Considerable effort has been devoted to investigate the neuroimaging correlates and predictors of antidepressant response to ketamine, yet inconsistency in the location and nature of the regional brain effects makes it difficult to unify this research. Despite the revolutionary notion that psychiatric therapeutics show network-level brain representations, investigations into network localization of brain functional effects of ketamine treatment are still lacking.

We initially identified the locations of longitudinal brain functional alterations (increase and decrease separately) induced by ketamine treatment from 16 published studies with 508 depressed patients. By integrating these affected brain locations with large-scale functional MRI datasets from 1113 healthy and 255 depressed individuals, we then leveraged a novel functional connectivity network mapping approach to construct ketamine-induced hyper-functional and hypo-functional networks respectively.

The hyper-functional network mainly involved the subcortical (caudate nucleus and thalamus) and default (medial prefrontal cortex) networks, while its hypo-functional counterpart predominantly implicated the limbic (temporal pole), subcortical (hippocampus and amygdala), and default (lateral temporal cortex) networks.

Our findings may shed light on the neurobiological effects of ketamine from a network perspective, which might represent a crucial step toward fostering the clinical application of ketamine in antidepressant treatment.

Volumetric changes in the superior temporal gyrus and anterior cingulate cortex have been repeatedly reported in studies on schizophrenia. Tractography and functional magnetic resonance imaging studies have suggested that alterations in connectivity involving the superior temporal gyrus and the anterior cingulate cortex are relevant to psychotic symptoms of schizophrenia.

We analyzed nanometer-scale three-dimensional structures of brain tissues of the superior temporal gyrus and the anterior cingulate cortex in eight schizophrenia and eight control cases and evaluated structural parameters of their neurons. We then examined the relation between the neuronal parameters and clinical information including auditory hallucination score.

The obtained results indicated that 1) neurites become thin and tortuous in schizophrenia and that 2) somata become small in schizophrenia. The frequency distribution of neurite curvatures had a broad profile in the schizophrenia cases, whereas the control cases showed sharp peaks. In the scatter diagram of the standard deviation of neurite curvatures, the schizophrenia and control cases formed separate clusters, indicating that all 16 cases analyzed in this study can be assigned to either the schizophrenia or control group simply by using the diagram. The cingulate/temporal ratio of the standard deviation of neurite curvatures showed a strong positive correlation with the auditory hallucination score.

The structural alteration of neurites observed in the schizophrenia cases should influence the function of affected brain areas by hindering communication between distant neurons. We suggest that the interplay of the temporal and cingulate cortices in the whole-brain network is relevant to auditory hallucination.

Ketamine and esketamine produce rapid and sustained antidepressant effects in persons with treatment-resistant depression (TRD). Although it is posited that these effects are largely attributed to N-methyl-D-aspartate receptor antagonism, the potential involvement of the opioid system remains unclear. This systematic review investigates whether ketamine and esketamine antidepressant efficacy is mediated through the opioid system.

We conducted a systematic search of preclinical and clinical studies investigating the potential involvement of the opioid system in the antidepressant effects of ketamine and esketamine. Database searches on PubMed, Cochrane Library, Embase and PsycINFO occurred from inception to September 27, 2025.

16 studies were identified: 12 clinical (n = 790) and 4 preclinical studies. Clinical designs included randomized controlled trials, case reports, pre-post studies and observational cohort studies. Preclinical studies utilized animal models of depression. Only one study examined esketamine. Naltrexone (nonselective opioid antagonist) attenuated ketamine’s effects in three studies, while four reported no such effect and one reported mixed evidence. Genetic markers of opioid receptor subtypes (i.e., OPRM1 and OPRD1) were examined in three studies, but results were inconclusive, potentially due to limited evidence. Separately, opioid use was not associated with ketamine response. Few studies directly examined opioid receptor subtypes.

The reported mixed findings suggest that the opioid system may exert a partial mediating effect of ketamine in TRD. However, given the inconsistent attenuation of ketamine’s antidepressant effects by opioid receptor antagonists, the opioid system likely functions as a context-dependent modulator rather than a primary mediator, particularly at standard antidepressant doses.

Major depressive disorder (MDD) exhibits significant heterogeneity in treatment responses, necessitating multiple pharmacological trials to achieve therapeutic success. Pharmacogenetic (PGx) testing has emerged as a promising tool to personalize antidepressant (AD) treatments, though its clinical utility remains controversial.

This study assessed the efficacy of PGx-guided treatment in improving clinical outcomes among 287 MDD patients within the PANDORA trial, a prospective randomized, participant- and rater-blinded, controlled trial conducted in Italy. A total of 268 adults with moderate-to-severe MDD were randomized into Treated as Usual (TAU) or Treated with Genetic Test Guide (TGTG). Patients were assessed using the Hamilton Depression Rating Scale (HAM-D17), Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory, MINI-ICF-APP for psychosocial functioning, and the UKU Side Effects Rating Scale, at baseline and at 4, 8, and 12 weeks.

Both groups demonstrated significant symptom improvement over the 12-week period. No significant differences were observed between the groups in terms of response and remission rates, measured by HAM-D17 and BDI-II, at weeks 8 and 12. Notably, in the BDI-II symptom cluster analysis, significant differences were found only in neurovegetative symptoms, with TGTG patients showing greater improvement at the 4-week and 8-week follow-up visits. Among patients with severe baseline symptoms, those in the TGTG group exhibited greater symptom reduction and higher response rates at week 8.

These findings suggest that while PGx testing did not significantly improve overall treatment efficacy in MDD compared to TAU, it may offer benefits in managing patients with severe symptoms and specific symptom domains.

A better mechanistic understanding of schizophrenia spectrum disorders is crucial to developing efficient treatment approaches. Therefore, this study investigated longitudinal interrelations between clinical outcomes, brain structure, and somatic health in post-acute individuals from the schizophrenia spectrum.

A sample of 63 post-acute patients from two independent physical exercise studies was included in the final analyses. Demographic, clinical, cognitive, and somatic data were acquired at baseline and follow-up, as were structural magnetic resonance imaging scans. Multivariate cross-lagged panel modeling including mediators was used to study the mutual interrelations over time between the clinical, neural, and somatic levels.

A higher baseline global gray matter volume and larger regional gray matter volumes of the hippocampal formation, precuneus, and posterior cingulate predicted improved clinical outcomes, such as daily-life functioning, negative symptoms, and cognition. Increases in white matter volume from baseline to follow-up resulted in significantly reduced positive symptoms and higher daily-life functioning.

Our findings suggest that stimulating neuroplasticity, especially in the hippocampal formation, precuneus, and posterior cingulate gyrus, may represent a promising treatment target in post-acute schizophrenia spectrum disorders. Physical exercise therapies and other lifestyle interventions, and brain stimulation approaches reflect potential treatment candidates. Given the exploratory character of the statistical analysis performed, these findings need to be replicated in independent longitudinal imaging cohorts of patients with schizophrenia spectrum disorders.

Epigenetic mechanisms might play a role in modulating susceptibility to bipolar disorder (BD) and response to lithium, the mainstay treatment for BD. Additionally, individuals with BD experience accelerated biological aging.

We compared blood DNA methylation profiles measured with EPIC v.2.0 arrays between patients with BD (33 lithium responders and 31 nonresponders) and nonpsychiatric controls (n = 32), as well as based on long-term lithium response. In addition, we compared cellular aging between these groups using epigenetic age, pace of aging, and, for the first time, transcriptional age acceleration based on bulk RNA sequencing in 93 patients and 56 controls.

We identified 191 differentially methylated positions (DMPs) and 8 differentially methylated regions between patients with BD and controls, located in genes enriched for “Postsynaptic Density” (odds ratio = 6.81, p = 0.001). No DMP was significantly associated with lithium response after multiple testing correction. Patients showed a significantly higher biological age acceleration than controls based on two epigenetic clocks (GrimAge, Mann–Whitney U = 551, p = 0.0009; GrimAge2: U = 477, p = 9.0E-05) and pace of aging (DunedinPACE, t = 3.01, p = 0.003), but not on transcriptional age. While we observed no significant difference in epigenetic aging based on lithium response, lithium responders showed lower epigenetic acceleration using all clocks, with a trend observed using the PhenoAge clock (t = 1.97, p = 0.053).

Our findings point to methylation patterns characterizing BD and support the hypothesis of accelerated cellular aging in BD.

Bipolar disorder (BD) is assumed to follow a progressive course, conceptualized through staging models. It is unclear whether white matter (WM) microstructure abnormalities, central to BD pathophysiology, parallel this development throughout disease progression. This study explored the link between WM and disease progression in BD, using a comprehensive approach based on clinical staging models.

This cross-sectional diffusion tensor-imaging study included 153 BD patients and 153 healthy controls (HCs) matched for age, sex, and study site. Using tract-based spatial statistics (TBSS), we examined associations between WM integrity and three criteria: (1) number of manic episodes, (2) remission quality between episodes, and (3) inter-episode global functioning.

Analyses revealed significant fractional anisotropy (FA) differences between early and late stages of BD based on the number of manic episodes (ptfce-FWE = 0.003), but not on remission quality (ptfce-FWE = 0.075). However, compared to HC, BD patients with persistent symptoms between episodes showed more widespread FA differences (ptfce-FWE < 0.001) than those with stable remission (ptfce-FWE = 0.031). Regression analyses indicated a positive association between global functioning and FA in euthymic BD patients (ptfce-FWE < 0.001).

Results indicated more severe WM disruptions in patients at advanced stages compared to earlier stages of the disease. While these findings may imply changes occurring with disease progression, the cross-sectional design cannot rule out that they instead reflect stable clinical subtypes of varying severity. The results highlight the clinical relevance of WM alterations and the need for longitudinal studies to better understand the neurobiology and complexity of BD.

Telomere shortening is shared by all psychiatric disorders and is hypothesized as resulting from decreased telomerase activity (TA) or expression of the TERT (Telomerase Reverse Transcriptase) gene.

A search in four English databases was conducted from inception to November 2024 to evaluate the association between psychiatric disorders and telomerase activity (TA) or TERT gene expression in peripheral blood. We performed two separate meta-analyses to generate pooled effect size (ES) for TA and TERT gene expression, followed by meta-regression.

The systematic review included 16 studies, 14 of which were included in the meta-analyses. When considering all psychiatric disorders, no associations were found for TA (ES = 0.08 [−0.50–0.67], p = 0.78 – I-squared = 95%), nor TERT gene expression (ES = 0.00 [−0.56–0.57], p = 0.99 – I-squared = 91%). However, TA was elevated in mood disorders (ES = 0.61 [0.06–1.16] – p = 0.03), while decreased in non-mood disorders (ES = −0.70 [−1.37 – −0.03] – p = 0.04). ES for TA were larger in mood disorders as compared to other disorders (p = 0.003).

This meta-analysis shows that psychiatric disorders – taken together – are not associated with peripheral blood TA or TERT gene expression. Nevertheless, we find that TA is increased in depressive disorders (unipolar or bipolar), whereas decreased in non-mood psychiatric disorders. The paucity of studies and small sample sizes are important limitations, especially for TERT gene expression. Further research is needed, incorporating a broader spectrum of psychiatric disorders and larger sample sizes.

Lithium treatment is associated with reduced mortality in bipolar disorder (BD), but the role of treatment continuity remains underexplored. This study investigated the association between patterns of lithium exposure and all-cause mortality in a population-based cohort.

We analyzed electronic health records from 15,384 individuals with BD in Catalonia, Spain (2010–2019). Patients were classified as having sustained, partial/intermittent, or no lithium exposure based on annual defined daily doses (DDDs). All-cause mortality was the primary outcome. Kaplan–Meier and Cox regression analyses (adjusted for sociodemographic, clinical, and treatment-related variables) estimated hazard ratios (HRs) for mortality risk. Interaction and sensitivity analyses were conducted to assess the role of comorbidity burden and dose effects.

Over the study period, 715 deaths were recorded. In fully adjusted models, sustained lithium exposure was associated with a significantly lower mortality risk compared to no exposure (HR = 0.69, 95% confidence interval [CI]: 0.51–0.93, p = 0.016). In the lithium-exposed subgroup, sustained use was also protective compared to partial/intermittent exposure (HR = 0.70, 95% CI: 0.51–0.97, p = 0.03). No significant interaction was observed between sustained lithium use and comorbidity burden. Sensitivity analyses confirmed this effect at lower dose thresholds but not at higher ones.

Sustained lithium use is associated with improved survival in BD. Discontinuous exposure does not confer the same benefit. Ensuring treatment continuity may maximize lithium’s protective effect and improve long-term outcomes.

Esketamine has been shown to produce a major antidepressant response in patients with treatment-resistant depression (TRD). We evaluated the factors associated with achieving remission in these individuals.

The study was carried out across four psychiatry departments in Madrid, Spain. Patients aged over 18 years were included if they received esketamine as an augmentation treatment for TRD. Standard esketamine protocol included an induction phase (4 weeks) and a maintenance phase (5 to 8 weeks). Subsequent treatment continuation was proposed. Clinical data and scores at the Clinical Global Impression scales were measured following each esketamine administration.

Sixty-five patients initiated the treatment, and 45 patients (69.2%) completed the standard protocol. The median number of esketamine administrations was 19. The mean age was 53.09 and 52.3% of the patients were females. Out of the whole sample, 36 (55%) of the patients achieved remission over the follow-up. Remission rates elevated to 67% in those who completed the standard protocol, and to 70% in those having received more than 19 esketamine administrations. Achieving remission over the follow-up was associated with the absence of dissociative symptoms, and with completing the standard esketamine protocol (OR = 0.229, p = 0.045; and OR = 4.538, p = 0.025, respectively). Receiving more than 19 esketamine administrations was associated with remission over the follow-up (OR = 6.513, p = 0.006).

Our results suggest that extending the numbers of esketamine administration may increase the chances to obtain remission. Adverse effects did not impact the treatment course.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Neurodevelopmental conditions are crucial risk factors for catatonia in pediatric and adult populations. Recent case reports and studies have identified an increasing number of genetic abnormalities likely contributing to catatonia. Catatonia associated with genetic abnormalities is challenging in terms of identification, chronicity, and resistance to treatment. In addition, understanding these genetic abnormalities through identifying rare single nucleotide and copy number variants may offer valuable insights into the underlying pathophysiology.

We conducted a systematic review of all genetic abnormalities reported with catatonia and performed a gene-set enrichment analysis. Our systematic literature search for relevant articles published through July 15, 2024, using combinations of “catatonia,” “catatonic syndrome,” “genetic,” and “genes” in PubMed, yielded 317 articles. Of these, 94 were included, covering 374 cases of catatonia and 78 distinct genetic abnormalities.

This review discusses the clinical presentation of catatonia for each genetic disorder, the treatment strategies, and the putative underlying mechanisms.

The review highlights that catatonia underpinned by genetic abnormalities presents specific clinical and treatment-response features. Therefore, we propose genetic testing guidelines for catatonia and advocate for systematically investigating catatonia in several genetic diseases. Regarding the pathophysiology of catatonia, the gene ontology of biological processes reveals significant enrichment of variants in synaptic and post-synaptic regulatory genes, particularly within GABAergic neurons, reinforcing the implication of the excitatory/inhibitory imbalance. Finally, genetic variants are enriched in microglial cells, highlighting the role of brain inflammation in triggering catatonia. This comprehensive insight could pave the way for more effective management strategies for this condition.

Clinical high risk for psychosis (CHR) is often managed with antipsychotic medications, but their effects on neurocognitive performance and clinical outcomes remain insufficiently explored. This study investigates the association between aripiprazole and olanzapine use and cognitive and clinical outcomes in CHR individuals, compared to those receiving no antipsychotic treatment.

A retrospective analysis was conducted on 127 participants from the Shanghai At Risk for Psychosis (SHARP) cohort, categorized into three groups: aripiprazole, olanzapine, and no antipsychotic treatment. Neurocognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB), while clinical symptoms were assessed through the Structured Interview for Prodromal Syndromes (SIPS) at baseline, 8 weeks, and one year.

The non-medicated group demonstrated greater improvements in cognitive performance, clinical symptoms, and functional outcomes compared to the medicated groups. Among the antipsychotic groups, aripiprazole was associated with better visual learning outcomes than olanzapine. Improvements in neurocognition correlated significantly with clinical symptom relief and overall functional gains at follow-up assessments.

These findings suggest potential associations between antipsychotic use and cognitive outcomes in CHR populations while recognizing that observed differences may reflect baseline illness severity rather than medication effects alone. Aripiprazole may offer specific advantages over olanzapine, underscoring the importance of individualized risk-benefit evaluations in treatment planning. Randomized controlled trials are needed to establish causality.

Scopolamine is a muscarinic receptor antagonist and is widely utilized as a “memory-loss model.” However, its impact across different memory and attention tasks and using different modes of administration has yet to be clearly evaluated. This systematic review and meta-analysis investigates the effect of scopolamine, across all routes of administration and across different dosages, on memory and attention performance in healthy humans (PROSPERO ID: CRD42024531634).

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched (on 20 April 2024) for studies that utilized scopolamine and assessed memory and/or attention. Random-effects meta-analyses were conducted across a range of memory and attention tasks using “Comprehensive Meta-Analysis,” Version 3, to evaluate differential pharmacological effects on cognitive tasks between the scopolamine and placebo groups.

Forty-six studies fulfilled the inclusion and exclusion criteria. Scopolamine negatively impaired performance on all memory tasks (immediate memory, delayed recall, digit span, Buschke selective reminding task, and recognition memory) and led to slower reaction times for three of the five attention tasks examined (choice reaction time, simple reaction time, and rapid visual information processing) compared to placebo. Scopolamine’s negative effect on memory and attention was greater with injectable (e.g., intramuscular, intravenous, and subcutaneous) compared to non-injectable routes of administration (e.g., intranasal, oral, and transdermal).

This study supports the use of scopolamine as a “memory-loss model,” particularly when given by an injectable route of administration. Future clinical trials should evaluate the bioavailability of scopolamine across different routes of administration to ensure therapeutic benefits outweigh any potential adverse cognitive effects.

Catatonia in psychotic patients presents unique challenges. While antipsychotics are the cornerstone of schizophrenia treatment, their use in catatonic patients is sometimes discouraged for fear of worsening the signs. Reports on the successful use of second-generation antipsychotics have been published. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to describe the outcomes of antipsychotic-treated catatonic events.

We searched Medline and Web of Science databases from 2000 to 2023 using search terms including “catatonia” and “antipsychotic agents” for all original peer-reviewed articles, including clinical trials, observational studies, and case-reports. We included antipsychotic-treated catatonic events and extracted data on patient characteristics, pharmacological context, agent involved, and treatment outcomes for each antipsychotic trial.

After screening 6,219 records, 79 full-text articles were included. Among them, we identified 175 antipsychotic trials (in 110 patients). Only 41.1% of the patients benefited from a previous benzodiazepine trial. Antipsychotic use was considered beneficial in 60.0% of the trials, neutral in 29.1%, and harmful in 10.9%. Trials tended to be reported as beneficial for amisulpride, clozapine, and risperidone, equivocal for aripiprazole and olanzapine, and mostly detrimental for haloperidol and quetiapine. Psychotic disorders were the most common underlying etiology (65.8%).

Antipsychotics could be an option in the treatment of catatonia in psychotic patients. However, with few exceptions, we found non-beneficial outcomes with all second-generation antipsychotics in varying proportions in this largest review to date. Although olanzapine is widely used, it is associated with mitigated reported outcomes.

Medication-induced dystonia (MID) is a movement disorder (MD), characterized by involuntary sustained or intermittent muscle contractions, causing abnormal, often repetitive, movements, postures, or both. Although MID is commonly associated with the use of antipsychotics, it also occurs with many other medications widely used in clinical practice.

A systematic literature search (from inception to November 2023), using the PubMed and Embase databases, was conducted without language restriction for articles reporting on MID in people without pre-existing MDs, and this for all potentially relevant non-antipsychotic medications. A narrative synthesis of the available evidence was undertaken.

MID is common (1 to 10%) with certain antiemetics. Selective serotonin reuptake inhibitors and the antiepileptics valproate, carbamazepine, and lamotrigine are rarely (0.01 to 0.1%) or very rarely (<0.01%) associated with MID. All other medications are very rarely (<0.01%) associated with MID or have a risk that cannot be precisely estimated. The actual rate of dystonic reactions with most non-antipsychotic agents remains unknown, owing to misdiagnosis and underreporting in the scientific literature. In general, MID seems to occur more often in children and adolescents, even with a single low dose, and with polymedication. In most cases, MID is acute in onset (occurring within hours to days) and involves the head and neck.

Although MID is most common with dopamine receptor-blocking antiemetics, many other medications may also produce dystonic reactions, particularly in children and adolescents. Although such incidents remain rare, there are indications that MID is underreported for many classes of medications.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

Recent years show an exponential increased interest (“renaissance”) in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit.

In this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments.

In addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation.

Four recommendations are formulated for further research and clinical implementation.