Internet- and mobile-based psychological interventions for post-traumatic stress symptoms in youth: a systematic review and meta-analysis.

Psychological interventions can help reduce posttraumatic stress symptoms (PTSS) in youth, but many do not seek help. Internet- and mobile-based interventions (IMIs) show promise in expanding treatment options. However, the overall evidence on IMIs in reducing PTSS among youth remains unclear. This systematic review and meta-analysis investigated the efficacy of IMIs in PTSS reduction for youth exposed to traumatic events. A comprehensive literature search was conducted in January 2023 including non-randomized and randomized-controlled trials (RCT) investigating the effects of IMIs on PTSS in youth aged ≤25 years. Six studies were identified with five providing data for the meta-analysis. The majority of studies included youth with different types of trauma irrespective of PTSS severity at baseline (k = 5). We found a small within-group effect in reducing PTSS from baseline to post-treatment (g = -0.39, 95% CrI: -0.67 to -0.11, k = 5; n = 558; 9 comparisons). No effect emerged when comparing the effect of IMIs to control conditions (g = 0.04; 95%-CrI: -0.52 to 0.6, k = 3; n = 768; k = 3; 4 comparisons). Heterogeneity was low between and within studies. All studies showed at least some concerns in terms of risk of bias. Current evidence does not conclusively support the overall efficacy of IMIs in addressing youth PTSS. This review revealed a scarcity of studies investigating IMIs for youth exposed to traumatic events, with most being feasibility studies rather than adequately powered RCTs and lacking a trauma focus. This underscores the demand for more high-quality research.

What to do when the unwanted happens? Negative event management in studies on internet- and mobile-based interventions for youths and adults with two case reports.

Background: Despite severely burdened individuals, often being excluded from research studies on internet- and mobile-based interventions (IMIs), negative events (NEs) including suicidal thoughts and behaviors (STBs) can still occur during a trial. NEs require monitoring and adequate safety measures. However, study protocols frequently lack comprehensive descriptions of procedures for managing NEs. Aims: This study aimed to illustrate the assessment, monitoring, and procedures for addressing NEs in two studies on IMIs in adults and youth using case reports, to identify strengths and weaknesses of the NE management approaches, and to derive key learnings and recommendations. Methods: Two case reports were drawn from two distinct IMI studies. The first study, PSYCHOnlineTHERAPY, evaluates the combination of an IMI with on-site psychotherapy for anxiety and depressive disorders in adults (adult blended study). The second study evaluates a standalone, therapist-guided IMI for post-traumatic stress disorder (PTSD) in youth (youth standalone study). Potential NEs were predefined depending on the study sample. The case studies thoroughly document the systematic recording and ongoing monitoring of NEs through self-report and observer-based assessments during the interventions. The cases illustrate a variety of NE management strategies, including automated and personalized approaches, adapted to the specific nature and severity of the NEs. The NE management approaches are visualized using decision trees. Results: In the adult blended case study, online questionnaires detected STBs and triggered automated support information. As on-site therapy had already ended, a telephone consultation session allowed for the identification and discussion of the heightened intensity of suicidal thoughts, along with the development of specific additional help options. In the youth standalone case study, heightened tension in an adolescent with PTSD during trauma processing could be addressed in a telephone therapeutic session focusing on resource activation and emotion regulation. The referral to on-site treatment was supported. Overall, advantages of the NE management included automated procedures, multimodal assessment of a wide range of NEs, and standardized procedures tailored to different severity levels. Weaknesses included the use of single-item assessments for STBs and lack of procedures in case of deterioration or nonresponse to treatment. Conclusion: This study provides practical insights and derives key learnings and recommendations regarding the management of NEs in different IMI contexts for both adults and youth.

COVID19-associated new-onset movement disorders: a follow-up study.

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited. METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed. RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence. CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.

Safety of Deep Repetitive Transcranial Magnetic Stimulation (drTMS) against Medical Refractory Symptoms in Parkinson Syndromes: First German Real-World Data with a Specific H5 Coil.

So far, deep repetitive transcranial magnetic stimulation (drTMS) has shown promising results as an add-on treatment for Parkinson's disease (PD) but not for non-idiopathic Parkinson Syndromes (PS). We aimed to investigate the safety and feasibility of drTMS application in patients with different Parkinson Syndromes and medical refractory symptoms. Multifaceted real-world data (n = 21) were retrospectively analyzed regarding adverse effects as well as short-term effects of the drTMS treatment on patients' self-rated symptom severity and motor, cognitive, and emotional functions. The drTMS treatment with H5 coil included a sequential 1 Hz primary motor cortex stimulation contralateral to the more-affected body side and a bilateral 10 Hz stimulation of the prefrontal cortex. Overall, drTMS could be safely administered to patients with different PSs and medical refractory symptoms, but large variation was apparent in the rate and severity ratings of the reported adverse event/adverse device effect. The treatment significantly decreased the subjective main symptom severity. This effect was more pronounced in older patients with PD. Furthermore, analysis showed an improvement in depression, but no effect could be established in terms of cognitive performance. drTMS can be safely administered to patients with PS and medical refractory symptoms and can decrease the subjective motor symptom severity and depression.

Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients.

Introduction: Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation therapy that uses short, repetitive shockwaves through a neuro-navigated device. Current research suggests that these pulses lead to a wide range of vascular, metabolic, and neurotrophic changes. This relatively new CE-marked treatment provided first promising results in a clinical pilot study for improving cognition in mild-to-moderate Alzheimer's. Data from other centers is lacking, so here we analyzed safety and pilot real-world short-term results of TPS from the first center in Germany. To gain information about effects in different stages, patients with not only mild but also moderate-to-severe Alzheimer's were analyzed. Methods: A total of 11 patients were retrospectively examined for cognitive and emotional function before and after the first stimulation series. The effect was assessed using several neuropsychological tests [Alzheimer's Disease Assessment Scale (ADAS), including the ADAS cognitive score (ADAS Cog) and ADAS affective scores, Mini-Mental Status Examination (MMSE), and Montreal Cognitive Assessment (MoCA)] including in comparison between the groups of mild-to-severe patients. Moreover, subjective improvement of symptom severity, potential effects on depressive symptoms, and side effects were analyzed using Numeric Rating Scales (NRS). Results: Side effects were rare (in 4% of sessions) with moderate subjective severity and only transient. Patients significantly improved in the ADAS and ADAS Cog, while there was no significant effect in MMSE and MoCA. Patients' self-reported symptom severity improved significantly. The depressive symptoms measured in an ADAS subscale also improved significantly. Statistical data analyses revealed no significant correlation of clinical improvement with baseline symptom severity. Conclusion: TPS might be a safe and promising add-on therapy for Alzheimer's, even for moderate-to-severe patients. More research on long-term effects in patients as well as studies with sham control groups is needed. Moreover, translational research on the mechanisms of action and effects on cerebral network physiology will be needed to understand this new neuromodulation technique.

Internet- and mobile-based trauma-focused intervention for adolescents and young adults with posttraumatic stress disorder: a study protocol of a proof-of-concept feasibility study.

Introduction: Although evidence-based treatments for posttraumatic stress disorder (PTSD) in adolescents and young adults exist, affected youth do not have sufficient access to these treatments due to structural and attitudinal barriers. Internet- and mobile-based interventions (IMIs) can help fill this healthcare gap, but such programmes have not yet been sufficiently evaluated in youth with PTSD. Aim: This study aims to investigate the feasibility of an IMI for youth with PTSD in a one-arm, non-randomised, prospective proof-of-concept feasibility study. Methods: We aim to recruit 32 youth between 15 and 21 years old with clinically relevant posttraumatic stress symptoms (CATS ≥ 21), who will receive access to the IMI. The IMI consists of nine sessions involving psychoeducation, emotion regulation and coping skills, written-based imaginal exposure, cognitive restructuring and relapse prevention. Participants will be guided by an eCoach, who provides weekly semi-standardised written feedback on completed sessions and adherence reminders. We will use a formal feasibility framework to assess different dimensions of feasibility: (1) recruitment capability and resulting sample characteristics, (2) data collection procedures and outcome measures, (3) acceptability of the IMI and study procedures, (4) resources and ability to manage and implement the study and IMI and (5) participants' responses to the IMI in terms of symptom severity and satisfaction. Additionally, potential negative effects related to the intervention will be assessed. Assessments take place pre-, mid- and post-intervention and at follow-up, including semi-structured clinical telephone interviews for PTSD diagnostics at pre- and post-intervention assessment. Qualitative interviews will be conducted to investigate the youth perspectives on the IMI. Discussion: This study aims to determine the feasibility of a guided IMI for youth with PTSD to adapt the IMI as closely as possible to youth needs and to inform the design, procedure and safety management of a large-scale efficacy RCT. Trial registration: German Clinical Trials Register identifier: DRKS00023341. HIGHLIGHTS: Evidence-based care for adolescents after trauma is not widely available.• This study evaluates the feasibility of a guided trauma-focused Internet intervention as a time- and location-independent low-threshold treatment option for adolescents and young adults with posttraumatic stress disorder.

Introducción: Aunque existen tratamientos basados en la evidencia para el trastorno de estrés postraumático (TEPT) en adolescentes y adultos jóvenes, los jóvenes afectados no tienen suficiente acceso a estos tratamientos debido a barreras estructurales y actitudinales. Las intervenciones basadas en Internet y dispositivos móviles (IMI en su sigla en inglés) pueden ayudar a llenar este vacío en la atención de salud, pero tales programas aún no se han evaluado suficientemente en jóvenes con TEPT.Objetivo: Este estudio tiene como objetivo investigar la factibilidad de una IMI para jóvenes con TEPT en un estudio de factibilidad de prueba de concepto prospectivo, no aleatorio, de un solo brazo.Métodos: Nuestro objetivo es reclutar a 32 jóvenes entre 15 y 21 años con síntomas de estrés postraumático clínicamente relevantes (CATS > 21), que recibirán acceso a la IMI. La IMI consta de nueve sesiones que involucran psicoeducación, regulación emocional y habilidades de afrontamiento, exposición imaginada basada en escritos, reestructuración cognitiva y prevención de recaídas. Los participantes serán guiados por un eCoach, que proporcionará comentarios escritos semiestandarizados semanales sobre las sesiones completadas y recordatorios de adherencia. Usaremos un marco de factibilidad formal para evaluar las diferentes dimensiones de factibilidad: (1) capacidad de reclutamiento y características de la muestra resultante, (2) procedimientos de recopilación de datos y de las medidas del resultado, (3) aceptabilidad de la IMI y los procedimientos del estudio, (4) recursos y capacidad para gestionar e implementar el estudio y la IMI y (5) las respuestas de los participantes a la IMI en términos de la gravedad de los síntomas y la satisfacción. Además, se evaluarán los posibles efectos negativos relacionados con la intervención. Las evaluaciones se realizan antes, durante y después de la intervención y durante el seguimiento, incluyendo entrevistas telefónicas clínicas semiestructuradas para el diagnóstico de TEPT en la evaluación previa y posterior a la intervención. Se realizarán entrevistas cualitativas para investigar las perspectivas de los jóvenes sobre la IMI.Discusión: Este estudio tiene como objetivo determinar la factibilidad de una IMI guiada para jóvenes con TEPT para adaptar la IMI lo más cerca posible a las necesidades de los jóvenes y para informar el diseño, el procedimiento y la gestión de la seguridad de un ECA de eficacia a gran escala.

The association of the 5-HTTLPR polymorphism and the response to different stressors in healthy males.

The experience of stress is related to individual wellbeing and vulnerability to psychopathology. Therefore, understanding the determinants of individual differences in stress reactivity is of great concern from a clinical perspective. The functional promotor polymorphism of the serotonin transporter gene (5-HTTLPR/rs25531) is such a factor, which has been linked to the acute stress response as well as the adverse effect of life stressors. In the present study, we compared the impact of two different stress induction protocols (Maastricht Acute Stress Test and ScanSTRESS) and the respective control conditions on affective ratings, salivary cortisol levels and cognitive performance. To this end, 156 healthy young males were tested and genotyped for the 5-HTTLPR/rs25531 polymorphism. While combined physiological and psychological stress in the MAST led to a greater cortisol increase compared to control conditions as well as the psychosocial ScanSTRESS, subjective stress ratings were highest in the ScanSTRESS condition. Stress induction in general affected working memory capacity but not response inhibition. Subjective stress was also influenced by 5-HTTLPR/rs25531 genotype with the high expression group showing lower stress ratings than lower expression groups. In line with previous research, we identified the low expression variant of the serotonin transporter gene as a risk factor for increased stress reactivity. While some dimensions of the human stress response may be stressor specific, cognitive outcomes such as working memory performance are influenced by stress in general. Different pathways of stress processing and possible underlying mechanisms are discussed.

Highly efficient integration and expression of piggyBac-derived cassettes in the honeybee (Apis mellifera).

Honeybees (Apis mellifera), which are important pollinators of plants, display remarkable individual behaviors that collectively contribute to the organization of a complex society. Advances in dissecting the complex processes of honeybee behavior have been limited in the recent past due to a lack of genetic manipulation tools. These tools are difficult to apply in honeybees because the unit of reproduction is the colony, and many interesting phenotypes are developmentally specified at later stages. Here, we report highly efficient integration and expression of piggyBac-derived cassettes in the honeybee. We demonstrate that 27 and 20% of queens stably transmitted two different expression cassettes to their offspring, which is a 6- to 30-fold increase in efficiency compared with those generally reported in other insect species. This high efficiency implies that an average beekeeping facility with a limited number of colonies can apply this tool. We demonstrated that the cassette stably and efficiently expressed marker genes in progeny under either an artificial or an endogenous promoter. This evidence of efficient expression encourages the use of this system to inhibit gene functions through RNAi in specific tissues and developmental stages by using various promoters. We also showed that the transgenic marker could be used to select transgenic offspring to be employed to facilitate the building of transgenic colonies via the haploid males. We present here the first to our knowledge genetic engineering tool that will efficiently allow for the systematic detection and better understanding of processes underlying the biology of honeybees.

Origin of a function by tandem gene duplication limits the evolutionary capability of its sister copy.

The most remarkable outcome of a gene duplication event is the evolution of a novel function. Little information exists on how the rise of a novel function affects the evolution of its paralogous sister gene copy, however. We studied the evolution of the feminizer (fem) gene from which the gene complementary sex determiner (csd) recently derived by tandem duplication within the honey bee (Apis) lineage. Previous studies showed that fem retained its sex determination function, whereas the rise of csd established a new primary signal of sex determination. We observed a specific reduction of nonsynonymous to synonymous substitution ratios in Apis to non-Apis fem. We found a contrasting pattern at two other genetically linked genes, suggesting that hitchhiking effects to csd, the locus under balancing selection, is not the cause of this evolutionary pattern. We also excluded higher synonymous substitution rates by relative rate testing. These results imply that stronger purifying selection is operating at the fem gene in the presence of csd. We propose that csd's new function interferes with the function of Fem protein, resulting in molecular constraints and limited evolvability of fem in the Apis lineage. Elevated silent nucleotide polymorphism in fem relative to the genome-wide average suggests that genetic linkage to the csd gene maintained more nucleotide variation in today's population. Our findings provide evidence that csd functionally and genetically interferes with fem, suggesting that a newly evolved gene and its functions can limit the evolutionary capability of other genes in the genome.