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| 2. |
- Aklillu, Eleni, et al.
(författare)
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Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression.
- 2009
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Ingår i: Pharmacogenetics and genomics. - 1744-6872. ; 19:4, s. 267-75
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Monoamine oxidase-A (MAO-A) is a key mitochondrial enzyme that metabolizes biogenic amine neurotransmitters such as dopamine and serotonin. Individuals with atypical depression (AD) are particularly responsive to treatment with MAO inhibitors (MAOIs). Biomarker tests are essential for prompt diagnosis of AD, and to identify those with an altered brain neurotransmitter metabolism who may selectively respond to MAOI therapy. METHODS: In a sample of 118 Scandinavian patients with treatment-resistant depression who are naive to MAOI therapy, we investigated the associations between a common MAOA functional promoter polymorphism (MAOA-uVNTR), cerebrospinal fluid (CSF) neurotransmitter metabolites, and AD susceptibility. The metabolites for dopamine (homovanillic acid, HVA), serotonin (5-hydroxyindoleacetic acid) and noradrenaline (3-methoxy-4-hydroxyphenylglycol) were measured in the CSF. RESULTS: AD was associated with the female sex and a higher HVA in CSF (P=0.008). The carriers of the MAOA-uVNTR short allele were significantly overrepresented among women with AD (P=0.005; odds ratio=4.76; 95% confidence interval=1.5-13.1; statistical power=80.0%). Moreover, the MAOA-uVNTR genotype significantly influenced the HVA concentration (P=0.01) and showed a strong trend in relation to 5-hydroxyindoleacetic acid concentration (P=0.057) in women. The mediational statistical analyses showed the CSF-HVA concentration as a key driver of the relationship between MAOA-uVNTR genotype and AD. CONCLUSION: The association of the MAOA-uVNTR with both susceptibility to AD and dopamine metabolite (HVA) concentration lends further biological plausibility for high MAO-A enzyme activity as a mechanistic factor for genetic predisposition to AD through altered dopamine turnover. Our observations provide new evidence on the in-vivo functional significance of the MAOA-uVNTR short allele as a high activity variant.
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| 3. |
- Backlund, Lena, et al.
(författare)
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Identifying predictors for good lithium response - A retrospective analysis of 100 patients with bipolar disorder using a life-charting method.
- 2009
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Cambridge University Press (CUP). - 0924-9338. ; 24:3, s. 171-7
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Our aim was to investigate bipolar patients in order to test the validity of various outcome measures and to identify prognostic predictors for pharmacological treatment. MATERIAL AND METHOD: One hundred patients were interviewed using a computerized life-charting program in a descriptive, retrospective analysis. The concept "Burden of illness" was defined as a combination of severity and duration of episodes. Response to treatment was defined as the difference in burden before and after treatment, a low burden during treatment, and freedom of episodes for at least 3 years after insertion of treatment. RESULTS: The absence of mixed episodes and a high initial burden predicted a good response measured as the difference in burden. If remission for 3 years or a low burden during lithium treatment was used, the absence of rapid cycling and of mixed episodes were the most important predictors. The severity of illness before treatment had no impact. DISCUSSION AND CONCLUSION: We suggest the use of absolute measures of severity during treatment as the most appropriate measure of the outcome. Furthermore, our data provide corroboration that treatment with lithium ameliorates the prognosis of the illness, but that mixed episodes and rapid cycling predict a poorer response to lithium.
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| 4. |
- Eriksson, Olle, et al.
(författare)
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Mood changes correlate to changes in brain serotonin precursor trapping in women with premenstrual dysphoria.
- 2006
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Ingår i: Psychiatry research. - : Elsevier BV. - 0165-1781 .- 0925-4927 .- 1872-7506. ; 146:2, s. 107-16
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Tidskriftsartikel (refereegranskat)abstract
- The cardinal mood symptoms of premenstrual dysphoria can be effectively treated by serotonin-augmenting drugs. The aim of the study was to test the serotonin hypothesis of this disorder, i.e. of an association between premenstrual decline in brain serotonin function and concomitant worsening of self-rated cardinal mood symptoms. Positron emission tomography was used to assess changes in brain trapping of 11C-labeled 5-hydroxytryptophan, the immediate precursor of serotonin, in the follicular and premenstrual phases of the menstrual cycle in eight women with premenstrual dysphoria. Changes in mood and physical symptoms were assessed from daily visual analog scale ratings. Worsening of cardinal mood symptoms showed significant inverse associations with changes in brain serotonin precursor trapping; for the symptom "irritable", r(s)=-0.83, and for "depressed mood" r(s)=-0.81. Positive mood variables showed positive associations, whereas physical symptoms generally displayed weak or no associations. The data indicate strong inverse associations between worsening of cardinal symptoms of premenstrual dysphoria and brain serotonin precursor (11C-labeled 5-hydroxytryptophan) trapping. The results may in part support a role for serotonin in premenstrual dysphoria and may provide a clue to the effectiveness of serotonin-augmenting drugs in this disorder but should, due to small sample size and methodological shortcomings, be considered preliminary.
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| 6. |
- Kishida, Ikuko, et al.
(författare)
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Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression.
- 2007
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X. ; 32:10, s. 2143-51
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Tidskriftsartikel (refereegranskat)abstract
- The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried out. We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders. Subjects were 119 Swedish patients with persistent mood disorders and 141 healthy subjects. In 112 of these patients, we measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol in CSF. Genotyping for 5-HTT polymorphisms from genomic DNA was carried out by PCR. There was no significant difference in allele/genotype frequency between patients and healthy subjects. In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p=0.03). Although the 5-HIAA concentration showed a tendency to be higher in short (S) carriers than in non-S carriers of the 5-HTTLPR in patients (p=0.06), when considering patients with major depressive disorder (MDD), the 5-HIAA concentration was significantly higher among S carriers than among non-S carriers (p=0.02). Moreover, the 5-HIAA concentration was higher in S/S subjects compared to long (L)/L (p=0.0001) and L/S (p=0.002) subjects in patients with MDD. Similarly, there was higher HVA concentration in S/S subjects compared to L/L (p=0.002) and L/S subjects (p=0.002). There was no effect of 5-HTTVNTR. Our findings show that the 5-HTTLPR polymorphism affects 5-HIAA and HVA concentrations among treatment-resistant patients with mood disorders.
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| 7. |
- Langworth, Sven, et al.
(författare)
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Efficacy and tolerability of reboxetine compared with citalopram: a double-blind study in patients with major depressive disorder.
- 2006
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Ingår i: Journal of clinical psychopharmacology. - Philadelphia : Ovid Technologies (Wolters Kluwer Health). - 0271-0749 .- 1533-712X. ; 26:2, s. 121-7
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to compare efficacy and tolerability of the selective noradrenaline reuptake inhibitor reboxetine with the selective serotonin reuptake inhibitor citalopram, in the treatment of major depressive disorder (MDD). In total, 357 outpatients with MDD were randomized to treatment with reboxetine 8-10 mg or citalopram 20-40 mg per day during 24 weeks. Primary end-point was change from baseline in the Hamilton Depression Rating Scale (HAM-D, 21 items). Sexual function/dysfunction was measured by the Sexual Function scale (SF). Observed case analysis showed that both treatments yielded a gradual reduction of HAM-D scores: reboxetine with -21.4 and citalopram with -22.1 points (NS). LOCF analysis showed a greater reduction of the HAM-D scores with citalopram compared with reboxetine (-19.6 vs. -17.8; P = 0.034). The response rate was 90.3% for reboxetine and 92.7% for citalopram (NS). The most common side effect in the reboxetine group was dry mouth, and in the citalopram group sexual dysfunction. At week 24, anorgasmia was reported by 5.9% of the sexually active women in the reboxetine group vs 39% in the citalopram group. The dropout number was 91 in the reboxetine group, and 54 in the citalopram group. To summarize, both treatments gave a satisfactory antidepressant effect. The side effect profile differed between the groups, with a notably high prevalence of sexual dysfunctions in the citalopram group. The high number of dropouts in the reboxetine group, is considered as a result of the non-titration starting dose of 8 mg reboxetine per day, which gave a high incidence of early side-effects.
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| 9. |
- Muhwezi, W W, et al.
(författare)
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Detection of major depression in Ugandan primary health care settings using simple questions from a subjective well-being (SWB) subscale
- 2007
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Ingår i: Soc Psychiatry Psychiatr Epidemiol. ; 42:1, s. 61-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To explore whether the 4-item subjective well-being subscale could be used to detect a major depressive illness. Secondly, to describe the prevalence and characteristics of depressed health care attendees at primary healthcare centres. METHOD: Using a descriptive, cross-sectional study design, we interviewed 199 consecutive patients about their socio-demographics, subjective well-being (SWB), major depressive illness symptoms and depression severity. The instruments used were translated into Luganda. RESULTS: Point prevalence of a current Major Depressive Episode (MDE) was 31.6%. Using a one week reference period, we found that experiencing a lot of distress, having less energy or poor health, having poor emotional and psychological adjustment and not being satisfied with life were significantly more common among patients with a current MDE. The 4-item SWB subscale detected depression of up to 87.1% (95% CI: 0.818-0.923). In logistic regression, all four SWB items predicted a current MDE. CONCLUSION: Major depressive illness is a common at primary healthcare level in Uganda. Four simple questions reflecting SWB items have potential to detect diagnosable patients likely to have a current MDE, making general screening procedures less necessary.
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| 10. |
- Roth, Göran, et al.
(författare)
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A longitudinal study of PTSD in a sample of adult mass-evacuated Kosovars, some of whom returned to their home country.
- 2006
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Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Cambridge University Press (CUP). - 0924-9338. ; 21:3, s. 152-9
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Tidskriftsartikel (refereegranskat)abstract
- PTSD among a sample of mass-evacuated adults from Kosovo was studied using a prospective design with a baseline study and follow-ups at 3 and 6 months in Sweden, and with an additional follow-up after 1.5 years in both Sweden and Kosovo. Trauma events and PTSD-related symptoms were measured by the Harvard Trauma Questionnaire (HTQ). At the additional follow-up after 1.5 years the same measure (HTQ) was used as well as clinical diagnostic interviews with the SCID instrument and measurement of saliva cortisol levels. Thirty-seven percent had PTSD-related symptoms at baseline. Morbidity increased at the three follow-ups. About 80% of the participants had PTSD at the additional follow-up after 1.5 years. The HTQ results were confirmed by clinical diagnoses and the participants diagnosed with PTSD also had low saliva cortisol levels. The results are discussed in terms of trauma, time needed to develop PTSD, post-migration stress and selection mechanisms.
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