title: Serum concentrations of mood stabilizers are associated with memory, but not other cognitive domains in psychosis spectrum disorders; explorative analyses in a naturalistic setting.
abstract: BACKGROUND
  Mood stabilizers like lithium and anticonvulsants are used in bipolar and related psychotic disorders. There is a lack of knowledge of the relationship of these medications and cognition in the psychosis spectrum. We studied the association between serum concentration of mood stabilizers and cognitive performance in a well-characterized sample of bipolar and schizophrenia spectrum disorders.
  
  
  METHODS
  Serum concentrations of valproate, lamotrigine, and lithium were analyzed for associations to performance on neuropsychological tests in six cognitive domains in individuals with bipolar disorder (n = 167) and in a combined sample of individuals with bipolar or schizophrenia spectrum disorders (n = 217). Linear regression with adjustments for gender, age, and symptom levels of depression, mania, and psychosis were applied for the association analyses.
  
  
  RESULTS
  There were negative associations between serum levels of valproate and short term delayed recall (bipolar: p = 0.043; combined: p = 0.044) and working memory (bipolar: p = 0.043). A positive association was suggested between serum level of lithium and working memory (bipolar: p = 0.039). There were no other significant relationships between serum levels of valproate, lamotrigine, or lithium and neuropsychological test performance in neither the bipolar disorder nor the combined group.
  
  
  CONCLUSIONS
  Serum levels of mood stabilizers were unrelated to cognitive performance in most domains, indicating that higher dose does not lead to broader cognitive impairments in bipolar and related psychotic disorder patients. However, worsened memory with increasing levels of valproate suggests cautious dosing of anticonvulsants, while increasing lithium level seems to be associated with improved memory. The findings should be interpreted with caution due to the explorative, naturalistic design.
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. n.e.steen@medisin.uio.no.|Drammen District Psychiatric Center, Clinic of Mental Health and Addiction, Vestre Viken Hospital Trust, 3004, Drammen, Norway. n.e.steen@medisin.uio.no.
authors.forename: Nils Eiel
authors.identifier: http://orcid.org/0000-0001-6442-1179
authors.initials: NE
authors.lastname: Steen
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Monica
authors.initials: M
authors.lastname: Aas
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Carmen
authors.initials: C
authors.lastname: Simonsen
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Dieset
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Lovisenberg Diakonale Hospital, Oslo, Norway.
authors.forename: Martin
authors.initials: M
authors.lastname: Tesli
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Mari
authors.initials: M
authors.lastname: Nerhus
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Erlend
authors.initials: E
authors.lastname: Gardsjord
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ragni
authors.initials: R
authors.lastname: Mørch
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Anja
authors.initials: A
authors.lastname: Vaskinn
authors.affiliation: Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.|Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Olav
authors.initials: O
authors.lastname: Spigset
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
keywords: Bipolar disorder; Cognition; Mood stabilizers; Neuropsychological test; Psychosis; Schizophrenia