[MDMA-assisted therapy for PTSD].

MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy for PTSD. Literature searches were done on PubMed, Web of Science and Google Scholar and references reviewed in identified articles. MDMA-assisted therapy for PTSD usually consists of a few preparatory sessions before two or three sessions where one or two oral doses of MDMA are given along with supportive psychotherapy. The therapy is delivered in the presence of two therapists for about eight hours each time. In addition, the patient receives up to 9 integrative sessions in due course. This use of MDMA as a part of psychotherapy for PTSD is proposed to lessen the psychological distress that often arises in the processing of traumatic events to facilitate the treatment process and reduce the risk of drop-out. Recent studies indicate that MDMA-assisted psychotherapy reduces PTSD symptoms and is generally well tolerated. These studies are necessary if this MDMA-assisted treatment is to be approved by licensing authorities. There is an urgent need for new effective treatments for PTSD and for comparisons between this MDMA-assisted psychotherapy and currently approved psychotherapies with and without MDMA-use.

Polygenic liability for antipsychotic dosage and polypharmacy - a real-world registry and biobank study.

Genomic prediction of antipsychotic dose and polypharmacy has been difficult, mainly due to limited access to large cohorts with genetic and drug prescription data. In this proof of principle study, we investigated if genetic liability for schizophrenia is associated with high dose requirements of antipsychotics and antipsychotic polypharmacy, using real-world registry and biobank data from five independent Nordic cohorts of a total of N = 21,572 individuals with psychotic disorders (schizophrenia, bipolar disorder, and other psychosis). Within regression models, a polygenic risk score (PRS) for schizophrenia was studied in relation to standardized antipsychotic dose as well as antipsychotic polypharmacy, defined based on longitudinal prescription registry data as well as health records and self-reported data. Meta-analyses across the five cohorts showed that PRS for schizophrenia was significantly positively associated with prescribed (standardized) antipsychotic dose (beta(SE) = 0.0435(0.009), p = 0.0006) and antipsychotic polypharmacy defined as taking ≥2 antipsychotics (OR = 1.10, CI = 1.05-1.21, p = 0.0073). The direction of effect was similar in all five independent cohorts. These findings indicate that genotypes may aid clinically relevant decisions on individual patients´ antipsychotic treatment. Further, the findings illustrate how real-world data have the potential to generate results needed for future precision medicine approaches in psychiatry.

Adverse childhood experiences and psychological functioning among women with schizophrenia or bipolar disorder: population-based study.

BACKGROUND: Adverse childhood experiences (ACEs) are well-known risk factors for schizophrenia and bipolar disorder. AIMS: The aim was to study the associations between specific ACEs and psychological functioning in women with schizophrenia or bipolar disorder. METHOD: Among 29 367 women (mean age 44 years) from the Icelandic Stress-And-Gene-Analysis (SAGA) study, 534 (1.8%, mean age 40) reported having been diagnosed with schizophrenia or bipolar disorder, which were combined to 'severe mental disorders'. Participants reported on 13 types of ACEs, childhood deprivation and psychological functioning (defined as coping ability and current symptoms of depression, anxiety and sleep disturbances). Adjusted Poisson regression calculated prevalence ratios (PRs) between ACEs and severe mental disorders. Linear regression assessed the association between ACEs and psychological functioning among women with a severe mental disorder. RESULTS: Women with a severe mental disorder reported more ACEs (mean 4.57, s.d. = 2.82) than women without (mean 2.51, s.d. = 2.34) in a dose-dependent manner (fully-adjusted PR = 1.23 per ACE, 95% CI 1.20-1.27). After mutual adjustment for other ACEs, emotional abuse, sexual abuse, mental illness of a household member, emotional neglect, bullying and collective violence were associated with severe mental disorders. Among women with severe mental disorders, a higher number of ACEs was associated with increased symptom burden of depression (ß = 2.79, 95% CI = 1.19-4.38) and anxiety (ß = 2.04, 95% CI = 0.99-3.09) including poorer sleep quality (ß = 0.83, 95% CI = 0.07-1.59). Findings were similar for schizophrenia and bipolar disorder separately. CONCLUSION: Women with schizophrenia or bipolar disorder show a strong history of ACEs, which may interfere with their psychological functioning and, therefore, need to be addressed as part of their treatment, for example, with trauma-focused psychotherapy.

[Psychedelics and treatment of mental disorders: A survey of attitudes and knowledge among psychiatrists, general practitioners and psychologists in Iceland].

INTRODUCTION: Interest in the use of psychedelics has increased following reports of their possible therapeutic potential. However, little is known about the knowledge of and attitudes towards the substances among health care professional who provide treatment for mental disorders in Iceland. An online survey was therefore conducted among members of the Icelandic associations of psychiatrists, general practitioners and psychologists. METHODS: Respondents were 256 in total, including 177 psychologists, 38 psychiatrists and 41 general practitioners that provided information on their background, type of work, knowledge of and attitude towards different types of psychedelic substances and their views on optimal service delivery if psychedelics were approved by licencing authorities and used for treatment. RESULTS: Around half of psychiatrists reported having received questions about treatment with psychedelics in their clinical work, compared to only 14,6% of general practitioners and 17,5% of psychologists. The majority of respondents had little, or no knowledge of the substances targeted in the survey. A majority also expressed negative attitudes towards treatment with psilocybin mushrooms, but was positive towards ongoing scientific research and felt that such a treatment should be prescribed and provided by psychiatrists. Moreover, the majority view was that psilocybin treatment should be provided in specialised clinics or psychiatric units in a hospital setting. Scientific articles on the topic, discussions with colleagues and information in the media were identified as having had most influence on respondents´ attitudes towards psychedelics. Most respondents were interested in further education on psychedelics. CONCLUSIONS: Respondents among these three professions felt that the time has not yet come to use psychedelics in the treatment of mental disorders in Iceland but thought more education on psychedelics, their potential efficacy and adverse health effects is important given the increased interest in psychedelics.

Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study.

BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.

Persistent symptoms are commonly reported after SARS-CoV-2 infection, and this is often described as long Covid. We compared different symptoms reported following SARS-CoV- 2 infection with the results obtained during various medical evaluations that are often used to assess health, such as blood tests, smell tests, taste tests, hearing tests, etc. We compared symptoms and test results between 1,706 Icelanders who had been infected previously with SARS-CoV-2 infection (cases) and 14,398 individuals who had not been infected (controls). Out of 88 assessed symptoms, 41 were more common in cases than controls. However, relatively few differences were seen in the results obtained from the various medical evaluations (cases had poorer smell and taste test results, slightly less grip strength, and slightly poorer memory recall than controls). The differences seen between symptoms and results of medical evaluations suggests that conventional clinical tests may not be informative in relating symptoms to a past SARS-CoV-2 infection.

[Methylphenidate-induced psychosis in a young adult with newly diagnosed ADHD: A case report].

In view of the ongoing rise of ADHD prescriptions among adults in Iceland, it is important that doctors are aware that psychosis is a rare but at times a serious adverse reaction to such treatment. In 2022 5% of adults were prescribed medication to treat ADHD in Iceland. In this case report we present a case of methylphenidate-induced psychosis in a young man with no previous history of psychotic episodes who required admission to the psychiatric intensive care unit.

Thirty novel sequence variants impacting human intracranial volume.

Intracranial volume, measured through magnetic resonance imaging and/or estimated from head circumference, is heritable and correlates with cognitive traits and several neurological disorders. We performed a genome-wide association study meta-analysis of intracranial volume (n = 79 174) and found 64 associating sequence variants explaining 5.0% of its variance. We used coding variation, transcript and protein levels, to uncover 12 genes likely mediating the effect of these variants, including GLI3 and CDK6 that affect cranial synostosis and microcephaly, respectively. Intracranial volume correlates genetically with volumes of cortical and sub-cortical regions, cognition, learning, neonatal and neurological traits. Parkinson's disease cases have greater and attention deficit hyperactivity disorder cases smaller intracranial volume than controls. Our Mendelian randomization studies indicate that intracranial volume associated variants either increase the risk of Parkinson's disease and decrease the risk of attention deficit hyperactivity disorder and neuroticism or correlate closely with a confounder.

[The use of psilocybin for treatment-resistant depression].

The hallucinogen psilocybin is a potential novel treatment for treatment-resistant depression (TRD). Our goal is to review current knowledge on psilocybin and its efficacy in TRD. Literature searches were done on PubMed, Web of Science and Google Scholar, references reviewed in identified articles and other articles found on the website of COMPASS Pathways. Psilocybin treatment consists usually of a single oral administration of 25 mg of psilocybin along with psychological support for 5-8 hours during the ensuing hallucinogenic trip. Common side-effects include headache, nausea, fatigue and insomnia. A systematic review has demonstrated significant antidepressant efficacy in certain groups and a double-blind randomized study found antidepressant efficacy of psilocybin comparable to the SSRI escitalopram. In the phase 2 study of COMPASS Pathways, the psilocybin-COMP360 treatment led to a rapid response and remission as early as three weeks following the treatment for around one third of participants. Recent studies have shown that psilocybin significantly decreases the severity of depressive symptoms and is generally well tolerated. Further research will reveal whether it will be granted a license to treat treatment-resistant depression in the near future. There remains an urgent need for novel treatments for those who do not respond to current antidepressant therapies.

HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry.

The atypical antipsychotic clozapine is the only effective medication for treatment-resistant schizophrenia. However, it can also induce serious adverse drug reactions, including agranulocytosis and neutropenia. The mechanism by which it does so is largely unknown, but there is evidence for contributing genetic factors. Several studies identified HLA-DQB1 variants and especially a polymorphism located in HLA-DQB1 (6672G>C, rs113332494) as associated with clozapine-induced agranulocytosis and neutropenia. We analysed the risk allele distribution of SNP rs113332494 in a sample of 1396 controls and 178 neutropenia cases of which 60 developed agranulocytosis. Absolute neutrophil counts of 500/mm3 and 1500/mm3 were used for defining agranulocytosis and neutropenia cases, respectively. We also performed association analyses and analysed local ancestry patterns in individuals of European ancestry, seeking replication and extension of earlier findings. HLA-DQB1 (6672G>C, rs113332494) was associated with neutropenia (OR = 6.20, P = 2.20E-06) and agranulocytosis (OR = 10.49, P = 1.83E-06) in individuals of European ancestry. The association signal strengthened after including local ancestry estimates (neutropenia: OR = 10.38, P = 6.05E-08; agranulocytosis: OR = 16.31, P = 1.39E-06), with effect sizes being considerably larger for agranulocytosis. Using local ancestry estimates for prediction, the sensitivity of rs113332494 increased from 11.28 to 55.64% for neutropenia and from 16.67 to 53.70% for agranulocytosis. Our study further strengthens the evidence implicating HLA-DQB1 in agranulocytosis and neutropenia, suggesting components of the immune system as contributing to this serious adverse drug reaction. Using local ancestry estimates might help in identifying risk variants and improve prediction of haematological adverse effects.

Evaluation of mechanism of change in transdiagnostic cognitive behaviour therapy using single case experimental design.

BACKGROUND AND OBJECTIVES: Transdiagnostic mechanisms of change (txMOC) specific to cognitive behaviour therapy are poorly understood. Salkovskis (1996) proposed one such mechanism in terms of the shift towards an alternative, less negative view of their problems or cognitive flexibility. This hypothesis has been described as involving a shift in beliefs, from "theory A″ to "theory B". The objective of this research was to evaluate this hypothesis. METHODS: Effectiveness of a novel txCBT and temporal changes in process and symptom measures were evaluated using a non-concurrent multiple baseline design and Tau-U calculations with thirteen participants (five with obsessive-compulsive disorder, two with panic disorder with agoraphobia and six with major depressive disorder). As a secondary analysis authors calculated Kendall's - Tau correlation between process and symptom measures, performed the Wilcoxon signed-rank test to assess treatment modules effect on negative thought and calculated Reliable change index (RCI). RESULTS: The txCBT was clearly effective for eight participants. The results varied dependent on the stimuli evaluated as negative or threatening. Level and trend of the ratings of belief in theory A followed the level and trend of symptom measures to a greater extent than the (inverse) level and trend of belief in theory B. LIMITATIONS: Only thirteen participants were recruited and evaluated. CONCLUSIONS: The results are consistent with the view that effective treatment may involve a txMOC characterized by the ability to shift from a relatively fixed negative view of their experience to a less negative psychologically focused alternative.

A polygenic resilience score moderates the genetic risk for schizophrenia.

Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531-538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known "polygenic resilience score" that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.

Integrative cognitive remediation for early psychosis: A 12-month follow-up.

In recent years, a growing number of studies have attempted to treat social-cognitive impairment within neurocognitive remediation as means of improving outcome in psychotic disorders with promising results. However, the durability of the effects is still under debate and little is known about the long-term efficacy of integrated neuro- and social-cognitive remediation in early psychosis. The purpose of this study was to examine long-term effects of a 12-week integrative cognitive remediation (ICR) for early psychosis. Thirty-seven patients diagnosed with primary psychotic disorder and previously treated with ICR as part of their standard treatment were assessed on cognitive performance, psychopathology, and functional outcome at baseline, 3 months (posttest) and 12 months (follow-up). After participating in ICT, individuals showed significant improvements on most neurocognitive and social cognitive domains. A significant increase in number of participants employed was found at 12-month. The study suggests ICR may have favorable effect on long-term cognitive improvements and functional gains in early psychosis.

Use of serotonin reuptake inhibitors is not associated with increased bleeding after CABG.

OBJECTIVES: Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs) are the most commonly prescribed antidepressants worldwide. Studies suggest that SSRI/SNRIs can increase bleeding following different surgical procedures, including open heart surgery, but results are conflicting. The objective of this study was to analyse their effects on bleeding after coronary artery bypass grafting (CABG). METHODS: Of 1237 patients that underwent CABG in Iceland in 2007-2016, 97 (7.8%) used SSRIs/SNRIs preoperatively and were compared to a reference group (n = 1140). Bleeding was assessed using 24-h chest-tube output, number of RBC units transfused and reoperation for bleeding. Thirty-day mortality rates and incidence of complications were also compared. RESULTS: The two groups were comparable with respect to preoperative and operative variables, with the exception of BMI being significantly higher in the SSRI/SNRI group (30.2 vs. 28.3 kg/m2, p < 0.001). No significant differences were observed between groups in 24-h chest-tube output [815 (SSRI/SNRI) vs. 877 ml (reference), p = 0.26], number of RBC units transfused (2.2 vs. 2.2, p = 0.99) or the rate of reoperation for bleeding (4.1% vs. 6.0%, p = 0.61). The incidences of complications and 30-day mortality rate were also similar. CONCLUSIONS: Using three different criteria, preoperative use of SSRIs/SNRIs was not shown to increase bleeding after CABG. Furthermore, short-term complications as well as 30-day mortality rates did not differ from those of controls. Thus, temporary cessation of SSRI/SNRI treatment prior to CABG to decrease the risk of bleeding is unwarranted.

[Effectiveness of medical treatment in the adult ADHD unit of Landspitali 2015-2017].

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder among children but symptoms may persist into adulthood. At Landspitali - the National University Hospital an interdisciplinary unit is responsible for ADHD-diagnosis and for commencing treatment of adult ADHD. The aim of this study is to evaluate the effectiveness of pharmaceu-tical treatment provided by the unit and the effects of psychiatric comorbidities. METHODS: The study is retrospective and includes all individuals ≥18 years of age who received pharmaceutical treatment in the adult ADHD unit at Landspitali 2015-2017. Individuals who had previously received treatment by the unit or were already on medication for ADHD were excluded. Information on symptoms and wellbeing before and after treatment were obtained from three questionnaires, an ADHD rating scale, DASS and QOLS. RESULTS: Of 211 patients who met inclusion criteria 144 (68%) completed the treatment provided by the unit on average 143 days. Impulsivity/hyperactivity predicted treatment failure with OR=0.96 (p=0.015). There was a statistically significant difference in all key response variables before and after pharmaceutical treatment (p<0.001). The Cohen's d effect size for ADHD variables were 3.18 for attention-deficit and 1.40 for impulsivity/hyperactivity. The effect size for quality of life was 1.00 and among the DASS subscales the maximum effect size was 1.43 for stress. Increased quality of life correlated with decreased symptoms as rated by DASS and the ADHD rating scale. Treatment success rates were significantly -higher for DASS but not for attention-deficit, impulsivity/hyperactivity and quality of life among individuals with psychiatric comorbidities alongside ADHD. Gender did not affect treatment effectiveness. CONCLUSIONS: Those who complete treatment within the ADHD unit achieve good results with decreased psychiatric symptoms and improved quality of life. Treatment discontinuation is a challenge.

Case Report: Successful Implementation of Integrative Cognitive Remediation for Early Psychosis.

Many individuals demonstrate functionally relevant impairment in neurocognition as well as social cognition early on in the course of their psychotic disorder. There is robust evidence supporting cognitive remediation as an effective treatment of cognitive dysfunction in schizophrenia. Increasingly it is accepted that earlier treatment is associated with better outcome and that it is important to systematically assess and treat cognitive dysfunction before the cognitive and functional disabilities are fully realized. However, the clinical availability of these interventions remains sparse. As we move forward with implementing evidence-based interventions into multi-component treatment for early psychosis, it is important to reflect on experience as well as evidence. This case report aims to describe the implementation of an integrative cognitive remediation program in coordinated specialty care (CSC) for early psychosis in Iceland and investigate whether the intervention is sustainable in a CSC setting. Data on the number of patients treated, facilitators trained, groups conducted, and funding was used to assess the sustainability. The results show that since initial implementation in 2016, the intervention has been routinely available as part of standard care, with over 100 patients having received the treatment. The report discusses key factors in the successful implementation of the program.

Schizophrenia, cognition, and aging: cognitive deficits and the relationship between test performance and aging.

Most measures of cognitive function decline with age during adulthood. Research indicates that people with schizophrenia experience considerable cognitive deficits. These deficits appear to become more troublesome with increasing age, but this has been debated. The aim of this research was to better understand the age related cognitive deficits of Icelandic subjects with schizophrenia in comparison to healthy individuals. Cognition of individuals 18 to 64 years of age was evaluated with 10 neuropsychological tests. People with schizophrenia performed significantly worse on all tests, as expected, indicating widespread cognitive deficits compared to healthy individuals, independent of age. Furthermore, the results suggest that people with schizophrenia follow a similar age-related trajectory of cognitive decline as healthy individuals. Overall, we conclude that the cognitive difficulties often experienced by older people with schizophrenia are better explained by lower cognitive function at the time of diagnosis than by faster cognitive decline with increasing age.

'You should always look at the washing machine without actually being in it!' Thematic framework analysis of patients' understanding of transdiagnostic cognitive behaviour therapy and its mechanisms.

OBJECTIVE: Transdiagnostic cognitive behaviour therapy (TCBT) is an efficacious treatment for anxiety and depression, but its mechanisms of change remain poorly understood. The current study used thematic framework analysis to analyse how patients, recruited in a recent trial on transdiagnostic group CBT (TGCBT), understood the treatment and its mechanisms. DESIGN: Cross-sectional thematic framework analysis. METHOD: The sample included 24 participants suffering from anxiety and/or depression, divided into two groups by treatment efficacy (i.e., group doing well and group doing not so well) in order to evaluate whether different understandings of the treatment affected its efficacy. The participants were interviewed and completed self-report measures. They were encouraged to discuss what they believed to be helpful and unhelpful in the TGCBT and what they believed to be the mechanisms of change in the treatment. Each interview was recorded, transcribed verbatim and themes were identified. RESULTS: The analysis revealed four overarching themes and 18 subthemes. The overarching themes were as follows: Cognitive and behavioural flexibility, Awareness/understanding of symptoms and triggers, Therapeutic alliance and engagement, and finally Attitudes towards treatment. Four of the 18 subthemes corresponded to a differentiation between the groups: Cognitive flexibility and Comparison with others in the group on the one hand and Cognitive inflexibility and Negative attitudes towards treatment on the other. CONCLUSION: The most important difference between the groups appeared to be CBT-specific, that is, cognitive flexibility that characterized the group doing well where thematic analysis did not indicate that other themes were important. PRACTITIONER POINTS: Findings The analysis revealed four overarching themes and 18 subthemes, four of which corresponded to the difference between the two groups of participants based on treatment efficacy. The four differentiating subthemes were cognitive flexibility and comparison with others, which characterized the group doing well, and cognitive inflexibility and negative attitude towards treatment, which characterized the group doing less well. The theme evaluated as the most important for the efficacy of the transdiagnostic cognitive behaviour therapy and patients' understanding of the treatment was cognitive flexibility, which characterized the group doing well. Limitations Use of qualitative methodology restricts the generalizability of our results. Data are built on answers from only 24 participants.

Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5-BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10-21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.