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  • 1. Andreou, Dimitrios
    et al.
    Saetre, Peter
    Werge, Thomas
    Andreassen, Ole A.
    Agartz, Ingrid
    Sedvall, Göran C.
    Hall, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
    Terenius, Lars
    Jonsson, Erik G.
    d-amino acid oxidase activator gene (DAOA) variation affects cerebrospinal fluid homovanillic acid concentrations in healthy Caucasians2012In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491, Vol. 262, no 7, p. 549-556Article in journal (Refereed)
    Abstract [en]

    The d-amino acid oxidase activator (DAOA) protein regulates the function of d-amino oxidase (DAO), an enzyme that catalyzes the oxidative deamination of d-3,4-dihydroxyphenylalanine (D-DOPA) and d-serine. D-DOPA is converted to l-3,4-DOPA, a precursor of dopamine, whereas d-serine participates in glutamatergic transmission. We hypothesized that DAOA polymorphisms are associated with dopamine, serotonin and noradrenaline turnover in the human brain. Four single-nucleotide polymorphisms, previously reported to be associated with schizophrenia, were genotyped. Cerebrospinal fluid (CSF) samples were drawn by lumbar puncture, and the concentrations of the major dopamine metabolite homovanillic acid (HVA), the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the major noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured. Two of the investigated polymorphisms, rs3918342 and rs1421292, were significantly associated with CSF HVA concentrations. Rs3918342 was found to be nominally associated with CSF 5-HIAA concentrations. None of the polymorphisms were significantly associated with MHPG concentrations. Our results indicate that DAOA gene variation affects dopamine turnover in healthy individuals, suggesting that disturbed dopamine turnover is a possible mechanism behind the observed associations between genetic variation in DAOA and behavioral phenotypes in humans.

  • 2.
    Edvinsson, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Six-Year Outcome in Subjects Diagnosed with Attention-Deficit/Hyperactivity Disorder as Adults2018In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491, Vol. 268, no 4, p. 337-347Article in journal (Refereed)
    Abstract [en]

    There are very few studies on the long-term outcome in subjects diagnosed with ADHD as adults. The objective of the present study was to assess this and relate the outcome to whether there was current medication or not and to other potential predictors of favourable outcome. A prospective clinical cohort of adults diagnosed with ADHD according to DSM-IV criteria was followed-up on an average of 6 years after first evaluation (n = 124; mean age 42 years, 51% males). ADHD symptom trajectories were assessed as well as medication, global functioning, disability, health-related quality of life, and alcohol and drug consumption at follow-up. Ninety percent of those diagnosed were initially treated pharmacologically and half of them discontinued treatment. One-third reported remission, defined as not fulfilling any ADHD subtype and a GAF-value last year ≥ 70, which was not affected by comorbidity at baseline. Current medication was not associated with remission. Subjects evaluated and first diagnosed with ADHD as adults are functionally improved at follow-up 6 years later despite a high percentage of psychiatric comorbidity at baseline. Half dropped out of medication, and there was no difference in ADHD remission between subjects with on-going medication at follow-up or subjects without medication, although current medication was related to a higher degree of self-reported global improvement.

  • 3.
    Isaksson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Grigorenko, Elena L
    Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.; Moscow MV Lomonosov State Univ, Moscow, Russia.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Af Klinteberg, Britt
    Stockholm Univ, Stockholm, Sweden.; Karolinska Inst, Stockholm, Sweden.
    Koposov, Roman A
    Univ Tromso, Tromso, Norway.
    Ruchkin, Vladislav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.; Sater Forens Psychiat Clin, Sater, Sweden.
    Exploring possible association between DβH genotype (C1021T), early onset of conduct disorder and psychopathic traits in juvenile delinquents.2016In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491, Vol. 266, no 8, p. 771-773Article in journal (Refereed)
    Abstract [en]

    Early onset of conduct disorder (CD) with callous-unemotional traits has been linked to low levels of dopamine β-hydroxylase (DβH), an enzyme involved in dopamine turnover. The C1021T polymorphism in the DβH gene is a major quantitative-trait locus, regulating the level of DβH. In this study of juvenile delinquents from Northern Russia (n = 180), the polymorphism at -1021 was associated neither with early-onset CD nor with psychopathic traits. Association was found between psychopathic traits and early-onset CD, ADHD and mania.

  • 4.
    Jansson, Lennart
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Sonnander, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Wiesel, Frits-Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Needs assessed by psychiatric health care and social services in a defined cohort of clients with mental disabilities2005In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491, Vol. 255, no 1, p. 57-64Article in journal (Refereed)
    Abstract [en]

    Background The identification of needs forsupport and service in clients with long-term mentaldisabilities is usually not done by staff personnel fromboth psychiatric care and social services.However, sucha process is probably necessary in order to provide adequatepsychiatric care and social services. Aims To estimatethe prevalence of mentally disabled clients and investigatewhether staff from psychiatric care and socialservices identified the same individuals and the samenumber of needs in the same areas. Methods Clientsfrom a defined catchment area were identified during athree-month period. A questionnaire was developed tocollect socio-demographic information and to assessneeds for support and service. Results The study identified1,290 clients with needs with a prevalence of5.72/1000 inhabitants. More than half of the clientsneeded support in activities of daily living. Only 18.1%of the clients were identified by both organizations. Ingeneral, the staff from psychiatric care and social servicesidentified the same needs at a group level. However,at the individual level, agreement was quite low.Conclusions The staffs from both psychiatric care andsocial services are necessary to evaluate the needs ofsupport and services in clients with mental disabilities.

  • 5.
    Persson, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Szalisznyo, Krisztina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Antoni, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fällmar, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Zora, Hatice
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study2019In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491Article in journal (Refereed)
    Abstract [en]

    Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.

  • 6.
    Pissiota, Anna
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fernandez, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Psychiatry, University hospital.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Psychiatry, University hospital.
    Fischer, Håkan
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Neurofunctional correlates of posttraumatic stress disorder: a PET symptom provocation study2002In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491, Vol. 252, no 2, p. 68-75Article in journal (Refereed)
    Abstract [en]

    SUMMARY: Patients with combat-related posttraumatic stress disorder (PTSD) show altered cognitive and affective processing and symptomatic responding following exposure to trauma reminders. Previous symptom provocation studies using brain imaging have involved Vietnam veterans. In this study neural correlates were investigated in patients with PTSD resulting from trauma in more recent war zones. (15)Oxygen water and positron emission tomography were used to measure regional cerebral blood flow (rCBF) in patients with war- and combat-related chronic PTSD during exposure to combat and neutral sounds. Self-reports and heart rate confirmed symptomatic responding during traumatic stimulation. The war-related condition, as compared to the neutral, increased rCBF in the right sensorimotor areas (Brodmann areas 4/6), extending into the primary sensory cortex (areas 1/2/3), and the cerebellar vermis. RCBF also increased in the right amygdala and in the periaqueductal gray matter adjacent to the pons. During provocation rCBF was lowered in the right retrosplenial cortex (areas 26/29/30 extending into area 23). Symptom provocation in PTSD promote sensorimotor, amygdaloid and midbrain activation. We conclude that perceptually induced symptom activation in PTSD is associated with an emotionally determined motor preparation and propose that subcortically initiated rather than cortically controlled memory mechanisms determine this pattern.

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