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Objective: Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia. Methods: Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 rag/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation. Results: Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores. Conclusion: Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.

Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p< 1 × 10−4were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10  × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p= 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

IMPORTANCE: Atopic dermatitis is a common and debilitating skin condition characterized by intense itching and chronic inflammation. Research on behavioral treatments with high accessibility is needed. OBJECTIVE: To investigate the efficacy of a highly scalable internet-delivered cognitive behavior therapy (CBT) for adults with atopic dermatitis. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial from a medical university in Stockholm, Sweden, included 102 adults with atopic dermatitis, recruited from across Sweden, who received 12 weeks of internet-delivered CBT (March 29, 2017, to February 16, 2018). The first participant provided screening data on November 27, 2016, and the last 1-year follow-up assessment was conducted on June 28, 2019. INTERVENTIONS: Participants were randomized in a 1:1 ratio to 12 weeks of therapist-guided internet-delivered CBT (n = 51) or a control condition (n = 51) that gave instructions about standard care. MAIN OUTCOMES AND MEASURES: The primary outcome was the between-group difference in mean reduction of atopic dermatitis symptoms as measured by the Patient-Oriented Eczema Measure and modeled intention to treat during the 12-week treatment period. RESULTS: A total of 102 participants (mean [SD] age, 37 [11] years; 83 [81%] female) were recruited and randomized. The primary analysis indicated that participants receiving internet-delivered CBT, relative to the controls, had a significantly larger mean weekly reduction in symptoms of atopic dermatitis as measured with the Patient-Oriented Eczema Measure (B = 0.32; 95% CI, 0.14-0.49; P &lt; .001), with a moderate to large, controlled effect size after treatment (d = 0.75; 95% CI, 0.32-1.16). Secondary analyses indicated that internet-delivered CBT also produced significantly larger reductions in itch intensity, perceived stress, sleep problems, and depression. Gains were sustained at 12 months of follow-up. Treatment satisfaction was high, and therapists spent a mean (SD) of 39.7 (34.7) minutes per treated patient providing internet-delivered CBT. CONCLUSIONS AND RELEVANCE: Internet-delivered CBT appears to be efficacious for reducing symptoms of atopic dermatitis, despite requiring minimal therapist resources. Thus, internet-delivered CBT has the potential to increase access to effective adjunct behavioral treatment for patients with this common skin condition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03051958

Background: Parkinson’s disease (PD) is often associated with psychological distress and lowered daily functioning. The availability of psychological interventions tailored for people with Parkinson is very limited.Objective: To study if guided individually-tailored internet-based cognitive behavioral therapy (ICBT) provide additional value to standard medical treatment for PD.Methods: Seventy-seven individuals with PD and self-reported problems with general function measured with the Work and Social Adjustment Scale (WSAS?>?15) were randomized to 10 weeks of either ICBT combined with standard medical treatment, or standard medical treatment plus being on waitlist to ICBT (CONTROL). Change in the main outcome WSAS, as well as secondary measures such as quality of life, depression, anxiety and insomnia symptoms were investigated post treatment.Results: Participants receiving ICBT reported significantly higher functioning after treatment (WSAS group difference –4.56, controlled effect size g?=?0.69, significant group by time interaction, W?2=?26.23, p?=?0.001). However, only around one third of participants in the treatment group were classified as treatment responders, defined as having a 30% reduction on the WSAS post treatment. Patient involvement and ratings of ICBT credibility were high. Symptoms of anxiety, depression and insomnia symptoms were significantly lower after treatment compared to CONTROL. There were also positive effects on Parkinson-specific function and quality of life in the treatment group.Conclusions: ICBT as an addition to standard medical treatment was credible and improved functioning for some individuals with PD. Still, the treatment needs further development in order to help a larger proportion of individuals with PD.Trial registration number: ClinicalTrials.gov NCT02627885.

Internet-delivered cognitive behaviour therapy (ICBT) has existed for 20 years and there are now several controlled trials for a range of problems. In this paper, we focused on recent meta-analytic reviews of the literature and found moderate to large effects reported for panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, and major depression. In total, we reviewed 9 recent meta-analytic reviews out of a total of 618 meta-analytic reviews identified using our search terms. In these selected reviews, 166 studies were included, including overlap in reviews on similar conditions. We also covered a recent review on transdiagnostic treatments and 2 reviews on face-to-face v. internet treatment. The growing number of meta-analytic reviews of studies now suggests that ICBT works and can be as effective as face-to-face therapy.

Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primary outcome score was measured using the Montgomery Åsberg Depression Rating Scale-Self Rated. Single-nucleotide polymorphism genotyping arrays were used to calculate the genomic risk scores based on large genetic studies of six phenotypes: major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intelligence, and educational attainment. Linear mixed-effect models were used to test the relationships between the six genetic risk scores and cognitive behavior therapy outcome. Our analyses yielded one significant interaction effect (B = 0.09, p< 0.001): the autism spectrum disorder genetic risk score correlated with Montgomery Åsberg Depression Rating Scale-Self Rated changes during treatment, and the higher the autism spectrum disorder genetic load, the less the depressive symptoms decreased over time. The genetic risk scores for the other psychiatric and cognitive traits were not related to depressive symptom severity or change over time. Our preliminary results indicated, as expected, that the genomics of the response of patients with major depression to cognitive behavior therapy were complex and that future efforts should aim to maximize sample size and limit subject heterogeneity in order to gain a better understanding of the use of genetic risk factors to predict treatment outcome.

Purpose of the Study:Cortisol hypersecretion plays a role in depression pathophysiology. Internet-based cognitive behavioural therapy (ICBT) and physical exercise (PE) are new treatment alternatives for depression, and their long-lasting effect on cortisol is unknown. We investigated cortisol level changes after 12 weeks of ICBT, PE or treatment as usual (TAU). Procedures:The present pre-post repeated measure study analysed data derived from a randomised controlled trial evaluating the effects of 12 weeks’ interventions of ICBT, PE and TAU in depressed primary care patients (Sweden 2011–2013) and aimed at prospectively evaluating the within-group effects of ICBT, PE and TAU on diurnal salivary cortisol levels in a small representative subsample (n= 56, 38 and 27, respectively). Results:We found a marked flattening of the diurnal cortisol slope (p= 0.004) and a reduced cortisol level at awakening (p= 0.017) after 12 weeks of PE treatment. No apparent effects of ICBT or TAU interventions were seen on diurnal cortisol levels. Conclusions and Message:PE reduced the rate of cortisol level decline across the day in depressed adults. ICBT and TAU treatments had no detectable effects on diurnal cortisol levels. Larger samples are required for the detection and comparison of smaller effects of PE, ICBT and TAU on diurnal cortisol levels.

ObjectivesDepression can negatively impact work capacity, but treatment effects on sick leave and employment are unclear. This study evaluates if internet-based cognitive behavioural therapy (ICBT) or physical exercise (PE), with already reported positive effects on clinical outcome and short-term work ability, has better effects on employment, sick leave and long-term work ability compared with treatment as usual (TAU) for depressed primary care patients (German clinical trials: DRKS00008745).MethodsAfter randomisation and exclusion of patients not relevant for work-related analysis, patients were divided into two subgroups: initially unemployed (total n=118) evaluated on employment, and employed (total n=703) evaluated on long-term sick leave. Secondary outcomes were self-rated work ability and average number of sick days per month evaluated for both subgroups. Assessments (self-reports) were made at baseline and follow-up at 3 and 12 months.ResultsFor the initially unemployed subgroup, 52.6% were employed after 1 year (response rate 82%). Both PE (risk ratio (RR)=0.44; 95% CI 0.23 to 0.87) and ICBT (RR=0.37; 95% CI 0.16 to 0.84) showed lower rates compared with TAU after 3 months, but no difference was found after 1 year (PE: RR=0.97; 95% CI 0.69 to 1.57; ICBT: RR=1.23; 95% CI 0.72 to 2.13). For those with initial employment, long-term sick leave (response rate 75%) decreased from 7.8% to 6.5%, but neither PE (RR=1.4; 95% CI 0.52 to 3.74) nor ICBT (RR=0.99; 95% CI 0.39 to 2.46) decreased more than TAU, although a temporary positive effect for PE was found. All groups increased self-rated work ability with no differences found.ConclusionsNo long-term effects were found for the initially unemployed on employment status or for the initially employed on sick leave. New types of interventions need to be explored.

To investigate the long-term effects of therapist-guided Internet-based insomnia treatment on insomnia severity and sleep medication use, compared with active control.

Despite high rates of attention-deficit/hyperactivity disorder (ADHD) among adult lawbreakers, particularly the long-term effects of ADHD pharmacotherapy remain unclear, not the least because of ethical challenges with preventing control subjects in randomized controlled trials from receiving medication over prolonged time. We followed up adult male prisoners with ADHD who completed a 5-week randomized, double-blind, placebo-controlled trial followed by a 47-week open-label extension of osmotic-release oral system methylphenidate in a Swedish high-security prison from 2007 to 2010 (ClinicalTrials.gov: NCT00482313). Twenty-five trial completers were prospectively followed up clinically 1 year (24/25, 96% participated fully or in part) and 3 years (20/25, 80% participation) after trial regarding ADHD symptoms (observer and self-reports), psychosocial functioning, substance misuse, and criminal reoffending. Methylphenidate-related improvements in ADHD symptoms and psychosocial functioning obtained during the 52-week trial were maintained at 1- and 3-year follow-ups. Specifically, after 3 years, 75% (15/20) of the respondents had been released from prison, and 67% of these (10/15) had employment, usually full time. In contrast, nonmedicated respondents at the 3-year follow-up (5/20) reported more ADHD symptoms, functional impairment, and substance misuse compared with currently medicated respondents (15/20). Further, 40% of the respondents self-reported reoffending, indicating a substantially lower relapse rate than expected (70%–80%).In summary, although these observations need validation from new and larger samples, positive effects were maintained after 4 years of methylphenidate treatment. Most study completers were employed and had no relapse in substance misuse or criminality. These results suggest that motivational support and continued medication are important for improved outcome in adult criminal offenders with ADHD.

To compare treatment effects when patients with insomnia and depression receive treatment for either insomnia or depression.

Internet-based cognitive behavior therapy (ICBT) for obsessive–compulsive disorder (OCD) has shown efficacy in randomized trials but many patients do not respond to the treatment, we therefore need to find predictors and moderators of treatment response. In this study, we analyzed predictors of ICBT response using both post-treatment as well as 24-month outcome data. As half of the participants were randomized to receive an Internet-based booster program as an adjunct to ICBT, we also investigated moderators of ICBT with or without booster. Results showed that more severe baseline OCD symptoms predicted worse end state outcome but also higher degree of change. Furthermore, high degree of working alliance predicted better outcome but patients with primary disgust emotions had worse treatment effects. The moderator analysis also indicated that scoring high on the obsessing subscale on the Obsessive–Compulsive Inventory-Revised predicted worse treatment outcome in the booster group. In conclusion, there are some possible predictors and moderators of ICBT for OCD but more research is needed with larger and clinically representative samples.

Cognitive behavior therapy (CBT) is an effective treatment for OCD when delivered face-to-face, in group-format and also via the internet. However, despite overall large effect sizes, a considerable amount of the patients relapse. One intervention that has the potential to reduce these relapse rates is booster programs, but if booster program is a cost-effective method of preventing relapse is still unknown. We used health economical data from a recent randomized controlled trial, where patients who had undergone an internet-based CBT were randomly allocated to receive an additional booster program. Assessment points were 4-, 7-, 12- and 24-month. Health economical data were primarily analyzed using a societal perspective. Results showed that the booster program was effective in preventing relapse, and the cost of one avoided relapse was estimated to $1066–1489. Cost-effectiveness acceptability curves showed that the booster program had a 90% probability of being cost-effective given a willingness to pay of $1000–1050 the first year, but this figure grew considerably after two years ($2500–5500). We conclude that internet-based booster programs are probably a cost-effective alternative within one-year time frame and that more treatment may be needed to maintain adequate cost-effectiveness up to two years.

The Dimensional Obsessive-Compulsive Scale (DOCS) was designed to address the current limitations of existing obsessive-compulsive (OC) symptom measures and is a self-report questionnaire that assesses the severity of the four most empirically supported OC symptom dimensions. The aim of this study was to examine the psychometric properties of a Swedish version of the DOCS when administered via the Internet. Internal consistency, factor structure, and convergent and discriminant validity were examined in a sample consisting of 101 patients diagnosed with obsessive-compulsive disorder. The DOCS sensitivity to treatment effects were examined in a sample consisting of 48 patients treated with Internet-delivered cognitive behavioral therapy were the main intervention was exposure with response prevention. Results showed that the internal consistency was high. The DOCS also showed adequate convergent and discriminant validity, as well as fair sensitivity to treatment effects. The factor analysis supported the DOCS four-factor solution. In summary, the results from the present study give initial support that the DOCS can be administered via the Internet with adequate psychometric properties.

AbstractThe aim of the paper is to provide an overview of some of the most important issues faced by acute inpatient facilities in three Scandinavian countries, including reflections and critical remarks for discussion in this field. Information was drawn from scientific articles and official reports published in recent years, as well as the authors' own knowledge of acute facilities in their home countries. Acute inpatient facilities, including General Hospital Psychiatric Units (GHPUs), in all Scandinavian countries have several issues and problems in common, which include the organisation and capacity of acute services, the assessment of dangerousness and suicidality, the use of coercion and efforts to reduce coercion, the need to define and improve the quality of acute services, and the necessity to improve collaboration and continuity between acute services and other services. Although the emphasis some of these issues receive can vary across the three countries, Scandinavian mental health professionals (and policy makers) have begun to systematically share their experiences in developing a growing spirit of collaboration. Despite the role of welfare state and the deployment of substantial resources in Scandinavian countries, mental health practitioners are struggling to implement best practices in acute wards, to develop differentiated forms of acute services, and to reach the right balance and coordination between acute services and other services.

The aim of this article is to review the emerging literature on the use of the Internet in the treatment of anxiety disorders. The questions asked are (1) are Internet-delivered treatments for anxiety disorders supported by the research literature (2) what is the quality of the evidence as it stands (3) is there any evidence to suggest that Internet interventions can be harmful

IN the light of earlier findings of reduced cholecystokinin (CCK) peptide and CCK mRNA levels in the cerebral cortex, we have used in situhybridization to examine possible regulation of mRNAs coding for two isoforms of the CCKBreceptor in frontal cortex (Brodmann's area 10) of schizophrenic patients. The hybridizations revealed a 51 decrease of the full length CCKBreceptor mRNA in the outer layers (II–III) of the frontal cortex. The corresponding alterations for the truncated isoform were a 65 reduction in the outer layers and a 62 reduction in the inner layers (IV–VI) of the frontal cortex. This strengthens the hypothesis that CCKergic transmission in this part of the brain is involved in the pathophysiology of schizophrenia.

In situ hybridization was used to study the expression of members of the nerve growth factor family of trophic factors in rat hippocampus following stimulation of afferent cholinergic and glutamatergic pathways with quisqualate. A transient increase in brain-derived neurotrophic factor (BDNF) andβ-nerve growth factor (NGF) mRNA expression in the hippocampus was seen 4 h after a quisqualate injection into the medial septal nucleus. Both BDNF and NGF mRNA levels increased more than 4-fold in the granule layer of the dentate gyrus and for BDNF mRNA also in the pyramidal cells of CA1, while the levels of BDNF mRNA in CA3 increased 2-fold. The increase in BDNF and NGF mRNA levels were completely prevented by pretreatment with systemic injections of either scopolamine or diazepam. A quisqualate injection into the entorhinal cortex, containing glutamatergic afferents to the hippocampus, resulted in a 15-, 5- and 17-fold increase in the expression of BDNF mRNA in the ipsilateral granule cells, CA3 and CA1 pyramidal cells, respectively. Similar increases were also seen in the hippocampus contralateral to the injections. In contrast, the level of NGF mRNA did not increase significantly in any of the subfields in the hippocampus. The increase in BDNF mRNA after cortex injections was attenuated by diazepam but not by scopolamine. These findings imply that increased activity in afferent cholinergic and glutamatergic pathways to the hippocampus differentially regulate expression of the NGF family of neurotrophic factors in the hippocampus.

Synthesis of the neurotrophic factor brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus have been proposed to be influenced by endogenous glutamate. To test this hypothesis we have investigated if increases in BDNF and trkB mRNAs are associated with changes in the synaptic release of glutamate in the dorsal hippocampus in the conscious rat by combining the technique of in vivo microdialysis with in situ hybridization histochemistry. A 35% and 66% increase in extracellular levels of glutamate in the dorsal CA1 region was detected following injection into the lateral entorhinal cortex of 2.4 and 9.6µg of the non-NMDA glutamate receptor agonist quisqualate, respectively. The increase in glutamate was attenuated by local administration of tetrodotoxin (TTX) indicating neuronal origin. Levels of BDNF and trkB mRNAs were increased in the hippocampus in a dose-dependent fashion following the stimulations. The extracellular levels of glutamate in individual animals correlated to the levels of BDNF and trkB mRNAs in the dorsal CA1 region of the hippocampus. This study provides for the first time evidence of an entorhinal cortex influenced concentration-dependent relationship between the release of endogenous glutamate in vivo and neuronal expression of mRNAs for BDNF and its receptor trkB in the hippocampus.

The effect of long-term oral treatment with caffeine on A1 and A2 receptors in the rat brain was studied. Caffeine was added to the drinking water and the animals were sacrificed after a 12 day treatment period. The plasma caffeine concentration was close to 100 µM. A1 receptors were studied using quantitative autoradiography with [3H]cyclohexyladenosine (CHA). Caffeine treatment increased the number of A1 receptors in the CA3 subfield of the hippocampus from 337 to 393 fmol/mg with no change in KD (0.692 vs. 0.675 nM). A1 mRNA was measured using Northern blots and quantitative in situ hybridization. There was no increase in A1 mRNA. A2a receptors, located in dopamine rich regions of the rat brain, were studied with quantitative autoradiography using [3H]CGS 21680 as the ligand, and the A2a mRNA was determined using quantitative in situ hybridization. Caffeine treatment produced no significant change in either receptor number or mRNA, even though the apparent Bmax tended to increase from 322±8 to 352±8 fmol/mg. The results show that treatment with caffeine in a dose that causes tolerance to several effects of caffeine and increases some effects of adenosine analogues increases the number of A1 receptors without any change in A1 mRNA, suggesting that the adaptive changes are at a post-translational level. There were no significant changes in A2 receptors indicating that the two types are regulated differently and/or that the amount of endogenous agonist is sufficient to regulate A1, but not A2 receptors.