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Manouilenko, I., Humble, M. B., Georgieva, J. & Bejerot, S. (2017). Brainstem Auditory Evoked Potentials for diagnosing Autism Spectrum Disorder, ADHD and Schizophrenia Spectrum Disorders in adults: A blinded study. Psychiatry Research, 257, 21-26
Open this publication in new window or tab >>Brainstem Auditory Evoked Potentials for diagnosing Autism Spectrum Disorder, ADHD and Schizophrenia Spectrum Disorders in adults: A blinded study
2017 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 257, p. 21-26Article in journal (Refereed) Published
Abstract [en]

The aim of the present study was to examine the clinical utility of complex auditory brainstem response (c-ABR) and investigate if c-ABR is helpful in the diagnostic procedure. Thirty-one adult psychiatric patients, thoroughly diagnosed with autism spectrum disorder (ASD) (n=16), ADHD (n=8), or schizophrenia spectrum disorder (SSD) (n=7) and 15 healthy controls (HC), were blindly assessed with SensoDetect BERA. This c-ABR correctly identified psychiatric diagnoses in 4 patients (13%) and provided partially correct diagnoses in 11 more patients. Of the 15 HC, 6 were misclassified as psychiatric patients. The Cohen´s kappa coefficient (κ) was substantial for HC (κ=0.67), fair for SSD (κ=0.37), slight for ADHD (κ=0.09) and without agreement in ASD (κ=-0.03). In conclusion, we found the c-ABR method unhelpful and unreliable as a tool in clinical diagnostics.

Place, publisher, year, edition, pages
Clare, Ireland: Elsevier, 2017
Keywords
Auditory brainstem response, double-blind method, mental disorder
National Category
Psychiatry Neurology
Identifiers
urn:nbn:se:oru:diva-61468 (URN)10.1016/j.psychres.2017.06.085 (DOI)000413385300004 ()28710948 (PubMedID)2-s2.0-85022338791 (Scopus ID)
Funder
Swedish Research Council, K2012-62X -22130-04-6
Note

Funding Agencies:

Praktikertjanst AB, Stockholm, Sweden  

Stockholm County Council  20110307 

Karolinska Institutet  20110307 

Region Örebro County, Sweden 

Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2018-08-06Bibliographically approved
Bejerot, S., Edman, G., Frisén, L. & Humble, M. B. (2017). Evidence-Based Brief Obsessive-Compulsive Scale [Letter to the editor]. Journal of Central Nervous System Disease, 9, Article ID UNSP 1179573517702867.
Open this publication in new window or tab >>Evidence-Based Brief Obsessive-Compulsive Scale
2017 (English)In: Journal of Central Nervous System Disease, ISSN 1179-5735, E-ISSN 1179-5735, Vol. 9, article id UNSP 1179573517702867Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Sage Publications, 2017
National Category
Neurology
Identifiers
urn:nbn:se:oru:diva-58957 (URN)10.1177/1179573517702867 (DOI)000404684800001 ()28579868 (PubMedID)
Available from: 2017-08-18 Created: 2017-08-18 Last updated: 2017-10-05Bibliographically approved
Glans, M., Bejerot, S. & Humble, M. B. (2017). Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population. BJPsych Open, 3(5), 236-242
Open this publication in new window or tab >>Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population
2017 (English)In: BJPsych Open, E-ISSN 2056-4724, Vol. 3, no 5, p. 236-242Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Generalised joint hypermobility (GJH) is reportedly overrepresented among clinical cases of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and developmental coordination disorder (DCD). It is unknown if these associations are dimensional and, therefore, also relevant among non-clinical populations.

AIMS: To investigate if GJH correlates with sub-syndromal neurodevelopmental symptoms in a normal population.

METHOD: Hakim-Grahame's 5-part questionnaire (5PQ) on GJH, neuropsychiatric screening scales measuring ADHD and ASD traits, and a DCD-related question concerning clumsiness were distributed to a non-clinical, adult, Swedish population (n=1039).

RESULTS: In total, 887 individuals met our entry criteria. We found no associations between GJH and sub-syndromal symptoms of ADHD, ASD or DCD.

CONCLUSIONS: Although GJH is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population. Thus, if GJH serves as a biomarker cutting across diagnostic boundaries, this association is presumably limited to clinical populations.

Place, publisher, year, edition, pages
Royal College of Psychiatrists, 2017
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-62454 (URN)10.1192/bjpo.bp.116.004325 (DOI)000418507300005 ()28959454 (PubMedID)
Funder
Swedish Research Council, K2012-62X-22130-04-6The Karolinska Institutet's Research FoundationStockholm County Council
Available from: 2017-12-04 Created: 2017-12-04 Last updated: 2018-08-13Bibliographically approved
Humble, M. B. & Reis, M. (2017). Paroxetine concentrations in obsessive-compulsive disorder: Support for a therapeutic interval. European psychiatry, 41(Suppl.), S322-S322
Open this publication in new window or tab >>Paroxetine concentrations in obsessive-compulsive disorder: Support for a therapeutic interval
2017 (English)In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 41, no Suppl., p. S322-S322Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Introduction: Previous studies of concentrations of serotonin reuptake inhibitors (SRIs) versus therapeutic efficacy have yielded inconsistent results. Even if the relationships between the individual's serotonergic system and the clinical symptoms of obsessive-compulsive disorder (OCD) are poorly understood, the SRIs are consistently effective in OCD. However, studies on SRI concentrations in OCD treatment are rare.

Objectives/aims: To identify possible links between paroxetine concentrations and anti-obsessive response.

Methods: In a randomised, double-blind trial, comparing clomipramine, paroxetine and placebo in OCD treatment, serum paroxetine levels were measured after 1 week and after 4 weeks of treatment in 18 patients. Anti-obsessive response was assessed with Yale-Brown obsessive compulsive scale (Y-BOCS) and patients’ global evaluation (PGE), after 12 weeks of treatment.

Results: Serum paroxetine concentrations after 4 weeks suggested a therapeutic interval between 50 and 240 nmol/L (13–63 ng/mL). The mean Y-BOCS decrease was 54% inside versus 7% outside this interval (t = 3.96; P = 0.0011).

Conclusions: Paroxetine levels seemingly predicted clinical outcome. Studies with a greater number of patients are necessary in order to confirm this finding and to discern whether it is useful in clinical practice.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:oru:diva-58970 (URN)10.1016/j.eurpsy.2017.02.245 (DOI)000404952400060 ()
Available from: 2017-08-04 Created: 2017-08-04 Last updated: 2018-08-01Bibliographically approved
Bejerot, S., Nilsonne, G. & Humble, M. B. (2017). Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults. Lancet psychiatry, 4(6), 437-437
Open this publication in new window or tab >>Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults
2017 (English)In: Lancet psychiatry, ISSN 2215-0374, E-ISSN 2215-0366, Vol. 4, no 6, p. 437-437Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:oru:diva-58103 (URN)10.1016/S2215-0366(17)30160-8 (DOI)000402787900011 ()28495546 (PubMedID)
Available from: 2017-06-19 Created: 2017-06-19 Last updated: 2018-07-31Bibliographically approved
Humble, M. B. (2016). Obsessive-compulsive disorder, serotonin and oxytocin: treatment response and side effects. (Doctoral dissertation). Örebro: Örebro university
Open this publication in new window or tab >>Obsessive-compulsive disorder, serotonin and oxytocin: treatment response and side effects
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obsessive-compulsive disorder (OCD), with a prevalence of 1-2 %, frequently leads a chronic course. Persons with OCD are often reluctant to seek help and, if they do, their OCD is often missed. This is unfortunate, since active treatment may substantially improve social function and quality of life. Serotonin reuptake inhibitors (SRIs) have welldocumented efficacy in OCD, but delayed response may be problematic. Methods to predict response have been lacking. Because SRIs are effective, pathophysiological research on OCD has focussed on serotonin. However, no clear aberrations of serotonin have been found, thus other mechanisms ought to be involved.

Our aims were to facilitate clinical detection and assessment of OCD, to search for biochemical correlates of response and side-effects in SRI treatment of OCD and to identify any possible involvement of oxytocin in the pathophysiology of OCD.

In study I, we tested in 402 psychiatric out-patients the psychometric properties of a concise rating scale, “Brief Obsessive Compulsive Scale” (BOCS). BOCS was shown to be easy to use and have excellent discriminant validity in relation to other common psychiatric diagnoses.

Studies II-V were based on 36 OCD patients from a randomised controlled trial of paroxetine, clomipramine or placebo. In study II, contrary to expectation, we found that the change (decrease) of serotonin in whole blood was most pronounced in non-responders to SRI. This is likely to reflect inflammatory influence on platelet turnover rather than serotonergic processes within the central nervous system.

In studies IV-V, we found relations between changes of oxytocin in plasma and the anti-obsessive response, and between oxytocin and the SRI related delay of orgasm, respectively. In both cases, the relation to central oxytocinergic mechanisms is unclear. In males, delayed orgasm predicted anti-obsessive response.

Place, publisher, year, edition, pages
Örebro: Örebro university, 2016. p. 133
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 148
Keywords
Adverse effects, Obsessive-compulsive disorder, Orgasm, Oxytocin, Randomised controlled trial, Rating scale, Response prediction, Serotonin, Serotonin uptake inhibitors, Sexual function
National Category
Psychiatry General Practice
Research subject
Psychiatry
Identifiers
urn:nbn:se:oru:diva-51438 (URN)978-91-7529-153-6 (ISBN)
Public defence
2016-09-26, Campus USÖ, hörsal C3, Södra Grev Rosengatan, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-07-25 Created: 2016-07-25 Last updated: 2018-01-10Bibliographically approved
Humble, M. B. & Bejerot, S. (2016). Orgasm, Serotonin Reuptake Inhibition, and Plasma Oxytocin in Obsessive-Compulsive Disorder. Gleaning From a Distant Randomized Clinical Trial. Sexual medicine, 4(3), e145-e155
Open this publication in new window or tab >>Orgasm, Serotonin Reuptake Inhibition, and Plasma Oxytocin in Obsessive-Compulsive Disorder. Gleaning From a Distant Randomized Clinical Trial
2016 (English)In: Sexual medicine, ISSN 2050-1161, Vol. 4, no 3, p. e145-e155Article in journal (Refereed) Published
Abstract [en]

Introduction: Serotonin reuptake inhibitors (SRIs) are widely used for the treatment of psychiatric disorders, including obsessive-compulsive disorder (OCD). SRIs commonly cause delayed orgasm, the mechanism of which is poorly understood. Oxytocin is involved in sexual function and is interconnected with serotonin within the brain. SRIs are reported to affect the oxytocin system, but possible relations between SRI-induced changes of sexual function and oxytocin are unexplored in humans. In a randomized, double-blinded, placebo-controlled trial of OCD, the anti-obsessive efficacy and adverse events of SRIs and oxytocin measurements were studied.

Aims: To identify possible correlates between oxytocin levels and sexual function; find out whether sexual side effects correlate with levels of oxytocin and/or paroxetine and clomipramine; and test whether changes in sexual functioning are related to an anti-obsessive response.

Methods Reported sexual function and oxytocin plasma levels at rest were studied in 31 adults (15 men and 16 women) with OCD who participated in a randomized, double-blinded trial comparing the SRIs clomipramine and paroxetine with placebo. Sexual adverse effects were quantified by a clinician-administered semistructured interview. Anti-obsessive response was based on the Yale-Brown Obsessive-Compulsive Scale.

Main outcome measures: Ratings on the Sexual Symptom Checklist, plasma oxytocin, serum paroxetine and clomipramine levels, and Yale-Brown Obsessive-Compulsive Scale scores.

RESULTS: Baseline oxytocin levels were positively correlated with baseline OCD severity, but not with sexual functioning. Impaired orgasm at week 6 was reported by 73% of SRI-treated and 20% of placebo-treated patients (P = .03). Impaired orgasm was related to higher oxytocin levels after 4 weeks of SRI treatment (P < .01) but not to SRI concentrations. In men, an association between impaired orgasm and anti-obsessive treatment response was found (P = .028).

CONCLUSION: This pilot study suggests that some collateral effects of SRIs, particularly delayed orgasm, might be influenced by changes within the oxytocinergic system and are related to anti-obsessive mechanisms. Early-onset delayed orgasm in SRI-treated patients could serve as a predictor for OCD treatment response.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Elsevier, 2016
Keywords
Obsessive-Compulsive Disorder; Oxytocin/Plasma; Serotonin; Clomipramine; Paroxetine; Serotonin Uptake Inhibitors; Response Prediction; Adverse Effects; Randomized Controlled Trial; Sexual Physiology
National Category
Psychiatry General Practice
Identifiers
urn:nbn:se:oru:diva-50976 (URN)10.1016/j.esxm.2016.04.002 (DOI)000389259700003 ()27320409 (PubMedID)2-s2.0-85006216627 (Scopus ID)
Available from: 2016-06-21 Created: 2016-06-21 Last updated: 2018-07-14Bibliographically approved
Meehan, A. D., Humble, M. B., Yazarloo, P., Järhult, J. & Wallin, G. (2016). Reply to comments From Dr Lozano, et al - Concerning the prevalence of lithium-associated hyperparathyroidism [Letter to the editor]. Journal of Clinical Psychopharmacology, 36(2), 191-192
Open this publication in new window or tab >>Reply to comments From Dr Lozano, et al - Concerning the prevalence of lithium-associated hyperparathyroidism
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2016 (English)In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 36, no 2, p. 191-192Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Philadelphia, USA: Lippincott Williams & Wilkins, 2016
National Category
Psychiatry Pharmacology and Toxicology
Research subject
Psychiatry
Identifiers
urn:nbn:se:oru:diva-49642 (URN)10.1097/JCP.0000000000000477 (DOI)000372100800024 ()26872121 (PubMedID)2-s2.0-84957900522 (Scopus ID)
Available from: 2016-04-12 Created: 2016-04-05 Last updated: 2019-03-01Bibliographically approved
Fernell, E., Bejerot, S., Westerlund, J., Miniscalco, C., Simila, H., Eyles, D., . . . Humble, M. B. (2015). Autism spectrum disorder and low vitamin D at birth: a sibling control study. Molecular Autism, 6, Article ID 3.
Open this publication in new window or tab >>Autism spectrum disorder and low vitamin D at birth: a sibling control study
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2015 (English)In: Molecular Autism, ISSN 2040-2392, ISSN 2040-2392, Vol. 6, article id 3Article in journal (Refereed) Published
Abstract [en]

Background: Insufficient vitamin D activity has attracted increasing interest as a possible underlying risk factor in disorders of the central nervous system, including autism.

Methods: In this study, 25-hydroxyvitamin D (25(OH) D) was analysed in 58 Sweden-born sibling pairs, in which one child had autism spectrum disorder (ASD) and the other did not. The study group consisted of two representative samples; 47 Gothenburg sibling pairs with mixed ethnicities and 11 Stockholm sibling pairs with Somali background. 25(OH) D levels were analysed in the stored dried blood spots taken in the neonatal period for metabolic screening.

Results: The collapsed group of children with ASD had significantly lower vitamin D levels (M = 24.0 nM, SD = 19.6) as compared with their siblings (M = 31.9 nM, SD = 27.7), according to a paired samples t-test (P = 0.013). The difference was-most likely-not only accounted for by a difference in season of birth between ASD and non-ASD siblings since the mean 25(OH)D levels differed with similar effect size between the sibling pairs born during winter and summer, respectively. All children with African/Middle East background, both the children with ASD and their non-ASD siblings, had vitamin D deficiency.

Conclusions: The findings suggest that low prenatal vitamin D may act as a risk factor for ASD, however, there is a need for replication with larger samples. Future research should study whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD in the offspring.

Keywords
Autism spectrum disorder, Vitamin D, 25-hydroxyvitamin D, Neonatal, Dried blood spots
National Category
Neurology
Research subject
Neurology
Identifiers
urn:nbn:se:oru:diva-44116 (URN)10.1186/2040-2392-6-3 (DOI)000350599000002 ()
Funder
Swedish Research Council, 523-2011-3646
Note

Funding Agency:

'Föreningen Mjölkdroppen' in Stockholm

Available from: 2015-04-08 Created: 2015-04-08 Last updated: 2018-08-30Bibliographically approved
Holländare, F., Eriksson, A., Lövgren, L., Humble, M. B. & Boersma, K. (2015). Internet-Based Cognitive Behavioral Therapy for Residual Symptoms in Bipolar Disorder Type II: A Single-Subject Design Pilot Study. JMIR Research Protocols, 4(2), Article ID e44.
Open this publication in new window or tab >>Internet-Based Cognitive Behavioral Therapy for Residual Symptoms in Bipolar Disorder Type II: A Single-Subject Design Pilot Study
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2015 (English)In: JMIR Research Protocols, ISSN 1929-0748, E-ISSN 1929-0748, Vol. 4, no 2, article id e44Article in journal (Refereed) Published
Abstract [en]

Background: Bipolar disorder is a chronic condition with recurring episodes that often lead to suffering, decreased functioning, and sick leave. Pharmacotherapy in the form of mood stabilizers is widely available, but does not eliminate the risk of a new depressive or (hypo) manic episode. One way to reduce the risk of future episodes is to combine pharmacological treatment with individual or group psychological interventions. However, access to such interventions is often limited due to a shortage of trained therapists. In unipolar depression there is now robust evidence of the effectiveness of Internet-based psychological interventions, usually comprising psychoeducation and cognitive behavioral therapy (CBT). Internet-based interventions for persons suffering from bipolar disorder could increase access to psychological treatment.

Objective: The aim of this study was to investigate the feasibility of an Internet-based intervention, as well as its effect on residual depressive symptoms in persons diagnosed with bipolar disorder type II (BP-II). The most important outcomes were depressive symptoms, treatment adherence, and whether the patient perceived the intervention as helpful.

Methods: A total of 7 patients diagnosed with bipolar disorder type II at a Swedish psychiatric outpatient clinic were offered the opportunity to participate. Of the 7 patients, 3 (43%) dropped out before treatment began, and 4 (57%) were treated by means of an online, Internet-based intervention based on CBT (iCBT). The intervention was primarily aimed at psychoeducation, treatment of residual depressive symptoms, emotion regulation, and improved sleep. All patients had ongoing pharmacological treatment at recruitment and established contact with a psychiatrist. The duration of BP-II among the treated patients was between 6 and 31 years. A single-subject design was used and the results of the 4 participating patients were presented individually.

Results: Initiating treatment was perceived as too demanding under current life circumstances for 3 patients who consequently dropped out during baseline assessment. Self-ratings using the Montgomery-sberg Depression Rating Scale-Self-rated (MADRS-S) showed symptom reduction in 3 (75%) of the 4 treated cases during iCBT. In the evaluation of the treatment, 2 patients reported that they perceived that the treatment had reduced symptoms a little, 1 that it had reduced symptoms very much, and 1 not at all. Treatment adherence (ie, module completion) was fairly high in 3 cases. In general, the modules were perceived as fairly helpful or very helpful by the patients. In one case, there was a reliable change-according to the Reliable Change Index-in self-rated symptoms of depression and perseverative thinking.

Conclusions: The treatment seemed to have acceptable feasibility. The iCBT intervention could be an effective way to treat residual symptoms in some patients with bipolar disorder type II. This should be investigated in a larger study.

Place, publisher, year, edition, pages
JMIR publications, 2015
Keywords
bipolar disorder, Internet, cognitive therapy, behavioral therapy, pilot projects
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-54700 (URN)10.2196/resprot.3910 (DOI)000360877600023 ()25908235 (PubMedID)
Available from: 2017-01-13 Created: 2017-01-13 Last updated: 2017-11-29Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6726-7787

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