Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2018 Association of polysubstance and non-medical prescription opioid use with alterations in social functioning from a behavioural and psychophysiological perspective Kroll, Sara L Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-152956 Dissertation Published Version Originally published at: Kroll, Sara L. Association of polysubstance and non-medical prescription opioid use with alterations in social functioning from a behavioural and psychophysiological perspective. 2018, University of Zurich, Faculty of Arts. ! ! ! Association!of!polysubstance!and!non2medical! prescription!opioid!use!with!alterations!in!social! functioning!from!a!behavioural!and! psychophysiological!perspective! ! ! ! ! ! ! Thesis!(cumulative!thesis)! ! Presented!to!the!Faculty!of!Arts!and!Social!Sciences! ! of!the!University!of!Zurich! ! for!the!Degree!of!Doctor!of!Philosophy! ! ! ! ! by!Sara!Liane!Kroll! ! ! ! ! Accepted!in!the!Spring!Term!2018! ! on!the!Recommendation!of!the!Doctoral!Committee:! ! Prof.!Dr.!rer.!nat.!Boris!Quednow!(main!advisor)! ! Prof.!Dr.!rer.!nat.!Lutz!Jäncke! ! ! ! ! Zurich,!2018! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! Homo!sum,!humani!nil!a!me!alienum!puto! ! –!Terenz!! (Heautontimorumenos!77)! ! ! ! ! ! ACKNOWLEDGEMENT! ! First!and!foremost,!I!want!to!thank!Prof.!Dr.!Boris!Quednow,!principal!supervisor!of!my!PhD!steering! committee,!for!giving!me!the!opportunity!to!work!autonomously!on!this!interesting!and!challenging! topic.!I!am!grateful!for!his!trust!and!expertise!he!offered!in!the!last!years.!I!would!like!to!extend!my! gratitude!to!Prof.!Dr.!Lutz!Jäncke!for!supporting!my!thesis!and!being!a!member!of!my!PhD!steering! committee.! ! Further,! I! want! to! thank! all! current! and! former! lab! members! and! colleagues! for! their! support,! refreshing!lunch!times,!and!after2lunch!walks!around!the!PUK:!Matthias,!Michi,!Sarah,!both!Monikas! (Näff!and!Visentini),!Bruno,!Anni!as!well!as!Etna!and!Hannes.!Special!thanks!go!to!Tom!and!Lukasz!for! inspiring!and!interesting!discussions!during!the!lunch2walks!and!feeding!the!lambs!especially!in!the! second!year!of!my!PhD.! ! I!am!deeply!thankful!to!all!my!friends!close!by!but!also!abroad!for!supporting!me!the!last!years.!I! want!to!point!out!Lisi!for!nice!dinners!at!home!and!for!interesting!discussions!about!our!PhDs;!Nathi,! Michi,!and!Pascale!for!our!weekly!Jour!Fix!meetings!and!for!taking!my!mind!off!things;!Anna,!Kirstin,! Laura,!Karina,!Juli,!Elli,!and!Nadine!for!their!fabulous!support!by!phone!and!for!being!always!there!for! me.! ! Finally,! I! want! to! thank! my! family.! My! deep! gratitude! goes! to! my! mother! Marita! and! her! unconditional!support!and!belief!in!me!without!any!doubt!since!day!one.!Furthermore,!I!am!deeply! thankful! to! my! love! Max! for! listening! patiently! to! all! my! problems! and! ideas,! for! providing!me!a! shoulder,!when!I!needed!it,!and!for!supporting!my!career!and!me!in!every!respect.! !! ! I ABSTRACT! ! In!recent!years,!polysubstance!use!(PSU)!occurred!more!frequently!than!monosubstance!use!and!also! non2medical! prescription! opioid! use! (NMPOU;! e.g.,! morphine,! oxycodone,! fentanyl,! or! codeine)! provides!a!serious!public!health!concern.!However,!only!few!studies!examined!social!functioning!in! individuals! with! PSU! and! opioid! use! revealing! confounding! factors! and! inconsistent! results.! Social! cognition!such!as!empathy,!theory!of!mind,!or!emotion!perception!is!crucial!for!daily!life!interactions! (e.g.,!social!relationships!or!in!therapist2patient!relationships).!Therefore,!this!thesis!aims!to!clarify! alterations!of!social!functioning!in!individuals!with!stimulant!PSU!and!NMPOU.! ! Part!I!of!the!thesis!addresses!the!question!of!potential!cumulative!effects!of!stimulant!PSU!on!social! functioning.! The! results! show! a! gradual! decrease! of! emotional! empathy! and! social! network! size! related!to!an!increased!number!of!used!substances.! ! Part!II!of!the!thesis!reports!two!studies!assessing!social!functioning!in!individuals!with!NMPOU.!The! findings! posit! distinct! deficits! of! cognitive! empathy! and! emotion! recognition! in! individuals! with! NMPOU!as!well!as!hyperreaction!of!endocrine!stress!parameters!to! social! rejection.! Furthermore,! high!opioid!craver!showed!poorer!emotion!regulation!during!social!exclusion.! ! The! thesis! contributes! to! basic! addiction! research! and! provides! clinical! implications! aiming! to! improve!interventions!as!well!as!therapy!outcome!and!to!reduce!relapse!in!individuals!with!PSU!and! NMPOU.! !! ! II! ZUSAMMENFASSUNG! ! In!den!letzten!Jahren!wurde!vermehrt!ein!Anstieg!des!Konsums!multipler!Substanzen!(PSU)!sowie!des! nicht2medizinischen! Gebrauchs! von! verschreibungspflichtigen! Opioiden!(NMPOU;! z.B.! Morphin,! Oxycodon,! Fentanyl! oder! Codein)! berichtet.! Bis! dato! befassten! sich! wenige! Studien! mit! sozialen! Funktionen! bei! Personen! mit! PSU! und! Opioidkonsum.! Soziale! Kognitionen! wie!Empathie! und! Emotionswahrnehmung! sind! v.a.! bei! alltäglichen! Interaktionen! wichtig! (z.B.! in! sozialen! und! Therapeuten2Patienten2Beziehungen).! Die! vorliegende! Arbeit! soll! deswegen! zu! einem! besseren! Verständnis!der!sozialen!Funktionen!bei!Personen!mit!PSU!und!NMPOU!beitragen.! ! Part!I!der!Arbeit!befasst!sich!mit!kumulierten!Substanzeffekten!bei!Personen!mit!PSU!auf!die!sozialen! Funktionen.!Die!Ergebnisse!zeigen!eine!graduelle!Verschlechterung!der!emotionalen!Empathie!sowie! eine!reduzierte!soziale!Netzwerkgrösse!bei!vermehrtem!Substanzkonsum.! ! ! Part! II! der! Arbeit! berichtet! zwei! Studien,! die! soziale! Funktionen! bei! Personen! mit! NMPOU! untersuchte.! Die! Ergebnisse! zeigen! distinkte! Defizite! in! der! kognitiven! Empathie! und! Emotionserkennung! sowie! eine! Hyperreaktion! endokriner! Stressparameter! auf! sozialen! Ausschluss! bei! Opioidkonsumenten.! Zudem! berichteten! Personen! mit!starkem! Opioidcraving! eine! schlechtere! Emotionsregulation!auf!sozialen!Ausschluss.! ! Diese! Arbeit! dient! der! Grundlagenforschung! und! bietet! klinische! Implikationen! für! verbesserte! Interventionen,!Therapieergebnisse!und!zur!Verhinderung!von!Rückfällen!bei!Personen!mit!PSU!und! NMPOU.! ! III ! CONTENTS! 1.! THEORETICAL!BACKGROUND!..................................................................................!1! 1.1! General!introduction!of!addiction!................................................................................!1! 1.1.1! Polysubstance!use!.....................................................................................................!3! 1.1.2! Non8medical!prescription!opioid!use!........................................................................!4! 1.2! General!introduction!of!social!functioning!...................................................................!6! 1.2.1! Empathy!and!emotion!perception!............................................................................!6! 1.2.2! Social!bonding:!the!Brain!Opioid!Theory!of!Social!Attachment!................................!7! 1.3! Social!functioning!in!substance!users!...........................................................................!9! 1.4.! Study!subjects!............................................................................................................!11! 1.4.1! Sample!of!stimulant!polysubstance!users!...............................................................!11! 1.4.2! Sample!of!non8medical!prescription!opioid!users!...................................................!11! 1.5! Thesis!structure!..........................................................................................................!12! 2.! SOCIO2COGNITIVE!FUNCTIONING!IN!STIMULANT!POLYSUBSTANCE!USERS!.........!14! 2.1! Abstract!......................................................................................................................!14! 2.2! Introduction!................................................................................................................!15! 2.3! Methods!.....................................................................................................................!18! 2.3.1! Recruitment!and!participants!.................................................................................!18! 2.3.2! PSU!sample!.............................................................................................................!18! 2.3.3! Clinical!Assessment!.................................................................................................!19! 2.3.4! Drug!assessment!....................................................................................................!20! 2.3.5! Socio8cognitive!assessment!....................................................................................!21! 2.3.6! Statistical!analysis!..................................................................................................!21! 2.4! Results!........................................................................................................................!23! 2.4.1! Demographic!characteristics!..................................................................................!23! 2.4.2! Socio8cognitive!functioning!....................................................................................!25! 2.4.3! Regression!models!..................................................................................................!27! 2.5!