Accelerated high frequency rTMS induces time-dependent dopaminergic alterations: a DaTSCAN brain imaging study in healthy beagle dogs.

Aim: The neurobiological effects of repetitive transcranial magnetic stimulation are believed to run in part through the dopaminergic system. Accelerated high frequency rTMS (aHF-rTMS), a new form of stimuli delivery, is currently being tested for its usefulness in treating human and canine mental disorders. However, the short-and long-term neurobiological effects are still unclear, including the effects on the dopaminergic system. In aHF-rTMS, multiple sessions are delivered within 1 day instead of one session per day, not only to accelerate the time to response but also to increase clinical efficacy. To gain more insight into the neurobiology of aHF-rTMS, we investigated whether applying five sessions in 1 day has direct and/or delayed effects on the dopamine transporter (DAT), and on dopamine metabolites of cerebrospinal fluid (CSF) in beagles. Materials and methods: Thirteen beagles were randomly divided into two groups: five active stimulation sessions (n = 9), and 5 sham stimulation sessions (n = 4). Using DaTSCAN, DAT binding indices (BI) were obtained at baseline, after 1 day, 1 month, and 3 months post stimulation. CSF samples were collected after each scan. Results: Active aHF-rTMS significantly reduced striatal DAT BI 1 day post-active stimulation session (p < 0.01), and the effect lasted to 1 month (p < 0.01). No significant DAT BI change was found in sham group. No significant changes in dopamine metabolites of CSF were found. Conclusion: Although no significant effects on CSF dopamine metabolites were observed, five sessions of active aHF-rTMS significantly decreased striatal DAT BI after 1 day and up to 1 month post stimulation, indicating immediate and delayed effects on the brain dopaminergic system. Our findings in healthy beagles further substantiate the assumption that (a)HF-rTMS affects the brain dopaminergic system and it may pave the way to apply (a)HF-rTMS treatment in behaviorally disturbed dogs.

The impact of the euthanasia assessment procedure: a qualitative interview study among adults with psychiatric conditions.

BACKGROUND: Assisted dying for adults with psychiatric conditions (APC) is highly controversial but legally possible in a few countries, including Belgium. Previous research has suggested that the complex euthanasia assessment procedure may cause additional suffering in APC but may also induce positive experiences. This study reports on the impact of the euthanasia assessment procedure as experienced by APC on three counts: 1) their mental state, including death ideation; 2) their treatment trajectory; 3) their social relationships. METHODS: We performed an in-depth qualitative interview study with 16 APC in Flanders, Belgium, who had voiced a euthanasia request between 2016-2020. Thematic coding was used. FINDINGS: We interviewed 16 APC. Euthanasia assessment procedures brought out a plethora of experiences in APC, both favourable and unfavourable. Whereas thoughts of suicide remain present to a certain extent, being in the assessment procedure allows some APC to reconsider alternatives towards life, and also to attempt new treatment options. However, many APC experience ambivalence about the supposedly inherent desirability and dignity in euthanasia. Worries also surfaced about the rationale behind and effects of involvement of APCs' social circle, and about the impact it could have on them. CONCLUSION: Further research, including other stakeholder perspectives, is recommended with a view to maximising favourable and minimising unfavourable impacts for all involved. In clinical practice attention to these impacts is paramount, and clear communication and management of expectations between physician and patient, seems appropriate to address the many ambivalent experiences that accompany APC during the euthanasia assessment procedure. Policy attention could in this regard go to clarifying certain sources of ambivalence and issues that are insufficiently addressed, such as modalities of relatives' involvement.

Concrete Experiences and Support Needs Regarding the Euthanasia Practice in Adults With Psychiatric Conditions: A Qualitative Interview Study Among Healthcare Professionals and Volunteers in Belgium.

Objective: Although euthanasia in the context of adult psychiatry is legalized in Belgium, it poses major ethical and clinical challenges for the health care professionals and volunteers involved. This study aimed to address these members' concrete experiences and support needs. Methods: A qualitative semi-structured interview study was conducted with 16 physicians and 14 other health care professionals and volunteers, with at least one concrete experience with euthanasia requests and procedures concerning adults with psychiatric conditions. Findings: Concrete experiences concerned the following 8 domains: (1) the impact of euthanasia on the clinical trajectory and (2) on the therapeutic relationship, (3) internal and (4) external collaborative partnerships, (5) patients' social inner circle (non-)involvement, (6) the use of recently published guidelines and, (7) the first criminal trials on this topic, and (8) the act of euthanasia. The following 8 main support needs emerged; (1) protocols addressing specific sub-populations and pathologies, (2) protocols specifically drawn up for non-medics, (3) guidance on how to adequately implement the two-track approach, (4) (after)care for patients, (5) (after)care for the health care team, (6) guidance on the patient's social inner circle involvement, (7) enhanced education measures, and (8) enhanced financial measures, including incentives for holistic, palliative care approaches. Conclusion: The health care professionals and volunteers reported many positive and negative experiences in dealing with euthanasia requests in adult psychiatry. They reported several support needs across the extensive euthanasia trajectory, pertaining to concrete management of thorny issues that guidelines do not (yet) touch on. Important implications of our study relate to tackling these existing issues, and to paying sufficient attention to the impact of a euthanasia trajectory on all actors, including the patients and their social inner circle, involved.

The Impact of Accelerated HF-rTMS on Canine Brain Metabolism: An [18F]-FDG PET Study in Healthy Beagles.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been proven to be a useful tool for the treatment of several severe neuropsychiatric disorders. Accelerated (a)rTMS protocols may have the potential to result in faster clinical improvements, but the effects of such accelerated paradigms on brain function remain to be elucidated. Objectives: This sham-controlled arTMS study aimed to evaluate the immediate and delayed effects of accelerated high frequency rTMS (aHF-rTMS) on glucose metabolism in healthy beagle dogs when applied over the left frontal cortex. Methods: Twenty-four dogs were randomly divided into four unequal groups: five active (n = 8)/ sham (n = 4) stimulation sessions (five sessions in 1 day), 20 active (n = 8)/ sham (n = 4) stimulation sessions (five sessions/ day for 4 days), respectively. [18F] FDG PET scans were obtained at baseline, 24 h poststimulation, after 1 and 3 months post the last stimulation session. We explicitly focused on four predefined regions of interest (left/right prefrontal cortex and left/right hippocampus). Results: One day of active aHF-rTMS- and not sham- significantly increased glucose metabolism 24 h post-active stimulation in the left frontal cortex only. Four days of active aHF-rTMS only resulted in a nearly significant metabolic decrease in the left hippocampus after 1 month. Conclusions: Like in human psychiatric disorders, active aHF-rTMS in healthy beagles modifies glucose metabolism, although differently immediately or after 1 month post stimulation. aHF-rTMS may be also a valid option to treat mentally disordered dogs.

Why adults with psychiatric conditions request euthanasia: A qualitative interview study of life experiences, motives and preventive factors.

OBJECTIVE: As the empirical picture of adults with psychiatric conditions (further referred to as 'patients') requesting euthanasia is still incomplete, this study aims to deepen our understanding of why these patients request euthanasia, how this relates to the option of suicide, and what could have prevented these patients from considering death and requesting euthanasia. METHODS: A qualitative study using in-depth, face-to-face interviews was conducted with 16 patients who had their euthanasia request under assessment in the period 2016-2020. Thematic coding was used. FINDINGS: Most patients were in a state of feeling emotionally worn-out as a result of the many accumulated misfortunes and setbacks, leading to the all-pervasive sense that life is no longer worth living. Whereas some patients reported lifelong adversity, others struggled predominantly in later life. Whereas some patients longed for death strongly, others expressed ambivalence towards death ideation, and some even requested euthanasia to hear of their ineligibility for it, to restore hope and to (re)find meaning in life. patients valued euthanasia over suicide as being more dignified and acceptable, both for themselves and for their inner circle. With regard to preventive factors, patients posited the need for improved accessibility and quality of mental healthcare, as well as a profound change in society's perception of, and support for, these patients. CONCLUSIONS: This study revealed the many complexities of euthanasia in the context of psychiatry, due to the many differences in patients' background characteristics, in their motives for requesting euthanasia, and the multi-layered aspects of mental suffering that go beyond the field of psychiatry.

Euthanasia in adults with psychiatric conditions: A descriptive study of the experiences of Belgian psychiatrists.

To investigate the experience of psychiatrists who completed assessment procedures of euthanasia requests from adults with psychiatric conditions (APC) over the last 12 months. Between November 2018 and April 2019 a cross-sectional survey was sent to a sample of 753 psychiatrists affiliated with Belgian organisations of psychiatrists to gather detailed information on their latest experience with a completed euthanasia assessment procedure, irrespective of its outcome (i.e. euthanasia being performed or not). Information on 46 unique cases revealed that most APC suffered from comorbid psychiatric and/or somatic disorders, and had received different kinds of treatment for many years prior to their euthanasia request. Existential suffering was the main reason for the request. The entire procedure spanned an average of 14 months, and an average of 13.5 months in the 23 cases that culminated in the performance of euthanasia. In all cases, the entire procedure entailed multidisciplinary consultations, including with family and friends. Psychiatrists reported fewer difficulties in assessing due care criteria related to the APC's self-contemplation - for example, unbearable suffering on top of the due care criteria related to their medical condition; incurability due to lack of reasonable treatment perspectives. In a few cases in which euthanasia was the outcome, not all legal criteria were fulfilled in the reporting physicians' opinions. Both positive and negative experiences of the assessment procedure were reported: for example, reduced suicide risk for the APC; an emotional burden and a feeling of being pressured for the psychiatrist. This study confirms that euthanasia assessment in APC entails a lengthy process with diverse complexities, and psychiatrists require support in more than one respect if the assessments are to be handled adequately. Thorough evaluation of current guidelines is recommended: that is, to what extent the guidelines sufficiently address the complexities around (e.g.) assessing legal criteria or involving relatives. We formulate various avenues for further research to build on this study's insights and to fill remaining knowledge gaps.

Is twice daily LF-rTMS a viable treatment option for treatment-resistant OCD? Results from an open-label feasibility study.

Several reports point to the beneficial effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of resistant obsessive-compulsive disorder (OCD). This study aimed to evaluate the safety and efficacy of rTMS targeting the dmPFC in the treatment of treatment-resistant OCD patients. Twelve patients received 20 sessions of low-frequency (LF) rTMS (1 Hz, 1200 pulses) in a twice daily protocol during 10 weekdays. Y-BOCS and IDS scores modestly but significantly decreased after treatment and at follow-up and HADS anxiety improved at follow-up. LF rTMS may improve OCD, anxiety, and depressive symptoms in treatment-resistant OCD and was a safe and well-tolerated treatment.

The engagement of psychiatrists in the assessment of euthanasia requests from psychiatric patients in Belgium: a survey study.

BACKGROUND: Since its legalisation in 2002, the number of times euthanasia has been carried out in response to requests from adults with psychiatric conditions (APC) has continued to increase. However, little is known about why and how psychiatrists become engaged in the assessment of such euthanasia requests. METHODS: A cross-sectional survey study was conducted between November 2018 and April 2019 of 499 psychiatrists affiliated with the Flemish Psychiatry Association. Chi square/Fisher's exact tests were performed to examine if, and to what extent, psychiatrists' backgrounds relate to their concrete experiences. The answers to the open question regarding motives for (non-) engagement were thematically coded. RESULTS: Two hundred one psychiatrists participated, a response rate of 40%. During their careers, 80% of those responding have been confronted with at least one euthanasia request from an APC patient and 73% have become involved in the assessment procedure. Their engagement was limited to the roles of: referring physician (in 44% of the psychiatrists), attending physician (30%), legally required 'advising physician' (22%), and physician participating in the actual administration of the lethal drugs (5%). Within the most recent 12 months of practice, 61% of the respondents have been actively engaged in a euthanasia assessment procedure and 9% have refused at least once to be actively engaged due to their own conscientious objections and/or the complexity of the assessment. The main motive for psychiatrists to engage in euthanasia is the patient's fundamental right in Belgian law to ask for euthanasia and the psychiatrist's duty to respect that. The perception that they were sufficiently competent to engage in a euthanasia procedure was greater in psychiatrists who have already had concrete experience in the procedure. CONCLUSIONS: Although the majority of psychiatrists have been confronted with euthanasia requests from their APC patients, their engagement is often limited to referring the request to a colleague physician for further assessment. More research is needed to identify the determinants of a psychiatrist's engagement in euthanasia for their APC patients and to discover the consequences of their non-, or their restricted or full engagement, on both the psychotherapeutic relationship and the course of the euthanasia request.

Belgian psychiatrists' attitudes towards, and readiness to engage in, euthanasia assessment procedures with adults with psychiatric conditions: a survey.

BACKGROUND: Although the Belgian assessment pathway for legal euthanasia requires the engagement of at least one psychiatrist, little is known about psychiatrists' attitudes towards euthanasia for adults with psychiatric conditions (APC). This study aims to gauge psychiatrists' attitudes towards and readiness to engage in euthanasia assessment and/or performance procedures in APC. METHODS: This cross-sectional survey study was performed between November 2018 and April 2019. The survey was sent to a sample of 499 eligible psychiatrists affiliated to the Flemish Association for Psychiatry, a professional association that aims to unite and represent all psychiatrists working in Flanders, the Dutch-speaking, northern part of Belgium. The Association's members comprise an estimated 80-90% of all psychiatrists active in Flanders. Only psychiatrists working with APC (83% of the association's total membership) were included. Factorial Anova and Chi Square tests were performed to examine if and to what extent psychiatrists' backgrounds were associated with, respectively, their attitudes and their readiness to play a role in euthanasia procedures concerning APC. RESULTS: One hundred eighty-four psychiatrists completed the questionnaire (response rate 40.2%); 74.5% agree that euthanasia should remain permissible for APC. However, 68.9% question some of the approaches taken by other physicians during the euthanasia assessment and only half consider euthanasia assessment procedures compatible with the psychiatric care relationship. Where active engagement is concerned, an informal referral (68%) or preliminary advisory role (43.8%) is preferred to a formal role as a legally required advising physician (30.3%), let alone as performing physician (< 10%). CONCLUSION: Although three quarters agree with maintaining the legal option of euthanasia for APC, their readiness to take a formal role in euthanasia procedures appears to be limited. More insight is required into the barriers preventing engagement and what psychiatrists need, be it education or clarification of the legal requirements, to ensure that patients can have their euthanasia requests assessed adequately.

Psychiatric patients requesting euthanasia: Guidelines for sound clinical and ethical decision making.

BACKGROUND: Since Belgium legalised euthanasia, the number of performed euthanasia cases for psychological suffering in psychiatric patients has significantly increased, as well as the number of media reports on controversial cases. This has prompted several healthcare organisations and committees to develop policies on the management of these requests. METHOD: Five recent initiatives that offer guidance on euthanasia requests by psychiatric patients in Flanders were analysed: the protocol of Ghent University Hospital and advisory texts of the Flemish Federation of Psychiatry, the Brothers of Charity, the Belgian Advisory Committee on Bioethics, and Zorgnet-Icuro. These were examined via critical point-by-point reflection, focusing on all legal due care criteria in order to identify: 1) proposed measures to operationalise the evaluation of the legal criteria; 2) suggestions of additional safeguards going beyond these criteria; and 3) remaining fields of tension. RESULTS: The initiatives are well in keeping with the legal requirements but are often more stringent. Additional safeguards that are formulated include the need for at least two positive advices from at least two psychiatrists; an a priori evaluation system; and a two-track approach, focusing simultaneously on the assessment of the patient's euthanasia request and on that person's continuing treatment. Although the initiatives are similar in intent, some differences in approach were found, reflecting different ethical stances towards euthanasia and an emphasis on practical clinical assessment versus broad ethical reflection. CONCLUSIONS: All initiatives offer useful guidance for the management of euthanasia requests by psychiatric patients. By providing information on, and proper operationalisations of, the legal due care criteria, these initiatives are important instruments to prevent potential abuses. Apart from the additional safeguards suggested, the importance of a decision-making policy that includes many actors (e.g. the patient's relatives and other care providers) and of good aftercare for the bereaved are rightly stressed. Shortcomings of the initiatives relate to the aftercare of patients whose euthanasia request is rejected, and to uncertainty regarding the way in which attending physicians should manage negative or conflicting advices, or patients' suicide threats in case of refusal. Given the scarcity of data on how thoroughly and uniformly requests are handled in practice, it is unclear to what extent the recommendations made in these guidelines are currently being implemented.

The long-term effects of single and repeated subanaesthetic ketamine administration on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT.

Subanaesthetic ketamine has recently been established as an effective and rapid treatment for major depressive disorder showing antidepressant effects for up to 1 week on average. The use of repeated ketamine infusions has been put forward to augment and to prolong the antidepressant response and increase the remission rates. The underlying neurobiological mechanisms responsible for ketamine's antidepressant effects remain unclear. Nevertheless, it has been shown, both in dogs and humans, that ketamine can alter neuronal perfusion and therefore neuronal function in brain regions involved in psychiatric and behavioural disorders. Consequently, the aim of the current placebo controlled study was to assess the long-term effects on cerebral perfusion of single and repeated subanaesthetic ketamine infusions in dogs. Twelve healthy, laboratory dogs were scanned at six different time points following single and repeated ketamine administration, using Single Photon Emission Computed Tomography with the radiotracer 99mTc-hexamethylpropylene amine oxime. We hypothesised that repeated infusions could lead to more prolonged perfusion alterations in brain regions critical for behaviour regulation. We found that repeated subanaesthetic ketamine administration did not result in more prolonged cerebral perfusion alterations compared to a single ketamine administration.

A 17-Year National Study of Prison Suicides in Belgium.

BACKGROUND: Suicide is a leading cause of mortality in prisoners worldwide, yet empirical data on this matter are lacking in Belgium. AIMS: This study sought to describe characteristics associated with a consecutive series of suicides in Belgian prisons from 2000 to 2016 inclusive, in order to inform suicide prevention strategies. METHOD: All documented cases of suicide ( N = 262) were reviewed using a standardized assessment checklist. Official records were abstracted for prisoners' sociodemographic, criminological, and clinical information, as well as for suicide-related characteristics. RESULTS: Over the 17-year study period, suicides accounted for one third of all deaths in Belgian prisons. The average annual suicide rate in Belgium from 2000 to 2016 was 156.2 per 100,000 prisoners. Examination of all cases highlights both individual (psychiatric disorders and a history of suicide attempt) and situational (the early period of incarceration, interfacility transfers, and placement in solitary confinement) factors common in many prison suicides; some of them amenable to (clinical) management, which presents several potential avenues for suicide prevention. LIMITATIONS: Given the absence of a matched control group, no conclusions could be ascertained regarding risk factors. CONCLUSION: Suicide is a common, preventable cause of death among prisoners in Belgium. The results underscore the timely need for national standards and guidelines for suicide prevention in Belgian prisons.

The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT.

Subanaesthetic ketamine has recently been proven to be a highly effective and fast acting alternative treatment for several psychiatric disorders. The mechanisms responsible for ketamine's antidepressant effects remain unclear, but a possible explanation could be that ketamine interacts with regional cerebral blood flow (rCBF). Therefore, the effects of two subanaesthetic ketamine doses on rCBF were evaluated. Twelve dogs were randomly assigned to one of the three treatment conditions (condition saline, condition 0.5 mg/kg ketamine or condition 2 mg/kg ketamine) and received in total five saline or ketamine infusions, with one week interval. Single Photon Emission Computed Tomography (SPECT) scans with the radiotracer 99mTc-hexamethylpropylene amine oxime were performed before the start of the infusions (baseline) and 24 hours after the first (single) and last (multiple) infusion. After a wash out period of 3 months, the animals were again assigned to one of the three treatment conditions described above and the infusion/scan protocol was repeated. During the infusions, cardiovascular parameters were evaluated every ten minutes. A one-way repeated measure ANOVA was set up to assess perfusion index for each ketamine dose for the left frontal cortex (alpha = 0.05). The remaining 11 brain regions were post hoc assessed. Perfusion index was significantly increased in the left frontal cortex and in the thalamus 24 hours after single and multiple ketamine infusions compared to baseline in the 2 mg/kg condition. No clinically relevant cardiovascular effects were observed during the ketamine infusions. This study shows that subanaesthetic ketamine can increase neuronal perfusion and therefore alter neuronal function in brain regions involved in depression and anxiety disorders. These perfusion increases may possibly contribute to ketamine's beneficial effects in these psychiatric disorders.

Family Support Groups for Family Members of Mentally Ill Offenders: Family Expectations and Experiences.

Family Support Groups (FSGs) are developed for family members of mentally ill offenders. This study investigates family treatment expectations and experiences of an FSG. Family members were interviewed before ( n = 20) and after ( n = 17) attending an FSG. Results show that family members hesitated or were curious about the FSG, expected to receive peer support and universality of problems, to receive information and advice and thought about the safety and respect of the group. Family members experienced the treatment as helpful because it was supportive, they gained new insights and they felt relieved and satisfied. Many family members see the guidance of the therapists and the differences in family and gender roles as an added value of attending an FSG. However, considering the limitations of the study, future studies should gain insight in and stress the importance of the meaning of therapeutic processes for family members confronted with different psychiatric disorders and/or situations.

Screening of quorum sensing peptides for biological effects in neuronal cells.

Quorum sensing peptides (QSP) are an important class of bacterial peptides which can have an effect on human host cells. These peptides are used by bacteria to communicate with each other. Some QSP are able to cross the blood-brain barrier and reach the brain parenchyma. However, nothing is known about the effects of these peptides in the brain. Therefore, 85 quorum sensing peptides were screened on six different neuronal cell lines using MTT toxicity, neurite differentiation, cytokine production and morphology as biological outcomes. This primary screening resulted in 22 peptides with effects observed on neuronal cell lines, indicating a possible role in the gut-brain axis. Four peptides (Q138, Q143, Q180 and Q212) showed induction of neurite outgrowth while two peptides (Q162 and Q208) inhibited NGF-induced neurite outgrowth in PC12 cells. Eight peptides (Q25, Q135, Q137, Q146, Q151, Q165, Q208 and Q298) induced neurite outgrowth in human SH-SY5Y neuroblastoma cells. Two peptides (Q13 and Q52) were toxic for SH-SY5Y cells and one (Q123) for BV-2 microglia cells based on the MTT assay. Six peptides had an effect on BV-2 microglia, Q180, Q184 and Q191 were able to induce IL-6 expression and Q164, Q192 and Q208 induced NO production. Finally, Q75 and Q147 treated C8D1A astrocytes demonstrated a higher fraction of round cells. Overall, these in vitro screening study results indicate for the first time possible effects of QSP on neuronal cells.

Suicidal ideation while incarcerated: Prevalence and correlates in a large sample of male prisoners in Flanders, Belgium.

Prisoners constitute a high-risk group for suicide. As an early stage in the pathway leading to suicide, suicidal ideation represents an important target for prevention, yet research on this topic is scarce in general prison populations. Using a cross-sectional survey design, correlates of suicidal ideation while incarcerated were examined in a sample of 1203 male prisoners, randomly selected from 15 Flemish prisons. Overall, a lifetime history of suicidal ideation and attempts was endorsed by 43.1% and 20.3% of respondents, respectively. Approximately a quarter of all prisoners (23.7%) reported past-year suicidal ideation during their current incarceration, which was significantly associated with both imported vulnerabilities (psychiatric diagnoses and a history of attempted suicide) and variables unique to the prison experience (lack of working activity, exposure to suicidal behaviour by peers, and low levels of perceived autonomy, safety and social support) in the multivariate regression analysis. A first-ever period of imprisonment and a shorter length of incarceration (≤12months) were also associated with increased odds of recent suicidal ideation. Collectively, the current findings underscore the importance of both vulnerability factors and prison-specific stressors for suicidal ideation in prisoners, and hence the need for a multi-faceted approach to suicide prevention in custodial settings. In addition to the provision of appropriate mental health care, environmental interventions that target modifiable aspects of the prison regime could provide a substantial buffer for the onset and persistence of suicidal ideation in this at-risk population.