Vetenskapliga publikationer från PRIMA Barn- och Vuxenpsykiatri AB
Lista över publikationer som återfinns i PubMed med minst en medförfattare från PRIMA
Eur Neuropsychopharmacol (2020) Nov 4;S0924-977X(20)30914-7.
Liu L Yang 1 , Miranda Stiernborg 1 , Elin Skott 2 , Åsa Söderström 3 , MaiBritt Giacobini 4 , Catharina Lavebratt 5
1 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
2 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden; PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
3 PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
4 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
5 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden. Electronic address: catharina.lavebratt@ki.se.
PMID: 33160793
DOI: 10.1016/j.euroneuro.2020.10.005
Abstract
Peripheral immune activation can influence neurodevelopment and is increased in autism, but is less explored in attention deficit hyperactivity disorder (ADHD). Patients with ADHD often display comorbid autism traits and gastrointestinal (GI) symptoms. Plasma protein levels of two acute phase reactants, C-reactive protein (CRP) and serum amyloid A (SAA), and two endothelial adhesion molecules, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1), which share important roles in inflammation, were analyzed in 154 patients with ADHD and 61 healthy controls. Their associations with ADHD diagnosis, severity, medication and comorbid autistic symptoms, emotion dysregulation and GI symptoms were explored. The ADHD patients had increased levels of sICAM-1 and sVCAM-1 compared to healthy controls (p = 8.6e-05, p = 6.9e-07, respectively). In children with ADHD, the sICAM-1 and sVCAM-1 levels were higher among those with ADHD medication than among children (p = 0.0037, p = 0.0053, respectively) and adults (p = 3.5e-09, p = 1.9e-09, respectively) without ADHD medication. Among the adult ADHD patients, higher sICAM-1 levels were associated with increased comorbid autistic symptoms in the domains attention to detail and imagination (p = 0.0081, p = 0.00028, respectively), and higher CRP levels were associated with more GI symptoms (p = 0.014). sICAM-1 and sVCAM-1 levels were highly correlated with each other, and so were CRP and SAA levels. To conclude, vascular inflammatory activity may be overrepresented in ADHD, with elevated sICAM-1 and sVCAM-1 levels and this may in children be a consequence of current ADHD medication, and in adults relate to increased comorbid autistic symptoms. Replication is warranted.
Keywords: ADHD; Adhesion molecules; Autism; Inflammation; Stimulants.
Dev Psychopathol (2020) Jul 24;1-48.
Torkel Carlsson 1 2 3 , Felix Molander 1 , Mark J Taylor 4 , Ulf Jonsson 1 2 5 , Sven Bölte 1 2 6
1 Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research; Department of Women’s and Children’s Health, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
2 Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
3 PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
4 Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden.
5 Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden.
6 Curtin Autism Research Group, School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, Western Australia.
PMID: 32703331
DOI: 10.1017/S0954579420000620
Abstract
While neurodevelopmental disorders (NDDs) are highly heritable, several environmental risk factors have also been suggested. However, the role of familial confounding is unclear. To shed more light on this, we reviewed the evidence from twin and sibling studies. A systematic review was performed on case control and cohort studies including a twin or sibling within-pair comparison of neurodevelopmental outcomes, with environmental exposures until the sixth birthday. From 7,315 screened abstracts, 140 eligible articles were identified. After adjustment for familial confounding advanced paternal age, low birth weight, birth defects, and perinatal hypoxia and respiratory stress were associated with autism spectrum disorder (ASD), and low birth weight, gestational age and family income were associated with attention-deficit/hyperactivity disorder (ADHD), categorically and dimensionally. Several previously suspected factors, including pregnancy-related factors, were deemed due to familial confounding. Most studies were conducted in North America and Scandinavia, pointing to a global research bias. Moreover, most studies focused on ASD and ADHD. This genetically informed review showed evidence for a range of environmental factors of potential casual significance in NDDs, but also points to a critical need of more genetically informed studies of good quality in the quest of the environmental causes of NDDs.
Keywords: confounding factors; environmental exposure; neurodevelopmental disorders; systematic review; twin and sibling studies.
Brain Behav Immun (2020) Oct;89:9-19.
Elin Skott 1 , Liu L Yang 2 , Miranda Stiernborg 2 , Åsa Söderström 3 , Joëlle Rȕegg 4 , Martin Schalling 2 , Yvonne Forsell 5 , MaiBritt Giacobini 6 , Catharina Lavebratt 7
1 Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Karolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden; PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
2 Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Karolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden.
3 PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
4 Karolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden; Uppsala University, Department of Organismal Biology, Uppsala, Sweden.
5 Karolinska Institutet, Department of Global Public Health Sciences, Stockholm, Sweden.
6 Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
7 Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Karolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden. Electronic address: catharina.lavebratt@ki.se.
PMID: 32497779
DOI: 10.1016/j.bbi.2020.05.056
Abstract
Some prebiotics and probiotics have been proposed to improve psychiatric symptoms in children with autism. However, few studies were placebo-controlled, and there is no study on persons with an attention deficit hyperactivity disorder (ADHD) diagnosis. Our aim was to study effects of Synbiotic 2000 on psychiatric symptoms and functioning in children and adults with ADHD without an autism diagnosis. Children and adults (n = 182) with an ADHD diagnosis completed the nine weeks randomized double-blind parallel placebo-controlled trial examining effects of Synbiotic 2000 on the primary endpoints ADHD symptoms, autism symptoms and daily functioning, and the secondary endpoint emotion regulation, measured using the questionnaires SNAP-IV, ASRS, WFIRS, SCQ, AQ and DERS-16. Levels at baseline of plasma C-reactive protein and soluble vascular cell adhesion molecule-1 (sVCAM-1), central to leukocyte-endothelial cell adhesion facilitating inflammatory responses in tissues, were measured using Meso Scale Discovery. Synbiotic 2000 and placebo improved ADHD symptoms equally well, and neither active treatment nor placebo had any statistically significant effect on functioning or sub-diagnostic autism symptoms. However, Synbiotic 2000, specifically, reduced sub-diagnostic autism symptoms in the domain restricted, repetitive and stereotyped behaviors in children, and improved emotion regulation in the domain of goal-directed behavior in adults. In children with elevated sVCAM-1 levels at baseline as well as in children without ADHD medication, Synbiotic 2000 reduced both the total score of autism symptoms, and the restricted, repetitive and stereotyped behaviors. In adults with elevated sVCAM-1 at baseline, Synbiotic 2000 significantly improved emotion regulation, both the total score and four of the five subdomains. To conclude, while no definite Synbiotic 2000-specific effect was detected, the analysis of those with elevated plasma sVCAM-1 levels proposed a reduction of autism symptoms in children and an improvement of emotion regulation in adults with ADHD. Trial registration number: ISRCTN57795429.
BJPsych Bull (2020) Apr 15;1-4.
Gabriella Bröms 1 , Lindah Cahling 2 , Anders Berntsson 2 , Lars Öhrmalm 2 3
1 Unit of Clinical Epidemiology, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden.
2 PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
3 Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
PMID: 32290892
DOI: 10.1192/bjb.2020.28
Abstract
Aims and method: To assess whether the combination of motivational interviewing and psychoeducation affects relapse rate and stimulates involvement of people with psychosis in their treatment. We conducted an interventional study including patients with schizophrenia or schizoaffective disorder treated with oral antipsychotics, without previous experience of long-acting injectable antipsychotics (LAIs). They were randomised to either psychoeducation with motivational interviewing or a control group. Hospital admissions 18 months before and after the intervention, and switches to LAIs 18 months after the intervention, were recorded.
Results: The two groups each comprised 101 participants. Fourteen from the intervention group and seven from the control group switched to LAIs. Five in the intervention group instigated the switch themselves, compared with zero controls (P = 0.06). Fourteen in the intervention group were readmitted to hospital during follow-up, compared with 23 in the control group (P = 0.14).
Clinical implications: Psychoeducation with motivational interviewing may increase patients’ involvement in their treatment and reduce the relapse frequency.
Keywords: Motivational interviewing; adherence; antipsychotics; psychoeducation; schizophrenia.
Early exposure to antibiotic drugs and risk for psychiatric disorders: a population-based study
Transl Psychiatry (2019) Nov 26;9(1):317.
Catharina Lavebratt 1 2 , Liu L Yang 3 4 , MaiBritt Giacobini 3 5 , Yvonne Forsell 6 , Martin Schalling 3 4 , Timo Partonen 7 , Mika Gissler 7 8 9
Affiliations
Affiliations
1 Karolinska Institutet, Department of Molecular Medicine and Surgery (MMK), Stockholm, Sweden. catharina.lavebratt@ki.se.
2 Karolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden. catharina.lavebratt@ki.se.
3 Karolinska Institutet, Department of Molecular Medicine and Surgery (MMK), Stockholm, Sweden.
4 Karolinska University Hospital Solna, Center for Molecular Medicine, Stockholm, Sweden.
5 PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
6 Karolinska Institutet, Department of Public Health Sciences, Stockholm, Sweden.
7 National Institute for Health and Welfare (THL), Department of Public Health Solutions, Helsinki, Finland.
8 Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
9 University of Turku, Research Centre for Child Psychiatry, Turku, Finland.
PMID: 31772217
PMCID: PMC6879739
DOI: 10.1038/s41398-019-0653-9
Abstract
Early life exposure to infection, anti-infectives and altered immune activity have been associated with elevated risk of some psychiatric disorders. However, the risk from exposure in fetal life has been proposed to be confounded by familial factors. The hypothesis of this study is that antibiotic drug exposure during the fetal period and the first two postnatal years is associated with risk for later development of psychiatric disorders in children. All births in Finland between 1996 and 2012, 1 million births, were studied for antibiotic drug exposure: mothers during pregnancy and the children the first two postnatal years. The children were followed up for a wide spectrum of psychiatric diagnoses and psychotropic drug treatment until 2014. Cox proportional hazards modeling was used to estimate effects of antibiotic drug exposure on offspring psychiatric disorders. Modestly (10-50%) increased risks were found on later childhood development of sleep disorders, ADHD, conduct disorder, mood and anxiety disorders, and other behavioral and emotional disorders with childhood onset (ICD-10 F98), supported by increased risks also for childhood psychotropic medication. The prenatal exposure effects detected were not explained by explored familial confounding, nor by registered maternal infections. To conclude, this longitudinal nation-wide study shows that early life antibiotic drug exposure is associated with an increased risk for childhood development of psychopathology. Given the high occurrence of early-life antibiotic exposure, these findings are of public health relevance. Whether the associations reflect effects of the antibiotic drug use or of the targeted infections remains to be explored further.
J Autism Dev Disord (2019) Jun;49(6):2281-2290.
Lucy Thompson 1 2 , Christopher Gillberg 3 4 , Sara Landberg 3 , Anne-Katrin Kantzer 3 , Carmela Miniscalco 3 , Martina Barnevik Olsson 3 5 , Mats A Eriksson 3 6 , Elisabeth Fernell 3
1 Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. Lucy.Thompson@gnc.gu.se.
2 Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland, UK. Lucy.Thompson@gnc.gu.se.
3 Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
4 Institute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland, UK.
5 PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
6 Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
PMID: 30734177
PMCID: PMC6546868
DOI: 10.1007/s10803-018-03871-4
Abstract
Two community-based cohorts of children with autism spectrum disorder, examined using similar assessment protocols, were pooled (n = 301) and subdivided according to history of regression. Those with regression (n = 62), 20.5% of the combined cohort, were contrasted with those without regression (n = 241) at first assessment (age range 19-60 months) and at 2-year follow-up on a range of measures. The regression group was significantly more functionally impaired, with regard to intellectual function (p < .001), language development (p < .001), and to severity of autism (p < .01) at both T1 and T2. Only 14 (23.3%) had a clearly identified underlying etiology [24 (18.6%) in the non-regressive group]. There were no significant differences between those who had regressed ’from normal’ and those who had regressed ’from low’ functioning.
Keywords: ASD; Autism; Developmental language disorder; Intellectual developmental disorder; Non-regressive autism; Regressive autism.
Mitochondrial DNA copy number is associated with psychosis severity and anti-psychotic treatment
Sci Rep (2018) Aug 24;8(1):12743.
Parvin Kumar 1 2 , Paschalis Efstathopoulos 3 4 , Vincent Millischer 3 4 , Eric Olsson 5 6 , Ya Bin Wei 3 4 7 , Oliver Brüstle 8 , Martin Schalling 3 4 , J Carlos Villaescusa 3 4 , Urban Ösby 4 5 6 , Catharina Lavebratt 9 10
1 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. parvin.kumar@ki.se.
2 Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. parvin.kumar@ki.se.
3 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
4 Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
5 Department of Adult Psychiatry, PRIMA Child and Adult Psychiatry AB, Stockholm, Sweden.
6 Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
7 Department of Psychiatry, University of California San Diego, California, USA.
8 Institute of Reconstructive Neurobiology, University of Bonn Medical Faculty, Bonn, Germany.
9 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Catharina.lavebratt@ki.se.
10 Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. Catharina.lavebratt@ki.se.
PMID: 30143692
PMCID: PMC6109159
DOI: 10.1038/s41598-018-31122-0
Abstract
Mitochondrial pathology has been implicated in the pathogenesis of psychotic disorders. A few studies have proposed reduced leukocyte mitochondrial DNA (mtDNA) copy number in schizophrenia and bipolar disorder type I, compared to healthy controls. However, it is unknown if mtDNA copy number alteration is driven by psychosis, comorbidity or treatment. Whole blood mtDNA copy number was determined in 594 psychosis patients and corrected for platelet to leukocyte count ratio (mtDNAcnres). The dependence of mtDNAcnres on clinical profile, metabolic comorbidity and antipsychotic drug exposure was assessed. mtDNAcnres was reduced with age (β = -0.210, p < 0.001), use of clozapine (β = -0.110,p = 0.012) and risperidone (β = -0.109,p = 0.014), dependent on prescribed dosage (p = 0.006 and p = 0.026, respectively), and the proportion of life on treatment (p = 0.006). Clozapine (p = 0.0005) and risperidone (p = 0.0126) had a reducing effect on the mtDNA copy number also in stem cell-derived human neurons in vitro at therapeutic plasma levels. For patients not on these drugs, psychosis severity had an effect (β = -0.129, p = 0.017), similar to age (β = -0.159, p = 0.003) and LDL (β = -0.119, p = 0.029) on whole blood mtDNAcnres. Further research is required to determine if mtDNAcnres reflects any psychosis-intrinsic mitochondrial changes.
BMC Psychiatry (2018) Jul 13;18(1):223.
E Ahnemark 1 , M Di Schiena 2 , A-C Fredman 2 3 , E Medin 4 5 , J K Söderling 6 , Y Ginsberg 7 8
1 Shire, Vasagatan 7, SE-111 20, Stockholm, Sweden. eahnemark@shire.com.
2 Prima Child and Adult Psychiatry AB, Stockholm, Sweden.
3 Present Address: Psychiatry Centre, Stockholm County Council, Södertälje, Sweden.
4 PAREXEL International, Stockholm, Sweden.
5 Department of Learning, Informatics, Management and Ethics, Karolinska Institute, Stockholm, Sweden.
6 Bell Analytics, Stockholm, Sweden.
7 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
8 Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden.
PMID: 30005675
PMCID: PMC6044069
DOI: 10.1186/s12888-018-1803-y
Abstract
Background: This observational, cross-sectional, retrospective chart review aimed to identify factors determining health-related quality of life (HRQoL) in adults with newly diagnosed attention-deficit/hyperactivity disorder (ADHD) in Sweden.
Methods: Adult participants with a new clinical diagnosis of ADHD were enrolled from two specialist outpatient clinics in Stockholm, Sweden, from 2013 to 2015. Data extracted from patient records included demographics, clinical characteristics and comorbid psychiatric diagnoses identified using the Mini International Neuropsychiatric Interview (MINI). Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale – Self-reported (MADRS-S). The self-rated five-dimension EuroQol questionnaire (EQ-5D) was used to measure HRQoL. Predictors of EQ-5D index score were identified using multivariate linear regression adjusting for age, sex, education level, and main income source.
Results: The mean age of the 189 enrolled patients was 35.2 years (standard deviation [SD], 12.3), and 107 (57%) were female. Psychiatric comorbidities were present in 92 patients (49%), with anxiety and depression being the most common diagnoses. The mean EQ-5D index score was 0.63 (SD, 0.28). Low EQ-5D index scores were significantly associated with high MADRS-S scores, multiple comorbid psychiatric disorders, low educational achievement, female sex, and not having a main income derived from employment or self-employment.
Conclusions: These findings suggest that adults with newly diagnosed ADHD experience low HRQoL, which may often be exacerbated by psychiatric comorbidities such as anxiety and depression. Patients presenting with ADHD and psychiatric comorbidities in adulthood may require particular care and resources in the management of their ADHD.
Keywords: ADHD; HRQoL; Psychiatric comorbidities.
Scand J Public Health (2019) Mar;47(2):121-126.
Jonas Hällgren 1 , Urban Ösby 1 2 3 , Jeanette Westman 1 , Mika Gissler 1 4 5
1 1 Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
2 2 Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
3 3 Department of Adult Psychiatry, PRIMA Psychiatry AB, Stockholm, Sweden.
4 4 THL National Institute for Health and Welfare, Helsinki, Finland.
5 5 Research Centre for Child Psychiatry, University of Turku, Finland.
PMID: 29493432
Abstract
Aim: We investigated mortality from external causes in Swedish people who had been hospitalised with a severe mental disorder.
Methods: Hospitalisations in people aged 15 years or older admitted to hospital with a main diagnosis of schizophrenia, bipolar mood disorder or unipolar mood disorder between 1987 and 2010 were linked to their causes of death.
Results: The mortality rate from all external causes was 20-fold higher in those with unipolar mood disorder, 15-fold higher in those with bipolar disorder and 12-fold higher in those with schizophrenia than in the general population. Over the study periods, the mortality rate declined more for people with unipolar mood disorder (-35%) and schizophrenia (-29%) than the total population (-25%) and those with bipolar mood disorder (-15%). The suicide rate declined most for those with unipolar mood disorder and schizophrenia (-42% for both) and less for the general population (-37%) and those with bipolar mood disorder (-21%). For external causes other than suicide, the mortality rate declined in the general population (-17%) but increased in people with schizophrenia (14%), bipolar mood disorder (30%) and unipolar mood disorder (52%).
Conclusions: People with mental disorders have high but declining excess mortality from suicide. Mortality from other external causes has increased, as has the gap in mortality rates between psychiatric patients and the general population.
Keywords: Depression; mortality; public mental health; suicide.
Resilience concepts in psychiatry demonstrated with bipolar disorder
Int J Bipolar Disord (2018) Feb 9;6(1):2.
David G Angeler 1 , Craig R Allen 2 , Maj-Liz Persson 3
1 Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences, PO Box 7050, 750 07, Uppsala, Sweden. david.angeler@slu.se.
2 U.S. Geological Survey, Nebraska Cooperative Fish and Wildlife Research Unit, School of Natural Resources, University of Nebraska-Lincoln, Lincoln, NE, USA.
3 PRIMA Adult Psychiatric Ward, Katrinebergsvägen 6, 117 43, Stockholm, Sweden.
PMID: 29423550
PMCID: PMC6161999
DOI: 10.1186/s40345-017-0112-6
Abstract
Background: The term resilience describes stress-response patterns of subjects across scientific disciplines. In ecology, advances have been made to clearly distinguish resilience definitions based on underlying mechanistic assumptions. Engineering resilience (rebound) is used for describing the ability of subjects to recover from adverse conditions (disturbances), and is the rate of recovery. In contrast, the ecological resilience definition considers a systemic change: when complex systems (including humans) respond to disturbances by reorganizing into a new regime (stable state) where structural and functional aspects have fundamentally changed relative to the prior regime. In this context, resilience is an emergent property of complex systems. We argue that both resilience definitions and uses are appropriate in psychology and psychiatry, but although the differences are subtle, the implications and uses are profoundly different.
Methods: We borrow from the field of ecology to discuss resilience concepts in the mental health sciences.
Results: In psychology and psychiatry, the prevailing view of resilience is adaptation to, coping with, and recovery (engineering resilience) from adverse social and environmental conditions. Ecological resilience may be useful for describing vulnerability, onset, and the irreversibility patterns of mental disorders. We discuss this in the context of bipolar disorder.
Conclusion: Rebound, adaptation, and coping are processes that are subsumed within the broader systemic organization of humans, from which ecological resilience emanates. Discerning resilience concepts in psychology and psychiatry has potential for a mechanistically appropriate contextualization of mental disorders at large. This might contribute to a refinement of theory and contextualize clinical practice within the broader systemic functioning of mental illnesses.
Keywords: Bipolar disorder; Ecological resilience; Ecological theory; Engineering resilience; Interdisciplinary research; Mental disorders; Stress-recovery.
Neuropsychiatr Dis Treat (2017) Oct 4;13:2519-2526.
Martina Barnevik Olsson 1 2 , Anette Holm 3 , Joakim Westerlund 1 4 , Åsa Lundholm Hedvall 1 3 , Christopher Gillberg 1 , Elisabeth Fernell 1
1 Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg.
2 PRIMA Child and Adult Psychiatry.
3 Department of Psychology, Astrid Lindgren Children’s Hospital.
4 Department of Psychology, Stockholm University, Stockholm, Sweden.
PMID: 29042781
PMCID: PMC5634384
DOI: 10.2147/NDT.S143234
Abstract
Background: Studies on autism have tended to focus either on those with intellectual disability (ie, those with intellectual quotient [IQ] under 70) or on the group that is referred to as ”high-functioning”, that is, those with borderline, average or above average IQ. The literature on cognition and daily functioning in autism spectrum disorder combined specifically with borderline intellectual functioning (IQ 70-84) is limited.
Methods: From a representative group of 208 preschool children diagnosed with autism spectrum disorder, those 50 children in the group with borderline intellectual functioning at ages 4.5-6.5 years were targeted for follow-up at a median age of 10 years. A new cognitive test was carried out in 30 children. Parents were interviewed with a semi-structured interview together with the Vineland Adaptive Behavior Scales (n=41) and the Autism-Tics, attention-deficit/hyperactivity disorder (AD/HD) and other comorbidities inventory (A-TAC) (n=36).
Results: Most children of interviewed parents presented problems within several developmental areas. According to A-TAC and the clinical interview, there were high rates of attention deficits and difficulties with regulating activity level and impulsivity. Vineland Adaptive Behavior Scales composite scores showed that at school age, a majority of the children had declined since the previous assessment at ages between 4.5 and 6.5 years. Almost half the tested group had shifted in their IQ level, to below 70 or above 84.
Conclusion: None of the children assessed was without developmental/neuropsychiatric problems at school-age follow-up. The results support the need for comprehensive follow-up of educational, medical and developmental/neuropsychiatric needs, including a retesting of cognitive functions. There is also a need for continuing parent/family follow-up and support.
Keywords: A-TAC; AD/HD; Vineland; autism spectrum disorder; borderline intellectual functioning; developmental disorders.
Perceptions and knowledge of antipsychotics among mental health professionals and patients
BJPsych Bull (2017) Oct;41(5):254-259.
Lindah Cahling 1 , Anders Berntsson 1 , Gabriella Bröms 2 , Lars Öhrmalm 1 2
1 PRIMA, Stockholm, Sweden.
2 Karolinska Instituted Stockholm, Sweden.
PMID: 29018549
PMCID: PMC5623883
Abstract
Aims and method To assess the patients’ most influential concerns regarding long-acting injectable antipsychotics (LAIs) and mental health professionals’ preconceptions about these concerns. For both groups, to assess the level of knowledge about LAIs. This cross-sectional study used semi-structured interviews of patients with schizophrenia or schizoaffective disorder (n = 164), nurses (n = 43) and physicians (n = 20). Results The mental health professionals overestimated many of the patients’ fears of LAIs, and the expressed fears exceeded the actual experiences of patients already on LAIs. Acceptance to switch to LAIs was associated with shorter time from diagnosis. Nurses and patients disclosed limited knowledge of antipsychotics. Clinical implications Physicians and nurses should aim to identify the individual patient’s concerns about LAIs in the discussion about choice of antipsychotic treatment early in the course of illness.
JMIR Res Protoc (2017) Aug 24;6(8):e158.
Kristoffer Nt Månsson 1 2 3 , Hugo Klintmalm 4 , Ragnar Nordqvist 4 , Gerhard Andersson 3 5
1 Department of Psychology, Stockholm University, Stockholm, Sweden.
2 Department of Adult Psychiatry, PRIMA Barn- och Vuxenpsykiatri, Stockholm, Sweden.
3 Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
4 Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
5 Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.
PMID: 28838884
PMCID: PMC5590006
DOI: 10.2196/resprot.6035 Free PMC article
Abstract
Background: Cognitive behavioral therapies have been shown to be effective for a variety of psychiatric and somatic disorders, but some obstacles can be noted in regular psychiatric care; for example, low adherence to treatment protocols may undermine effects. Treatments delivered via the Internet have shown promising results, and it is an open question if the blend of Internet-delivered and conventional face-to-face cognitive behavioral therapies may help to overcome some of the barriers of evidence-based treatments in psychiatric care.
Objective: We evaluated the feasibility of an Internet-based support system at an outpatient psychiatric clinic in Sweden. For instance, the support system made it possible to send messages and share information between the therapist and the patient before and after therapy sessions at the clinic.
Methods: Nine clinical psychologists participated and 33 patients were enrolled in the current study. We evaluated the usability and technology acceptance after 12 weeks of access. Moreover, clinical data on common psychiatric symptoms were assessed before and after the presentation of the support system.
Results: In line with our previous study in a university setting, the Internet-based support system has the potential to be feasible also when delivered in a regular psychiatric setting. Notably, some components in the system were less frequently used. We also found that patients improved on common outcome measures for depressive and anxious symptoms (effect sizes, as determined by Cohen d, ranged from 0.20-0.69).
Conclusions: This study adds to the literature suggesting that modern information technology could be aligned with conventional face-to-face services.
Keywords: Internet-treatment; blended therapy; cognitive behavioral therapy; psychiatry.
Plasma GDF15 level is elevated in psychosis and inversely correlated with severity
Sci Rep (2017) Aug 11;7(1):7906.
Parvin Kumar 1 2 , Vincent Millischer 3 4 , J Carlos Villaescusa 3 4 , Ida A K Nilsson 3 4 , Claes-Göran Östenson 3 , Martin Schalling 3 4 , Urban Ösby 4 5 6 , Catharina Lavebratt 7 8
1 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. parvin.kumar@ki.se.
2 Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. parvin.kumar@ki.se.
3 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
4 Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
5 Department of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB, Stockholm, Sweden.
6 Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
7 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. catharina.lavebratt@ki.se.
8 Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. catharina.lavebratt@ki.se.
PMID: 28801589
PMCID: PMC5554200
DOI: 10.1038/s41598-017-07503-2
Abstract
Accumulating evidence suggests that GDF15 is a biomarker for ageing and morbidity of many somatic disorders such as cancer and inflammatory disorders. Recently, elevated serum GDF15 level was proposed as a marker for mood disorder. However, psychosis severity was not investigated in relation to plasma GDF15 levels. In the present study we measured GDF15 levels in plasma of 120 psychosis patients compared to 120 age and gender matched healthy controls. Within the patient cohort GDF15 levels were evaluated for association with age, gender, lifestyle factors, C-reactive protein levels, psychosis severity and metabolic disorder. Psychosis patients had elevated GDF15 levels compared to controls (medianPsychosis = 744 ng/mL, mediancontrols = 516 ng/mL, p < 0.001). Within the psychosis cohort, GDF15 levels, when corrected for age, metabolic health and lifestyle factors, were negatively correlated with psychosis severity (β = -0.218, p = 0.012). While GDF15 levels were elevated in patients versus healthy controls, the negative correlation between psychosis severity and GDF15 suggests a loss of anti-inflammatory GDF15 mediated functionality in severe psychosis. Study replication in larger cohorts will be necessary to assess the potential of GDF15 as a prognostic biomarker in psychosis.
Genetic variants of increased waist circumference in psychosis
Psychiatr Genet (2017) Dec;27(6):210-218.
Dzana S Hukic 1 , Urban Ösby, Eric Olsson, Agneta Hilding, Claes-Göran Östenson, Harvest F Gu, Ewa Ehrenborg, Gunnar Edman, Martin Schalling, Catharina Lavebratt, Louise Frisén
1 Departments of aMolecular Medicine and Surgery, Neurogenetics Unit bNeurobiology, Care Sciences and Society, Centre for Family Medicine cClinical Neuroscience dMolecular Medicine and Surgery, Endocrine and Diabetes Unit eMedicine, Cardiovascular Medicine Unit, Karolinska Institutet fCenter for Molecular Medicine, Karolinska University Hospital Solna gDepartment of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB hChild and Adolescent Psychiatry Research Center, Stockholm, Sweden.
PMID: 28737528
PMCID: PMC5662154
DOI: 10.1097/YPG.0000000000000181
Abstract
Objective: We examined whether established metabolic risk genetic variants in the population confer a risk for increased waist circumference in patients with schizophrenia spectrum disorders and also an association with schizophrenia spectrum disorders irrespective of waist circumference.
Patients and methods: We analyzed the association in (i) a case-case model in which patients with schizophrenia spectrum disorder with increased waist circumference (≥80 cm for women and ≥94 cm for men) (n=534) were compared with patients with normal waist circumference (<80 cm for women; <94 cm for men) (n=124), and in (ii) a case-control model in which schizophrenia spectrum disorder patients with increased waist circumference or irrespective of waist circumference were compared with population-derived controls (n=494) adjusted for age, sex, fasting glucose, smoking, and family history of diabetes.
Results: Genetic variants in five genes (MIA3, MRAS, P2RX7, CAMKK2, and SMAD3) were associated with increased waist circumference in patients with schizophrenia spectrum disorder (P<0.046). Genetic variants in three other genes (PPARD, MNTR1B, and NOTCH2) were associated with increased waist circumference in patients when compared with control individuals (P<0.037). Genetic variants in the PPARD, MNTR1B, NOTCH2, and HNF1B were nominally associated with schizophrenia spectrum disorder irrespective of waist circumference (P<0.027). No differences in waist circumference between specific psychosis diagnoses were detected.
Conclusion: Increased waist circumference in patients with schizophrenia spectrum disorder may be explained, in part, by increased metabolic risk gene burden, and it indicates a shared genetic susceptibility to metabolic disorder and psychosis per se. Along these lines, common metabolic risk genetic variants confer a risk for increased waist circumference in patients with schizophrenia spectrum disorders.
J Atten Disord (2020) Apr;24(6):904-917.
Berkeh Nasri 1 2 , Malin Castenfors 3 , Peggy Fredlund 2 , Ylva Ginsberg 1 2 , Nils Lindefors 1 2 , Viktor Kaldo 1 2
1 Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
2 Stockholm Health Care Services, Stockholm County Council, Huddinge hospital, Stockholm, Sweden.
3 PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
PMID: 28178870
Abstract
Objectives: To evaluate feasibility and preliminary effects of a new group treatment manual for adults with ADHD and to explore adherence to treatment and its relation to outcome. Method: Eighteen adults with ADHD recruited from neuropsychiatric units in Stockholm underwent a 14-week program including combined cognitive and dialectical behavior therapy. Assessments were made at baseline, posttreatment, and follow-up, at one and six months after treatment end. Primary outcome measure was the Adult ADHD Self Report Scale version 1.1. Results/Conclusion: ADHD symptoms significantly decreased (d = 1.29) and remained stable for 6 months. Measures of depression, perceived stress, and anxiety were also significantly reduced. Attendance and patient satisfaction was high. Use, comprehension, and perceived benefit of treatment components varied from medium to high. Total use of treatment components was, in general, positively correlated with favorable outcome. The current combination of treatment components may be a valuable addition to available treatments in psychiatric care.
Keywords: ADHD; adults; cognitive behavior therapy; dialectical behavior therapy; feasibility pilot; group treatment; novel treatment; psychological treatment; psychotherapy.
Troponin T levels associated with genetic variants in NOTCH2 and MTNR1B in women with psychosis
Psychiatry Res (2017) Apr;250:217-220.
Dzana Sudic Hukic 1 , Catharina Lavebratt 2 , Eric Olsson 3 , Claes-Göran Östenson 4 , Sven V Eriksson 5 , David Erlinge 6 , Martin Schalling 2 , Urban Ösby 7
1 Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB, Stockholm, Sweden. Electronic address: dzana.hukic@ki.se.
2 Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
3 Department of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
4 Endocrine and Diabetes Unit, Department of Molecular Medicine and Surgery; Karolinska Institutet, Stockholm, Sweden.
5 Department of Clinical Sciences, Karolinska Institutet, Danderyd University; Hospital, Stockholm, Sweden.
6 Department of Clinical Sciences, Lund University, Lund, Sweden.
7 Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB, Stockholm, Sweden; Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
PMID: 28167435
DOI: 10.1016/j.psychres.2017.01.030
Abstract
Psychosis patients have increased prevalence of metabolic disorders, which increase the risk for cardiovascular disease. Elevated troponin T level is an early biomarker of cardiovascular damage. We tested for association between troponin T levels and genetic risk variants of elevated blood glucose level in psychosis. Glucose and troponin T levels correlated positively. MTNR1B rs10830963 and NOTCH2 rs10923931 associated with troponin T levels in women, adjusted for glucose levels. These findings may indicate metabolic genetic influences on troponin T levels among women with psychosis.
Keywords: Cardiovascular biomarker; Schizophrenia; Type 2 diabetes.
Medical history of discordant twins and environmental etiologies of autism
Transl Psychiatry (2017) Jan 31;7(1):e1014.
C Willfors 1 2 , T Carlsson 1 3 , B-M Anderlid 4 5 , A Nordgren 4 5 , E Kostrzewa 1 2 , S Berggren 1 2 6 , A Ronald 7 , R Kuja-Halkola 8 , K Tammimies 1 2 , S Bölte 1 2 6
1 Karolinska Institutet Center for Neurodevelopmental Disorders, Pediatric Neuropsychiatry Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Solna, Sweden.
2 Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.
3 Prima Child and Adult Psychiatry, Stockholm, Sweden.
4 Department of Molecular Medicine and Surgery, Center of Molecular Medicine, Karolinska Institutet, Solna, Sweden.
5 Department of Clinical Genetics, Karolinska University Hospital, Solna, Sweden.
6 Child and Adolescent Psychiatry, Stockholm County Council, Stockholm, Sweden.
7 Genes Environment Lifespan laboratory, Department of Psychological Sciences, Birkbeck, University of London, London, UK.
8 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
PMID: 28140403
PMCID: PMC5299390
DOI: 10.1038/tp.2016.269
Abstract
The environmental contributions to autism spectrum disorder (ASD) and their informative content for diagnosing the condition are still largely unknown. The objective of this study was to investigate associations between early medical events and ASD, as well as autistic traits, in twins, to test the hypothesis of a cumulative environmental effect on ASD risk. A total of 80 monozygotic (MZ) twin pairs (including a rare sample of 13 twin pairs discordant for clinical ASD) and 46 dizygotic (DZ) twin pairs with varying autistic traits, were examined for intra-pair differences in early medical events (for example, obstetric and neonatal factors, first year infections). First, differences in early medical events were investigated using multisource medical records in pairs qualitatively discordant for ASD. The significant intra-pair differences identified were then tested in relation to autistic traits in the remaining sample of 100 pairs, applying generalized estimating equations analyses. Significant association of the intra-pair differences in the MZ pairs were found for the cumulative load of early medical events and clinical ASD (Z=-2.85, P=0.004) and autistic traits (β=78.18, P=0.002), as well as infant dysregulation (feeding, sleeping abnormalities, excessive crying and worriedness), when controlling for intelligence quotient and attention deficit hyperactivity disorder comorbidity. The cumulative load of early medical events in general, and infant dysregulation in particular, may index children at risk of ASD owing to non-shared environmental contributions. In clinical practice, these findings may facilitate screening and early detection of ASD.
Preschool to School in Autism: Neuropsychiatric Problems 8 Years After Diagnosis at 3 Years of Age
J Autism Dev Disord (2016) Aug;46(8):2749-2755.
M Barnevik Olsson 1 2 , S Lundström 3 , J Westerlund 3 4 , M B Giacobini 5 , C Gillberg 3 , E Fernell 3
1 Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. martina.barnevik-olsson@primabarn.se.
2 PRIMA Child and Adult Psychiatry, Götgatan 71, 116 21, Stockholm, Sweden. martina.barnevik-olsson@primabarn.se.
3 Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
4 Department of Psychology, Stockholm University, Stockholm, Sweden.
5 PRIMA Child and Adult Psychiatry, Götgatan 71, 116 21, Stockholm, Sweden.
PMID: 27230761
DOI: 10.1007/s10803-016-2819-0
Abstract
The study presents neuropsychiatric profiles of children aged 11 with autism spectrum disorder, assessed before 4.5 years, and after interventions. The original group comprised a community sample of 208 children with ASD. Parents of 128 participated-34 with average intellectual function, 36 with borderline intellectual function and 58 with intellectual disability. They were interviewed using the Autism-Tics, AD/HD and other Comorbidities interview. Criteria for a clinical/subclinical proxy of ASD were met by 71, 89 and 95 %, respectively. Criteria for at least one of ASD, AD/HD, Learning disorder or Developmental Coordination Disorder were met by 82, 94 and 97 %. More than 90 % of children with a preschool diagnosis of ASD have remaining neuropsychiatric problems at 11, despite early intervention.
Keywords: A-TAC interview; AD/HD; ASD; Autism spectrum disorder; Developmental coordination disorder; Follow-up; Intellectual disability; Learning disorder; Oppositional defiant disorder; Outcome.
Suicide risk and antipsychotic side effects in schizophrenia: nested case-control study
Hum Psychopharmacol (2016) Jul;31(4):341-5.
Johan Reutfors 1 , Eric Clapham 2 , Shahram Bahmanyar 1 3 , Lena Brandt 1 , Erik G Jönsson 4 5 , Anders Ekbom 1 , Robert Bodén 1 2 , Urban Ösby 6 7 8
1 Centre for Pharmacoepidemiology (CPE), Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
2 Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
3 Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
4 Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
5 NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
6 Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
7 Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
8 Department of Adult Psychiatry, PRIMA Psychiatry AB, Stockholm, Sweden.
PMID: 27108775
DOI: 10.1002/hup.2536
Abstract
Objective: This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication.
Methods: Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression.
Results: A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk.
Conclusions: A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords: akathisia; antipsychotics; schizophrenia; side effects; suicide.
Acta Paediatr (2016) Jul;105(7):823-8.
Lotta Höglund Carlsson 1 2 , Joakim Westerlund 1 3 , Martina Barnevik Olsson 1 4 , Mats A Eriksson 1 5 , Åsa Hedvall 1 6 , Christopher Gillberg 1 , Elisabeth Fernell 1
1 Gillberg Neuropsychiatry Centre, Gothenburg University, Gothenburg, Sweden.
2 Department of Pediatrics, Karolinska University Hospital, Stockholm, Sweden.
3 Department of Psychology, Stockholm University, Stockholm, Sweden.
4 Prima Child and Adult Psychiatry, Stockholm, Sweden.
5 Department of Neuropaediatrics, Karolinska University Hospital, Stockholm, Sweden.
6 Department of Psychology, Karolinska University Hospital, Stockholm, Sweden.
PMID: 27059171
DOI: 10.1111/apa.13418
Abstract
Aim: This study investigated the results from the national, routine 18-month developmental surveillance at Child Healthcare Centres (CHCs) on children later diagnosed with autism spectrum disorder (ASD).
Methods: Child Healthcare Centre records of 175 children, diagnosed with ASD before 4.5 years in Stockholm County, Sweden, were reviewed regarding the results of the eight-item neurodevelopmental surveillance. Results were contrasted with normative data from the general child population in Stockholm County.
Results: More than one-third of the total ASD group, including half of the group with ASD and intellectual disability (ID), did not pass the required number of items, compared to one in 50 in the general child population. Of those with ASD and ID who had passed, more than one-third experienced developmental regression after 18 months of age. If the CHC surveillance had considered reported regulatory problems – crying, feeding and sleeping – then another 10% of the children with ASD and ID could have been identified during this surveillance.
Conclusion: The existing CHC surveillance traced half of the group of children who were later diagnosed with ASD combined with intellectual disability. Adding an item on regulatory problems to the 18-month surveillance would have increased this number by another 10%.
Keywords: Autism; Child Healthcare Centre; Children; Development; Surveillance.
Lithium treatment and cancer incidence in bipolar disorder
Bipolar Disord (2016) Feb;18(1):33-40.
Lina Martinsson 1 2 , Jeanette Westman 3 , Jonas Hällgren 3 , Urban Ösby 3 4 5 , Lena Backlund 2 6
1 Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
2 Centre for Psychiatric Research and Education, Stockholm, Sweden.
3 Division for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
4 Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
5 Department of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB, Stockholm, Sweden.
6 Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
PMID: 26880208
DOI: 10.1111/bdi.12361
Abstract
Objectives: To investigate whether there is an increased risk of cancer associated with lithium treatment in patients with bipolar disorder compared to the general population.
Methods: A nationwide Swedish register study of incidence rate ratios (IRRs) of total cancer and site-specific cancer in the 50-84-year age range was carried out in patients with bipolar disorder (n = 5,442) with and without lithium treatment from July 2005 to December 2009 compared to the general population using linked information from The Swedish Cancer Register, The National Patient Register, and The Drug Prescription Register.
Results: The overall cancer risk was not increased in patients with bipolar disorder. There was no difference in risk of unspecified cancer, neither in patients with lithium treatment compared to the general population [IRR = 1.04, 95% confidence interval (CI): 0.89-1.23] nor in patients with bipolar disorder without lithium treatment compared to the general population (IRR = 1.03, 95% CI: 0.89-1.19). The cancer risk was significantly increased in patients with bipolar disorder without lithium treatment in the digestive organs (IRR = 1.47, 95% CI: 1.12-1.93), in the respiratory system and intrathoracic organs (IRR = 1.72, 95% CI: 1.11-2.66), and in the endocrine glands and related structures (IRR = 2.60, 95% CI: 1.24-5.47), but in patients with bipolar disorder with lithium treatment, there was no significantly increased cancer risk compared to the general population.
Conclusions: Bipolar disorder was not associated with increased cancer incidence and neither was lithium treatment in these patients. Specifically, there was an increased risk of respiratory, gastrointestinal, and endocrine cancer in patients with bipolar disorder without lithium treatment.
Keywords: bipolar disorder; cancer; comorbidity; lithium; register; tumors.
Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder
Transl Psychiatry (2016) Feb 2;6(2):e727.
K N T Månsson 1 2 , A Salami 3 4 , A Frick 5 , P Carlbring 6 , G Andersson 1 7 , T Furmark 5 , C-J Boraxbekk 4 8
1 Division of Psychology, Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.
2 Department of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri, Stockholm, Sweden.
3 Department of Neurobiology, Care Sciences and Society, Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
4 Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden.
5 Department of Psychology, Uppsala University, Uppsala, Sweden.
6 Department of Psychology, Stockholm University, Stockholm, Sweden.
7 Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
8 CEDAR, Center for Demographic and Aging Research, Umeå University, Umeå, Sweden.
PMID: 26836415
PMCID: PMC4872422
DOI: 10.1038/tp.2015.218
Abstract
Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brain’s adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure-function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood-oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time × treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected P(FWE) = 0.02) and BOLD responsivity (P(FWE) = 0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (P(FWE)=0.04), and CBT-induced reduction of amygdala GM volume (pre-post) correlated positively with reduced anticipatory anxiety after treatment (P(FWE) ⩽ 0.05). In addition, we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants, as compared with controls (P(FWE) = 0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P=0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT.
Leukocyte telomere length and hippocampus volume: a meta-analysis
F1000Res (2015) Oct 15;4:1073.
Gustav Nilsonne 1 , Sandra Tamm 1 , Kristoffer N T Månsson 2 , Torbjörn Åkerstedt 1 , Mats Lekander 1
1 Stress Research Institute, Stockholm University, Stockholm, Sweden ; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
2 Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden ; PRIMA Psychiatry, Stockholm, Sweden.
PMID: 26674112
PMCID: PMC4670011
DOI: 10.12688/f1000research.7198.1
Abstract
Leukocyte telomere length has been shown to correlate to hippocampus volume, but effect estimates differ in magnitude and are not uniformly positive. This study aimed primarily to investigate the relationship between leukocyte telomere length and hippocampus gray matter volume by meta-analysis and secondarily to investigate possible effect moderators. Five studies were included with a total of 2107 participants, of which 1960 were contributed by one single influential study. A random-effects meta-analysis estimated the effect to r = 0.12 [95% CI -0.13, 0.37] in the presence of heterogeneity and a subjectively estimated moderate to high risk of bias. There was no evidence that apolipoprotein E (APOE) genotype was an effect moderator, nor that the ratio of leukocyte telomerase activity to telomere length was a better predictor than leukocyte telomere length for hippocampus volume. This meta-analysis, while not proving a positive relationship, also is not able to disprove the earlier finding of a positive correlation in the one large study included in analyses. We propose that a relationship between leukocyte telomere length and hippocamus volume may be mediated by transmigrating monocytes which differentiate into microglia in the brain parenchyma.
Keywords: Hippocampus; Microglia; Morphometry; Telomeres.
Eur Child Adolesc Psychiatry (2016) Jul;25(7):769-80.
Eric Zander 1 2 3 , Charlotte Willfors 4 5 , Steve Berggren 4 5 , Nora Choque-Olsson 4 5 6 , Christina Coco 4 5 7 , Anna Elmund 8 9 , Åsa Hedfors Moretti 10 , Anette Holm 11 , Ida Jifält 12 13 , Renata Kosieradzki 14 15 , Jenny Linder 16 , Viviann Nordin 7 , Karin Olafsdottir 17 , Lina Poltrago 8 , Sven Bölte 4 5
1 Pediatric Neuropsychiatry Unit, Department of Women’s and Children’s Health, Center of Neurodevelopmental Disorders (KIND), Karolinska Institutet, Gävlegatan 22B, 113 30, Stockholm, Sweden. eric.zander@ki.se.
2 Child and Adolescent Psychiatry, Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden. eric.zander@ki.se.
3 Neurodevelopmental Psychiatry Unit South East, Child and Adolescent Psychiatry, Stockholm County Council, Stockholm, Sweden. eric.zander@ki.se.
4 Pediatric Neuropsychiatry Unit, Department of Women’s and Children’s Health, Center of Neurodevelopmental Disorders (KIND), Karolinska Institutet, Gävlegatan 22B, 113 30, Stockholm, Sweden.
5 Child and Adolescent Psychiatry, Center for Psychiatry Research, Stockholm County Council, Stockholm, Sweden.
6 BUP Södertälje, Child and Adolescent Psychiatry, Stockholm County Council, Södertälje, Sweden.
7 Neuropediatric Unit, Sachs’ Children and Youth Hospital, Stockholm County Council, Stockholm, Sweden.
8 PRIMA Child and Adolescent Psychiatry, Stockholm, Sweden.
9 Citypsykologhus, Stockholm, Sweden.
10 BUP Sollentuna, Child and Adolescent Psychiatry, Stockholm County Council, Sollentuna, Sweden.
11 Astrid Lindgrens Children’s Hospital, Karolinska University Hospital Solna, Stockholm County Council, Solna, Sweden.
12 Astrid Lindgrens Children’s Hospital, Karolinska University Hospital Huddinge, Stockholm County Council, Huddinge, Sweden.
13 Pupil Health Unit, Tiohundra, Norrtälje, Sweden.
14 BUP Malmö, Child and Adolescent Psychiatry, Region Skåne, Malmö, Sweden.
15 Pupil Health Unit, Resource Team for Learning Disabled, City of Malmö, Sweden.
16 Södra Älvsborg Hospital (SÄS), Child and Adolescent Psychiatry, Region Västra Götaland, Borås, Sweden.
17 BUP Lund, Child and Adolescent Psychiatry, Region Skåne, Lund, Sweden.
PMID: 26584575
DOI: 10.1007/s00787-015-0793-2
Abstract
The Autism Diagnostic Observation Schedule (ADOS) is a first-choice diagnostic tool in autism spectrum disorder (ASD). Excellent interpersonal objectivity (interrater reliability) has been demonstrated for the ADOS under optimal conditions, i.e., within groups of highly trained ”research reliable” examiners in research setting. We investigated the spontaneous interrater reliability among clinically trained ADOS users across multiple sites in clinical routine. Forty videotaped administrations of the ADOS modules 1-4 were rated by five different raters each from a pool of in total 15 raters affiliated to 13 different clinical sites. G(q,k) coefficients (analogous to intraclass correlations), kappas (ĸ) and percent agreement (PA) were calculated. The median interrater reliability for items across the four modules was G(q,k) = .74-.83, with the single ADOS items ranging from .23 to .94. G(q,k) for total scores was .85-.92. For diagnostic classification (ASD/non-spectrum), PA was 64-82 % and Fleiss’ ĸ .19-.55. Objectivity was lower for pervasive developmental disorder not otherwise specified and non-spectrum diagnoses as compared to autism. Interrater reliabilities of the ADOS items and domain totals among clinical users across multiple sites were in the same range as previously reported for research reliable users, while the one for diagnostic classification was lower. Differences in sample characteristics, rater skills and statistics compared with previous studies are discussed. Findings endorse the objectivity of the ADOS in naturalistic clinical settings, but also pinpoint its limitations and the need and value of adequate and continuous rater training.
Keywords: Autism spectrum disorder; Diagnostic instrument; Interrater reliability.
Diabetes and glucose disturbances in patients with psychosis in Sweden
BMJ Open Diabetes Res Care (2015) Oct 9;3(1):e000120.
Eric Olsson 1 , Jeanette Westman 2 , Dzana Sudic Hukic 3 , Sven V Eriksson 4 , Gunnar Edman 5 , Robert Bodén 6 , Erik Jedenius 7 , Johan Reutfors 8 , Anders Berntsson 9 , Agneta Hilding 10 , Martin Schalling 11 , Claes-Göran Östenson 10 , Urban Ösby 5
1 Department of Clinical Neuroscience , Karolinska Institutet , Stockholm , Sweden ; Department of Adult Psychiatry , PRIMA Barn och Vuxenpsykiatri AB , Stockholm , Sweden.
2 Department of Neurobiology , Care Sciences and Society, Centre of Family Medicine, Karolinska Institutet , Stockholm , Sweden.
3 Department of Adult Psychiatry , PRIMA Barn och Vuxenpsykiatri AB , Stockholm , Sweden ; Center for Molecular Medicine , Karolinska University Hospital , Stockholm , Sweden.
4 Department of Clinical Sciences , Karolinska Institutet , Danderyd University Hospital, Stockholm , Sweden.
5 Department of Neurobiology , Care Sciences and Society, Centre of Family Medicine, Karolinska Institutet , Stockholm , Sweden ; Center for Molecular Medicine , Karolinska University Hospital , Stockholm , Sweden ; Department of Psychiatry , Tiohundra AB , Norrtälje , Sweden.
6 Department of Medicine Solna , Centre for Pharmacoepidemiology, Karolinska Institutet , Stockholm , Sweden ; Department of Neuroscience, Psychiatry , Uppsala University , Uppsala , Sweden.
7 Department of Clinical Neuroscience , Karolinska Institutet , Stockholm , Sweden.
8 Department of Medicine Solna , Centre for Pharmacoepidemiology, Karolinska Institutet , Stockholm , Sweden.
9 Department of Adult Psychiatry , PRIMA Barn och Vuxenpsykiatri AB , Stockholm , Sweden.
10 Department of Molecular Medicine and Surgery , Karolinska Institutet , Stockholm , Sweden.
11 Center for Molecular Medicine , Karolinska University Hospital , Stockholm , Sweden ; Department of Molecular Medicine and Surgery , Karolinska Institutet , Stockholm , Sweden.
PMID: 26468398
PMCID: PMC4600183
DOI: 10.1136/bmjdrc-2015-000120
Abstract
Objective: The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication.
Method: We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ(2) test, and factors associated with antidiabetic treatment were evaluated with logistic regression.
Results: Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1-6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness.
Conclusions: The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.
Keywords: Metabolic Syndrome; Schizophrenia.
Atten Defic Hyperact Disord (2016) Jun;8(2):101-11.
E Morgensterns 1 , J Alfredsson 2 , T Hirvikoski 3 4
1 Department of Women’s and Children’s Health, Pediatric Neuropsychiatry Unit, Center for Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska Institutet, CAP Research Center, Gävlegatan 22, 113 30, Stockholm, Sweden.
2 PRIMA Neuropsychiatry, Stockholm, Sweden.
3 Department of Women’s and Children’s Health, Pediatric Neuropsychiatry Unit, Center for Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska Institutet, CAP Research Center, Gävlegatan 22, 113 30, Stockholm, Sweden. tatja.hirvikoski@ki.se.
4 Habilitation and Health, Stockholm County Council, Stockholm, Sweden. tatja.hirvikoski@ki.se.
PMID: 26410823
DOI: 10.1007/s12402-015-0182-1
Abstract
The aim of the current study was to evaluate the feasibility, acceptability, and effectiveness of Dialectical Behavioral Therapy-based skills training groups for adults with ADHD in an outpatient psychiatric context. Furthermore, the purpose was to analyze the impact of clinical characteristics on the effect and attrition. Ninety-eight adults (out of 102) with ADHD were allocated to the treatment. Self-rating scales were administered as baseline before the first session (T1), post-treatment (T2), and at 3-month follow-up (T3). Approximately 80 % (74 individuals) attended at least two-thirds of the sessions. Treatment satisfaction was good. ADHD symptoms and ADHD-related functional impairment in every-day life were reduced. Well-being, ability to be mindful, acceptance of emotions and quality of life were increased. The results were stable at 3-month follow-up. None of the predictors, i.e., age, comorbidity, ADHD medication status, IQ-level, treatment credibility, or functional impairment at the beginning of treatment, significantly predicted treatment outcome (change in ADHD symptoms from T1 to T2). Likewise, none of the predictors, i.e., irritability/aggression, comorbidity, and functional impairment, were significantly associated with attrition. Due to the difficulties in predicting treatment outcome, as well as attrition, based on clinical characteristics, broad inclusion criteria should be applied.
Keywords: ADHD; Adults; Group therapy; Multimodal; Psychotherapy; Skills training group.
J Manipulative Physiol Ther (2015) Sep;38(7):465-476.e4.
Gunnel E Peterson 1 , Maria H Landén Ludvigsson 2 , Shaun P O’Leary 3 , Åsa M Dedering 4 , Thorne Wallman 5 , Margaretha I N Jönsson 6 , Anneli L C Peolsson 7
1 PhD Student, Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden; PhD Student, Department of Medical and Health Sciences, Division of Physiotherapy, Faculty of Health Sciences, Linköping University, Linköping, Sweden. Electronic address: gunnel.peterson@liu.se.
2 PhD Student, Department of Medical and Health Sciences, Division of Physiotherapy, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Registered Physical Therapist, Rehab Väst, County Council of Östergötland, Östergötland, Sweden.
3 Principal Research Fellow, NHMRC CCRE (Spinal Pain, Injury and Health), the University of Queensland, Brisbane, Australia; Principal Research Fellow, Physiotherapy Department, Royal Brisbane and Women’s Hospital, Queensland Health, Brisbane, Australia.
4 Associate Professor, Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet; Associate Professor, Department of Physical Therapy, Karolinska University Hospital, Stockholm, Sweden.
5 Deputy Director, Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden; Adjunct Senior Lecturer, Public Health & Caring Sciences, Family Medicine & Preventive Medicine Section, Uppsala University, Uppsala, Sweden.
6 Registered Physical Therapist, Prima Rehab, Herrgärdet Health Care Center, County Council of Västmanland, Västmanland, Sweden.
7 Associate Professor, Department of Medical and Health Sciences, Division of Physiotherapy, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Associate Professor, NHMRC CCRE (Spinal Pain, Injury and Health), the University of Queensland, Brisbane, Australia.
PMID: 26387858
DOI: 10.1016/j.jmpt.2015.06.011
Abstract
Objective: The purpose of this study was to compare the effects of 3 different exercise approaches on neck muscle endurance (NME), kinesiophobia, exercise compliance, and patient satisfaction in patients with chronic whiplash.
Methods: This prospective randomized clinical trial included 216 individuals with chronic whiplash. Participants were randomized to 1 of 3 exercise interventions: neck-specific exercise (NSE), NSE combined with a behavioral approach (NSEB), or prescribed physical activity (PPA). Measures of ventral and dorsal NME (endurance time in seconds), perceived pain after NME testing, kinesiophobia, exercise compliance, and patient satisfaction were recorded at baseline and at the 3- and 6-month follow-ups.
Results: Compared with individuals in the prescribed physical activity group, participants in the NSE and NSEB groups exhibited greater gains in dorsal NME (P = .003), greater reductions in pain after NME testing (P = .03), and more satisfaction with treatment (P < .001). Kinesiophobia and exercise compliance did not significantly differ between groups (P > .07).
Conclusion: Among patients with chronic whiplash, a neck-specific exercise intervention (with or without a behavioral approach) appears to improve NME. Participants were more satisfied with intervention including neck-specific exercises than with the prescription of general exercise.
Keywords: Exercise Therapy; Neck Pain; Rehabilitation; Whiplash Injuries.
Genetic and Clinical Factors Affecting Plasma Clozapine Concentration
Prim Care Companion CNS Disord (2015) Feb 19;17(1):10.4088/PCC.14m01704.
Eric Olsson 1 , Gunnar Edman 1 , Leif Bertilsson 1 , Dzana Sudic Hukic 1 , Catharina Lavebratt 1 , Sven V Eriksson 1 , Urban Ösby 1
1 Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, and Department of Adult Psychiatry, PRIMA Barn och Vuxenpsykiatri AB, Stockholm (Dr Olsson); Department of Psychiatry, Tiohundra AB, Norrtälje (Drs Edman and Ösby and Ms Hukic); Department of Neurobiology, Care Sciences and Society, Centre of Family Medicine, Karolinska Institutet, Stockholm (Drs Edman and Ösby); Center for Molecular Medicine, Karolinska University Hospital, Stockholm (Drs Edman, Lavebratt, and Ösby); Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm (Dr Bertilsson); Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm (Drs Hukic and Lavebratt); and Department of Cardiology, Danderyd University Hospital, Karolinska Institutet, Stockholm (Dr Eriksson), Sweden.
PMID: 26137357
PMCID: PMC4468884
DOI: 10.4088/PCC.14m01704
Abstract
Objective: To assess (1) the variance of plasma clozapine levels; (2) the relative importance of sex, smoking habits, weight, age, and specific genetic variants of cytochrome P450 1A2 (CYP1A2), uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), and multidrug resistance protein 1 (MDR1) on plasma levels of clozapine; and (3) the relation between plasma clozapine levels, fasting glucose levels, and waist circumference.
Method: There were 113 patients on clozapine treatment recruited from psychosis outpatient clinics in Stockholm County, Sweden. Patients had genotype testing for single nucleotide polymorphisms: 2 in MDR1, 3 in CYP1A2, and 1 in UGT1A4. Multiple and logistic regression were used to analyze the relations.
Results: There was a wide variation in plasma concentrations of clozapine (mean = 1,615 nmol/L, SD = 1,354 nmol/L), with 37% of the samples within therapeutic range (1,100-2,100 nmol/L). Smokers had significantly lower plasma clozapine concentrations than nonsmokers (P ≤ .03). There was a significant association between the rs762551 A allele of CYP1A2 and lower plasma clozapine concentration (P ≤ .05). Increased fasting glucose level was 3.7-fold more frequent in CC and CA genotypes than AA genotype (odds ratio = 0.27; 95% confidence interval, 0.10-0.72). There was no significant relation between higher fasting glucose levels, larger waist circumference, and higher clozapine levels.
Conclusions: It is difficult to predict plasma clozapine concentration, even when known individual and genetic factors are considered. Therefore, therapeutic drug monitoring is recommended in patients who are treated with clozapine.
J Autism Dev Disord (2015) Nov;45(11):3624-33.
Åsa Hedvall 1 2 , Joakim Westerlund 3 , Elisabeth Fernell 4 5 , Fritjof Norrelgen 4 6 , Liselotte Kjellmer 4 6 7 , Martina Barnevik Olsson 4 8 , Lotta Höglund Carlsson 4 9 , Mats A Eriksson 4 10 , Eva Billstedt 11 , Christopher Gillberg 4
1 Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg, 411 19, Gothenburg, Sweden. asa.lundholm-hedvall@gnc.gu.se.
2 Department of Psychology, Karolinska University Hospital, Stockholm, Sweden. asa.lundholm-hedvall@gnc.gu.se.
3 Department of Psychology, Stockholm University, Stockholm, Sweden.
4 Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg, 411 19, Gothenburg, Sweden.
5 Research and Development Centre, Skaraborgs´s Hospital, Skövde, Sweden.
6 Department of Speech and Language Pathology, Karolinska University Hospital, Stockholm, Sweden.
7 CLINTEC, Division of Speech and Language Pathology, Karolinska Institutet, Stockholm, Sweden.
8 PRIMA Child and Adolescent Psychiatry, Stockholm, Sweden.
9 Department of Pediatrics, Astrid Lindgren Children’s Hospital, Liljeholmen, Stockholm, Sweden.
10 Department of Pediatric Neurology, Karolinska University Hospital, Stockholm, Sweden.
11 Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, University of Gothenburg, 411 19, Gothenburg, Sweden. eva.billstedt@gnc.gu.se.
PMID: 26123008
DOI: 10.1007/s10803-015-2509-3
Abstract
Clinical predictors of 2-year outcome in preschoolers with ASD were studied in a population-based group of very young children with ASD (n = 208). Children who gained the most (n = 30) and lost the most (n = 23), i.e., increased or decreased their adaptive functioning outcome according to the Vineland Composite Score between study entry (T1) and follow-up (T2), 2 years later were compared. Individual factors that differed significantly between the two outcome groups were cognitive level, age at referral, not passing expected milestones at 18 months, autistic type behavior problems and regression. However, logistic regression analysis showed that only cognitive level at T1 (dichotomized into IQ < 70 and IQ ≥ 70) made a unique statistically significant contribution to outcome prediction (p = <.001) with an odds ratio of 18.01. The findings have significant clinical implications in terms of information at diagnosis regarding clinical prognosis in ASD.
Keywords: Autism spectrum disorder; Clinical characteristics; Outcome; Predictors; Preschool children.
”Recovery” from the diagnosis of autism – and then?
Neuropsychiatr Dis Treat (2015) Apr 7;11:999-1005.
Martina Barnevik Olsson 1 , Joakim Westerlund 2 , Sebastian Lundström 3 , MaiBritt Giacobini 4 , Elisabeth Fernell 5 , Christopher Gillberg 3
1 Gillberg Neuropsychiatry Centre, Institution of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden ; PRIMA Child and Adult Psychiatry, Stockholm, Sweden.
2 Gillberg Neuropsychiatry Centre, Institution of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden ; Department of Psychology, Stockholm University, Stockholm, Sweden.
3 Gillberg Neuropsychiatry Centre, Institution of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
4 PRIMA Child and Adult Psychiatry, Stockholm, Sweden ; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
5 Gillberg Neuropsychiatry Centre, Institution of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden ; Research and Development Centre, Skaraborg’s Hospital, Skövde, Sweden.
PMID: 25897237
PMCID: PMC4397923
DOI: 10.2147/NDT.S78707
Abstract
Background: The aim of this study was to follow up the 17 children, from a total group of 208 children with autism spectrum disorder (ASD), who ”recovered from autism”. They had been clinically diagnosed with ASD at or under the age of 4 years. For 2 years thereafter they received intervention based on applied behavior analysis. These 17 children were all of average or borderline intellectual functioning. On the 2-year follow-up assessment, they no longer met criteria for ASD.
Methods: At about 10 years of age they were targeted for a new follow-up. Parents were given a semistructured interview regarding the child’s daily functioning, school situation, and need of support, and were interviewed using the Vineland Adaptive Behavior Scales (VABS) and the Autism – Tics, Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC) telephone interview.
Results: The vast majority of the children had moderate-to-severe problems with attention/activity regulation, speech and language, behavior, and/or social interaction. A majority of the children had declined in their VABS scores. Most of the 14 children whose parents were A-TAC-interviewed had problems within many behavioral A-TAC domains, and four (29%) had symptom levels corresponding to a clinical diagnosis of ASD, AD/HD, or both. Another seven children (50%) had pronounced subthreshold indicators of ASD, AD/HD, or both.
Conclusion: Children diagnosed at 2-4 years of age as suffering from ASD and who, after appropriate intervention for 2 years, no longer met diagnostic criteria for the disorder, clearly needed to be followed up longer. About 3-4 years later, they still had major problems diagnosable under the umbrella term of ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations). They continued to be in need of support, educationally, from a neurodevelopmental and a medical point of view. According to parent interview data, a substantial minority of these children again met diagnostic criteria for ASD.
Keywords: A-TAC; AD/HD; Vineland; autism spectrum disorder; autistic traits; cure.
J Atten Disord (2018) Jan;22(1):3-13.
MaiBritt Giacobini 1 , Emma Medin 2 3 , Ewa Ahnemark 4 , Leo J Russo 5 , Peter Carlqvist 3
1 1 PRIMA Barn och Vuxenpsykiatri AB, Stockholm, Sweden.
2 2 LIME/Karolinska Institutet, Stockholm, Sweden.
3 3 PAREXEL, Stockholm, Sweden.
4 4 Shire, Danderyd, Sweden.
5 5 Shire, Wayne, PA, USA.
PMID: 25376193
Abstract
Objective: The objective of this study was to describe the epidemiology of diagnosed ADHD and the pharmacological treatment of patients with ADHD in Sweden. Specifically, this study estimates the prevalence of patients with a newly registered diagnosis of ADHD over a 5-year period, and the prevalence of all patients with a registered ADHD diagnoses over a 6-year period in Sweden.
Method: Two population-based registries were used as data sources for this study; the National Patient Register (NPR) and the Prescribed Drug Register (PDR). The international Classification of Diseases 10th Revison (ICD-10) was used to identify patients with ADHD.
Results: The annual prevalence of ADHD in the general population of Sweden was found to be 1.1 per 1,000 persons in the year 2006 increasing to 4.8 per 1,000 persons in 2011. The corresponding prevalence for newly diagnosed patients increased from 0.6 per 1,000 persons in 2007 to 1.3 per 1,000 persons in 2011. The majority of diagnosed patients received pharmacological treatment, with methylphenidate being the most common dispensed drug. Comorbidities in the autism spectrum were most common for younger patients, while substance abuse, anxiety, and personality disorder were the most common comorbidities in older patients.
Conclusion: From 2006 to 2011, the number of patients diagnosed with ADHD has increased in Sweden over all ages. The majority of patients diagnosed with ADHD in Sweden received a pharmacological treatment regardless of age. An ADHD diagnosis was often accompanied with psychiatric comorbidity.
Keywords: ADHD; psychostimulants; treatment.
Clin Neuropharmacol Sep-Oct 2010;33(5):260-4.
Anders Lundin 1 , Espen Dietrichs, Sara Haghighi, Marie-Louise Göller, Arvid Heiberg, Ghada Loutfi, Håkan Widner, Klas Wiktorin, Leif Wiklund, Anders Svenningsson, Clas Sonesson, Nicholas Waters, Susanna Waters, Joakim Tedroff
1 Prima Psychiatry, Danderyd Hospital, Stockholm, Sweden. anderslundin1@gmail.com
PMID: 20616707
DOI: 10.1097/WNF.0b013e3181ebb285
Abstract
Objectives: To evaluate the efficacy and safety of the dopaminergic stabilizer pridopidine (ACR16) in patients with Huntington’s disease (HD).
Methods: In a randomized, double-blind, placebo-controlled, 4-week trial, patients with HD received pridopidine (50 mg/d, n = 28) or placebo (n = 30). The primary outcome measure was the change from baseline in weighted cognitive score, assessed by cognitive tests (Symbol Digit Modalities, verbal fluency, and Stroop tests). Secondary outcome measures included changes in the Unified Huntington’s Disease Rating Scale, Hospital Anxiety and Depression Scale, Leeds Sleep Evaluation Questionnaire, Reitan Trail-Making Test A, and Clinical Global Impression of Change. Safety assessments were also performed.
Results: There was no significant difference between pridopidine and placebo in the change from baseline of the weighted cognitive score. However, secondary measures such as affective symptoms showed trends toward improvement, and there was significant improvement in voluntary motor symptoms compared with placebo (P < 0.05). Pridopidine was well tolerated, with a safety profile similar to placebo.
Conclusions: Pridopidine shows promise as a treatment for some of the symptoms of HD. In this small-scale study, the most notable effect was improvement in voluntary motor symptoms. Larger, longer-term trials are warranted.
Acta Paediatr (2010) May;99(5):743-747.
Elisabeth Fernell 1 , Martina Barnevik-Olsson 1 , Gunnel Bågenholm 1 , Christopher Gillberg 1 , Sven Gustafsson 1 , Maria Sääf 1
1 .Autism Centre for Young Children, Handicap and Habilitation, Stockholm, Sweden.Unit of Developmental Disorders, Department of Paediatrics, and FoU centre, Skaraborg Hospital, Sweden.PRIMA Child and Adolescent Psychiatry, Stockholm, Sweden.Department of Paediatrics, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.Institute of Neuroscience and Physiology, Child and Adolescent Psychiatry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Department of Molecular Medicine and Surgery, Karolinska Institute, and Karolinska University Hospital, Stockholm, Sweden.Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
PMID: 20219032
DOI: 10.1111/j.1651-2227.2010.01755.x
Abstract
Aim: To analyse serum levels of 25-hydroxyvitamin D in mothers of Somali origin and those of Swedish origin who have children with and without autism as there is a growing evidence that low vitamin D impacts adversely on brain development.
Method: Four groups of mothers were invited to participate; 20 with Somali origin with at least one child with autism, 20 with Somali origin without a child with autism, 20 of Swedish origin with at least one child with autism and 20 with Swedish origin without a child with autism. Two blood samples were collected from each individual; during autumn and spring.
Results: Between 12 and 17 mothers from the different groups accepted to participate, both groups of mothers of Somali origin had significantly lower values of 25-hydroxyvitamin D compared with Swedish mothers. The difference of 25-hydroxyvitamin D between mothers of Somali origin with and without a child with autism was not significant.
Conclusion: Our findings of low vitamin D levels in Somali women entail considerable consequences in a public health perspective. The observed tendency, i.e. the lowest values in mothers of Somali origin with a child with autism was in the predicted direction, supporting the need for further research of vitamin D levels in larger samples of Somali mothers of children with and without autism.
