventions such as prevention and treatment.