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- Bohman, Hannes, 1965-
(författare)
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Clozapine protects adult neural stem cells from ketamine-induced cell death in correlation with decreased apoptosis and autophagy.
- 2010
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Ingår i: Bioscience Reports. - Portland. - 0144-8463 .- 1573-4935. ; 31:40
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis, the production of newborn neurons from neural stem cells (NSCs) has been suggested to be decreased in patients with schizophrenia. A similar finding was observed in an animal model of schizophrenia, as indicated by decreased bromodeoxyuridine (BrdU) labelling cells in response to a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist. The antipsychotic drug clozapine was shown to counteract the observed decrease in BrdU-labelled cells in hippocampal dentate gyrus (DG). However, phenotypic determination by immunohistochemistry analysis could not reveal whether BrdU-positive cells were indeed NSCs. Using a previously established cell model for analysing NSC protection in vitro, we investigated a protective effect of clozapine on NSCs. Primary NSCs were isolated from the mouse subventricular zone (SVZ), we show that clozapine had a NSC protective activity alone, as evident by employing an ATP cell viability assay. In contrast, haloperidol did not show any NSC protective properties. Subsequently, cells were exposed to the non-competitive NMDA-receptor antagonist ketamine. Clozapine, but not haloperidol, had a NSC protective/anti-apoptotic activity against ketamine-induced cytotoxicity. The observed NSC protective activity of clozapine was associated with increased expression of the anti-apoptotic marker Bcl-2, decreased expression of the pro-apoptotic cleaved form of caspase-3 and associated with decreased expression of the autophagosome marker 1A/1B-light chain 3 (LC3-II). Collectively, our findings suggest that clozapine may have a protective/anti-apoptotic effect on NSCs, supporting previous in vivo observations, indicating a neurogenesis-promoting activity for clozapine. If the data are further confirmed in vivo, the results may encourage an expanded use of clozapine to restore impaired neurogenesis in schizophrenia.
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| 2. |
- Bohman, Hannes, 1965-, et al.
(författare)
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Long term follow up of adolescent depression : a population based study
- 2010
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 115:1, s. 21-29
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Tidskriftsartikel (refereegranskat)abstract
- Adolescent depression is common. Earlier studies indicate that relapses and recurrences are common. But many questions are still unanswered. The aim of the present study has been to follow subjects with adolescent depressions, identified in a population-based study, over a 15-year period. Subjects with adolescent depression (n = 362) and a comparison group (n = 250) were followed in the National Swedish registers.The formerly depressed females had significantly more out-patient visits, and a significantly higher proportion (78.4% versus 69.6%) had at least one out-patient visit. Among the males, no significant differences were found as concerns out-patient visits. The formerly depressed females had significantly more in-patient stays (3.6 versus 2.4) and a significantly higher total number of in-patient days (27.4 versus 10.1). A significantly higher proportion had in-patient days due to mental disorders (9.5% versus 4.6%), in particular anxiety disorders (4.9% versus 1.0%). As concerns the males, a significantly higher proportion had in-patient days due to mental disorders (16.5% versus 1.8%), in particular alcohol and drug abuse (7.6% versus 0%).Among the formerly depressed females there were no significant differences against the comparison group as concerns the proportion of being a mother, number of children per woman, or age at first child. However, a significantly higher proportion of the formerly depressed females had had different, usually mild, disorders related to pregnancy (8.6% versus 0.6%). The children of the women with adolescent depressions were not affected.
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| 3. |
- Bohman, Hannes, 1965-, et al.
(författare)
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Prognostic significance of functional somatic symptoms in adolescence : a 15-year community-based follow-up study of adolescents with depression compared with healthy peers
- 2012
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Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 12, s. 90-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThere is a lack of population-based long-term longitudinal research on mental health status and functional physical/somatic symptoms. Little is known about the long-term mental health outcomes associated with somatic symptoms or the temporal relationship between depression and such symptoms. This 15-year study followed up adolescents with depression and matched controls, screened from a population-based sample, who reported different numbers of somatic symptoms.MethodsThe total population of 16–17-year-olds in Uppsala, Sweden, was screened for depression in 1991–1993. Adolescents who screened positive and an equal number of healthy controls took part in a semi-structured diagnostic interview. In addition, 21 different self-rated somatic symptoms were assessed. Sixty-four percent of those adolescents participated in a follow-up structured interview 15 years later.ResultsSomatic symptoms in adolescence predicted depression and other adult mental disorders regardless of the presence of adolescent depression. In adolescents with depression, the number of functional somatic symptoms predicted, in a dose response relationship, suicidal behavior, bipolar episodes, and psychotic episodes as well as chronic and recurrent depression. Contrary to expectations, the somatic symptoms of abdominal pain and perspiration without exertion better predicted depression than all DSM-IV depressive symptoms. Abdominal pain persisted as an independent strong predictor of depression and anxiety, even after controlling for other important confounders.ConclusionsSomatic symptoms in adolescence can predict severe adult mental health disorders. The number of somatic symptoms concurrent with adolescent depression is, in a stepwise manner, linked to suicidal attempts, bipolar disorders, psychotic disorders, and recurrent and chronic depression. These findings can be useful in developing treatment guidelines for patients with somatic symptoms.
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| 4. |
- Bohman, Hannes, 1965-, et al.
(författare)
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Thicker carotid intima layer, thinner media layer and higher intima/media ratio in women with recurrent depressive disorders : a pilot study using non-invasive high frequency ultrasound
- 2010
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Ingår i: World Journal of Biological Psychiatry. - : Informa Healthcare. - 1562-2975 .- 1814-1412. ; 11:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- Background. Growing evidence indicates that depression is an important risk factor for coronary heart disease. Thus, the aim of the present study has been to investigate if young women with adolescent onset and recurrent depressive disorders have signs of carotid intima and media changes already at the age of 30. Methods. Fifteen subjects with adolescent onset recurrent depressive disorders, mean age 31.5 years, were compared to 20 healthy women with a mean age of 39.6 years. The thickness of carotid artery intima and media was assessed, using non-invasive high-frequency ultrasound (25MHz). Results. The subjects with recurrent depressive disorders had significantly thicker carotid intima, significantly thinner carotid media and significantly higher intima/media ratio despite the fact that they were about 10 years younger than the healthy women. Hypertension, obesity or smoking could not explain the results. Conclusion. Already at the age of 30, subjects with recurrent depressive disorders with adolescent onset do have early signs of carotid intima and media changes, indicating a less healthy artery wall, despite otherwise no clinical signs of cardiovascular disease.
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| 5. |
- Jonsson, Ulf, 1974-, et al.
(författare)
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Mental health outcome of long-term and episodic adolescent depression : 15-year follow-up of a community sample
- 2011
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 130:3, s. 395-404
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies have highlighted the unfavourable natural course of chronic/long-term depression. We investigated the adult mental health outcome of adolescent depression, with specific focus on long-term and episodic adolescent major depression (MD). METHODS: A community sample of depressed adolescents and non-depressed peers was followed-up with a structured diagnostic interview after 15years. The participants (n=382) were divided into five groups depending on their status in adolescence: no depression (n=155); long-term MD (n=91); episodic MD (n=63); dysthymia (n=33); and subthreshold symptoms (n=40). Outcomes (age 19-31) included mood disorders, other mental disorders, suicidality, and treatment for mental disorders. RESULTS: The long-term group overall had a poorer outcome than the non-depressed group, with the episodic group in an intermediate position. The outcome of the dysthymic group was similar to that of the long-term group, while the subsyndromal group did not differ markedly from the non-depressed group. The long-term group was more likely than the episodic group to report adult anxiety disorders, multiple mental disorders, suicide attempts, and treatment; they also seemed to develop more persistent adult depressions, with a higher number of recurrent episodes and longer duration of antidepressant treatment. Even after adjustment for adolescent factors of clinical and etiological importance, the long-term group had a markedly less favourable outcome than the episodic group. LIMITATION: The participation rate at follow-up was 64.6%. CONCLUSION: Longstanding depression in adolescence is a powerful predictor of continued mental health problems in adulthood. It is now important to evaluate if early interventions can alter this severe course.
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| 6. |
- Päären, Aivar, 1965-, et al.
(författare)
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Early risk factors for adult bipolar disorder in adolescents with mood disorders : A 15-year follow-up of a community sample
- 2014
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Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 14:1, s. 363-
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to outline the early risk factors for adult bipolar disorder (BPD) in adolescents with mood disorders.Methods: Adolescents (16-17 years old) with mood disorders (n=287; 90 participants with hypomania spectrum episodes and 197 with major depressive disorder [MDD]) were identified from a community sample. Fifteen years later (at 30-33 years of age), mood episodes were assessed (n=194). The risk of developing BPD (n=22), compared with MDD (n=104) or no mood episodes in adulthood (n=68), was estimated via logistic regression. Adolescent mood symptoms, non-mood disorders, and family characteristics were assessed as potential risk factors.Results: Among the adolescents with mood disorders, a family history of BPD was the strongest predictor of developing BPD compared with having no mood episodes in adulthood (OR=5.94; 95% CI=1.11-31.73), whereas disruptive disorders significantly increased the risk of developing BPD compared with developing MDD (OR=2.94; CI=1.06-8.12). The risk that adolescents with MDD would develop adult BPD, versus having no mood episodes in adulthood, was elevated among those with an early disruptive disorder (OR=3.62; CI=1.09-12.07) or multiple somatic symptoms (OR=6.60; CI=1.70-25.67). Only disruptive disorders significantly predicted adult BPD among adolescents with MDD versus continued MDD in adulthood (OR=3.59; CI=1.17-10.97). Only a few adolescents with hypomania spectrum episodes continued to have BPD as adults, and anxiety disorders appeared to increase this risk.Conclusions: Although most of the identified potential risk factors are likely general predictors of continued mood disorders, disruptive disorders emerged as specific predictors of developing adult BPD among adolescents with MDD.
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