| 5481. |
- Lichtenstein, Paul, et al.
(författare)
-
Familial risk and heritability of intellectual disability : a population-based cohort study in Sweden
- 2022
-
Ingår i: Journal of Child Psychology and Psychiatry. - Hoboken, New Jersey : Wiley-Blackwell Publishing Inc.. - 0021-9630 .- 1469-7610. ; 63:9, s. 1092-1102
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Intellectual disability (ID) aggregates in families, but factors affecting individual risk and heritability estimates remain unknown. Methods: A population-based family cohort study of 4,165,785 individuals born 1973–2013 in Sweden, including 37,787 ID individuals and their relatives. The relative risks (RR) of ID with 95% confidence intervals (95% CI) were obtained from stratified Cox proportional-hazards models. Relatives of ID individuals were compared to relatives of unaffected individuals. Structural equation modeling was used to estimate heritability. Results: Relatives of ID individuals were at increased risk of ID compared to individuals with unaffected relatives. The RR of ID among relatives increased proportionally to the degree of genetic relatedness with ID probands; 256.70(95% CI 161.30–408.53) for monozygotic twins, 16.47(13.32–20.38) for parents, 14.88(12.19–18.16) for children, 7.04(4.67–10.61) for dizygotic twins, 8.38(7.97–8.83) for full siblings, 4.56(4.02–5.16) for maternal, 2.90(2.49–3.37) for paternal half-siblings, 3.03(2.61–3.50) for nephews/nieces, 2.84(2.45–3.29) for uncles/aunts, and 2.04(1.91–2.20) for cousins. Lower RRs were observed for siblings of probands with chromosomal abnormalities (RR 5.53, 4.74–6.46) and more severe ID (mild RR 9.15, 8.55–9.78, moderate RR 8.13, 7.28–9.08, severe RR 6.80, 5.74–8.07, and profound RR 5.88, 4.52–7.65). Male sex of relative and maternal line of relationship with proband was related to higher risk (RR 1.33, 1.25–1.41 for brothers vs. sisters and RR 1.49, 1.34–1.68 for maternal vs. paternal half-siblings). ID was substantially heritable with 0.95(95% CI 0.93–0.98) of the variance in liability attributed to genetic influences. Conclusions: The risk estimates will benefit researchers, clinicians, families in understanding the risk of ID in the family and the whole population. The higher risk of ID related to male sex and maternal linage will be of value for planning and interpreting etiological studies in ID. © 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health
|
|
| 5482. |
|
|
| 5483. |
- Lichtenstein, Paul, et al.
(författare)
-
The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood.
- 2010
-
Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 167:11, s. 1357-1363
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Autism spectrum disorders are considered to be among the most heritable mental disorders, a notion based on surprisingly sparse data from small clinical studies. Population-based studies of the heritability of other neuro-psychiatric disorders and comorbidities among them have also been sparse. The authors sought to address both of these issues. Method: Parents of all Swedish 9- and 12-year-old twin pairs born between 1992 and 2000 (N=10,895) were interviewed regarding autism spectrum disorders and associated conditions (response rate, 80%). Concordance rates and structural equation modeling were used for evaluating causes for familial aggregation and overlap between conditions. Results: Monozygotic twins had higher concordance rates than dizygotic twins for autism spectrum disorders, attention defcit hyperactivity disorder (ADHD), developmental coordination disorder, and tic disorder. Genetic effects accounted for 80% (95% CI=29-91) of the variation in liability for autism spectrum disorders, 79% (95% CI=61-88) for ADHD, 70% (95% CI=35-83) for developmental coordination disorder, and 56% (95% CI=37-68) for tic disorder. Among monozygotic co-twins of children with autism spectrum disorders, the probability of having a diagnosis of ADHD was 44%, compared with 15% for dizygotic co-twins. Differences in cross-disorder effects between monozygotic and dizygotic twins were observed for most other comorbidities, and substantial proportions of the genetic variance for autism spectrum disorders was shared with each of the other disorders. Conclusions: Different neuropsychiatric disorders seem to have a common genetic etiology, suggesting caution in the use of diagnostic entities and proband status in efforts to uncover genes predisposing to autism spectrum disorders.
|
|
| 5484. |
- Lidberg, Lars, et al.
(författare)
-
Nedsatt serotoninhalt predisponerar för våld : Enkelt blodprov förutsäger farlighet
- 1997
-
Ingår i: Läkartidningen. - Stockholm. - 0023-7205 .- 1652-7518. ; 94:39, s. 3385-3388
-
Tidskriftsartikel (refereegranskat)abstract
- Deficient serotonergic function in the brain is associated with a risk of impulsive violence. The level of serotonergic function can be assessed indirectly in several ways: 1. determination of CSF (cerebrospinal fluid) content of the serotonin metabolite 5-HIAA (5-hydroxyindoleacetic acid); 2. determination of the plasma level of the amino acid tryptophan, the serotonin precursor (passage of tryptophan into the brain is dependent on the ratio of tryptophan to other competing amino acids); 3. analysis of platelet monoamine oxidase content, a putative correlate of serotonergic capacity in the brain; 4. by determining response to an OGTT (oral glucose tolerance test), another putative correlate of serotonergic function.
|
|
| 5485. |
- Lidö Höifödt, Helga, 1976, et al.
(författare)
-
A role for accumbal glycine receptors in modulation of dopamine release by the glycine transporter-1 inhibitor org25935.
- 2011
-
Ingår i: Frontiers in psychiatry / Frontiers Research Foundation. - : Frontiers Media SA. - 1664-0640. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Accumbal glycine modulates basal and ethanol-induced dopamine levels in the nucleus accumbens (nAc) as well as voluntary ethanol consumption. Also, systemic administration of the glycine transporter-1 inhibitor Org25935 elevates dopamine levels in nAc, prevents a further ethanol-induced dopamine elevation and robustly and dose-dependently decreases ethanol consumption in rats. Here we investigated whether Org25935 applied locally in nAc modulates dopamine release, and whether accumbal glycine receptors or NMDA receptors are involved in this tentative effect. We also addressed whether Org25935 and ethanol applied locally in nAc interact with dopamine levels, as seen after systemic administration. We used in vivo microdialysis coupled to HPLC-ED in freely moving male Wistar rats to monitor dopamine output in nAc after local perfusion of Org25935 alone, with ethanol, or Org25935-perfusion after pre-treatment with the glycine receptor antagonist strychnine or the NMDA receptor glycine site antagonist L-701.324. Local Org25935 increased extracellular dopamine levels in a subpopulation of rats. Local strychnine, but not systemic L-701.324, antagonized the dopamine-activating effect of Org25935. Ethanol failed to induce a dopamine overflow in the subpopulation responding to Org25935 with a dopamine elevation. The study supports a role for accumbal glycine receptors rather than NMDA receptor signaling in the dopamine-activating effect of Org25935. The results further indicate that the previously reported systemic Org25935-ethanol interaction with regard to accumbal dopamine is localized to the nAc. This adds to the growing evidence for the glycine receptor as an important player in the dopamine reward circuitry and in ethanol's effects within this system.
|
|
| 5486. |
- Lie, Anders, 1959, et al.
(författare)
-
Automated vehicles: How do they relate to vision zero
- 2022
-
Ingår i: The Vision Zero Handbook: Theory, Technology and Management for a Zero Casualty Policy. - Cham : Springer International Publishing. ; , s. 1057-1071
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The Swedish Transport Administration (STA) work to reduce the number of suicides in the transport system. Fatalities, i.e., on roads, railways, and bridges, originate from either accidents or suicides, natural death excluded. Knowing the correct manner of death is needed to work with optimal prevention strategies. The aims are to separate fatalities due to suicides, follow the development, and implement measures for suicide prevention. Methods are developed for suicide classification and criteria for the selection in which suicides were suspected. Fatalities in level one and two of five were classified as suicides. Data from the STA's databases are used and so are data from the psychosocial investigations done by a trained investigator in the topic and with clinical experience from counselling at hospitals. 2129 persons died on the roads in Sweden, 10% (206 persons) were classified as suicides. 336 persons died after being hit by trains, 85% (284 persons) were suicides. 130 persons died by jumping from bridges. The number of suicides increases with population density. Suicide in the transport system is a major problem; firstly personal tragedies, it is also a work environment problem for truck and train drivers and for the emergency staff. It generates delays and costs for passenger and cargo transport. By analyzing the results of countermeasures in the form of obstructive barriers, the physical environment can be improved and high-risk areas can be accentuated. Restricting access to the means of suicide is important in suicide prevention. Strategies for the STA include suicide prevention in the design of new roads, railways, and bridges, as well as by identifying and reducing existing high-risk locations. Sharing the results with other authorities and organizations and cooperation within suicide prevention missions are vital for the enhancement of the overall suicide prevention work in society.
|
|
| 5487. |
- Lieber, Ingrid, 1990-
(författare)
-
Affective disorders and their treatments : implications for thyroid function
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundThe relationship between affective disorders, mood-stabilisers and thyroid dysfunction is complex and poorly understood. Symptoms of thyroid dysfunction can overlap with symptoms of affective disorder, destabilise mood, and impact physical health. Subjective symptoms and biochemical abnormalities may not always match, especially when changes in thyroid function are only mild. Therefore, diagnosis and treatment of both hypothyroidism and hyperthyroidism in individuals with affective disorders remain complex. For lithium, a first-line treatment for bipolar disorder, an impact on thyroid function was first described in 1968. Since that time, it has become evident that lithium is much more frequently associated with hypothyroidism than hyperthyroidism. But even for lithium, many aspects of how associated thyroid dysfunction should be handled remain unclear. Aims The overall aim of this thesis was, in five studies, to examine aspects of the diagnosis and treatment of thyroid dysfunction in individuals with affective disorders, with a particular focus on lithium. The individual aims of the five studies were todetermine if lithium-associated hypothyroidism was reversible in individuals who had discontinued lithium.identify patterns and trends in thyroid hormone replacement therapy prescribed for individuals with bipolar or schizoaffective disorder.assess whether elevated thyroxine concentrations (hyperthyroxinaemia) were a risk factor for lithium intoxication caused by a change in tubular renal function.examine the incidence rate and aetiology of lithium-associated hyperthyroidism in individuals with bipolar or schizoaffective disorder.explore the attitudes of practising clinicians towards the diagnosis and treatment of subclinical hypothyroidism in individuals with or without affective disorder or anxiety.MethodsStudies 1–4 were part of the LiSIE (Lithium - Study into Effects and Side Effects) retrospective cohort study. LiSIE compares the effects and adverse effects of lithium treatment and other mood stabilisers in the Norrbotten Region and the Region of Västerbotten over a time period of up to 21 years between 1997–2017. For our studies, we used data from the Norrbotten Region only. Study 5 used a three-round modified Delphi consensus-building process. Study 5 was conducted with clinicians from three specialties, general practice, endocrinology and psychiatry, from two countries with similar health care systems, Sweden and the UK. ResultsStudy 1: Of 1340 potentially eligible individuals with lithium treatment, 90 individuals (who had developed hypothyroidism while treated with lithium and later discontinued lithium), were included. Of these, 27% had overt hypothyroidism at the start of thyroid hormone replacement therapy. Of the 85 individuals available for follow-up, 41% stopped thyroid hormone replacement therapy after lithium discontinuation. Only six individuals reinstated thyroid hormone replacement therapy subsequently. Only one had overt hypothyroidism.Study 2: Of 1564 potentially eligible individuals with bipolar or schizoaffective disorder, 291 (27%) had received thyroid hormone replacement therapy at some point during the 21-year review period. In 41% of cases, thyroid hormone replacement therapy was started for subclinical hypothyroidism. At the start of thyroid hormone replacement therapy, the median thyroid stimulating hormone (TSH) concentration was 6.0 (IQR 4.0) mIU/L. The median free serum thyroxine (fT4) was 11.8 (IQR 3.9) pmol/L. The median TSH concentration at the start of thyroid hormone replacement therapy decreased annually by 0.10 mIU/L, being significantly higher in individuals treated with lithium than in individuals treated with other mood stabilisers.Study 3: Of 1562 potentially eligible individuals with bipolar or schizoaffective disorder, 53 individuals had experienced a total of 65 episodes of unintentional lithium intoxication during the review period. In nine episodes, there was elevated fT4 at the time of lithium intoxication, corresponding to an incidence of 1.3 episodes/1000 person-years. For all nine episodes of unintentional lithium intoxication, we could identify alternative explanations that were more plausible than hyperthyroxinaemia. Study 4: In 1562 individuals with bipolar disorder or schizoaffective disorder, we identified 16 episodes of hyperthyroidism, corresponding to an incidence rate of 0.9 episodes/1000 person-years. Individuals who had concurrently been exposed to lithium, had an incidence rate of 1.3 episodes/1000 person-years. Individuals who had been previously exposed to lithium had an incidence rate of 0.8/1000 person-years. Individuals who had never been exposed to lithium (lithium naïve) had a 0.5/1000 person-years incidence rate. There were no significant differences in the risk ratios for individuals with concurrent or previous exposure compared to lithium-naïve individuals, neither for hyperthyroidism overall, nor for thyrotoxicosis or thyroiditis. Study 5: For the expert panel, 60 clinicians; 20 general practitioners, 20 endocrinologists and 20 psychiatrists were recruited. Fifty-three (88%) participants completed all three rounds. The participants reached a consensus on five of the 26 practice statements. The participants agreed that (a) repeated testing was required for the diagnosis of subclinical hypothyroidism, (b) antibody screening should usually occur, and (c and d) antibody screening would strengthen the indication for thyroid hormone replacement therapy in both individuals with and without affective disorder or anxiety. The participants disagreed with (e) requiring a TSH threshold of ≥ 20 mIU/L before starting thyroid hormone replacement therapy.ConclusionsStudy 1: In most cases, lithium-associated hypothyroidism appears reversible. Therefore, thyroid hormone replacement therapy could be discontinued more often once lithium is stopped. Study 2: In most cases, thyroid hormone replacement therapy was started with mild or absent thyroid function changes. The TSH level at which thyroid hormone replacement therapy was initiated decreased over time. When starting thyroid hormone replacement therapy for subclinical hypothyroidism in people with bipolar or schizoaffective disorder, clinicians must carefully weigh the benefits and risks.Study 3: Lithium intoxication with simultaneously elevated fT4 is uncommon. A direct causal link between elevated fT4 and altered tubular renal function remains elusive. An increased frequency of routine thyroid function tests is unlikely to decrease the risk of lithium intoxication. Study 4: Lithium-associated hyperthyroidism is uncommon. The risk of hyperthyroidism does not differ significantly between lithium-exposed and lithium-naïve individuals.Study 5: Attitudes toward diagnosing and treating subclinical hypothyroidism remain diverse. A threshold of an TSH of at least 20 mIU/L for thyroid hormone replacement therapy start, suggested in a previously published guideline, was deemed too high. As the evidence regarding diagnosis and treatment of subclinical hypothyroidism remains limited, future guidelines should consider the views of a broad range of practising clinicians to increase their clinical acceptability and usefulness.
|
|
| 5488. |
- Lieber, Ingrid, et al.
(författare)
-
Lithium-associated hypothyroidism : Reversible after lithium discontinuation?
- 2021
-
Ingår i: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 64:S1, s. S76-S76
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The association between lithium and thyroid dysfunction has long been known. Yet it is not known whether lithium-associated hypothyroidism is reversible, once lithium treatment has been stopped.ObjectivesTo determine whether lithium-associated hypothyroidism was reversible in patients who subsequently discontinued lithium.MethodsRetrospective cohort study in the Swedish region of Norrbotten into the effects and side- effects of lithium treatment and other drugs for relapse prevention (LiSIE). For this particular study, we reviewed medical records between 1997 and 2015 of patients treated with lithium.ResultsOf 1340 patients screened, we identified 90 patients with lithium-associated hypothyroidism who subsequently discontinued lithium. Of these, 27% had overt hypothyroidism at the time when thyroid replacement therapy was initiated. The mean delay from lithium start to thyroid replacement therapy start was 2.3 (SD 4.7) years. Fifty percent received thyroid replacement therapy within 10 months of starting lithium. Of 85 patients available for follow up, 35 (41%) stopped thyroid replacement therapy after lithium discontinuation. Six patients reinstated thyroid replacement therapy subsequently. Only one of these had overt hypothyroidism, occurring 13 days after stopping lithium and 11 days after stopping thyroid replacement therapy.ConclusionsLithium-associated hypothyroidism seems reversible in most patients, once lithium has been discontinued. In such cases, thyroid replacement therapy discontinuation could be attempted much more often than currently done. Based on the limited evidence of our study, we can expect hypothyroidism to recur early after discontinuation of thyroid replacement therapy if at all.DisclosureMO: scient adv. board member Astra Zeneca Sweden; UW: educ. activities Norrbotten Region: Astra Zeneca, Eli Lilly, Janssen, Novartis, Otsuka/Lundbeck, Servier, Shire and Sunovion. All others: none.
|
|
| 5489. |
- Lieber, Ingrid, et al.
(författare)
-
Treating subclinical hypothyroidism in individuals with or without mental health problems – a Delphi based expert consensus study in two countries
- 2023
-
Ingår i: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Subclinical hypothyroidism (SCH) is a common endocrine problem with prevalence estimates between 4% and 20%. Symptoms are often non-specific but can substantially affect well-being leading to repeated medical consultations. The effect of thyroid hormone replacement therapy (THRT) in patients with SCH remains uncertain. Current guidelines, limited by the lack of high-quality evidence, have been controversial with limited adherence in clinical practice.Methods: Three-round modified Delphi method to establish consensus regarding diagnosis and treatment of individuals with SCH with and without affective disorder or anxiety, conducted with clinicians from three specialties, general practice, endocrinology and psychiatry, and two countries, Sweden and the United Kingdom.Results: Sixty clinicians, 20 per specialty, were recruited. Fifty-three (88%) participants completed all three rounds. The participants reached consensus on five of the 26 practice statements that (a) repeated testing was required for the diagnosis of subclinical hypothyroidism, (b) antibody screening should usually occur, and (c and d) antibody screening would strengthen the indication for thyroid hormone replacement therapy in both individuals with or without affective disorder or anxiety. The participants disagreed with (e) a requirement of a TSH threshold ≥ 20 mIU/L for thyroid hormone replacement therapy start. Psychiatrists and GPs but not endocrinologists, agreed that there was a frequent discrepancy between laboratory results and clinical symptoms, and disagreed that testing for thyroid dysfunction was overused in patients presenting with depression or anxiety, or fatigue.Conclusions: In many aspects, attitudes toward diagnosing and treating SCH remain diverse. The inability of our Delphi panel to achieve consensus on most items and the disagreement with a TSH ≥ 20 mIU/L threshold for treatment suggest that the concept of SCH may need rethinking with a better understanding of the hypothalamic-pituitary-thyroid physiology. Given that the scientific evidence is currently not conclusive, guidelines in this area should not be taken as definitive.
|
|
| 5490. |
- Liebetrau, Martin, et al.
(författare)
-
Depression as a risk factor for the incidence of first-ever stroke in 85-year-olds.
- 2008
-
Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628. ; 39:7, s. 1960-5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Depression may increase the risk for stroke. Few studies have examined whether depression increases the risk for stroke in the very old and among the demented. We examined the relation between depression in 85-year-olds and the 3-year incidence of first-ever stroke. METHODS: A representative sample of 494 85-year-olds (147 demented, 347 nondemented) in Gothenburg, Sweden, was examined with psychiatric examinations and key informant interviews. Diagnoses of depression and dementia were made according to the Diagnostic and Statistical Manual of Mental Disorders, Third Revision. The sample was followed for 3 years regarding the incidence of stroke. Information on stroke was obtained from the Swedish Hospital Discharge Register, death certificates, self-reports, and key informants. Those with known stroke history at baseline (n=93) were excluded from the incidence study. RESULTS: The prevalence of depression at age 85 was 19%. Depression at baseline (hazard ratio, 2.7; 95% CI, 1.5 to 4.7; P=0.0006) and systolic blood pressure (hazard ratio, 1.014 per 1 mm Hg; 95% CI, 1.00 to 1.03; P=0.019) were related to increased incidence of first-ever stroke during follow-up. Depression increased stroke risk both among demented and nondemented individuals. Among the symptoms of depression, only depressed mood was an independent predictor of incidence first-ever stroke in multivariate analyses. Stroke history at age 85 was not associated with clinical depression. CONCLUSIONS: Depression and stroke are both common in elderly populations. The finding that depression increases risk for first-ever stroke indicates that detection and treatment of depression may have implications for stroke prevention.
|
|
