START - physical exercise and person-centred cognitive skills training as treatment for adult ADHD: protocol for a randomized controlled trial.

BACKGROUND: Core symptoms in attention deficit hyperactivity disorder (ADHD) are inattention, impulsivity and hyperactivity. Many individuals with this disorder also have a sedentary lifestyle, co-morbid mental illness such as depressive and anxiety disorders, and reduced quality of life. People with ADHD often have impaired executive function, which among other things may include difficulty in time management and structuring of everyday life. Pharmacological treatment is often the first-line option, but non-pharmacological treatment is also available and is used in clinical settings. In children and adolescents with ADHD, physical exercise is used as a non-pharmacological treatment. However, the evidence for the effectiveness of exercise in adults is sparse. OBJECTIVE: To implement the START intervention (START = Stöd i Aktivitet, Rörelse och Träning [Support in activity, movement and exercise]) consisting of a 12-week, structured mixed exercise programme with or without a cognitive intervention, in adults with ADHD, and study whether it has an effect on core symptoms of ADHD as well as physical, cognitive, mental and everyday functioning compared with usual treatment. A secondary aim is to investigate the participants' experiences of the intervention and its possible benefits, and to evaluate the cost-effectiveness of START compared with usual treatment. METHODS: This is a randomized controlled trial planned to be conducted in 120 adults with ADHD, aged 18-65. The intervention will be given as an add-on to standard care. Participants will be randomized to three groups. Group 1 will be given a physiotherapist-led mixed exercise programme for 12 weeks. Group 2 will receive the same intervention as group 1 with the addition of occupational therapist-led cognitive skills training. Group 3 will be the control group who will receive standard care only. The primary outcome will be reduction of ADHD symptoms measured using the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS-v1.1), Clinical Global Impression-Severity scale (CGI-S) and CGI-Improvement scale (CGI-I). The effect will be measured within 1 week after the end of the intervention and 6 and 12 months later. DISCUSSION: Data collection began in March 2021. The final 12-month follow-up is anticipated to be completed by autumn 2024. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT05049239). Registered on 20 September 2021 (last verified: May 2021).

"InMotion"-Mixed physical exercise program with creative movement as an intervention for adults with schizophrenia: study protocol for a randomized controlled trial.

Background: Schizophrenia is among the world's top 10 causes of long-term disability with symptoms that lead to major problems in social and occupational functioning, and in self-care. Therefore, it is important to investigate the efficacy of complementary treatment options for conventionally used antipsychotic medication, such as physical training, and psychosocial interventions. Objective: To combine aerobic and strength training with cognitive, emotional and social stimulation in one intervention for people with schizophrenia and test the feasibility and effects of this intervention. Methods: The study is a mixed-method randomized controlled trial to evaluate the effects of a 12-week intervention for adults with schizophrenia. The treatment group (30 participants) will receive the intervention in addition to standard care and the control group (30 participants) only standard care. The intervention consists of 24 biweekly sessions with a duration of 60 min. The pre-test (weeks from 4 to 2 prior to the intervention) and post-test (week 12) include clinical measure (PANSS), quality of life, social performance, movement quantity, brain function and eye tracking measures. In addition, a treatment subgroup of 12-15 participants and their family member or other next of kin will complete a qualitative interview as a part of their post-test. Two follow-up tests, including clinical, quality of life, brain function and eye tracking will be made at 6 and 12 months from the completion of the intervention to both study groups. The primary outcome is change in negative symptoms. Secondary outcome measures include general and positive symptoms, quality of life, social performance, movement quantity, brain function and eye tracking. Explorative outcome includes patient and family member or other next of kin interview. Results: Pilot data was collected by June 2023 and the main data collection will begin in September 2023. The final follow-up is anticipated to be completed by 2026. Conclusion: The InMotion study will provide new knowledge on the feasibility, efficacy, and experiences of a novel intervention for adults with schizophrenia. The hypothesis is that regular participation in the intervention will reduce clinical symptoms, normalize physiological measures such as brain activation, and contribute to new active habits for the participants. Trial registration: ClinicalTrials.gov, identifier NCT05673941.

Salience and hedonic experience as predictors of central stimulant treatment response in ADHD - A resting state fMRI study.

BACKGROUND: Roughly 20-30% of patients with Attention-deficit/hyperactivity disorder (ADHD) fail to respond to central stimulant (CS) medication. Genetic, neuroimaging, biochemical and behavioral biomarkers for CS response have been investigated, but currently there are no biomarkers available for clinical use that help identify CS responders and non-responders. METHODS: In the present paper, we studied if incentive salience and hedonic experience evaluated after a single-dose CS medication could predict response and non-response to CS medication. We used a bipolar visual analogue 'wanting' and 'liking' scale to gauge incentive salience and hedonic experience in 25 healthy controls (HC) and 29 ADHD patients. HC received 30 mg methylphenidate (MPH) and ADHD patients received either MPH or lisdexamphetamine (LDX) as selected by their clinician, with dosage individually determined for optimal effect. Clinician-evaluated global impression - severity (CGI-S) and improvement (CGI-I) and patient-evaluated improvement (PGI-I) were used to assess response to CS medication. Resting state functional magnetic resonance imaging (fMRI) was conducted before and after single-dose CS to correlate wanting and liking scores to changes in functional connectivity. RESULTS: Roughly 20% of the ADHD patients were CS non-responders (5 of 29). CS responders had significantly higher incentive salience and hedonic experience scores compared to healthy controls and CS non-responders. Resting state fMRI showed that wanting scores were significantly associated to changes in functional connectivity in ventral striatum including nucleus accumbens. CONCLUSION: Incentive salience and hedonic experience evaluated after a single-dose CS medication segregate CS responders and non-responders, with corresponding neuroimaging biomarkers in the brain reward system.

Similarities and differences in the induction and regulation of the negative emotions fear and disgust: A functional near infrared spectroscopy study.

Affective processing, including induction and regulation of emotion, activates neural networks, induces physiological responses, and generates subjective experience. Dysregulation of these processes can lead to maladaptive behavior and even psychiatric morbidity. Multimodal studies of emotion thus not only help elucidate the nature of emotion, but also contribute to important clinical insights. In the present study, we compared the induction (EI) and effortful regulation (ER) with reappraisal of fear and disgust in healthy subjects using functional near infrared spectroscopy (fNIRS) in conjunction with electrodermal activity (EDA). During EI, there was significant activation in medial prefrontal cortex (PFC) for fear and more widespread activation for disgust, with right lateral PFC significantly more active during disgust compared to fear. ER was equally effective for fear and disgust reducing subjective emotion rating by roughly 45%. Compared to baseline, there was no increased PFC activity for fear during ER, while for disgust lateral PFC was significantly more active. Significant differences between the two negative emotions were also observed in sympathetic nerve activity as reflected in EDA during EI, but not during ER. Lastly, compared to men, women had higher emotion rating for both fear and disgust without corresponding differences in EDA. In conclusion, in the present study we show that emotion induction was associated with differential activation in both PFC and sympathetic nerve activity for fear and disgust. These differences were however less prominent during emotion regulation. We discuss the potential interpretation of our results and their implications regarding our understanding of negative emotion processing.

Reduced prefrontal cortex and sympathetic nervous system activity correlate with fatigue after aHSCT.

Long-term fatigue and cognitive dysfunction affects 35% of allogeneic haematopoietic stem cell transplantation (aHSCT) survivors, suggesting a dysfunctional prefrontal cortex. In this study, we assessed prefrontal cortex and sympathetic nervous system activity in aHSCT patients with fatigue (n = 12), non-fatigued patients (n = 12) and healthy controls (n = 27). Measurement of near-infrared spectroscopy and electrodermal activity was carried out at rest and during cognitive performance (Stroop, verbal fluency and emotion regulation tasks). Prefrontal cortex and sympathetic nervous system activity were also analyzed in response to dopamine and noradrenaline increase after a single dose of methylphenidate. Baseline cognitive performance was similar in the two patient groups. However, after methylphenidate, only non-fatigued patients improved in Stroop accuracy and had better verbal fluency task performance compared to the fatigued group. Task-related activation of prefrontal cortex in fatigued patients was lower compared to non-fatigued patients during all cognitive tests, both before and after methylphenidate administration. During the Stroop task, reaction time, prefrontal cortex activation, and sympathetic nervous system activity were all lower in fatigued patients compared to healthy controls, but similar in non-fatigued patients and healthy controls.Reduced prefrontal cortex activity and sympathetic arousal suggests novel treatment targets to improve fatigue after aHSCT.

Behavioral, cortical and autonomic effects of single-dose escitalopram on the induction and regulation of fear and disgust: Comparison with single-session psychological emotion regulation with reappraisal.

Introduction: Adaptive and successful emotion regulation, the ability to flexibly exert voluntary control over emotional experience and the ensuing behavior, is vital for optimal daily functioning and good mental health. In clinical settings, pharmacological and psychological interventions are widely employed to modify pathological emotion processing and ameliorate its deleterious consequences. Methods: In this study, we investigated the acute effects of single-dose escitalopram on the induction and regulation of fear and disgust in healthy subjects. Furthermore, we compared these pharmacological effects with psychological emotion regulation that utilized a cognitive strategy with reappraisal. Emotion induction and regulation tasks were performed before and 4 h after ingestion of placebo or 10 mg escitalopram in a randomized, double-blind design. The International Affective Picture System (IAPS) was used as a source of images, with threat-related pictures selected for fear and disease and contamination-related pictures for disgust. Behavioral data, electrodermal activity (EDA), and functional near-infrared spectroscopy (fNIRS) recordings were collected. Results: Escitalopram significantly reduced emotion intensity for both fear and disgust during emotion induction, albeit with differing electrodermal and hemodynamic activity patterns for the two negative emotions. At rest, i.e., in the absence of emotive stimuli, escitalopram increased sympathetic activity during the fear but not during the disgust experiments. For both fear and disgust, emotion regulation with reappraisal was more effective in reducing emotion intensity compared to pharmacological intervention with escitalopram or placebo. Discussion: We concluded that emotion regulation with reappraisal and acute administration of escitalopram, but not placebo, reduce emotion intensity for both fear and disgust, with cognitive regulation being significantly more efficient compared to pharmacological regulation under the conditions of this study. Results from the fNIRS and EDA recordings support the concept of differential mechanisms of emotion regulation that could be emotion-specific.

Electroconvulsive therapy and psychiatric readmission in major depressive disorder - A population-based register study.

OBJECTIVE: The primary aim was to determine whether electroconvulsive therapy (ECT) is associated with reduced risk of psychiatric readmission in major depressive disorder (MDD). METHODS: This study was based on data from multiple Swedish population-based registries. All adult patients admitted to any Swedish hospital for moderate-to-severe MDD between 2012 and 2018 were included. Participants were divided into two groups depending on whether they received ECT during inpatient care. Follow-up was set at 30 and 90 days from discharge. Data were analyzed using logistic regression, and matching was conducted. RESULTS: A total of 27,851 unique patients contributed to 41,916 admissions. ECT was used in 26.8% of admissions. In the main multivariate analysis, the risk of both 30- and 90-day readmission was lower in the ECT group than in the non-ECT group. In a matched sensitivity model, the results pointed in the same direction for readmission risk within 30 days, but statistical significance was not reached. ECT-treated subgroups with superior outcomes on readmission risk compared with non-ECT treatment were older, unemployed, married, or widowed patients, those treated with antipsychotics or benzodiazepines before admission, with psychotic features, prior psychiatric hospitalizations, or family history of suicide. However, in patients below 35 years of age, ECT was associated with increased readmission risk. CONCLUSION: This study suggests that ECT reduces the risk of psychiatric readmission in certain subgroups of patients with MDD. Since patients receiving ECT tend to be more difficult to treat, there is a risk of residual confounding.

Feasibility and Acceptability of a Healthy Nordic Diet Intervention for the Treatment of Depression: A Randomized Controlled Pilot Trial.

Healthy diet interventions have been shown to improve depressive symptoms, but there is a need for randomized controlled trials (RCTs) that are double blind and investigate biological mechanisms. The primary objectives of this randomized controlled pilot trial were to test the palatability of the meals and the acceptability of the intervention in preparation for an 8-week RCT in the future, which will investigate whether a healthy Nordic diet improves depressive symptoms in individuals with major depressive disorder, and associated biological mechanisms. Depressed (n = 10) and non-depressed (n = 6) women and men were randomized to receive either a healthy Nordic diet (ND) or a control diet (CD) for 8 days. Participants were blinded to their diet allocation and the study hypotheses. Health questionnaires were completed before and after the intervention and, throughout the study, questionnaires assessed participants' liking for the meals, their sensory properties, adherence, and open-ended feedback. In the ND group, 75% of participants consumed only the provided foods, as instructed, compared to 50% of CD participants. The meals of both diets, on average, received good ratings for liking and sensory properties, though the ND ratings were somewhat higher. Overall, results were positive and informative, indicating that the planned RCT will be feasible and well-accepted, with some proposed modifications.

[New national guidelines for the treatment of schizophrenia in Sweden]. / Nya nationella riktlinjer för vård och stöd vid schizofreni - Lyfter fram ¼återhämtningsperspektivet«: Rehabilitering i kombination med läkemedel kan ge bättre livskvalitet.

Schizophrenia affects about 0.7 % of the population and is characterized by hallucinations, delusions and reduced functioning affecting the ability to study, work and socialize. Life expectancy for patients with schizophrenia is approximately 15-20 years shorter mostly due to cardiovascular disease. Stigmatization is  common despite the fact that it is a treatable disorder with a combination of medication and psychosocial interventions. Case management, psycho-education and supported employment are proven strategies, but less than half of individuals with schizophrenia are adequately treated. The National Board of Health and Welfare is currently launching updated National Guidelines (2018). The aim is to provide an overview of evidence-based interventions enabling patients with schizophrenia to live a fairly normal life. An evaluation has revealed that previous guidelines for antipsychotic medications have been satisfactorily implemented, but not those for psychosocial interventions. These will now be emphasized as ¼central recommendations« and will be followed up with specific indicators based on data from national registers.

Health care use, drug treatment and comorbidity in patients with schizophrenia or non-affective psychosis in Sweden: a cross-sectional study.

BACKGROUND: This study investigated the prevalence of schizophrenia (ICD-10 F 20) and of other non-affective psychosis (NAP, ICD-10 F 21 - F 29) in Sweden. It further assessed health care use, comorbidity and medication for these patient groups. Most studies either have a study population of patients with strictly defined schizophrenia or a psychosis population of which strict schizophrenia cases form a smaller set. The present study permits comparison of the two mutually exclusive patient groups using data at the individual level in the diagnosis of non-affective psychosis, use of health care, medical treatment and comorbidity by diagnosis or medical treatment. METHODS: In 2012, data were extracted from a regional registry containing patient-level data on consultations, hospitalisations, diagnoses and dispensed drugs for the total population in the region of Stockholm (2.1 million inhabitants). The size of the total psychosis population was 18,769, of which 7284 had a diagnosis of schizophrenia. Crude prevalence rates and risk rates with 95% confidence intervals were calculated. RESULTS: In 2012, the prevalence of schizophrenia and NAP was 3.5/1000 and 5.5/1000, respectively. Schizophrenia was most common among patients aged 50-59 years and NAP most common among patients aged 40-49 years. Schizophrenia patients used psychiatric health care more often than the NAP patients but less overall inpatient care (78.6 vs. 60.0%). The most prevalent comorbidities were substance abuse/dependence (7.9% in the schizophrenia group vs. 11.7% in the NAP group), hypertension (7.9 vs. 9.7%) and diabetes (6.9 vs. 4.8%). The parenteral form of long-acting injectable antipsychotics was more often dispensed to patients with schizophrenia (10 vs. 2%). CONCLUSIONS: This study, analysing all diagnoses recorded in a large health region, confirmed prevalence rates found in previous studies. Schizophrenia patients use more psychiatric and less overall inpatient health care than NAP patients. Differences between the two patient groups in comorbidity and drug treatment were found. The registered rates of a substance abuse/dependence diagnosis were the most common comorbidity observed among the patients investigated. The observed differences between the schizophrenia and the NAP patients in health care consumption, comorbidity and drug treatment are relevant and warrant further studies.

Studying Sub-Dendrograms of Resting-State Functional Networks with Voxel-Wise Hierarchical Clustering.

Hierarchical clustering is a useful data-driven approach to classify complex data and has been used to analyze resting-state functional magnetic resonance imaging (fMRI) data and derive functional networks of the human brain at very large scale, such as the entire visual or sensory-motor cortex. In this study, we developed a voxel-wise, whole-brain hierarchical clustering framework to perform multi-stage analysis of group-averaged resting-state fMRI data in different levels of detail. With the framework we analyzed particularly the somatosensory motor and visual systems in fine details and constructed the corresponding sub-dendrograms, which corroborate consistently with the known modular organizations from previous clinical and experimental studies. The framework provides a useful tool for data-driven analysis of resting-state fMRI data to gain insight into the hierarchical organization and degree of functional modulation among the sub-units.

[Participation is the foundation of successful treatment of psychotic disorders]. / Delaktighet grunden för en lyckad behandling av psykossjukdomar.

Schizophrenia is among the most severe psychiatric disorders, but due to extensive research we now have evidence-based interventions that may enable these patients to live a fairly normal life.  Every decision regarding the choice of intervention or treatment should be made according to a shared decision making, meaning that the patient and Case Manager are equal parties and equally responsible for the choice. The individual coordinated care plan prepared in agreement by the patient and Case Manager should be the governing principle for the rehabilitation process. Antipsychotic medication is a prerequisite for any rehabilitation but should typically be combined with psychosocial intervention for an optimal outcome. In order to properly judge treatment response, symptom ratings should be combined with global ratings to take into account aspects that are not accounted for in symptom rating scales. If the effect of an antipsychotic medication is inadequate, a psychosocial intervention may be considered as an alternative to increasing the dosage or adding another antipsychotic medication to minimize side effects. One of the most important rehabilitating interventions is supported employment with individual placement and support.

Differential Effects of Single-Dose Escitalopram on Cognitive and Affective Interference during Stroop Task.

BACKGROUND AND OBJECTIVE: Our aim was to study the regulatory role of serotonin [(5-hydroxytryptamine (5-HT)] on two key nodes in the cognitive control networks - the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). We hypothesized that increasing the levels of 5-HT would preferentially modulate the activity in ACC during cognitive control during interference by negative affects compared to cognitive control during interference by a superimposed cognitive task. METHODS: We performed a functional magnetic resonance imaging investigation on 11 healthy individuals, comparing the effects of the selective 5-HT reuptake inhibitor escitalopram on brain oxygenation level dependent signals in the ACC and the DLPFC using affective and cognitive counting Stroop paradigms (aStroop and cStroop). RESULTS: Escitalopram significantly decreased the activity in rostral ACC during aStroop compared to cStroop (p < 0.05). In the absence of escitalopram, both aStroop and cStroop significantly activated ACC and DLPFC (Z ≥ 2.3, p < 0.05). CONCLUSION: We conclude that escitalopram in a region and task specific manner modified the cognitive control networks and preferentially decreased activity induced by affective interference in the ACC.

Rostro-caudal and dorso-ventral gradients in medial and lateral prefrontal cortex during cognitive control of affective and cognitive interference.

Characterizing the anatomical substrates of major brain functions such as cognition and emotion is of utmost importance to the ongoing efforts of understanding the nature of psychiatric ailments and their potential treatment. The aim of our study was to investigate how the brain handles affective and cognitive interferences on cognitive processes. Functional magnetic resonance imaging investigation was performed on healthy individuals, comparing the brain oxygenation level dependent activation patterns during affective and cognitive counting Stroop tasks. The affective Stroop task activated rostral parts of medial prefrontal cortex (PFC) and rostral and ventral parts of lateral PFC, while cognitive Stroop activated caudal parts of medial PFC and caudal and dorsal parts of lateral PFC. Our findings suggest that the brain may handle affective and cognitive interference on cognitive processes differentially, with affective interference preferentially activating rostral and ventral PFC networks and cognitive interference activating caudal and dorsal PFC networks.