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  • 1.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Psykoser hos äldre2009Inngår i: Incitament, ISSN 1103-503x, nr 2Artikkel i tidsskrift (Fagfellevurdert)
  • 2.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Schizofreni2011Inngår i: Kognitiv medicin / [ed] Lars-Olof Wahlund, Christer Nilsson, Anders Wallin, Stockholm: Norstedts Förlag, 2011, 1Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 3.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Äldrepsykiatri2012Inngår i: Psykisk hälsa, ISSN 0033-3212, nr 1Artikkel i tidsskrift (Fagfellevurdert)
  • 4.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Äldrepsykiatri - eftersatt trots att behoven finns.2008Inngår i: Primärvårdens nyheter, ISSN 1400-2906, nr 6/7Artikkel i tidsskrift (Fagfellevurdert)
  • 5.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Äldrepsykiatri: en bristvara2012Inngår i: Äldre i centrum, ISSN 1401-5110, nr 1Artikkel i tidsskrift (Fagfellevurdert)
  • 6.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Äldrepsykiatri: en nödvändighet i framtidens sjukvård2013Inngår i: Äldre i centrum, ISSN 1401-5110, nr 4Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Alafuzoff, I
    Carlsson, A
    Eriksson, K
    Ericson, E
    Gottfries, C G
    Marcusson, J O
    Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease.1990Inngår i: European Neurology, ISSN 0014-3022, E-ISSN 1421-9913, Vol. 30, nr 4, s. 181-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30-40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR-12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites.

  • 8.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Danielsson, M
    Papworth, K
    Marcusson, J O
    [3H]GBR-12935 binding to human cerebral cortex is not to dopamine uptake sites.1994Inngår i: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 62, nr 1, s. 338-41Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The binding of the dopamine uptake inhibitor [3H]GBR-12935 to 16 regions of the human brain was investigated in competition experiments with increasing concentrations of GBR-12909, mazindol, and dopamine. The methodology used included a relatively high tissue concentration (8 mg/ml) and addition of 5 mM KCl in the assay buffer. GBR-12909 inhibited 80-90% of the binding in most regions, whereas dopamine only inhibited the binding in the striatum. Mazindol inhibited only part of the cortical binding at concentrations of > 1 microM, whereas the inhibition in the caudate and the putamen also contained a high-affinity component representing the dopamine uptake site. It is concluded that the [3H]GBR-12935 binding sensitive to GBR-12909 cannot be regarded as specific binding to the dopamine uptake site because the displaceable binding most likely is not related to the dopamine uptake site.

  • 9.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Englund, E
    Marcusson, J
    Reduced number of caudate nucleus dopamine uptake sites in vascular dementia.1999Inngår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 10, nr 2, s. 77-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dopamine (DA) uptake sites in the caudate nucleus were studied in patients with vascular dementia (VAD) and in a control group using the presynaptic DA uptake site marker [3H][2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane] as radioligand. There was a significant decrease in the number of DA uptake sites in the VAD group, while the binding affinity was unchanged. The present results indicate that in the patients investigated, the cerebrovascular disease process involves dopaminergic neuron terminals in the caudate nucleus. Our findings are discussed in relation to the reductions in number of DA uptake sites that have previously been revealed in Alzheimer's and Parkinson's diseases.

  • 10.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Englund, Elisabet
    Marcusson, Jan
    Caudate nucleus dopamine d(2) receptors in vascular dementia.2002Inngår i: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 14, nr 1, s. 22-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Caudate nucleus dopamine (DA) D(2) receptors were studied in patients with vascular dementia (VaD) and in a control group using [(3)H]raclopride as a radioligand. There was no significant difference in the number of DA D(2) receptors in the VaD group as compared with controls. The binding affinity was significantly lower in the VaD group. When the VaD group was subdivided into subjects with or without neuroleptic treatment, there were no differences in the numbers of receptors as compared with controls, and the significant differences in binding affinity remained for both VaD subgroups. The present results are discussed with reference to the previous finding of a reduced density of caudate nucleus DA uptake sites in the same VaD group and to results from studies on DA D(2) receptors in Alzheimer's disease and Parkinson's disease.

  • 11.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eriksson, K
    Ross, S B
    Marcusson, J O
    [3H]GBR-12935 binding to dopamine uptake sites in rat striatum.1990Inngår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 23, nr 4, s. 177-81Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The binding of the selective dopamine uptake inhibitor [3H]GBR-12935 to rat striatum was studied. Competition by mazindol and dopamine against [3H]GBR-12935 binding revealed monophasic binding curves. The addition of 100 microM dopamine to the mazindol competition inhibited only 80% of the binding, indicating more than one [3H]GBR-12935 binding site in rat striatum. When a binding fraction that could be discriminated by 1 microM mazindol or 1 mM dopamine was defined as specific binding, a single site binding model was obtained. The [3H]GBR-12935 binding was of protein nature, since it was abolished after protease treatment. Drug inhibition studies with the addition of low concentrations of mazindol and dopamine resulted in alterations in apparent Kd values only, suggesting competitive inhibition by these compounds against [3H]GBR-12935 binding. It is concluded that the [3H]GBR-12935 binding to rat striatum discriminated by 1 microM mazindol reflects binding to the substrate recognition site for the dopamine uptake.

  • 12.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eriksson, K
    Ross, S B
    Marcusson, J O
    Unaltered [3H]GBR-12935 binding after chronic treatment with dopamine active drugs.1990Inngår i: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 102, nr 3, s. 291-4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rats were injected intraperitoneally with haloperidol 0.5 mg/kg, raclopride 1 mg/kg, bromocriptine 2.5 mg/kg, d-amphetamine 2.5 mg/kg, or cocaine 10 mg/kg twice daily for 21 days. The animals were sacrificed 72 h after last injection. Control rats were injected with saline, following the same schedule. The radioligand [3H]GBR-12935 was used as a presynaptic marker for dopamine neurites. There were no significant differences in [3H]GBR-12935 binding to striatum between drug-treated rats and controls.

  • 13.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Gram, Lars
    Timdahl, Kristina
    Behnke, Kirsten
    Hanson, Martin
    Søgaard, Jesper
    Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram.2004Inngår i: International Journal of Geriatric Psychiatry, ISSN 0885-6230, E-ISSN 1099-1166, Vol. 19, nr 12, s. 1123-30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The objectives of the study were to compare efficacy and tolerability of venlafaxine ER 75-150 mg/day with that of citalopram 10-20 mg/day in elderly patients with major depression according to DSM-IV criteria. METHODS: A randomised, double-blind, parallel group 6-month study. Efficacy was assessed by MADRS, CGI Global Improvement, CGI Severity of Illness and GDS-20 scores and safety by physical examinations, vital signs, adverse events and UKU side effect rating. Plasma levels of venlafaxine, its major metabolite O-desmethylvenlafaxine and citalopram were followed. RESULTS: One hundred and fifty-one male and female patients (64-89 years) were enrolled and 118 patients completed the study. Comparable improvements in MADRS, CGI Severity of Illness, CGI Global Improvement and GDS-20 were observed during venlafaxine and citalopram treatment. The MADRS remission rate was 19% for venlafaxine and 23% for citalopram. Side effects were common during both treatments but differed in tremor being more common during citalopram and nausea/vomiting during venlafaxine treatment. There were no clinically significant changes in blood pressure or body weight. CONCLUSION: The observed benefits of venlafaxine treatment in elderly patients with major depression were similar to those observed in younger adults as were reported adverse events and side effects. Treatment with venlafaxine ER was well tolerated and induced beneficial effects of similar magnitude as those of citalopram.

  • 14.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Gustafson, Lars
    Karlsson, Ingvar
    Björkstén, Karin Sparring
    Geriatric psychiatry in Sweden must be developed--not dismantled: New investigation shows depressing results2009Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, nr 1-2, s. 36-9Artikkel i tidsskrift (Fagfellevurdert)
  • 15.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Marcusson, J O
    Age-correlated loss of dopamine uptake sites labeled with [3H]GBR-12935 in human putamen.1989Inngår i: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 10, nr 6, s. 661-4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The effects of age (19-100 years) upon dopamine uptake sites labeled with [3H]GBR-12935 in human postmortem putamen from 20 individuals were studied. There was a 70% decrease in binding density (Bmax) over the adult age range. No significant changes in binding affinity (Kd) were detected, the mean Kd being 1.0 +/- 0.2 nM (mean +/- S.E.M.). Nor were there any changes in binding related to the postmortem delay. Based on the findings that [3H]GBR-12935 labels the uptake site for dopamine, it is suggested that the age-related loss of [3H]GBR-12935 binding in human putamen reflects a degeneration of dopamine neurites.

  • 16.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Marcusson, J O
    Ross, S B
    [3H]GBR-12935 binding to cytochrome P450 in the human brain.1994Inngår i: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 62, nr 1, s. 342-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The presence of multiple [3H]GBR-12935 binding sites in the human brain has been revealed in several recent studies. One site represents the dopamine uptake site. In rat brain it was demonstrated that [3H]GBR-12935 also binds to nondopaminergic "piperazine acceptor sites." One of these sites has been identified as cytochrome P450IID1 in canine brain. [3H]GBR-12935 binding to the piperazine acceptor sites in the human brain was investigated in the present study. A pharmacological definition of the piperazine acceptor sites is presented: the [3H]GBR-12935 binding fraction that could be discriminated by 10 microM GBR-12909 in the presence of 0.3 microM mazindol. This binding fraction was saturable, with binding affinity in the range of 3-8 nM. It was also demonstrated that the piperazine acceptor or cytochrome P450-sensitive drugs cis-flupentixol and proadifen (SKF 525 A) compete for the same binding sites, suggesting the cytochrome P450 nature of the binding. The findings presented support the proposal that at least part of this fraction represents cytochrome P450IID6, the human form of P450IID1. The distribution of [3H]GBR-12935 binding to the suggested P450IID6-site in 12 brain regions was examined, without significant differences in binding densities between the regions. The significance of the present findings on the cytochrome P450 system in brain is discussed.

  • 17.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Marcusson, J O
    Ross, S B
    [3H]WIN 35,428 binding in the human brain.1996Inngår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 706, nr 2, s. 347-50Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The binding of [3H]WIN 35,428 was studied in post-mortem human brain, including extrastriatal regions. In the putamen, dopamine almost completely inhibited the [3H]WIN 35,428 binding. Paroxetine inhibited the binding with similar affinity as cocaine, in the range 200-300 nM. In the frontal cortex, [3H]WIN 35,428 labelled cocaine- and alaproclate sensitive binding sites, of which a major fraction was of protein nature. The elucidation of the cocaine sensitive sites in the frontal cortex should be the subject of further research.

  • 18.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norlén, M
    Caudate nucleus dopamine D(2) receptors in depressed suicide victims.2001Inngår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 44, nr 2, s. 70-3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several lines of evidence indicate the involvement of the dopamine system in depressive states. In this post-mortem study, the binding of [(3)H]raclopride to dopamine D(2) receptors in the caudate nucleus was investigated in 13 depressed suicide victims and 19 controls. There were no differences in B(max) or K(d) between the two groups. A subgroup consisting of individuals with major depression, however, had significantly higher K(d) values than controls. Previous findings regarding changes in dopamine metabolism in depression and antidepressant effects of dopamine agonists seem, according to the present study, not to be reflected by alterations in density or affinity of dopamine D(2) receptors in depressed suicide victims.

  • 19.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norlén, M
    Unchanged density of caudate nucleus dopamine uptake sites in depressed suicide victims.1997Inngår i: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 104, nr 11-12, s. 1353-60Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In depressive states, theories concerning serotonin and norepinephrine have been dominating, but there are several lines of evidence indicating the involvement of the dopamine system as well, especially in suicidal depression. In this post-mortem study, the binding of the ligand [3H]WIN 35,428 to dopamine uptake sites in the caudate nucleus was investigated in 13 depressed suicide victims and 19 controls. There were no differences in Bmax or Kd between the suicide group and controls. Subdividing the suicide group into subgroups regarding the presence of major depression, antidepressant medication and suicide method, respectively, did not yield any differences. Previous findings regarding reduced CSF HVA in suicidal depression and indications of striatal dopaminergic biochemical and receptor changes in depression seem, according to the present study, not to be reflected by alterations in density or affinity of dopamine uptake sites in depressed suicide victims.

  • 20.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Ohman, A S
    Gustafson, L
    Karlsson, I
    Lundmark, J
    [Inventory of geriatric psychiatry in Sweden. In short supply where demand does not determine resource allocation].2000Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 97, nr 24, s. 2976-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    In 1999 The Swedish Society for Old Age Psychiatry conducted an investigation in all Swedish counties in order to survey existing organizations and resources for medical services intended for elderly people with psychiatric complaints. In some counties there were no out-patient units specifically aimed at elderly people with psychiatric diseases, while more than half had no out-patient units for the large group of elderly with psychiatric ailments other than dementia. The total number of beds was far less than international recommendations. Less than 5 per cent of the total number of Swedish psychiatrists and geriatricians hold positions exclusively for geriatric psychiatry. Access to geriatric psychiatry resources appears to be unevenly distributed, and may be found mainly in or near university cities.

  • 21.
    Allard, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Rinne, J
    Marcusson, J O
    Dopamine uptake sites in Parkinson's disease and in dementia of the Alzheimer type.1994Inngår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 637, nr 1-2, s. 262-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The binding of [3H]GBR-12935 to dopamine (DA) uptake sites was studied in post-mortem putamen from a control group and from patients with Parkinson's disease (PD) or dementia of the Alzheimer type (DAT). The specific binding (Bmax) was almost completely abolished in the PD group and reduced by 65% in the DAT group. There were no significant differences in apparent binding affinity (Kd) between the DAT group and controls. The decreases in [3H]GBR-12935 binding to DA uptake sites in this study indicate a marked degeneration of DA neurites in the putamen in PD and also in DAT.

  • 22.
    Bergdahl, Ellinor
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Aléx, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Lundman, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Gender differences in depression among the very old2007Inngår i: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 19, nr 6, s. 1125-1140Artikkel i tidsskrift (Fagfellevurdert)
  • 23.
    Bergdahl, Ellinor
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Depression among the very old with dementia2011Inngår i: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 23, nr 5, s. 756-763Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim of this study was to investigate the prevalence of depression among very old individuals with dementia compared to those without dementia and to examine if there were any differences regarding associated factors between people with or without depression in these conditions.

    Methods: In a population-based study in Sweden, 363 participants aged 85 years and above, were evaluated for depression and dementia.

    Results: The prevalence of depression was significantly higher among the people with dementia than without dementia, 43% vs. 24% (p < 0.001). Approximately 2/3 of the depressed in both groups used antidepressants and of those, approximately 50% had responded. Depression in the group without dementia was, among other factors, associated with higher total number of medication, the use of significant more analgesics and benzodiazepines, loneliness, inability of going outside and recent loss of child. The loss of a child was the only factor that was independently associated with depression in those with dementia.

    Conclusions: The present study confirms that in the very old, depression is more common among people with dementia than without dementia. A large proportion, both with and without dementia, are under-diagnosed and untreated, and in addition many subjects in both groups studied were non-responders to treatment. Many of the factors associated with depression among people without dementia in this study were not associated with depression among those with dementia, thus supporting the theory that the spectrum of associated factors for depression in dementia seems to be different from that for depression in people without dementia.

  • 24.
    Bergdahl, Ellinor
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lundman, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Gustafson, Yngve
    Depression in the oldest old in urban and rural municipalities2007Inngår i: Aging & Mental Health, ISSN 1360-7863, E-ISSN 1364-6915, Vol. 11, nr 5, s. 570-578Artikkel i tidsskrift (Fagfellevurdert)
  • 25. Bixo, M
    et al.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bäckström, T
    Mjörndal, T
    Nyberg, S
    Spigset, O
    Sundström-Poromaa, I
    Binding of [3H]paroxetine to serotonin uptake sites and of [3H]lysergic acid diethylamide to 5-HT2A receptors in platelets from women with premenstrual dysphoric disorder during gonadotropin releasing hormone treatment.2001Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 26, nr 6, s. 551-64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Changes in serotonergic parameters have been reported in psychiatric conditions such as depression but also in the premenstrual dysphoric disorder (PMDD). In addition, hormonal effects on serotonergic activity have been established. In the present study, binding of [3H]paroxetine to platelet serotonin uptake sites and binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5-HT)2A receptors were studied in patients with PMDD treated with a low dose of a gonadotropin releasing hormone (GnRH) agonist (buserelin) or placebo and compared to controls. The PMDD patients were relieved of premenstrual symptoms like depression and irritability during buserelin treatment. The number of [3H]paroxetine binding sites (Bmax) were significantly higher in the follicular phase in untreated PMDD patients compared to controls. When treated with buserelin the difference disappeared. No differences in [3H]LSD binding between the three groups were shown. The present study demonstrated altered platelet [3H]paroxetine binding characteristics in women with PMDD compared to controls. Furthermore, [3H]paroxetine binding was affected by PMDD treatment with a low dose of buserelin. The results are consistent with the hypothesis that changes in serotonergic transmission could be a trait in the premenstrual dysphoric disorder.

  • 26.
    Boström, Gustaf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Hörnsten, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Brännström, Jon
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Conradsson, Mia
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Littbrand, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Antidepressant use and mortality in very old people2016Inngår i: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 28, nr 7, s. 1201-1210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Antidepressant treatment may increase the risk of death. The association between antidepressants and mortality has been evaluated in community-dwelling older people, but not in representative samples of very old people, among whom dementia, multimorbidity, and disability are common.

    METHODS: Umeå 85+/GERDA study participants (n = 992) aged 85, 90, and ≥95 years were followed for up to five years. Cox proportional hazard regression models were used to analyze mortality risk associated with baseline antidepressant treatment, adjusted for potential confounders.

    RESULTS: Mean age was 89 years; 27% of participants had dementia, 20% had stroke histories, 29% had heart failure, and 16% used antidepressants. In age- and sex-adjusted analyses, antidepressant use was associated with a 76% increased mortality risk (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.41-2.19). Adding adjustment for Geriatric Depression Scale score, HR was 1.62 (95% CI, 1.29-2.03). The association was not significant when adjusting for additional confounding factors (HR = 1.08; 95% CI, 0.85-1.38). Interaction analyses in the fully adjusted model revealed a significant interaction between sex and antidepressant use (HR: 1.76; 95% CI, 1.05-2.94). Among male and female antidepressant users, the HRs for death were 0.76 (95% CI, 0.47-1.24) and 1.28 (95% CI, 0.97-1.70), respectively.

    CONCLUSION: Among very old people, baseline antidepressant treatment does not seem to be independently associated with increased mortality risk. However, the risk may be different in men and women. This difference and the potential risk of initial treatment require further investigation in future cohort studies of very old people.

  • 27.
    Eriksson, I S
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Allard, P
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Marcusson, J
    [3H]tiagabine binding to GABA uptake sites in human brain.1999Inngår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 851, nr 1-2, s. 183-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The binding of [3H]tiagabine ((RS-1-(4,4-(3-methyl-2-thienyl)-3-butenyl)-3-piperidine carboxylic acid) to homogenates of frozen post-mortem human brain has been characterized. Inhibition experiments with gamma-aminobutyric acid (GABA), GABA uptake inhibitors, ligands active at postsynaptic GABA receptors and receptors for other neurotransmitters, suggest that [3H]tiagabine binds with high affinity to GABA uptake sites. Inhibition and kinetic experiments suggests that 70%-80% of the binding is to a high affinity site. Saturation experiments showed that the binding was saturable. Bmax was 3.4 pmol/mg protein and Kd 16 nM in frontal cortex. The dissociation constants (Kd) measured in kinetic and equilibrium experiments were in the same range (16-56 nM). The regional distribution was studied in nine brain regions and the binding was heterogenous, with the highest binding in frontal cortex and parietal cortex and the lowest binding in nucleus caudatus and putamen. This is, to our knowledge, the first study on [3H]tiagabine binding in human tissue. It is concluded that [3H]tiagabine binding can be used as a specific marker for the GABA transporter GAT-1 in homogenates of human brain.

  • 28. Güzey, Cüneyt
    et al.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Spigset, Olav
    Radioligand binding to brain dopamine and serotonin receptors and transporters in Parkinson's disease: relation to gene polymorphisms2012Inngår i: International Journal of Neuroscience, ISSN 0020-7454, E-ISSN 1563-5279, Vol. 122, nr 3, s. 124-132Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The influence of variations in genes coding for dopamine and serotonin transporters and receptors on the expression of these structures in the brains of patients with Parkinson's disease (PD) is not known. In order to investigate the significance of dopamine and serotonin transporter and receptor gene polymorphisms on the expression of dopamine and serotonin transporters and the dopamine D(2) and serotonin 5HT(2A) receptors in brain tissue in PD, we conducted a study on brain autopsy material from 16 patients diagnosed with clinical PD and 11 controls. The polymorphisms studied were DAT1 VTNR, DRD2 Taq1A, 5HTTLPR, and 5HTR2A 102 T>C, 516 C>T, His425Tyr and Thr25Asn. Compared to control subjects, patients with PD had a significantly lowered radioligand binding to the dopamine transporter in nucleus caudatus (P = 0.001) and putamen (P = 0.008), and to the serotonin transporter in gyrus cingulatus (P = 0.010) and nucleus caudatus (P = 0.032). We did not observe any significant associations between genetic polymorphisms and the extent of radioligand binding or between the polymorphisms and a diagnosis of PD. In conclusion, the density of brain dopamine and serotonin transporters in patients with PD was reduced. However, there were no associations between the investigated genotypes and the expression of the corresponding receptors and transporters.

  • 29.
    Israelsson, Hanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Symptoms of Depression are Common in Patients With Idiopathic Normal Pressure Hydrocephalus: The INPH-CRasH Study2016Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 78, nr 2, s. 161-168Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: If patients with idiopathic normal pressure hydrocephalus (INPH) also have depression, this could have important clinical ramifications in assessment and management of their cognitive function and response to shunting. In many dementias, depression is overrepresented, but the prevalence of depression in shunted patients with INPH is unknown.

    OBJECTIVE: The objective of this case-control study was to assess the prevalence of symptoms of depression in shunted INPH patients compared with population-based controls.

    METHODS: INPH patients consecutively shunted from 2008 to 2010 in Sweden were analyzed. Patients remaining after inclusion (within 60-85 years and not having dementia, ie, mini-mental state examination >=23) had a standardized visit to their healthcare provider and answered an extensive questionnaire. Age- and sex-matched population-based controls underwent the same procedure. Symptoms of depression were assessed using the Geriatric Depression Scale 15 (suspected depression defined as >=5 points, suspected severe depression as >=12 points). This study is part of the INPH-CRasH study.

    RESULTS: One hundred seventy-six INPH patients and 368 controls participated. After adjustment for age, sex, cerebrovascular disease, and systolic and diastolic blood pressure, patients had a higher mean depression score (patients: 4.9 ± 3.7 SD, controls: 1.9 ± 2.3 SD; OR 1.4, 95% CI 1.3-1.6, P < .001), more patients had suspected depression (46% vs 13%, OR 6.4, 95% CI 3.8-10.9, P < .001), and more patients had suspected severe depression (7.3% vs 0.6%, OR 14.4, 95% CI 3.0-68.6, P < .005).

    CONCLUSION: Symptoms of depression are overrepresented in INPH patients compared with the population, despite treatment with a shunt. Screening for depression should be done in the evaluation of INPH patients in order to find and treat a coexisting depression.

  • 30. Jonsson, Ulf
    et al.
    Bertilsson, Goran
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Gyllensvard, Harald
    Soderlund, Anne
    Tham, Anne
    Andersson, Gerhard
    Psychological Treatment of Depression in People Aged 65 Years and Over: A Systematic Review of Efficacy, Safety, and Cost-Effectiveness2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 8, artikkel-id e0160859Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Depression in elderly people is a major public health concern. As response to antidepressants is often unsatisfactory in this age group, there is a need for evidence-based non-pharmacological treatment options. Our objectives were twofold: firstly, to synthesize published trials evaluating efficacy, safety and cost-effectiveness of psychological treatment of depression in the elderly and secondly, to assess the quality of evidence. Method The electronic databases PubMed, EMBASE, Cochrane Library, CINAL, Scopus, and Psyc-INFO were searched up to 23 May 2016 for randomized controlled trials (RCTs) of psychological treatment for depressive disorders or depressive symptoms in people aged 65 years and over. Two reviewers independently assessed relevant studies for risk of bias. Where appropriate, the results were synthesized in meta-analyses. The quality of the evidence was graded according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results Twenty-two relevant RCTs were identified, eight of which were excluded from the synthesis due to a high risk of bias. Of the remaining trials, six evaluated problem-solving therapy (PST), five evaluated other forms of cognitive behavioural therapy (CBT), and three evaluated life review/reminiscence therapy. In frail elderly with depressive symptoms, the evidence supported the efficacy of PST, with large but heterogeneous effect sizes compared with treatment as usual. The results for life-review/reminiscence therapy and CBT were also promising, but because of the limited number of trials the quality of evidence was rated as very low. Safety data were not reported in any included trial. The only identified cost-effectiveness study estimated an incremental cost per additional point reduction in Beck Depression Inventory II score for CBT compared with talking control and treatment as usual. Conclusion Psychological treatment is a feasible option for frail elderly with depressive symptoms. However, important questions about efficacy, generalizability, safety and cost-effectiveness remain.

  • 31.
    Mathillas, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Olofsson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Lövheim, Hugo
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Prevalence of depressive disorders among very old people in 2000-2002 and 2005-2007: the Umeå 85+/GERDA studyManuskript (preprint) (Annet vitenskapelig)
  • 32.
    Mathillas, Johan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Petersson, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Wallin, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Olofsson, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Risk factors for depressive disorders in very old age: a population-based cohort study with a five-year follow-up2014Inngår i: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 49, nr 5, s. 831-839Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Depressive disorders are common among the very old, but insufficiently studied. The present study aims to identify risk factors for depressive disorders in very old age.

    The present study is based on the GERDA project, a population-based cohort study of people aged a parts per thousand yen85 years (n = 567), with 5 years between baseline and follow-up. Factors associated with the development of depressive disorders according to DSM-IV criteria at follow-up were analysed by means of a multivariate logistic regression.

    At baseline, depressive disorders were present in 32.3 % of the participants. At follow-up, 69 % of those with baseline depressive disorders had died. Of the 49 survivors, 38 still had depressive disorders. Of the participants without depressive disorders at baseline, 25.5 % had developed depressive disorders at follow-up. Baseline factors independently associated with new cases of depressive disorders after 5 years were hypertension, a history of stroke and 15-item Geriatric Depression Scale score at baseline.

    The present study supports the earlier findings that depressive disorders among the very old are common, chronic and malignant. Mild depressive symptoms as indicated by GDS-15 score and history of stroke or hypertension seem to be important risk factors for incident depressive disorders in very old age.

  • 33. Norlén, M
    et al.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    [3H]GBR 12935 binding in platelets: a possible association with cytochrome P-450IID6?1997Inngår i: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 332, nr 2, s. 227-30Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The nature of [3H] (1-[2-(diphenylmethoxy)ethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) (GBR 12935) binding to human platelets was investigated. A common property of the inhibitors of this binding was their association with the cytochrome P-450 system. cis-Flupenthixol and (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl) piperazine dihydrochloride) (GBR 12909) biphasically inhibited the binding. The fraction of [3H]GBR 12935 binding that was inhibited by low concentrations of cis-flupenthixol was sensitive to protease treatment. [3H]GBR 12935 binding in this fraction was saturable and of high affinity (Kd 4.5 nM). The present results reveal that [3H]GBR 12935 binds to multiple sites in platelets and suggest that part of the binding is associated with cytochrome P-450IID6.

  • 34. Norlén, M
    et al.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Reduction in number of dopamine uptake sites but unchanged number of piperazine-acceptor/CYP450IID6 binding sites in the human caudate nucleus in aging.1996Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 209, nr 3, s. 161-4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A substantial decrease in number of striatal dopamine uptake sites is a characteristic finding in aging. This decrease resembles the dopaminergic nigro-striatal degeneration in Parkinson's disease (PD). A dysfunction of cytochrome P450IID6 (debrisoquine-4-hydroxylase) is suggested to be involved in the pathogenesis of PD. In this study, binding sites associated with the neuronal form of P450IID6 were studied in the caudate nucleus from individuals in the age range 20-81 years using [3H]GBR 12935 as a radioligand. No significant changes in binding parameters were obtained, while in the same region a significant decrease in number of dopamine uptake sites occurred. Thus, in aging, P450IID6 and dopaminergic degeneration seem not to be functionally related in this region. Whether such a relation exists in PD is still to be examined.

  • 35. Norlén, M
    et al.
    Norström, A
    Spigset, O
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    [3H]GBR 12935 binding in platelets from poor and extensive cytochrome P-4502D6 metabolizers.1999Inngår i: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 366, nr 2-3, s. 329-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have indicated that part of the binding of [3H] [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride] ([3H]GBR 12935) to human platelets is to a piperazine acceptor site, which might be associated with cytochrome P-450IID6 (CYP4502D6, debrisoquine-4-hydroxylase). Due to mutant CYP4502D6 alleles, 5-10% of Caucasians are poor metabolizers of CYP4502D6 substrates such as debrisoquine and dextromethorphan. In the present study, possible differences in binding characteristics of [3H]GBR 12935 in platelets from CYP4502D6 poor and extensive metabolizers were investigated. The most prominent finding was a gender difference, with males having significantly higher Kd values than females. There were no differences in Bmax. After correction for gender, there was a tendency towards higher Kd values in poor metabolizers than in extensive metabolizers, although the difference was not statistically significant. Whether this finding corresponds to reduced CYP4502D6 activity is a matter of further investigation.

  • 36.
    Sigurdh, Jeanette
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Spigset, Olav
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Platelet serotonin transporter and 5-HT2A receptor binding in adolescents with eating disorders2013Inngår i: International Journal of Neuroscience, ISSN 0020-7454, E-ISSN 1563-5279, Vol. 123, nr 5, s. 333-338Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The pathogenetic involvement of the serotonergic system in eating disorders is an established finding. Conclusions from platelet studies are based on results from investigations of subjects with a mean age of 20 years or more. The aim was to investigate whether previous findings in adults are valid also for adolescents who are examined within a relatively short interval after the onset of the eating disorder. [H-3] paroxetine binding to the platelet serotonin transporter and [H-3] lysergic acid diethylamide ([H-3] LSD) binding to the 5-HT2A receptor was studied in 15 female adolescents with eating disorders (11 with anorexia nervosa and 4 with clearly anorectic eating behaviour not fulfilling the criteria for anorexia nervosa) and 32 controls. The patients revealed a higher density of serotonin transporters and a lower density of 5-HT2A receptors compared with healthy controls of the same age (775 +/- 165 vs. 614 +/- 111 fmol/mg protein (p = 0.003) for [H-3] paroxetine binding and 215 +/- 59 vs. 314 +/- 151 fmol/mg protein (p = 0.005) for [H-3] LSD binding). The findings of increased density of platelet serotonin transporters and reduced density of 5-HT2A receptors differ from previous results in older patients. The lower patient age and the short duration of disease in the present study, possibly in conjunction with variations in stress-related psychological and biological factors, may have caused these differences. Although the present findings contradict prevailing evidence, they add further information concerning the nature of serotonergic involvement in eating disorders and indicate that demographic and course-related factors might influence the regulation of the serotonin system in these disorders.

  • 37.
    Sigurdh, Jeanette
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Spigset, O
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Mjörndal, T
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Binding of [(3)H]lysergic acid diethylamide to serotonin 5-HT(2A) receptors and of [(3)H]paroxetine to serotonin uptake sites in platelets from healthy children, adolescents and adults.1999Inngår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 40, nr 4, s. 183-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Possible age effects on binding of [(3)H]lysergic acid diethylamide ([(3)H]LSD) to serotonin 5-HT(2A) receptors and of [(3)H]paroxetine to serotonin uptake sites were studied in platelets from healthy children (11-12 years of age), adolescents (16-17 years of age) and adults. Significant overall age effects were found both for the number of binding sites (B(max)) for [(3)H]LSD binding (p < 0.001), the affinity constant (K(d)) for [(3)H]LSD binding (p < 0.001), B(max) for [(3)H]paroxetine binding (p < 0.001) and K(d) for [(3)H] paroxetine binding (p = 0.006). In general, there was a decrease in B(max) with increasing age, which predominantly occurred between the ages 11-12 years and 16-17 years for the 5-HT(2A) receptor, and after 16-17 years of age for the serotonin uptake site. These developmental changes might have an impact on the effect of treatment with serotonergic drugs in children and adolescents. When the platelet serotonin variables investigated are employed in studies in children or adolescents, age matching or, alternatively, introduction of age control in the statistical analysis should be performed.

  • 38. Smedh, K
    et al.
    Spigset, O
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Mjörndal, T
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Platelet [3H]paroxetine and [3H]lysergic acid diethylamide binding in seasonal affective disorder and the effect of bright light therapy.1999Inngår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 45, nr 4, s. 464-70Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Seasonal affective disorder (SAD) has been regarded as a melatonin disorder, but the pathophysiological mechanisms of SAD are to a large extent unclarified. Serotonergic mechanisms have also been studied, but they have shown inconsistent results. METHODS: We have compared [3H]paroxetine and [3H]lysergic acid diethylamide (LSD) binding in platelets from 23 SAD patients and 23 controls. Then SAD patients had 4 weeks of light therapy. On the last treatment day new blood samples were drawn. Symptoms before and after light treatment were measured by SIGH-SAD. RESULTS: Bmax for paroxetine binding before light treatment was higher in SAD patients compared to controls and also higher in responders than in nonresponders. Bmax decreased significantly during light treatment. We also found a negative correlation between the two Bmax values before but not after light treatment. There was a negative correlation between Bmax for paroxetine binding before treatment and clinical status after treatment. Patients with reduced Bmax for LSD binding after treatment had a better clinical treatment response. CONCLUSIONS: The present study indicates that serotonin receptor parameters might be suitable in the prediction of clinical response to light treatment.

  • 39. Sparring Björkstén, Karin
    et al.
    Karlsson, Ingvar
    Almqvist, Ove
    Waern, Margda
    Eriksdotter, Maria
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lökk, Johan
    Äldrepsykiatri: kliniska riktlinjer för utredning och behandling2013Bok (Fagfellevurdert)
  • 40. Spigset, O
    et al.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Mjörndal, T
    Circannual variations in the binding of [3H]lysergic acid diethylamide to serotonin2A receptors and of [3H]paroxetine to serotonin uptake sites in platelets from healthy volunteers.1998Inngår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 43, nr 10, s. 774-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Circannual variations occur in several serotonergic parameters, including platelet serotonin uptake and platelet [3H]imipramine binding. METHODS: Binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5-HT)2A receptors and binding of [3H]paroxetine to platelet serotonin uptake sites were studied longitudinally for 1 year in 12 healthy volunteers. RESULTS: For [3H]LSD, the number of binding sites (Bmax) showed no significant seasonal variation (two-way analysis of variance), although Bmax was significantly higher during the months October through February than during the months April through August (32.6 vs. 29.8 fmol/mg protein; p = .015). For [3H]paroxetine, Bmax showed a significant seasonal variation (p = .003) with maximum in August (1322 fmol/mg protein) and minimum in February (1168 fmol/mg protein). The affinity constant (Kd) showed a significant seasonal variation for [3H]LSD binding (p = .046), but not for [3H]paroxetine binding. The seasonal fluctuations in [3H]LSD binding and in paroxetine binding tended to be inversely correlated for Bmax (r = -.70; p = .08) and were significantly negatively correlated for Kd (r = -.88; p = .009). CONCLUSIONS: The present study demonstrates a seasonal effect on platelet serotonin uptake site binding and indicates a possible seasonal effect on 5-HT2A receptor binding. The results imply that circannual fluctuations should be taken into account when these platelet serotonin markers are studied.

  • 41.
    Sundman, Ingrid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eriksson, A
    Marcusson, J
    GABA uptake sites in frontal cortex from suicide victims and in aging.1997Inngår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 35, nr 1, s. 11-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The binding of [3H]nipecotic acid to GABA uptake sites was studied in post mortem human frontal cortex from 17 suicide victims and 21 controls without known neurological or psychiatric disorder. The suicide victims were subclassified according to the use of violent or non-violent methods and to the presence or absence of a known history of a depressive disorder. No difference was found between the suicide victims and the controls with regard to [3H]nipecotic acid binding to GABA uptake sites (Bmax) and apparent affinity (Kd). No differences were found either with regard to method of suicide or whether a depressive symptom existed or not. The binding of [3H]nipecotic acid to GABA uptake sites was also studied in post mortem human frontal cortex with regard to aging. The age of the subjects ranged from 16 to 84 years. No significant difference in either Bmax or Kd was found. The present findings suggest that the GABA uptake sites in the human frontal cortex are not subjected to regulation or degenerative changes in conditions investigated.

  • 42.
    Sundman-Eriksson, Ingrid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    [(3)H]Tiagabine binding to GABA transporter-1 (GAT-1) in suicidal depression.2002Inngår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 71, nr 1-3, s. 29-33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In depressive disorders, alterations of GABA concentrations and number of postsynaptic GABA related receptor binding sites, as well as antidepressant effects exerted by GABA agonists, suggest a pathogenetic involvement of the GABA system. METHOD: The binding of the presynaptic GABA ligand [(3)H]tiagabine to GABA transporter-1 (GAT-1) was studied in post mortem human frontal cortex and cingulate gyrus from 13 suicide victims and 19 controls without known neurological or psychiatric disorder. RESULTS: No differences were found between the suicide victims and the controls with regard to the number of [(3)H]tiagabine binding sites (B(max)) or apparent affinity (K(d)). LIMITATIONS: The study was limited to two brain regions. CONCLUSION: Findings in other studies of alterations in the GABA system in depression seem according to the present results not to be associated with significant changes in the GABA uptake binding sites in the regions investigated.

  • 43.
    Sundman-Eriksson, Ingrid
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Age-correlated decline in [3H]tiagabine binding to GAT-1 in human frontal cortex.2006Inngår i: Aging Clinical and Experimental Research, ISSN 1594-0667, E-ISSN 1720-8319, Vol. 18, nr 3, s. 257-60Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: In spite of the fact that GABA is a significant transmitter, little is known about the GABA system in aging, compared with other transmitter systems. [(3)H]tiagabine is a ligand for GABAergic neurons, which binds with 10-fold higher affinity to the GABA uptake site than [(3)H]nipecotic acid. The aim of this study was to study the binding of [(3)H]tiagabine to the GABA transporter 1, GAT-1, in human frontal cortex and cingulate cortex from individuals of varying ages. METHODS: [(3)H]tiagabine binding experiments were conducted on post-mortem brain tissue from 19 individuals (age range 17-78 years) without known neurological or psychiatric disorders. Binding data vs age and postmortem interval was analysed by Pearson correlation. RESULTS: The density of [(3)H]tiagabine binding to GAT- 1 decreased significantly with increasing age in the frontal cortex, whereas binding affinity was unchanged. No significant alterations in binding parameters were observed in the cingulate cortex. No correlation was found between post-mortem delay and the number of [(3)H]tiagabine binding sites. CONCLUSIONS: According to the present study, presynaptical alterations in the GABA system are correlated with aging in the frontal cortex of the human brain. Further studies involving a broader range of brain regions seem warranted, to confirm the present findings and to enlarge knowledge about the GABA system in aging.

  • 44.
    Wihlbäck, A C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, I
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Mjörndal, T
    Spigset, O
    Bäckström, T
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Influence of postmenopausal hormone replacement therapy on platelet serotonin uptake site and serotonin 2A receptor binding.2001Inngår i: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 98, nr 3, s. 450-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To examine whether binding of [3H]paroxetine to the platelet serotonin transporter or binding of [3H]lysergic acid diethylamide (LSD) to the platelet 5-HT(2A) receptor are influenced by postmenopausal estrogen/progestogen treatment. METHODS: Twenty-three postmenopausal women with climacteric symptoms completed this double-blind, randomized, crossover study. The women received 2 mg of estradiol continuously during four 28-day cycles. In the last 14 days of each cycle, 10 mg of medroxyprogesterone acetate, 1 mg of norethindrone acetate, or placebo was given. Before treatment, as well as once during the last week of each treatment, blood samples were collected for analysis of [3H]LSD and [3H]paroxetine binding. The power of the study setup was 81%. The study had an effect size of 0.36, corresponding to the ability to detect a 15% difference in [3H]paroxetine and [3H]LSD binding between treatments with alpha =.05 and beta =.20, based on a previously reported standard deviation within cells of 20% of the mean binding values. RESULTS: The number of platelet receptors (B(max)), or the affinity of the radioligand to the receptor (K(d)), for [3H]paroxetine binding did not change during estrogen or estrogen-progestogen treatment, nor did B(max) or K(d) for [3H]LSD binding change during the different treatments. However, in a subgroup of depressed patients, the decrease in B(max) for [3H]LSD binding during treatment was significantly more pronounced than in the nondepressed subgroup (P <.05). CONCLUSION: Estrogen treatment with or without the addition of progestogen does not affect binding to the serotonin transporter or to the serotonergic 5-HT(2A) receptor in healthy postmenopausal women.

  • 45.
    Wihlbäck, Anna-Carin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström Poromaa, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bixo, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Mjörndal, Tom
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Spigset, Olav
    Influence of menstrual cycle on platelet serotonin uptake site and serotonin2A receptor binding2004Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 29, nr 6, s. 757-766Artikkel i tidsskrift (Fagfellevurdert)
  • 46.
    Wihlbäck, Anna-Carin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundström-Poromaa, I
    Allard, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Mjörndal, T
    Spigset, O
    Bäckström, T
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Influence of postmenopausal hormone replacement therapy on platelet serotonin uptake site and 5-HT2A receptor binding2001Inngår i: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 98, nr 3, s. 450-457Artikkel i tidsskrift (Fagfellevurdert)
1 - 46 of 46
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