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  • 1. Angst, Jules
    et al.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Benazzi, Franco
    Gamma, Alex
    Hantouche, Elie
    Meyer, Thomas D
    Skeppar, Peter
    Vieta, Eduard
    Scott, Jan
    The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients2005In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 88, no 2, p. 217-233Article in journal (Refereed)
    Abstract [en]

    Background: Bipolar disorders (BP) are frequently diagnosed and treated as pure depression initially; accurate diagnosis often being delayed by 8 to 10 years. In prospective studies, the presence of hypomanic symptoms in adolescence is strongly predictive of later bipolar disorders. As such, an instrument for self-assessment of hypomanic symptoms might increase the detection of suspected and of manifest, but under-treated, cases of bipolar disorders.

    Methods: The multi-lingual hypomania checklist (HCL-32) has been developed and is being tested internationally. This preliminary paper reports the performance of the scale in distinguishing individuals with BP (N=266) from those with major depressive disorder (MDD; N= 160). The samples were adult psychiatry patients recruited in Italy (N= 186) and Sweden (N=240).

    Results: The samples reported similar clinical profiles and the structure for the HCL-32 demonstrated two main factors identified as "active/elated" hypomania and "risk-taking/irritable" hypomania. The HCL-32 distinguished between BP and MDD with a sensitivity of 80% and a specificity of 51%.

    Limitations: Although the HCL-32 is a sensitive instrument for hypomanic symptoms, it does not distinguish between BP-1 and BP-11 disorders.

    Conclusions: Future studies should test if different combinations of items. possibly recording the consequences of hypomania, can distinguish between these BP subtypes.

  • 2.
    Asellus, Peter
    et al.
    Karolinska Inst, Dept Clin Neurosci Psychiat, Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
    Nordström, P
    Karolinska Inst, Dept Clin Neurosci Psychiat, Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Karolinska Inst, Dept Clin Neurosci Psychiat, Karolinska Univ Hosp, SE-17176 Stockholm, Sweden.
    Cholesterol and CSF 5-HIAA in attempted suicide2010In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 125, no 1-3, p. 388-92Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low serum cholesterol has been linked to suicide and violent behaviour. The same kind of associations has been reported regarding low levels of 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and suicidal behaviour. The hypothesis of the link between serum cholesterol and suicide incorporate serotonin. It proposes that low cholesterol is related to altered serotonergic neurotransmission. A correlation between CSF 5-HIAA and serum cholesterol has been shown in animal studies, but has not been found in humans.

    AIM: To study the interrelationship between serum cholesterol and CSF 5-HIAA in suicide attempters. Since both cholesterol and CSF 5-HIAA are associated with suicide and violent suicide attempts, we also investigated the correlation with suicide, violent suicide attempt method, suicide intent, hopelessness and depression severity.

    METHODS: Serum total cholesterol and CSF 5-HIAA were measured in 42 medication free suicide attempters. Patients were assessed with Becks's Hopelessness scale (BHS), Suicide Intent Scale (SIS) and Montgomery-Asberg depression rating scale (MADRS) and followed-up for causes of death.

    RESULTS: Serum total cholesterol and CSF 5-HIAA showed a significant positive correlation adjusted for age, body mass index and substance abuse diagnosis. Cholesterol and CSF 5-HIAA levels did not differ between violent and non-violent suicide attempters or between suicide completers and survivors.

    CONCLUSIONS: These findings indicate that the serotonergic system may be connected to serum cholesterol in patients with a recent suicide attempt.

  • 3.
    Asellus, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordström, Peter
    Nordström, Anna-Lena
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience, Karolinska Institutet, R5, Karolinska University Hospital/Solna, Stockholm, Sweden.
    CSF Apolipoprotein E in attempted suicide2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 225, p. 246-249Article in journal (Refereed)
    Abstract [en]

    Background: Cholesterol and cholesterol metabolism, involved in continued neural plasticity, has been associated to suicide and suicidal behavior. Apolipoprotein E (ApoE) plays an important role in the cholesterol metabolism. The purpose of this study was to investigate whether ApoE in cerebrospinal fluid was related to severity of suicidal behavior as measured by number of earlier suicide attempts, reversibility/interruptabilty and violent method of suicide attempt. Methods: CSF ApoE and 5-hydroxyindolacetic acid (5-HIAA) were measured in 42 medication free suicide attempters. Earlier suicide attempts and the reversibility of suicide attempt method were assessed with the Suicide Intent Scale (SIS) and the Freeman Scale. Suicide attempts were classified according to violence of method. Results: CSF ApoE levels significantly negatively correlated to the scores on Freeman Reversibility and there was a trend for lower CSF ApoE levels in suicide attempters using a violent method. Patients with at least one earlier suicide attempt (repeaters) showed a trend for higher CSF ApoE levels compared to suicide attempters debuting with suicidal behavior at inclusion in the study. The correlation between CSF ApoE and 5-HIAA was not significant. Limitations: The main limitations to this study were a relatively small sample size and lack of a healthy control group. Conclusion: Irreversible suicide attempts, representing a high risk for completed suicide, may be associated with lower level of ApoE in CSF.

  • 4. Asellus, Peter
    et al.
    Nordström, Peter
    Nordström, Anna-Lena
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, R5, Karolinska University Hospital/Solna.
    Plasma apolipoprotein E and severity of suicidal behaviour2016In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 190, p. 137-142Article in journal (Refereed)
    Abstract [en]

    There is evidence for association between low cholesterol levels and suicidal behaviour. Since apolipoprotein E (ApoE) is involved in the cholesterol metabolism in both the periphery and in the central nervous system; it may be of particular interest in the neurobiology of suicidal behaviour. Furthermore, hypothalamic-pituitary-adrenal (HPA) axis function, one of the main biological systems implicated in both suicidal behaviour and early-life adversity, affect ApoE levels. Very few studies have assessed plasma ApoE in relation to suicidal behaviour. The purpose of this study was to investigate levels of ApoE in plasma in relation to the severity of suicidal behaviour and life-time adversity in the form of exposure to interpersonal violence in suicide attempters. A total of 100 suicide attempters (67 women and 33 men) were enroled in the study. Information on earlier suicide attempts and age at onset of suicidal behaviour was gathered using the Karolinska Suicide History Interview. The Karolinska Interpersonal Violence Scale was used to assess exposure to interpersonal violence. Plasma ApoE was measured by immunonephelometry according to accredited routines. Patients with at least one earlier suicide attempt had significantly higher ApoE levels compared to suicide attempters debuting with suicidal behaviour at inclusion in the study. A higher number of earlier suicide attempts was significantly correlated with higher plasma ApoE levels. Age at onset was significantly negatively correlated with ApoE after adjusting for age. ApoE showed a significant positive correlation with exposure to interpersonal violence as a child in male suicide attempters. Our findings indicate that ApoE may be related to stress and trauma and the temporal severity of suicidal behaviour.

  • 5. Beckman, Karin
    et al.
    Lindh, Åsa
    Waern, Margda
    Strömsten, Lotta M. J.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Salander Renberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Runesson, Bo
    Dahlin, Marie
    Impulsive suicide attempts among young people: a prospective multicentre cohort study in Sweden2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 243, p. 421-426Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to compare the prevalence of impulsive suicide attempts (ISA) among young adults and those over 25 who present at hospital in connection with attempted suicide. We also aimed to identify factors associated with ISA in young adults and to assess medical severity as well as the probability of repeated suicide attempts in this age group.

    Method: A prospective multicentre cohort study included hospital known cases of suicide attempt (N = 666). The prevalence of ISA was compared between young adults (18-25) and adults aged > 26. We used logistic regression models to identify factors associated with ISA, associations of ISA with high medical severity and prediction of new fatal or non-fatal suicide attempts within 6 months.

    Results: 43.7% of the young patients had made an ISA, and 30.2% among those aged > 26 (p = 0.001). Among the young, substance use disorder was associated with ISA; crude odds ratio (OR) 2.0 (1.0-4.2), and adjusted OR 2.1 (0.99-4.4). Affective disorder and unemployment/sickness absence implied lower odds of ISA. ISA resulted in injuries of high medical severity as often as more planned attempts and non-fatal or fatal repetition within 6 months was equally common (30%) in both groups.

    Limitations: The study was set in psychiatric emergency services, which limits the generalizability.

    Conclusions: Clinicians should acknowledge that suicide attempts among youth often occur without previous planning and may result in medically severe injuries. The probability of new fatal or non-fatal suicide attempts should be kept in mind also after an impulsive suicide attempt.

  • 6. Carlbring, Per
    et al.
    Hägglund, Malin
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Luthström, Anne
    Dahlin, Mats
    Kadowaki, Åsa
    Vernmark, Kristofer
    Andersson, Gerhard
    Internet-based behavioral activation and acceptance-based treatment for depression: A randomized controlled trial2013In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 148, no 2-3, p. 331-337Article in journal (Refereed)
    Abstract [en]

    Background: Internet-based cognitive behavior therapy for depression has been tested in several trials but there are no internet studies on behavioral activation (BA), and no studies on BA over the internet including components of acceptance and commitment therapy (ACT). The aim of this study was to develop and test the effects of internet-delivered BA combined with ACT against a waiting list control condition as a first test of the effects of treatment. Methods: Selection took place with a computerized screening interview and a subsequent semi-structured telephone interview. A total of 80 individuals from the general public were randomized to one of two conditions. The treatment lasted for 8 weeks after which both groups were assessed. We also included a 3 month follow-up. The treatment included interactive elements online and a CD-ROM for mindfulness and acceptance exercises. In addition, written support and feedback was given by a therapist every week. Results: Results at posttreatment showed a large between group effect size on the Beck Depression inventory II d = 0.98 (95%CI = 0.51-1.44). In the treated group 25% (10/40) reached remission defined as a BDI score <= 10 vs. 5% (2/40) in the control group. Results on secondary measures were smaller. While few dropped out from the study (N = 2) at posttreatment, the average number of completed modules was M = 5.1 out of the seven modules. Limitations: The study only included a waiting-list comparison and it is not possible to determine which treatment components were the most effective. Conclusions: We conclude that there is initial evidence that BA with components of ACT can be effective in reducing symptoms of depression.

  • 7.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Salander Renberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Season of birth variations in suicide methods in relation to any history of psychiatric contacts support an independent suicidality trait.2002In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 69, no 1-3, p. 69-81Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Due to reports on season of birth variations in suicidal behaviour as well as in cerebrospinal fluid levels of monoamine metabolites, we investigated season of birth variations in suicide methods for completed suicides in relation to any history of psychiatric contacts. Relationships with the psychiatric diagnoses for those with psychiatric contacts were also studied. METHODS: Sociodemographic variables and suicide methods were examined for all the 693 suicide victims during 1961-1980 in Västerbotten, Sweden. Information on any history of psychiatric contacts was obtained from psychiatric in-patient and out-patient records. RESULTS: Gender differences in the choice of suicide method were found in the group without any history of psychiatric contacts, but not in those with such a history. Only those without a history of psychiatric contacts showed season of birth variations for suicide methods -- those born during February to April were significantly more likely, and those born during October to January significantly less likely, to have preferred hanging rather than poisoning or petrol gases. These associations were stronger for the determined suicides, for males, and for urban residence. Suicide victims with a history of psychiatric contacts were significantly younger than those without. LIMITATIONS: No psychological autopsies for those without psychiatric contacts. No information on eventual contacts with general practitioners. No measures of monoamine neurotransmitters were available. CONCLUSIONS: Season of birth association for suicide methods is likely to be mediated by a suicidality trait independently of specific major psychiatric disorders. Monoamine neurotransmitters, particularly serotonin, are likely to underlie such a trait.

  • 8.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Smedh, Kristina
    Nilsson, Lars-Göran
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    A dual vulnerability hypothesis for seasonal depression is supported by the seasonal pattern assessment questionnaire in relation to the temperament and character inventory of personality in a general population.2004In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 82, no 1, p. 61-70Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Personality structure obtained from the psychobiological Temperament and Character Inventory (TCI) was studied in relation to self-reported seasonal variations in mood and behavior measured by the Seasonal Pattern Assessment Questionnaire (SPAQ). METHODS: The subjects comprised 1761 adults (57.6% women) in the age range 35-85 years, enrolled in the Betula prospective random cohort study of Umea, Sweden. RESULTS: Personality profiles of subjects who reported the occurrence of a high degree of seasonal variation as such were associated with a combination of high self-transcendence (ST) and high persistence (PS), irrespective of the level of harm avoidance (HA). Subjects who reported feeling worst in winter were associated with high HA, irrespective of the levels of ST and PS. Also, subjects feeling worst in summer or experiencing overall problems with seasonal variation were associated with high HA in their personality profiles. Using the SPAQ criteria to define seasonal affective disorder (SAD) or subsyndromal SAD (S-SAD), subjects with these disorders often had combinations of high self-transcendence (ST) and high persistence (PS), but with different associations with HA. LIMITATIONS: No evaluations were made for SAD or subsyndromal SAD according to the DSM-IV or ICD 10 criteria. CONCLUSIONS: Our results relating SPAQ with TCI give support for a dual vulnerability hypothesis for seasonal depression proposed in the literature, where it is attributed to a combination of a seasonal factor and a depression factor. Examining the literature regarding the relationships between the different TCI scales and monoamine neurotransmitter functions, those relationships suggest that these two vulnerability factors for seasonal depression may be modulated by different neurotransmitter systems.

  • 9. Connolly, Colm G.
    et al.
    Ho, Tiffany C.
    Henje Blom, Eva
    Department of Psychiatry, Division of Child and Adolescent Psychiatry, and Weill Institute for Neurosciences, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA, USA; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    LeWinn, Kaja Z.
    Sacchet, Matthew D.
    Tymofiyeva, Olga
    Simmons, Alan N.
    Yang, Tony T.
    Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 207, p. 86-94Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents.

    Method: We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24).

    Results: Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later.

    Limitations: Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized.

    Conclusions: Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time.

  • 10. De Leo, D
    et al.
    Padoani, W
    Lonnqvist, J
    Kerkhof, A J F M
    Bille-Brahe, U
    Michel, K
    Salander Renberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Schmidtke, A
    Wasserman, D
    Caon, F
    Scocco, P
    Repetition of suicidal behaviour in elderly Europeans: a prospective longitudinal study.2002In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 72, no 3, p. 291-5Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to assess any predictive factors for repeated attempted suicide and completed suicide in a 1-year follow-up on a sample of elderly European suicide attempters (60 years and over). From 1990 to 1993, 63 subjects completed the first interview and were recontacted after 1 year. At follow-up, eight subjects (12.7%) had taken their lives and seven (11.1%) had repeated at least one suicide attempt. On comparison of repeaters and non-repeaters, differences emerged in terms of death of the father in childhood and for mean Suicidal Intent Score. At the end of follow-up period, repeaters reported a more frequent desire to repeat suicidal behaviour and judged their mental health and social assistance received to be worse. Suicides and non-repeaters differed especially in relation to death of father during childhood and number of contacts with General Practitioner. Interpretation of the results must take into account the smallness of the test sample, the difficulties in obtaining complete data for the follow-up interview, the lack of a control group and a diagnosis formulated in a hospital consultation setting. The study confirms, however, the high risk of repetition of suicidal behaviour in the elderly. In old age suicidal ideation is often sustained over long periods of time and requests for help are addressed to relatives and GPs. An interesting finding is the more frequent death of the father during childhood among repeaters.

  • 11. Engström, C
    et al.
    Thornlund, A S
    Johansson, E L
    Långström, M
    Chotai, Jayanti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nylander, P O
    Anticipation in unipolar affective disorder.1995In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 35, no 1-2, p. 31-40Article in journal (Refereed)
    Abstract [en]

    Anticipation describes an inheritance pattern within a pedigree with an increase in disease severity and/or decrease in age at onset in successive generations. The phenomenon of anticipation has recently been shown to be correlated with the expansion of trinucleotide repeat sequences in a neuromuscular disease, various neurodegenerative disorders and mental retardation. We have studied parent-offspring differences in age at onset and disease severity in 31 pairs with unilineal inheritance of unipolar affective disorder (UPAD). Life-table analyses showed a significant decrease in survival to 1st episode of major depression in the offspring generation compared with the parental generation (P = 0.0007). There was also a significant difference in age at onset (P < 0.001) between parents and offsprings. The offspring generation experienced onset 15.6 years earlier and illness 1.5 x more severe than did the parent generation. Furthermore, there was a significant correlation (P < 0.05) in age at onset between parent and offspring generations. When we excluded pairs where the affected parent has an age of onset greater than the age of the child at the time of ascertainment (i.e., 23 pairs left), there was still a significant (P = 0.02) decrease in age at onset (8.4 years) and 1.5 x more severe disease in the offspring generation. No evidence for specific maternal or paternal inheritance was found. We found evidence of anticipation in 75-80% of this sample of unilineal family pairs of UPAD. Anticipation is, thus, an inheritance pattern in a large group of UPAD which suggests that the expansion of trinucleotide repeat sequences is a possible mode of inheritance in this group of UPAD. The findings of anticipation in this study of families with UPAD and previous findings in families with BPAD suggest that the variable expression of unstable expansions of trinucleotide repeats may turn out to be the basis of the continuum of liability in affective disorders.

  • 12. Engström, Christer
    et al.
    Brändström, Sven
    Sigvardsson, Sören
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Social medicine.
    Cloninger, Robert
    Nylander, Per-Olof
    Bipolar disorder I. Temperament and character2004In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 82, no 1, p. 131-134Article in journal (Refereed)
    Abstract [en]

    Background: The nature of the relationship between personality and bipolar affective disorders is an important but unanswered question. Methods: We have studied personality in bipolar patients by using the Temperament and Character Inventory (TCI). TCI were administered to 100 euthymic bipolar patients and 100 controls from the normal population.

    Results: Bipolar patients were significantly higher in harm avoidance (HA) and lower in reward dependence (RD), self-directedness (SD), and cooperativeness (CO) than controls. Bipolar patients are more fatigable, less sentimental, more independent, less purposeful, less resourceful, less empathic, less helpful, less pure-hearted, and have less impulse control than controls. Bipolar II patients are more impulsive, more fatigable, less resourceful, and have less impulse control than bipolar I patients.

    Limitations: Our results are limited to euthymic bipolar patients and cannot be generalized to affective disorders.

    Conclusions: Even when clinically euthymic on lithium maintenance, bipolar patients continue to have a characteristic cognitive deficit. This is in agreement with cognitive theories about cognitive deficits in depression that are regarded as important vulnerability factors in mood disorders.

  • 13.
    Fekadu, Abebaw
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Alem, Atalay
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Medhin, Girmay
    Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
    Shibre, Teshome
    Department of Psychiatry, Addis Ababa University, Addis Ababa, Ethiopia.
    Cleare, Anthony
    King's College London, Institute of Psychiatry, London, UK.
    Prince, Martin
    King's College London, Institute of Psychiatry, London, UK.
    Kebede, Derege
    World Health Organization, Regional Office for Africa, Brazzaville, Congo.
    Utility of the concept of minor depressive disorder: evidence from a large rural community sample in a developing country setting2007In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 104, no 1-3, p. 111-118Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Evidence on the utility of the minor depressive disorder diagnostic construct in rural communities and developing countries is scarce. AIM: To assess the utility and validity of definitive minor depressive disorder in Ethiopia by determining its impact and sociodemographic correlates.

    METHODS: Assessment of 68,378 adults, aged 15-49 years, living in a largely rural district in Ethiopia using the Composite International Diagnostic Interview.

    RESULTS: The lifetime prevalence of minor depressive disorder was 2.2% (95% CI=2.1%, 2.3%). Age, marital status, education and unemployment independently predicted minor depressive disorder. Over 80% of cases used health services, 55.1% experienced persistent thoughts of death and 14.6% attempted suicide.

    LIMITATION: Findings are based on lifetime estimates.

    CONCLUSIONS: Minor depressive disorder is an important public health problem in rural Ethiopia, as shown by the associated high health service use and risk behaviour. Sociodemographic correlates suggest aetiological continuity with major depression. Thus our findings extend the clinical and public health utility of this diagnostic construct to rural community and developing country settings.

  • 14.
    Fekadu, Abebaw
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Shibre, Teshome
    Department of Psychiatry and Department of Community Medicine, Addis Ababa University Medical Faculty, Addis Ababa, Ethiopia.
    Alem, Atalay
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Kebede, Derge
    Department of Psychiatry and Department of Community Medicine, Addis Ababa University Medical Faculty, Addis Ababa, Ethiopia.
    Kebreab, Samuel
    Department of Psychiatry and Department of Community Medicine, Addis Ababa University Medical Faculty, Addis Ababa, Ethiopia.
    Negash, Alemayehu
    Department of Psychiatry and Department of Community Medicine, Addis Ababa University Medical Faculty, Addis Ababa, Ethiopia.
    Owen, Michael J
    Department of Psychological Medicine, University of Wales College Medicine, Cardiff, UK.
    Bipolar disorder among an isolated island community in Ethiopia2004In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 80, no 1, p. 1-10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Psychiatric data on population groups of geographic and social isolates are rare, but can potentially give insights into factors of aetiological importance. The Zeway islanders have lived in geographic and cultural isolation for over three centuries.

    AIM: To determine the prevalence of major psychiatric disorders among the adult population of Zeway islands.

    METHODS: A three stage screening design that included the use of structured interview instruments (CIDI and SCAN), key informants, and clinical assessment by psychiatrists was employed for case identification.

    RESULTS: Prevalence of bipolar disorders among the adult population (n = 1691) was 1.83% (n = 31) with 66% of the cases originating from one of the islands that constitutes only 17.33% of the study population. Only one subject was identified with schizophrenia.

    CONCLUSIONS: A pattern of differential prevalence for bipolar disorders and schizophrenia appears to exist in this isolated population, which also seems shared by other isolated population groups. The high prevalence of bipolar disorders with clustering of cases on one island may represent an environmental or genetic factor of etiologic relevance that deserves further exploration.

  • 15. Forsell, Erik
    et al.
    Bendix, Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Holländare, Fredrik
    Szymanska von Schultz, Barbara
    Nasiell, Josefine
    Blomdahl-Wetterholm, Margareta
    Eriksson, Caroline
    Kvarned, Sara
    Lindau van der Linden, Johanna
    Söderberg, Elin
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Sweden.
    Wide, Katarina
    Kaldo, Viktor
    Internet delivered cognitive behavior therapy for antenatal depression: A randomised controlled trial2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 221, p. 56-64Article in journal (Refereed)
    Abstract [en]

    Major depression occurs in 5-10% of pregnancies and is associated with many negative effects for mother and child, yet treatment options are scarce. To our knowledge, this is the first published randomised controlled trial on Internet delivered Cognitive Behavior Therapy (ICBT) for this group.

    Objective: To test the efficacy of a pregnancy adapted version of an existing 10-week ICBT-program for depression as well as assessing acceptability and adherence.

    Design: Randomised controlled trial.

    Setting: Online and telephone.

    Population or sample: Self-referred pregnant women (gestational week 10-28 at intake) currently suffering from major depressive disorder.

    Methods: 42 pregnant women (gestational week 12-28) with major depression were randomised to either treatment as usual (TAU) provided at their antenatal clinic or to ICBT as an add-on to usual care.

    Main outcome measures: The primary outcome was depressive symptoms measured with the Montgomery-Asberg depression rating scale-self report (MADRS-S). The Edinburgh Postnatal Depression Scale and measures of anxiety and sleep were used. Credibility, satisfaction, adherence and utilization were also assessed.

    Results: The ICBT group had significantly lower levels of depressive symptoms post treatment (p < 0.001, Hedges g = 1.21) and were more likely to be responders (i.e. achieve a statistically reliable improvement) (RR = 0.36; p = 0.004). Measures of treatment credibility, satisfaction, utilization, and adherence were comparable to implemented ICBT for depression.

    Limitations: Small sample size and no long-term evaluation.

    Conclusion: Pregnancy adapted ICBT for antenatal depression is feasible, acceptable and efficacious. These results need to be replicated in larger trials to validate these promising findings.

  • 16. Hanlon, Charlotte
    et al.
    Medhin, Girmay
    Alem, Atalay
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Araya, Mesfin
    Abdulahi, Abdulreshid
    Hughes, Marcus
    Tesfaye, Markos
    Wondimagegn, Dawit
    Patel, Vikram
    Prince, Martin
    Detecting perinatal common mental disorders in Ethiopia: validation of the self-reporting questionnaire and Edinburgh Postnatal Depression Scale.2008In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 108, no 3, p. 251-62Article in journal (Refereed)
    Abstract [en]

    EPDS demonstrated limited clinical utility as a screen for perinatal CMD in this rural, low-income setting. The SRQ-20 was superior to EPDS across all domains for evaluating cultural equivalence and showed validity as a dimensional measure of perinatal CMD.

  • 17.
    Hansson, Maja
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bodlund, Owe
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Chotai, Jayanti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Patient education and group counselling to improve the treatment of depression in primary care: a randomized controlled trial2008In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 105, no 1-3, p. 235-240Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Contactus program for depressed patients in primary care, consists of six lectures about depression, each followed by a group discussion. The aim of this study was to investigate if Contactus can improve treatment outcome in comparison to a control group. METHODS: Forty-six primary care centres in Sweden, each randomly allocated either to the Contactus group or to the control group, included depressed patients, 205 in the Contactus group and 114 in the control group. Besides regular treatment of depression, the Contactus group participated in the educational program. At start and after 6 weeks, patients filled in a questionnaire and the self-reports: HADS (Hospital Anxiety and Depression Scale) and GAF-self (Global Assessment of Functioning). RESULTS: After 6 weeks, clinically depressed patients (HAD-depression score >10) had a mean improvement in HAD-D of 4.6 in Contactus vs. 3.0 in controls (p=0.02), and 72% vs. 47% considered themselves to feel better (p=0.01). Increase in GAF score was 11.8 vs. 5.8 (p=0.04), respectively. According to HADS, 55% in Contactus were responders vs. 29% among controls (p=0.006), and 42% vs. 21% (p=0.02) were in remission. LIMITATIONS: Only 40% of the patients in Contactus and 35% among controls were clinically depressed according to the HADS (>10 points) at inclusion. CONCLUSIONS: Patient education and group counselling contributes significantly to better improvement among depressed patients. Group treatment is inexpensive and could be implemented in the routine care of depressed patients in primary care.

  • 18.
    Hansson, Maja
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Chotai, Jayanti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bodlund, Owe
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Patients' beliefs about the cause of their depression2010In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 124, no 1-2, p. 54-59Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients' beliefs about the cause of their depression can affect their help-seeking behavior, treatment preferences, coping strategies and treatment compliance. There are few studies exploring depressed patients' beliefs about the causes and to our knowledge none in a Swedish population. However, previous studies show that the patients more often mention environmental and psychological causes than biological. The aim of this study was to further explore depressed patients' answers to an open-ended question about the etiology of their depression. METHODS: Primary care patients, participating in a study evaluating patient education, were asked an open-ended question about their beliefs about what had caused their depression. Answers were obtained from 303 patients. RESULTS: The analysis of the patients' beliefs emerged into 16 different categories of explanations for depression that could be organized into three larger themes: current life stressors, past life events and constitutional factors. Work-related stress was the most commonly mentioned cause, followed by personality and current family situation. Only 3.6% stated biological reasons. LIMITATIONS: We could only count the frequency of mentioned causes, but no ranking of the importance of these causes. CONCLUSIONS: Primary care patients often gave multi-causal explanations to their depression. Biological explanations were rare. Their beliefs were predominantly current life stressors such as work or family situation and also their own personality. Patients' beliefs about their illness are important in the patient-doctor encounter, when developing new treatment strategies aiming at improved adherence to both psychopharmacological and psychotherapeutic treatments and also in patient education programs.

  • 19.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Connolly, Colm G
    Ho, Tiffany C
    LeWinn, Kaja Z
    Mobayed, Nisreen
    Han, Laura
    Paulus, Martin P
    Wu, Jing
    Simmons, Alan N
    Yang, Tony T
    Altered insular activation and increased insular functional connectivity during sad and happy face processing in adolescent major depressive disorder.2015In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 178, p. 215-23, article id S0165-0327(15)00141-XArticle in journal (Refereed)
    Abstract [en]

    BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide and occurs commonly first during adolescence. The insular cortex (IC) plays an important role in integrating emotion processing with interoception and has been implicated recently in the pathophysiology of adult and adolescent MDD. However, no studies have yet specifically examined the IC in adolescent MDD during processing of faces in the sad-happy continuum. Thus, the aim of the present study is to investigate the IC during sad and happy face processing in adolescents with MDD compared to healthy controls (HCL).

    METHODS: Thirty-one adolescents (22 female) with MDD and 36 (23 female) HCL underwent a well-validated emotional processing fMRI paradigm that included sad and happy face stimuli.

    RESULTS: The MDD group showed significantly less differential activation of the anterior/middle insular cortex (AMIC) in response to sad versus happy faces compared to the HCL group. AMIC also showed greater functional connectivity with right fusiform gyrus, left middle frontal gyrus, and right amygdala/parahippocampal gyrus in the MDD compared to HCL group. Moreover, differential activation to sad and happy faces in AMIC correlated negatively with depression severity within the MDD group.

    LIMITATIONS: Small age-range and cross-sectional nature precluded assessment of development of the AMIC in adolescent depression.

    CONCLUSIONS: Given the role of the IC in integrating bodily stimuli with conscious cognitive and emotional processes, our findings of aberrant AMIC function in adolescent MDD provide a neuroscientific rationale for targeting the AMIC in the development of new treatment modalities.

  • 20.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Larsson, Jan-Olov
    Serlachius, Eva
    Ingvar, Martin
    The differentiation between depressive and anxious adolescent females and controls by behavioural self-rating scales2010In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 122, no 3, p. 232-240Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This study aimed to validate the ability of frequently used self-assessment scales in Swedish child and adolescent psychiatric practice to differentiate between adolescent girls with manifest anxiety disorders and depression from those with less severe symptoms.

    METHODS: The receiver-operating characteristic (ROC) curve was calculated for Beck's Depression Inventory (BDI), Beck's Anxiety Inventory (BAI), Hospital Anxiety and Depression Scale (HAD), the emotional subscale (SDQ-em), the impact score and the total difficulties score of the Strengths and Difficulties Questionnaire and Sense of Coherence (SOC) in a sample of 73 adolescent, female patients, diagnosed with one or several anxiety disorders and/or depression. ROC was also calculated for 66 age-matched controls.

    RESULTS: SOC and the SDQ-em showed the best ability to differentiate cases of anxiety disorders and/ or depression from non-cases. SOC and SDQ-em had an equivalent ability to differentiate depression from non-cases compared to the specialised scales for depression, BDI and HAD-dep. SOC and SDQ-em were significantly better in differentiating cases of anxiety from non-cases than the specialised scales BAI and HAD-anx. Selection bias and several forms to fill in can have influenced the result.

    CONCLUSIONS: SOC and SDQ-em seemed to be valid tools for identifying girls with anxiety disorders and depression. This is of clinical importance since self-reported symptoms of anxiety and depression show a major increase in adolescent girls and methods to identify those in need of treatment are needed.

  • 21.
    Henje Blom, Eva
    et al.
    Karolinska Institutet, University of California San Francsisco.
    Lekander, Mats
    Ingvar, Martin
    Åsberg, Marie
    Mobarrez, Fariborz
    Serlachius, Eva
    Pro-inflammatory cytokines are elevated in adolescent females with emotional disorders not treated with SSRIs.2012In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 136, no 3, p. 716-23Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adults with major depressive disorder (MDD) show elevated levels of IL-6 and TNF-alpha. Studies of adolescents with MDD or anxiety disorders (AD) are few and present conflicting results.

    METHODS: We studied plasma cytokines in a clinical sample of adolescent females with MDD and/or clinical AD (n=60, mean age 16.8 years), compared to healthy controls (n=44; mean age 16.5 years).

    RESULTS: The clinical sample showed significantly higher values of IL-2 (Z=-4.09, p>0.0001), IL1-beta (Z=-2.40, p<0.05) and IL-10 (Z=-2.38, p<0.05) as compared to controls. The subgroup of the clinical sample not treated with SSRIs had a significant difference of IL-6 (Z=-2.26, p<0.05) in addition to the difference of IL-2 and IL1-beta, but showed no difference of IL-10 as compared to the controls. SSRI treatment was related to IL-6, explaining 26% of the variance in the clinical sample after controlling for BMI and symptom severity. In the clinical sample, levels of IL-6 and IFN-gamma were positively correlated with self-assessed symptoms of anxiety and/or depression (corr.coeff 0.35 resp 0.40 at p<0.05).

    LIMITATIONS: The cross-sectional design does not allow for conclusions on causality. The sample sizes were relatively small and a large drop-out in the clinical sample may have influenced the representativity.

    DISCUSSION: The study suggests that pro-inflammatory cytokines are part of the pathophysiology of emotional disorders in adolescent females and that SSRIs have anti-inflammatory properties. The findings prompt further studies on the specific mechanisms involved and may contribute to the development of more effective treatment and prevention.

  • 22. Ho, Tiffany C
    et al.
    Yang, Guang
    Wu, Jing
    Cassey, Pete
    Brown, Scott D
    Hoang, Napoleon
    Chan, Melanie
    Connolly, Colm G
    Henje Blom, Eva
    Karolinska Institutet, University of California San Francsisco.
    Duncan, Larissa G
    Chesney, Margaret A
    Paulus, Martin P
    Max, Jeffrey E
    Patel, Ronak
    Simmons, Alan N
    Yang, Tony T
    Functional connectivity of negative emotional processing in adolescent depression.2014In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 155, p. 65-74, article id S0165-0327(13)00767-2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The subgenual anterior cingulate cortex (sgACC) and its connected circuitry have been heavily implicated in emotional functioning in adolescent-onset major depressive disorder (MDD). While several recent studies have examined sgACC functional connectivity (FC) in depressed youth at rest, no studies to date have investigated sgACC FC in adolescent depression during negative emotional processing.

    METHODS: Nineteen medication-naïve adolescents with MDD and 19 matched healthy controls (HCL) performed an implicit fear facial affect recognition task during functional magnetic resonance imaging (fMRI). We defined seeds in bilateral sgACC and assessed FC using the psychophysiological interaction method. We also applied cognitive behavioral modeling to estimate group differences in perceptual sensitivity in this task. Finally, we correlated connectivity strength with clinical data and perceptual sensitivity.

    RESULTS: Depressed adolescents showed increased sgACC-amygdala FC and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus FC compared to HCL (p<0.05, corrected). Among the MDD, sgACC-precuneus FC negatively correlated with depression severity (p<0.05, corrected). Lastly, MDD adolescents exhibited poorer perceptual sensitivity in the task than HCL, and individual differences in perceptual sensitivity significantly correlated with sgACC FC and depression scores (p<0.05, corrected).

    LIMITATIONS: Subjects were clinically homogenous, possibly limiting generalizability of the findings.

    CONCLUSIONS: Adolescent depression is associated with biased processing of negative stimuli that may be driven by sgACC dysregulation and may possibly lead to an imbalance among intrinsic functional brain networks. This work also establishes the use of combining neuroimaging and cognitive behavioral modeling methods to investigate cognitive and neural differences between psychiatric and healthy populations.

  • 23. Kebede, Derege
    et al.
    Alem, Atalay
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Shibire, Teshome
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Deyassa, Negussie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Negash, Alemayehu
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Beyero, Teferra
    Medhin, Ghirmay
    Fekadu, Abebaw
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Symptomatic and functional outcome of bipolar disorder in Butajira, Ethiopia2006In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 90, no 2-3, p. 239-249Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Limited information is available on the outcome of bipolar disorder in developing countries.

    OBJECTIVE: To describe the symptomatic and functional outcome of bipolar disorder.

    METHODS: The psychoses and affective disorder modules of the CIDI were used to screen 68,378 individuals by a door-to-door survey of a defined district in Ethiopia. In addition, key informants were used to identify individuals with probable major mental illnesses. SCAN interviews were completed at the second stage to confirm the diagnosis. A total of 315 cases of bipolar disorder were identified, of which 264 (69 recent-onset and 195 prevalent cases) were prospectively followed for a mean of 2.5 (range 1-4) years by baseline and annual clinical assessments using symptom rating scales. Functional dimensions of the SF-36 scale were used to describe functional outcome. Random coefficient analyses were used to evaluate potential correlates of outcome.

    RESULTS: The magnitudes of mania and depression symptoms were elevated at baseline but improved with follow-up, although the improvement was less marked for depression. Sociodemographic or clinical variables were not associated with the improvements in symptomatic outcome. Between 35% and 47% of the recent-onset cases had functional role restrictions, while 42-52% of long-standing cases had such restrictions during the follow-up years. Similarly, social and physical functioning deficits were also present in 52-86% and 35-47% of recent-onset and long-standing cases, respectively. The magnitude of depression and mania symptoms was associated with poor functional outcome, while male sex, rural residence and being married were associated with better functional outcome.

    CONCLUSION: Although there were improvements in function with follow-up, between one-third and one-half of cases continued to have functional deficits.

  • 24. LeWinn, Kaja Z.
    et al.
    Strigo, Irina A.
    Connolly, Colm G.
    Ho, Tiffany C.
    Tymofiyeva, Olga
    Sacchet, Matthew D.
    Weng, Helen Y.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Simmons, Alan N.
    Yang, Tony T.
    An exploratory examination of reappraisal success in depressed adolescents: Preliminary evidence of functional differences in cognitive control brain regions2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 240, p. 155-164Article in journal (Refereed)
    Abstract [en]

    Background: Most neuroimaging studies of adolescent depression employ tasks not designed to engage brain regions necessary for the cognitive control of emotion, which is central to many behavioral therapies for depression. Depressed adults demonstrate less effective activation of these regions and greater amygdala activation during cognitive reappraisal; we examined whether depressed adolescents show similar patterns of brain activation.

    Methods: We collected functional magnetic resonance imaging (fMRI) data during cognitive reappraisal in 41 adolescents with major depressive disorder (MDD) and 34 matched controls (ages 13-17). We examined group differences in (1) activations associated with reappraisal and reappraisal success (i.e., negative affect reduction during reappraisal) using whole brain and amygdala region-of-interest analyses, and (2) functional connectivity of regions from the group-by-reappraisal success interaction.

    Results: We found no significant group differences in whole brain or amygdala analyses during reappraisal. In the group-by-reappraisal success interaction, activations in the left dorsomedial prefrontal cortex (dmPFC) and left dorsolateral PFC (dlPFC) were associated with reappraisal success in healthy controls but not depressed adolescents. Depressed adolescents demonstrated reduced connectivity between the left dmPFC and the anterior insula/inferior frontal gyri bilaterally (AI/IFG) and between left dlPFC and left AI/IFG.

    Limitations: Our results should be considered exploratory given our less conservative statistical threshold in the group-by-reappraisal interaction.

    Conclusions: We find preliminary evidence that depressed adolescents engage cognitive control regions less efficiently than healthy controls, suggesting delayed maturation of regulatory prefrontal cortex regions; more research is needed to determine whether cognitive therapies improve functioning of these regions in depressed youth.

  • 25.
    Maripuu, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wikgren, Mikael
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Hyper- and hypocortisolism in bipolar disorder: A beneficial influence of lithium on the HPA-axis?2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 213, p. 161-167Article in journal (Refereed)
    Abstract [en]

    Background: A hyperactive hypothalamic-pituitary-adrenal axis (HPA-axis) is a well-known phenomenon in bipolar disorder (BD). However, hypocortisolism has also been described and found associated with depression, low quality of life and cardiovascular risk factors in BD patients. Although the pathophysiology related to hypocortisolism in BD is largely unknown, hypocortisolism is associated with chronic stress exposure and after inducing an initial rise in cortisol long-term stress may result in a transition to hypocortisolism. BD patients are throughout life often exposed to chronic stress. We therefore hypothesized that higher age would be associated with lower HPA-axis activity especially among patients without previous mood stabilizing treatment. Methods: This cross-sectional study consisted of 159 bipolar outpatients and 258 controls. A low-dose-dexamethasone-suppression-test (DST) was used to measure HPA-axis activity. Results: Patients with BD showed a negative association between post DST cortisol and age (-3.0 nmol/l per year; p=0.007). This association gradually increased in subgroups that were naive to lithium (-7.7 nmol/l per year; p=0.001) and "all mood stabilizers" (-11.4 nmol/l per year; p=0.004). Patients exhibiting hypercortisolism were characterized by younger age and female gender, whereas patients exhibiting hypocortisolism were characterized by long disease duration without prophylactic lithium treatment as well as absence of current lithium medication. Limitations: Cross sectional study design. Conclusions: There was a negative association between HPA-axis activity and age in BD, rendering BD patients at risk for developing hypocortisolism. This association was most pronounced among patients without previous or current lithium prophylaxis.

  • 26.
    Maripuu, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wikgren, Mikael
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders2016In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 204, p. 187-196Article in journal (Refereed)
    Abstract [en]

    Background: Cardiovascular disease (CVD) is one of the main causes of excess deaths in affective disorders. Affective disorders are associated with increased frequencies of CVD risk-factors such as obesity, dyslipidemia, and metabolic syndrome. Stress-induced chronic cortisol excess has been suggested to promote obesity and metabolic syndrome. Chronic stress with frequent or persisting hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity may, over time, lead to a state of low HPA-axis activity, also denoted hypocortisolism. A low-dose weight-adjusted dexamethasone-suppression-test (DST) is considered to be a sensitive measure of hypocortisolism.

    Methods: 245 patients with recurrent depression or bipolar disorder and 258 controls participated in a low-dose DST and were also examined with regard to metabolic status.

    Results: Patients with hypocortisolism (low post-DST cortisol) compared with patients without hypocortisolism (normal or high post-DST cortisol) exhibited increased odds ratios (OR) for obesity (OR=4.0), overweight (OR=4.0), large waist (OR=2.7), high LDL (OR=4.2), low HDL (OR=2.4), high LDL/HDL ratio (OR=3.3), high TC/HDL ratio (OR=3.4) and metabolic syndrome (OR=2.0). A similar pattern but less pronounced was also found in the control sample.

    Limitations: The cross sectional study design and absence of analyses addressing lifestyle factors.

    Conclusions: Our findings suggest that a substantial portion of the metabolic disorders and cardiovascular risk factors seen in recurrent affective disorders are found among individuals exhibiting hypocortisolism. This might indicate that long-term stress is a central contributor to metabolic abnormalities and CVD mortality in recurrent affective disorders.

  • 27. Moberg, T
    et al.
    Nordström, P
    Forslund, K
    Kristiansson, M
    Asberg, M
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    CSF 5-HIAA and exposure to and expression of interpersonal violence in suicide attempters2011In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 132, no 1-2, p. 173-178Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Serotonin is implicated in impaired impulse control, aggression and suicidal behaviour. Low cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been found in violent suicide attempters, suicide victims and in violent offenders. CSF 5-HIAA concentrations have both genetic and environmental determinants. Childhood trauma may have an effect on central monoamine function as an adult.

    AIM: The aim of this study was to assess the relationship of CSF 5-HIAA and the exposure to and the expression of violence in childhood and during adult life measured with the Karolinska Interpersonal Violence Scale (KIVS).

    METHOD: 42 medication free suicide attempters underwent lumbar puncture and were assessed with the Karolinska Interpersonal Violence Scale (KIVS) to assess history of childhood exposure to violence and lifetime expressed violent behaviour.

    RESULTS: In women, but not in men, CSF 5-HIAA showed a significant negative correlation to exposure to violence during childhood. Furthermore, suicide attempters with low CSF 5-HIAA were more prone to commit violent acts as an adult if exposed to violence as a child compared to suicide attempters with high CSF 5-HIAA. In the non-traumatized group, CSF 5-HIAA showed a significant negative correlation to expressed violent behaviour in childhood.

    CONCLUSIONS: Although central serotonergic function has important genetic determinants, exposure to childhood trauma may also affect serotonergic function. Low serotonergic function may facilitate impaired aggression control in traumatized suicide attempters.

  • 28. Modin Asper, Michaela
    et al.
    Hallén, Nino
    Lindberg, Lene
    Månsdotter, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Carlberg, Magdalena
    Wells, Michael B.
    Screening fathers for postpartum depression can be cost-effective: an example from Sweden2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 241, p. 154-163Article in journal (Refereed)
    Abstract [en]

    Background: Postpartum depression negatively affects the whole family and its prevalence in Sweden ranges between 6-10% for fathers and 13-16% for mothers. However, only mothers in Sweden are currently routinely screened.

    Aim: The aim of this study was to determine if a postpartum depression screening for fathers in Stockholm County could be cost-effective.

    Methods: National Swedish databases were used to find registry data and a literature review was undertaken to identify the model data inputs associated with postpartum depression in Sweden. The generated evidence was used to build a Markov model in TreeAge. One-way and probabilistic sensitivity analyses were performed to account for parameter uncertainties. Alternative scenario analyses were further undertaken to test the assumptions in the base case analysis.

    Results: A postpartum screening for depression in fathers is cost-effective in base case and alternative scenarios. The results indicate that the screening program is associated with lower costs and higher health effects. The results were sensitive to variables of quality adjusted life years for the depressed fathers, probabilities of remission in treatment and no treatment groups and start age and productivity losses. The probabilistic sensitivity analysis resulted in a 70% probability of the postnatal depression screening intervention being cost-effective.

    Limitations: The current study only uses secondary data; therefore future research should assess the cost-effectiveness of screening fathers for depression.

    Conclusion: The postpartum screening intervention for fathers could be cost-effective compared to no screening. Future research should replicate the potential cost-effectiveness for screening fathers for postpartum depression.

  • 29. Negash, Alemayehu
    et al.
    Alem, A
    Kabede, D
    Deyessa, N
    Shibre, T
    Kullgren, G
    Prevalence and clinical characteristics of bipolar I disorder in Butajira, Ethiopia: a community-based study2005In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 87, no 2/3, p. 193-201Article in journal (Refereed)
    Abstract [en]

    Background Bipolar disorders have been extensively studied in the high-income countries but community-based studies from low-income countries are very rare. The main objectives of the current study are to estimate the lifetime prevalence of bipolar I disorder in the general population of the Butajira district in Ethiopia and to characterize the onset and course of the disorder in a predominantly treatment naïve population.

    Method Cases were identified by a door-to-door screening of the district's entire adult population aged 15 to 49 years (N = 83,387), where 68,378 were successfully screened. CIDI and key informant method were used in the first stage of screening followed by confirmatory SCAN interviews.

    Results Three hundred fifteen cases were identified and complete information could be collected for 295 individuals. Of these, 55.3% were males, 83.1% were from a rural area, and 70.2% were illiterate. Lifetime prevalence of bipolar I disorder was estimated to be 0.6% for males and 0.3% for females. The mean age of cases was 29.5 years, with no significant sex difference. The mean age of first recognition of illness was 22.0 years; for men 22.3 years and for women 21.2 years. The mean age at onset of manic phase of the illness was found to be 22.0 years (22.5 for men and 21.4 for women). The mean age at onset of depressive phase was 23.4 years (24.1 for men and 22.5 for women). There was no significant sex difference in the age of onset of manic or depressive phases. In 22.7% of the cases bipolar I illness started with a depressive episode and in 77.3% of the cases it started with a manic episode. Two or more episodes of the illness were reported by 64.1%. Over half of the study subjects (55.9%) had never sought any help from modern healthcare sector, and only 13.2% had ever been admitted to psychiatric hospital. During the survey 7.1% of the cases were undergoing treatment. A previous suicide attempt was reported by 8.1% of the males and 5.4% of the females.

    Conclusion The overall lifetime prevalence and age of onset are within the range of findings from other studies in Western countries. In contrast to most previous studies, prevalence of the disorder among females was half of that among males. Our finding that prevalence of this disorder among males and females appeared to be different from many other studies warrants further research.

  • 30.
    Negash, Alemayehu
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Kabede, D
    Alem, Atalay
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Melaku, Z
    Deyessa, Negussie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Shibire, Teshome
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Fekadu, Abebaw
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Fekadu, Daniel
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Jacobsson, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Kullgren, Gunnar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Neurological soft signs in bipolar I disorder patients2004In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 80, no 2/3, p. 221-230Article in journal (Refereed)
    Abstract [en]

    Background: Neurological soft signs (NSS) have been reported to be more prevalent in patients with schizophrenia compared to other psychiatric and non-psychiatric controls. However, this issue in bipolar I disorder seems to be understudied.

    Aims: The aims of the study were to examine the extent to which NSS are associated with bipolar I disorder cases compared to healthy controls, to assess the possible relationship between NSS and clinical dimensions of the disorder, and to explore the association of sociodemographic characteristics with the occurrence of NSS in cases with this disorder.

    Methods: Predominantly treatment naïve cases of bipolar I disorder from rural communities were assessed for NSS using the Neurological Evaluation Scale (NES).

    Results: This study showed that patients with bipolar I disorder performed significantly worse on two NES items from the sensory integration subscale, on one item from motor coordination and on four items from the ‘others’ subscale, the highest difference in performance being in items under the sequencing of complex motor acts subscale. Clinical dimensions and sociodemographic characteristics appeared to have no relationship with NES total score.

    Conclusions: Bipolar I disorder patients seem to have more neurological dysfunction compared to healthy controls particularly in the area of sequencing of complex motor acts. In addition, the finding suggests that NSS in bipolar I disorder are stable neurological abnormalities established at its onset or may be essential characteristic features of the disorder representing stable disease process that existed long before its onset.

  • 31.
    Nyström, Markus B. T.
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Stenling, Andreas
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Sjöström, Emma
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Neely, Gregory
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Lindner, Philip
    Hassmén, Peter
    Umeå University, Faculty of Social Sciences, Department of Psychology. School of Health and Human Sciences, Southern Cross University, Australia.
    Andersson, Gerhard
    Martell, Christopher
    Carlbring, Per
    Behavioral activation versus physical activity via the internet: A randomized controlled trial2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 215, p. 85-93Article in journal (Refereed)
    Abstract [en]

    Background: A major problem today is that only about fifty percent of those affected by depression seeks help. One way to reach more sufferers would be by offering easily accessible internet based treatments. The purpose of this study was to compare/evaluate four therapist supported internet administered treatments.

    Method/results: Two hundred eighty six participants were included. The treatment period lasted twelve weeks, consisting of the following treatments: 1) physical activity without treatment rational, 2) physical activity with treatment rational, 3) behavioral activation without treatment rational and 4) behavioral activation with treatment rational. All groups (including a control-group) showed a significant decrease in depressive symptoms. When the treatment groups were pooled and compared to the control group, there were significant differences from pretest to posttest (Hedges gav treatment =1.01, control group =0.47). This held true also when each of the four treatment groups was compared to the control group, with one exception: Physical activity without treatment rationale.

    Limitations: The differences between how many modules the participants completed could indicate that there are other factors than the treatments that caused the symptom reduction, however, the dose-response analysis did not detect any significant differences on account of modules completed.

    Conclusions: The results support the positive effects of internet administered treatments for depression, and highlights the importance of psychoeducation, which tends to affect both the treatment outcome and the probability of remaining in treatment. These aspects need to be considered when developing and conducting new treatments for depression, since they would increase the likelihood of positive treatment outcomes.

  • 32.
    Rajalin, Mia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm.
    Hirvikoski, Tatja
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Karolinska Univ Hosp, Karolinska Inst, Dept Clin Neurosci Psychiat, SE-17176 Stockholm, Sweden.
    Family history of suicide and exposure to interpersonal violence in childhood predict suicide in male suicide attempters2013In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 148, no 1, p. 92-97Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Family studies, including twin and adoption designs, have shown familial transmission of suicidal behaviors. Early environmental risk factors have an important role in the etiology of suicidal behavior. The aim of the present study was to assess the impact of family history of suicide and childhood trauma on suicide risk and on severity of suicide attempt in suicide attempters.

    METHODS: A total of 181 suicide attempters were included. Family history of suicide was assessed with the Karolinska Suicide History Interview or through patient records. Childhood trauma was assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behavior in childhood (between 6 and 14 years of age) and during adult life (15 years or older). Suicide intent was measured with the Freeman scale.

    RESULTS: Male suicide attempters with a positive family history of suicide made more serious and well planned suicide attempts and had a significantly higher suicide risk. In logistic regression, family history of suicide and exposure to interpersonal violence as a child were independent predictors of suicide in male suicide attempters.

    LIMITATIONS: The information about family history of suicide and exposure to interpersonal violence as a child derives from the patients only. In the first part of the inclusion period the information was collected from patient records.

    CONCLUSIONS: The results of this study imply that suicides among those at biological risk might be prevented with the early recognition of environmental risks.

  • 33. Sköld, Mia
    et al.
    Källstrand, Johan
    Nehlstedt, Sara
    Nordin, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nielzén, Sören
    Holmberg, Jens
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Thalamocortical abnormalities in auditory brainstem response patterns distinguish DSM-IV bipolar disorder type I from schizophrenia2014In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 169, p. 105-11Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bipolar disorder type I (BP-I) belongs to a spectrum of affective disorders that are expressed in many different ways and therefore can be difficult to distinguish from other conditions, especially unipolar depression, schizoaffective disorder, schizophrenia (SZ), but also anxiety and personality disorders. Since early diagnosis and treatment have shown to improve the long-term prognosis, complementary specific biomarkers are of great value. The auditory brainstem response (ABR) has previously been applied successfully to identify specific abnormal ABR patterns in SZ and Asperger syndrome.

    METHODS: The current study investigated the early auditory processing of complex sound stimuli e.g. forward masking, in BP-I compared to SZ patients. The ABR curves of BP-I patients (n=23) and SZ patients (n=20) were analyzed in terms of peak amplitudes and correlation with an ABR norm curve based on a non-psychiatric control group (n=20).

    RESULTS: BP-I patients had significantly higher wave III (p=0.0062) and wave VII (p=0.0472) amplitudes compared with SZ patients. Furthermore, BP-I patients, and to a lesser extent SZ patients, showed low correlation with the norm ABR curve in the part of the curve comprising waves VI-VII.

    LIMITATIONS: Sample size was relatively small and study groups were not matched for age and gender.

    CONCLUSIONS: BP-I patients showed specific aberrances, specifically in the latter part of the ABR curve, implicating abnormalities in thalamocortical circuitry. The abnormal ABR wave patterns significantly separated BP-I patients from SZ patients suggesting that ABR might serve as a biomarker for BP-I.

  • 34. Stefansson, J
    et al.
    Nordström, P
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Karolinska Inst, Karolinska Univ Hosp, Dept Clin Neurosci, Psychiat Sect, SE-17176 Stockholm, Sweden.
    Suicide intent scale in the prediction of suicide2012In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 136, no 1-2, p. 167-71Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the predictive value of the Suicide Intent Scale in patients with high suicide risk. The secondary aim was to assess if the use of the factors of the Suicide Intent Scale may offer a better predictive value in suicide risk detection. Finally a shorter version of the scale was created after an item analysis.

    METHOD: Eighty-one suicide attempters were assessed with the Beck's Suicide Intent Scale (SIS). All patients were followed up for cause of death. Receiver-operating characteristic (ROC) curves and tables were created to establish the optimal cut-off values for SIS and SIS factors to predict suicide.

    RESULTS: Seven patients committed suicide during a mean follow up of 9.5 years. The major finding was that mean SIS scores distinguished between suicides and survivors. The positive predictive value was 16.7% and the Area Under Curve (AUC) was 0.74. Only the planning subscale reached statistical significance. Four items were used to test a shorter version of the SIS in the suicide prediction. The positive predictive value was 19% and the AUC was 0.82.

    CONCLUSIONS: The Suicide Intent Scale is a valuable tool in clinical suicide risk assessment, a shorter version of the scale may offer a better predictive value.

  • 35.
    Sundman-Eriksson, Ingrid
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Allard, Per
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    [(3)H]Tiagabine binding to GABA transporter-1 (GAT-1) in suicidal depression.2002In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 71, no 1-3, p. 29-33Article in journal (Refereed)
    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.

  • 36. Tesfaye, Markos
    et al.
    Hanlon, Charlotte
    Wondimagegn, Dawit
    Alem, Atalay
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Detecting postnatal common mental disorders in Addis Ababa, Ethiopia: validation of the Edinburgh postnatal depression scale and Kessler scales2010In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 122, no 1-2, p. 102-108Article in journal (Refereed)
    Abstract [en]

    The EPDS, K6 and K10 all demonstrated acceptable clinical utility as screening scales for postnatal CMD in an urban setting in Ethiopia. The marked urban-rural difference in EPDS performance within Ethiopia highlights the difficulty of applying urban-validated instruments to rural settings in LAMIC.

  • 37. Tymofiyeva, Olga
    et al.
    Connolly, Colm G.
    Ho, Tiffany C.
    Sacchet, Matthew D.
    Henje Blom, Eva
    Department of Psychiatry, University of California San Francisco, United States; Department of Clinical Neuroscience, Karolinska Institute, Sweden.
    LeWinn, Kaja Z.
    Xu, Duan
    Yang, Tony T.
    DTI-based connectome analysis of adolescents with major depressive disorder reveals hypoconnectivity of the right caudate2017In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 207, p. 18-25Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adolescence is a vulnerable period for the onset of major depressive disorder (MDD). While some studies have shown white matter alterations in adolescent MDD, there is still a gap in understanding how the brain is affected at a network level.

    METHODS: We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 57 adolescents with MDD and 41 well-matched healthy controls who completed self-reports of depression symptoms and stressful life events. Using atlas-based brain regions as network nodes and tractography streamline count or mean fractional anisotropy (FA) as edge weights, we examined weighted local and global network properties and performed Network-Based Statistic (NBS) analysis.

    RESULTS: While there were no significant group differences in the global network properties, the FA-weighted node strength of the right caudate was significantly lower in depressed adolescents and correlated positively with age across both groups. The NBS analysis revealed a cluster of lower FA-based connectivity in depressed subjects centered on the right caudate, including connections to frontal gyri, insula, and anterior cingulate. Within this cluster, the most robust difference between groups was the connection between the right caudate and middle frontal gyrus. This connection showed a significant diagnosis by stress interaction and a negative correlation with total stress in depressed adolescents.

    LIMITATIONS: Use of DTI-based tractography, one atlas-based parcellation, and FA values to characterize brain networks represent this study's limitations.

    CONCLUSIONS: Our results allowed us to suggest caudate-centric models of dysfunctional processes underlying adolescent depression, which might guide future studies and help better understand and treat this disorder.

  • 38. Tymofiyeva, Olga
    et al.
    Henje Blom, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry. Department of Psychiatry and Weill Institute for Neurosciences, University of California San Francisco, United States.
    Ho, Tiffany C.
    Connolly, Colm G.
    Lindqvist, Daniel
    Wolkowitz, Owen M.
    Lin, Jue
    LeWinn, Kaja Z.
    Sacchet, Matthew D.
    Han, Laura K. M.
    Yuan, Justin P.
    Bhandari, Sarina P.
    Xu, Duan
    Yang, Tony T.
    High levels of mitochondrial DNA are associated with adolescent brain structural hypoconnectivity and increased anxiety but not depression2018In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 232, p. 283-290Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adolescent anxiety and depression are highly prevalent psychiatric disorders that are associated with altered molecular and neurocircuit profiles. Recently, increased mitochondrial DNA copy number (mtDNA-cn) has been found to be associated with several psychopathologies in adults, especially anxiety and depression. The associations between mtDNA-cn and anxiety and depression have not, however, been investigated in adolescents. Moreover, to date there have been no studies examining associations between mtDNA-cn and brain network alterations in mood disorders in any age group.

    METHODS: The first aim of this study was to compare salivary mtDNA-cn between 49 depressed and/or anxious adolescents and 35 well-matched healthy controls. The second aim of this study was to identify neural correlates of mtDNA-cn derived from diffusion tensor imaging (DTI) and tractography, in the full sample of adolescents.

    RESULTS: There were no diagnosis-specific alterations in mtDNA-cn. However, there was a positive correlation between mtDNA-cn and levels of anxiety, but not depression, in the full sample of adolescents. A subnetwork of connections largely corresponding to the left fronto-occipital fasciculus had significantly lower fractional anisotropy (FA) values in adolescents with higher than median mtDNA-cn.

    LIMITATIONS: Undifferentiated analysis of free and intracellular mtDNA and use of DTI-based tractography represent this study's limitations.

    CONCLUSIONS: The results of this study help elucidate the relationships between clinical symptoms, molecular changes, and neurocircuitry alterations in adolescents with and without anxiety and depression, and they suggest that increased mtDNA-cn is associated both with increased anxiety symptoms and with decreased fronto-occipital structural connectivity in this population.

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