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1.
  • Fransson, Filip, et al. (author)
  • Kidney function in patients with bipolar disorder with and without lithium treatment compared with the general population in northern Sweden : results from the LiSIE and MONICA cohorts
  • 2022
  • In: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 9:10, s. 804-814
  • Journal article (peer-reviewed)abstract
    • Background: The clinical relevance of lithium nephropathy is subject to debate. Kidney function decreases with age and comorbidities, and this decline might lead to attribution bias when erroneously ascribed to lithium. We aimed to investigate whether patients with bipolar or schizoaffective disorder had faster decline in estimated glomerular filtration rate (eGFR) compared with the general population, whether observed differences in the steepness of the decline were attributable to lithium, and whether such changes depended on the length of lithium exposure.Methods: In this cross-sectional cohort study, we used clinical data from the Lithium–Study into Effects and Side-effects (LiSIE) retrospective cohort study, which included patients with bipolar disorder or schizoaffective disorder whose medical records were reviewed up to Dec 31, 2017, and the WHO Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, covering a representative sample of the general population in northern Sweden aged 25–74 years. The primary outcome was the age-associated decline of creatinine-based eGFR, assessed using linear regression. We adjusted for sex and grouped for different lengths of lithium exposure (never or <1 year, 1–5 years, >5–10 years, and >10 years). For patients with moderate-to-severe kidney disease we identified the underlying nephropathy in the case records.Findings: From LiSIE, we included 785 patients (498 [63%] female and 287 [37%] male), with a mean age of 49·8 years (SD 13·2; range 25–74). From MONICA, we included 1549 individuals (800 [52%] female and 749 [48%] male), with a mean age of 51·9 years (13·8; 25–74). No ethnicity data were collected. Adjusted for duration of lithium exposure, eGFR declined by 0·57 mL/min/1·73 m2/year (95% CI 0·50–0·63) in patients with bipolar disorder or schizoaffective disorder and by 0·57 mL/min/1·73 m2/year (0·53–0·61) in the reference population. Lithium added 0·54 mL/min/1·73 m2 (0·43–0·64) per year of treatment (p<0·0001). After more than 10 years on lithium, decline was significantly steeper than in all other groups including the reference population (p<0·0001). Lithium nephropathy was judged to be the commonest cause of moderate-to-severe chronic kidney disease, but comorbidities played a role. The effect of lithium on eGFR showed a high degree of inter-individual variation.Interpretation: Steeper eGFR decline in patients with bipolar disorder or schizoaffective disorder can be attributed to lithium, but the trajectory of kidney function decline varies widely. Comorbidities affecting kidneys should be treated assertively as one possible means to affect the trajectory. In patients with a fast trajectory, a trade-off is required between continuing lithium to treat mental health problems and discontinuing lithium for the sake of renal health.Funding: Norrbotten County Research and Learning Fund Sweden, Visare Norr (Northern County Councils Regional Federation Fund), Swedish Kidney Foundation (Njurfonden), Swedish Kidney Association (Njurförbundet), Norrbotten section.Translation: For the Swedish translation of the Summary see Supplementary Materials section.
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2.
  • Lindh, A. U., et al. (author)
  • Predicting suicide: A comparison between clinical suicide risk assessment and the Suicide Intent Scale
  • 2020
  • In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 263, s. 445-449
  • Journal article (peer-reviewed)abstract
    • Background: How suicide risk should be assessed is under discussion with arguments for both actuarial and clinical approaches. The aim of the present study was to compare the predictive accuracy of a clinical suicide risk assessment to that of the Suicide Intent Scale (SIS) in predicting suicide within one year of an episode of self-harm with or without suicidal intent. Methods: Prospective clinical study of 479 persons assessed in a psychiatric emergency department after an episode of self-harm. The clinical risk assessment and the SIS rating were made independently of each other. Suicides within one year were identified in the National Cause of Death Register. Receiver operating characteristic (ROC) curves were constructed, optimal cut-offs were identified and accuracy statistics were calculated. Results: Of 479 participants, 329 (68.7%) were women. The age range was 18-95 years. During one-year follow up, 14 participants died by suicide. The area under the curve (AUC) for the clinical risk assessment and the SIS score were very similar, as were the accuracy statistic measures at the optimal cut-offs of the respective methods. The positive predictive value (PPV) of each assessment method was 6%. Limitations: The clinical suicide risk assessment is not standardized. The number of suicides is small, not allowing for stratification by e.g. gender or diagnosis. Conclusion: Predictive accuracy was similar for a clinical risk assessment and the SIS, and insufficient to guide treatment allocation.
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3.
  • Naesström, Matilda, 1987- (author)
  • Deep brain stimulation in obsessive-compulsive disorder
  • 2021
  • Doctoral thesis (other academic/artistic)abstract
    • Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. As a crucial part of the anxiety circuit in the brain, the bed nucleus of stria terminalis (BNST) has been proposed as a target for DBS in OCD. However, the mechanism of action of BNST DBS in OCD is not yet fully understood. In our studies, the aim was to evaluate the effect and side effects of DBS in the BNST in severe OCD, to investigate which anatomical areas are being affected by the stimulation and what could be the potential mechanism of action of DBS in this target. We also explored the knowledge and concerns regarding DBS in OCD among psychiatrists, psychotherapists and patients suffering from the disorder. We investigate clinical outcomes and safety of DBS in the BNST in a series of 11 participants with severe therapy-refractory OCD. The primary outcome was a change in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores one year after surgery. Using image and stimulation parameter data from the study above, we investigate through participant-specific simulation of the electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Six of the participants were evaluated with symptom provocation fMRI pre-operatively and in DBS ON and OFF conditions. A web-based study surveyed psychiatrists, patients, and cognitive-behavioural therapists regarding previous knowledge of DBS, source of knowledge, attitudes, and concerns towards the therapy.At baseline, the mean±SD YBOCS score was 33±3.0. One year after DBS, mean±SD YBOCS score was 20±4.8 (38% improvement (range 10- 60%) p <0.01). Of the 11 participants, six were considered responders (decrease in YBOCS ≥35%) and four partial responders (decrease in YBOCS 25-34%). Surgical adverse events included one case of skin infection leading to reimplantation. The most common transient stimulation-related side-effects were anxiety and insomnia. The individual electric stimulation fields by stimulation in the BNST were similar at the 12 and 24-months follow up, involving mainly the anterior limb of the internal capsule (ALIC), genu of the internal capsule, BNST, fornix, anteromedial globus pallidus externa (GPe) and the anterior commissure. A statistically significant correlation (p < 0.05) between clinical effect measured by the YBOCS and simulation was found at the 12-month follow-up in the ventral ALIC and anteromedial GPe. A significant decrease in anxiety-related brain activity in the pre-supplementary motor area (pre-SMA) and the anterior insula was seen in 3/6 participants, with a comparable reduction (below significance level) in the other three participants. Results from the survey found that the primary source of information was from scientific sources among psychiatrists and psychotherapists. The patients' primary source of information was the media. Common concerns among the groups included complications from surgery, anaesthesia, stimulation side effects, and the novelty of the treatment. Specific concerns for the groups included; personality changes mentioned by patients and psychotherapists and ethical concerns among psychiatrists.BNST DBS is a promising therapy in severe therapy-refractory OCD. Our results are in line with previous publications regarding effect and safety profiles. We hypothesise that possible mechanisms of BNST DBS in OCD could be modulation of anxiety-related activity in the pre-SMA and anterior insula, two regions that play an important role in the pathophysiology of OCD. Many of the targets under investigation for OCD are in anatomical proximity, and as seen in our study, offtarget effects overlap. Therefore, DBS in the region of ALIC, NA, and BNST may perhaps be considered to be stimulation of the same target. DBS challenges in obsessive-compulsive disorder consist of source and quality of information, potential long-term adverse effects and eligibility. A broad research agenda is needed for studies as we advance in this field.
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4.
  • Olsson, Petter, et al. (author)
  • Attention deficit hyperactivity disorder in adults who present with self-harm : a comparative 6-month follow-up study
  • 2022
  • In: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 22:1
  • Journal article (peer-reviewed)abstract
    • Background: ADHD is common in psychiatric populations. This study aimed to compare clinical characteristics in adults with and without ADHD who presented with self-harm, and to compare later risk of suicidal behaviour within 6 months.Methods: Eight hundred four adults presented with self-harm (with and without suicidal intent) at psychiatric emergency services at three Swedish hospitals. Persons with a discharge ICD-10 diagnosis F90.0-F90.9 or a prescription for ADHD medication were considered to have ADHD (n = 93). Medical records were reviewed for evidence of subsequent suicide attempts (SA) within 6 months; suicides were identified by national register.Results: Recent relationship problems were more prevalent in the ADHD group. While the index episodes of those with ADHD were more often non-suicidal, and actual SAs more often rated as impulsive, medical lethality at presentation did not differ in attempters with and without ADHD. Subsequent SAs (fatal or non-fatal) were observed in 29% of the ADHD group and 20% in all others (P = .005). A logistic regression model showed elevated risk of suicidal behaviour during follow-up in the ADHD group (OR = 1.70, CI 1.05–2.76), although a final regression model suggested that this association was partly explained by age and comorbid emotionally unstable personality disorder.Conclusions: Findings highlight the need for clinicians to take self-harm seriously in adults with ADHD.
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5.
  • Rajalin, Mia, et al. (author)
  • Exposure to Early Life Adversity and Interpersonal Functioning in Attempted Suicide
  • 2020
  • In: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 11
  • Journal article (peer-reviewed)abstract
    • Background: Early life adversity (ELA) may lead to an increased risk for mental health problems including suicidal behavior. ELA alters biological stress systems that affect behavior and control within the individual that in turn will affect interpersonal behavior. Strained relations and interpersonal conflicts leading to rejection and isolation have been shown to be factors for suicidal behavior. Difficulties in interpersonal relationships are a common reason for seeking help in psychiatric care. In the present study, we examined relationship between different types of interpersonal problems and adverse childhood experiences in patients with a recent suicide attempt.Method: The study included 181 recent suicide attempters. We assessed early life adversity and specific interpersonal problems by using the Karolinska Interpersonal Violence Scale and the Inventory of Interpersonal problems respectively.Results: Suicide attempters with high levels of early life adversity expressed a more socially avoidant, non-assertive, and exploitable personal style even after adjustment for comorbidities with personality disorder and substance use disorder.Conclusions: Patients with a recent suicide attempt with high levels of early life adversity tend to isolate themselves, of being introvert, and having difficulties to open up and confide in others. They report low self-confidence and self-esteem and problems with feeling and expressing anger. These behaviors complicate interaction with others and make establishment of solid relationships more difficult. In regards to detection of suicidal communication and treatment of suicidal patients, this may lead to misinterpretations and difficulties to fully benefit from treatment given or for professionals to provide the appropriate treatment. Clinicians should closely investigate the presence of early life adversity in suicidal patients and pay attention to their personal style and their difficulties in interpersonal exchange.
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6.
  • Waern, Margda, 1955, et al. (author)
  • Overlapping Patterns of Suicide Attempts and Non-suicidal Self-Injuries in Adults: A Prospective Clinical Cohort Study
  • 2022
  • In: Journal of Clinical Psychiatry. - : Physicians Postgraduate Press, Inc. - 0160-6689 .- 1555-2101. ; 83:6
  • Journal article (peer-reviewed)abstract
    • Objective: An overlap of non-suicidal self-injuries (NSSIs) and suicide attempts (SAs) is observed in young cohorts, but there are few robust prospective studies for adults. We compared 1-year outcomes in adults with different self-harm patterns: NSSI only, NSSI + SA, and SA only.Methods: 793 patients (67% women) consecutively presenting with NSSI (17%) or SA (83%) at 3 Swedish hospitals took part in face-to-face interviews. Past and current self-harm was characterized by the Columbia-Suicide Severity Rating Scale. Clinical records and national register data were employed to determine 1-year outcomes.Results: At inclusion, over half of the participants had engaged in both NSSI and SA; 41% had SA only and 5%, NSSI only. During follow-up, non-fatal SAs were observed in approximately onethird of the total group (n = 269). Suicides occurred in 2% of those with NSSI + SA; the same proportion was seen in the SA only group. No suicides were observed in those with NSSI only. In a multiple logistic regression analysis, the NSSI + SA pattern was associated with a more than 3-fold risk of subsequent fatal/ non-fatal suicidal behavior compared to "pure" NSSI; risk was not elevated in those with "pure" SA. Neither sex nor age group predicted subsequent suicidal behavior.Conclusions: Switching between behaviors with and without suicidal intent was common in this adult clinical cohort. Risk of subsequent suicidal behavior was tripled in the combined group. Clinicians who assess adults with NSSI must evaluate not only current but also previous episodes when assessing future risk of suicidal behavior.
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7.
  • Wiktorsson, Stefan, 1955, et al. (author)
  • Clinical Characteristics in Older, Middle-Aged and Young Adults Who Present With Suicide Attempts at Psychiatric Emergency Departments : A Multisite Study
  • 2022
  • In: The American journal of geriatric psychiatry. - : Elsevier. - 1064-7481 .- 1545-7214. ; 30:3, s. 342-351
  • Journal article (peer-reviewed)abstract
    • Objectives: To study age group differences in clinical characteristics in older, middle-aged and younger adults with actual suicide attempts (SA).Design: Cross-sectional cohort study.Setting: 3 Swedish university hospitals.Participants: 821 persons who presented with self-harm at psychiatric emergency departments participated. Those with non-suicidal self-injury according to the Columbia Suicide Severity Rating Scale (C-SSRS) were excluded, leaving a total of 683 with an actual SA (18–44 years, n = 423; 45-64 years, n = 164; 65+, n = 96).Measurements: Suicidal behavior was characterized with the C-SSRS and the Suicide Intent Scale (SIS); symptoms associated with suicide were rated with the Suicide Assessment Scale (SUAS). Diagnoses were set using the Mini-International Neuropsychiatric Interview. Patients self-rated their symptoms with the Karolinska Affective and Borderline Symptoms Scale (KABOSS).Results: Older adults scored higher than the younger group on SIS total score and on the subjective subscale, but no age group differences were detected for the objective subscale. Half of the 65+ group fulfilled criteria for major depression, compared to 3-quarters in both the middle-aged and young groups. Anxiety disorders, as well as alcohol and substance use disorders were also less prevalent in the 65+ group, while serious physical illness was more common. Older adults scored lower on all symptom scales; effect sizes were large.Conclusions: While older adults with an SA showed higher suicide intent than young adults, they had lower scores on all ratings of psychiatric symptomatology. Low ratings might interfere with clinicians’ assessments of the needs of older adults with intentional self-harm.
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8.
  • Öhlund, Louise, et al. (author)
  • Psychiatric hospital utilisation following lithium discontinuation in patients with bipolar I or II disorder : A mirror-image study based on the lisie retrospective cohort
  • 2021
  • In: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 64, s. S79-S79
  • Journal article (other academic/artistic)abstract
    • Evidence for lithium as a maintenance treatment for bipolar disorder type II remains limited since most treatment-prevention studies focus on bipolar disorder type I or do not distinguish between types of bipolar disorder.ObjectivesTo compare the impact of lithium discontinuation on hospital utilisation in patients with bipolar disorder type I or schizoaffective disorder and patients with bipolar disorder type II or other bipolar disorder.MethodsMirror-image study, examining hospital utilisation within two years before and after lithium discontinuation as part of LiSIE, a retrospective cohort study into effects and side-effects of lithium for the maintenance treatment of bipolar disorder as compared to other mood stabilisers.ResultsFor the whole sample, the number of admissions increased from 86 to 185 admissions after lithium discontinuation, with the mean number of admissions/patient/review period doubling from 0.44 to 0.95 (p < 0.001). The number of bed days increased from 2218 to 4240, with the mean number of bed days/patient/review period doubling from 11 to 22 (p = 0.025). This increase in admissions and bed days was exclusively attributable to patients with bipolar disorder type I or schizoaffective disorder.ConclusionsOur findings suggest that due to a higher relapse risk in patients with bipolar disorder type I or schizoaffective disorder there is a need to apply a higher threshold for discontinuing lithium than for patients with bipolar disorder type II or other bipolar disorder.DisclosureMichael Ott has been a scientific advisory board member of Astra Zeneca Sweden, Ursula Werneke has received funding for educational activities on behalf of Norrbotten Region (Masterclass Psychiatry Programme 2014–2018 and EAPM 2016, Luleå, Sweden): Astra
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9.
  • Öhlund, Louise, et al. (author)
  • Self-injurious behaviour in patients with bipolar disorder and attention deficit hyperactivity disorder after central stimulant start : a retrospective study based on the lisie cohort
  • 2021
  • In: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 64:S1, s. S79-S80
  • Journal article (other academic/artistic)abstract
    • Currently, our understanding remains limited of how co-occurring bipolar disorder and attention deficit hyperactivity disorder (ADHD) should be treated.ObjectivesTo evaluate the impact of central stimulant treatment on self-injurious behaviour in patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD.MethodsRetrospective cohort study (LiSIE) into effects and side-effects of lithium as compared to other mood stabilisers. Here, using a mirror-image design, we compared suicide attempts and non-suicidal self-injury events within 6 months and 2 years before and after central stimulant treatment start.ResultsOf 1564 eligible patients, 206 patients met inclusion criteria; having a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD at first central stimulant initiation. In these, suicide attempts and non-suicidal self-injury events decreased significantly within both 6 months (p = 0.004) and 2 years (p = 0.028) after central stimulant start. After multiple adjustments, this effect was preserved 2 years after central stimulant start (OR 0.63, 95% CI; 0.40 – 0.98, p = 0.041).ConclusionsCentral stimulant treatment may reduce the risk of self-injurious behavior in patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD. However, to reduce the risk of manic switches, concomitant mood stabilising treatment remains warranted.DisclosureMichael Ott has been a scientific advisory board member of Astra Zeneca Sweden, Ursula Werneke has received funding for educational activities on behalf of Norrbotten Region (Masterclass Psychiatry Programme 2014–2018 and EAPM 2016, Luleå, Sweden): Astra
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10.
  • Öhlund, Louise, et al. (author)
  • Suicidal and non-suicidal self-injurious behaviour in patients with bipolar disorder and comorbid attention deficit hyperactivity disorder after initiation of central stimulant treatment : a mirror-image study based on the LiSIE retrospective cohort
  • 2020
  • In: Therapeutic Advances in Psychopharmacology. - : Sage Publications. - 2045-1253 .- 2045-1261. ; 10, s. 1-19
  • Journal article (peer-reviewed)abstract
    • Background: Currently, our understanding regarding treatment of adult attention deficit hyperactivity disorder (ADHD) co-occurring with bipolar disorder (BD) remains limited. The aim of this study was to evaluate the impact of central stimulant (CS) treatment on suicidal and non-suicidal self-injurious behaviour in patients with a pre-existing diagnosis of BD or schizoaffective disorder (SZD). Specifically, we tested the hypothesis that CS treatment significantly decreased the number of suicide attempts and non-suicidal self-injury events.Methods: A mirror-image study in patients with a dual diagnosis of BD or SZD and ADHD, comparing suicide attempts and non-suicidal self-injury events within 6 months and 2 years before and after CS initiation. This study was part of a retrospective cohort study (LiSIE) into effects and side-effects of lithium for maintenance treatment of BD as compared with other mood stabilisers.Results: Of 1564 eligible patients, 206 patients met the inclusion criteria. Within the 6 months after CS initiation, suicide attempts and non-suicidal self-injury events decreased significantly, both in terms of numbers of patients having such events (p = 0.013) and numbers of events experienced (p = 0.004). These effects were preserved 2 years after CS initiation.Conclusions: CS treatment may reduce the risk of suicide attempts and non-suicidal self-injury events in patients with a dual diagnosis of BD or SZD and ADHD. Based on our findings, clinicians should not withhold CS treatment from patients with concomitant ADHD for fear of deterioration of the underlying BD. However, to minimise the risk of manic episodes concomitant mood stabiliser treatment and close monitoring remains warranted.
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