Religious Characteristics of Romanian Physicians: Towards an Integrative Support of Religious Psychiatric Patients.

BACKGROUND: The growing closeness between psychiatry and theology may impact positively the healthcare of the religious psychiatric patients. However, some significant divergences regarding the health care religious methods and the concept and believe in the demonic possession of psychiatric patients continue to shape the relationships between these professionals. While the religions generally admit the demonic or spirit possession as real, the current views of physicians and psychiatric patients are just taken for granted and therefore demands new investigations. In this study, we have performed a targeted survey on this subject. SUBJECTS AND METHODS: The survey was based on a questionnaire addressed to 216 psychiatrists and 201 non-psychiatrists, and 408 psychiatric patients. For physicians, the questionnaire was randomized sent to hospitals in Romania. The patients received the questionnaire on paper. Except for patients with dementia and those in the acute phase of a psychiatric illness, all psychiatric disorders available at the time of the investigation were randomized included in the study. RESULTS: The results showed that about 20% of physicians and 60% of psychiatric patients considered that demonic possession might be associated to a psychiatric illness, while the later would like a priest in the therapeutic team (89.4%, CI: 0.86-0.92). In addition, the psychiatrists declared a lower attendance of religious services, although the majority would accept a priest in the therapeutic team (p>0.05, CI: 0.61-0.70). CONCLUSION: These findings invite to a more practical collaboration between psychiatrists, clinical psychologists, and theologians/priests with training in psychiatry for a more integrative mental care of the religious psychiatric patients. The results call as well for more efficient practical solutions for psychiatric patients, raise awareness towards the personal religious needs and critical beliefs of such patients, and finally might narrow the gap of the controversy between psychiatrists, non-psychiatrists, psychologists and theologians/priests on the addressed issues.

SAFEvR MentalVeRse.app: Development of a Free Immersive Virtual Reality Exposure Therapy for Acrophobia and Claustrophobia.

Background: Specific phobias impact over 400 million people worldwide. Digitalizing mental health could alleviate the burden. Still, although the corporate-driven Metaverse is expanding rapidly, there needs to be more momentum in harnessing virtual reality exposure therapy uptake. Objective: This study aims to conceptualize, develop, and deploy a free Virtual Reality Exposure Therapy (VRET) application specifically designed for treating acrophobia and claustrophobia. This pilot study, which holds the promise of a future where mental health is more accessible and effective, explores the feasibility of leveraging transdisciplinary collaboration among specialists to create a safe, accessible, and effective VRET solution. Methods: We conducted a Delphi heuristic approach involving bioethicists, neuroscientists, and tech developers. Second, we reviewed the existing psychological theories and therapeutic strategies for addressing phobias in VR. Third, we conceptualized a thematic analysis-derived framework for a safe, adaptive-gamified free exposure to virtual reality acrophobia and claustrophobia (SAFEvR ACT). Finally, we provide an overview of the iterative improvements made during 12 workshops and 76 weekly briefings on developmental implementations. Results: We developed the SAFEvR ACT into a proof-of-concept application freely deployed on the MentalVerse app platform. Our safety-focused approach can benefit from prevalidation perspectives within future randomized control trials. Conclusions: The resulting application derived from the SAFEvR ACT framework represents a blueprint to counter the current lack of iVR mental health uptake by offering a free VRET alternative. Future research should aim towards developing similar free platforms to lessen mental health burdens and gather quantitative data. We conclude with a call to action to researchers to fine-tune our current approach and take a stand for free digital mental health within MentalVeRse.app.

The oxidative stress hypothesis in Alzheimer's disease.

Oxidative stress may be involved in many somatic and psychiatric pathological states including dementia. The hypothesis of oxidative stress involvement in dementia is supported by much scientific data through biochemical, genetic and molecular studies. Thus, there are many reports of an increased level of the markers for oxidative damage, alterations in the specific activity of the antioxidant system, mutations in specific genes, mitochondrial disturbances and also several connections between oxidative stress and amyloid plaques. Despite these evidence and clinical approaches in using antioxidant therapy in dementia treatment, studies have failed to prove a clear benefit for antioxidant treatment in dementia. Hence, there is a need for further research regarding antioxidant therapy in very early stages of dementia.

Changing the Antipsychotic in Early Nonimprovers to Amisulpride or Olanzapine: Randomized, Double-Blind Trial in Patients With Schizophrenia.

BACKGROUND AND HYPOTHESIS: Meta-analyses have shown that the majority of patients with schizophrenia who have not improved after 2 weeks of treatment with an antipsychotic drug are unlikely to fully respond later. We hypothesized that switching to another antipsychotic with a different receptor binding profile is an effective strategy in such a situation. STUDY DESIGN: In total, 327 inpatients with an acute exacerbation of schizophrenia were randomized to double-blind treatment with either olanzapine (5-20 mg/day) or amisulpride (200-800 mg/day). Those patients who had not reached at least 25% Positive-and-Negative-Syndrome-Scale (PANSS) total score reduction from baseline after 2 weeks (the "non-improvers") were rerandomized double-blind to either staying on the same compound ("stayers") or to switching to the other antipsychotic ("switchers") for another 6 weeks. The primary outcome was the difference in the number of patients in symptomatic remission between the combined "switchers" and the "stayers" after 8 weeks of treatment, analyzed by logistic regression. STUDY RESULTS: A total of 142 nonimprovers were rerandomized at week two. 25 (45.5 %) of the 'stayers' compared to 41 (68.3 %) of the "switchers" reached remission at endpoint (p = .006). Differences in secondary efficacy outcomes were not significant, except for the PANSS negative subscore and the Clinical-Global-Impression-Scale. "Switchers" and "stayers" did not differ in safety outcomes. CONCLUSIONS: Switching "non-improvers" from amisulpride to olanzapine or vice-versa increased remission rates and was safe. The superiority in the primary outcome was, however, not paralleled by significant differences in most secondary efficacy outcomes and the effect was only apparent at the last visit making replications of longer duration necessary.

Cardiovascular risk factors as potential markers for mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Mild cognitive impairment (MCI) is an early stage of cognitive decline that has a significant risk of converting to dementia. Cardiovascular pathology appears to have a major impact in cognitive decline, and it is clear that early identification and correction of cardiovascular morbidity could have a major impact on cognitive functioning. SUBJECTS AND METHODS: Our study was conducted in order to identify some cardiovascular risk factors among patients with cognitive decline (MCI or Alzheimer disease-AD) and to find if there is any correlation with the degree of cognitive decline. We evaluated the body mass index, total cholesterol, hypertension, history of smoking, alcohol consumption and diabetes mellitus in patients with MCI and AD, compared with an age-matched control group. RESULTS: Regarding the body mass index, we observed a progressive decrease in patients with MCI and AD, in comparison with the control group. Similar aspects were also observed in the case of cholesterol levels, only that post hoc analysis revealed no significantly statistical differences between MCI and AD groups. The systolic blood pressure was increased in the patients with MCI and AD. Also, as in the case of cholesterol levels, post hoc analysis revealed no significantly statistical differences between MCI and AD groups. Pearson's correlation showed significant connections between the cardiovascular risk factors and the results of the cognitive evaluation. CONCLUSIONS: Our results constitute additional evidence that cardiovascular risk factors are involved in cognitive regression. This finding could have an important impact on the management of dementia.

Oxidative stress in schizophrenia - focusing on the main markers.

Oxidative stress is the condition arising from imbalance between toxic reactive oxygen species and antioxidant systems. It is believed that increased oxidative stress may be relevant to the pathophysiology of schizophrenia. In this way, the main markers of the lipid peroxidation processes include 4-hydroxynonenal and malondialdehyde. On the other side, the potential toxicity of free radicals is counteracted by a number of cytoprotective antioxidant enzymes that limit the damage, such as superoxide dismutase and glutathione peroxidase. However, the reports regarding the status of oxidative stress markers schizophrenia are very inconsistent, with various authors stating both increased and decreased activities of the main antioxidant enzymes, while others did not observe any significant modifications, as compared to control groups. Similar aspects were also reported in the case of the lipid peroxidation markers, although in here the contradictions are much more reduced than in the case of the antioxidant defences. It is generally believed that the equivocal results mentioned above may be due to different tissues studies, different species or the administrated treatment and the duration of the disease/treatment. In this context, in the present paper we were interested to review some studies regarding the oxidative stress status in patients and animal models of schizophrenia, by referring mainly to antioxidant enzymes and lipid peroxidation markers.

New Metabolic, Digestive, and Oxidative Stress-Related Manifestations Associated with Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) represents a pressing and generally invalidating syndrome that is triggered by a terrifying or stressful experience, relying on recurrently reliving the traumatic event feelings associated to it, which is subsequently linked to ongoing activations of stress-related neurobiological pathways and is often associated with neurodegeneration. In this paper, we examine what lies beneath this disorder, reviewing evidence that connects PTSD with a wide array of mechanisms and its intertwined pathways that can lead to the decompensation of different pathologies, such as cardiovascular disease, gastrointestinal ailments, autoimmune disorders, and endocrine diseases. Also, the significance of the oxidative stress in this frame of reference is debated. Thus, knowing and identifying the main features of the distressing experience, the circumstances around it, as well as the neuropsychological and emotional characteristics of people prone to develop PTSD after going through disturbing incidents can offer an opportunity to anticipate the development of potential destructive consequences in several psychological dimensions: cognitive, affective, relational, behavioral, and somatic. We can also observe more closely the intricate connections of the disorder to other pathologies and their underlying mechanisms such as inflammation, oxidative stress, bacterial overgrowth syndrome, irritable bowel syndrome, metabolic disorders, oxytocin, and cortisol in order to understand it better and to optimize the course of treatment and its management. The complex foundation PTSD possesses is supported by the existing clinical, preclinical, and experimental data encompassed in the current review. Different biological systems and processes such as the hypothalamic-pituitary-adrenal axis, sympathetic nervous system, oxidative stress, inflammation, and microbiome suffer modifications and changes when it comes to PTSD; that is why targeted therapies exert tremendous alleviations of symptoms in patients diagnosed with this disorder. Therefore, this implies that PTSD is not restricted to the psychiatric domain and should be viewed as a systemic condition.

Minireview on the Connections between the Neuropsychiatric and Dental Disorders: Current Perspectives and the Possible Relevance of Oxidative Stress and Other Factors.

Although the connections between neuropsychiatric and dental disorders attracted the attention of some research groups for more than 50 years now, there is a general opinion in the literature that it remains a clearly understudied and underrated topic, with many unknowns and a multitude of challenges for the specialists working in both these areas of research. In this way, considering the previous experience of our groups in these individual matters which are combined here, we are summarizing in this minireport the current status of knowledge on the connections between neuropsychiatric and dental manifestations, as well as some general ideas on how oxidative stress, pain, music therapy or even irritable bowel syndrome-related manifestations could be relevant in this current context and summarize some current approaches in this matter.

Effects of Roluperidone (MIN-101) on two dimensions of the negative symptoms factor score: Reduced emotional experience and reduced emotional expression.

BACKGROUND: Recent research has suggested that negative symptoms (NS) can be considered in terms of two different dimensions: reduced expression (expressive deficit) and reduced experience (experiential deficit). Roluperidone, a compound with high affinities for 5 HT2A and sigma2 receptors, has previously shown superiority over placebo on improving NS in a prospective study in patients with schizophrenia. The objective here is to explore the effect of roluperidone compared to placebo, on the 2 domains of the Negative Symptoms. METHODS: This was a multi-national Phase 2b trial that enrolled 244 symptomatically stable patients with schizophrenia who had baseline scores ≥20 on the NS subscale of the PANSS. Patients were randomized to daily monotherapy with roluperidone 32 mg, roluperidone 64 mg, or placebo in a 1:1:1 ratio. All enrolled patients were Caucasian, and 137 (56%) were male. The 3 treatment groups were balanced on all demographic and illness-related baseline characteristics. RESULTS: Both doses of roluperidone were superior to placebo on both domains: Reduced Experience (p ≤ .006 for the 32 mg; p ≤ .001 for the 64 mg) with persistent superiority from Week 2 for the 64 mg dose and Week 8 for the 32 mg dose; Reduced Expression (p ≤ .003 for 32 mg; p ≤ .001 for 64 mg) with similar persistence. IMPLICATIONS: Both doses of roluperidone previously improved PANSS negative symptoms in general and demonstrated tolerability in stable schizophrenia patients. The post hoc analysis reported here found the drug to work on both the reduced emotional experience and reduced emotional expression sub-scales empirically derived from the PANSS.

Inhibition of central angiotensin II enhances memory function and reduces oxidative stress status in rat hippocampus.

While it is now well established that the independent brain renin-angiotensin system (RAS) has some important central functions besides the vascular ones, the relevance of its main bioactive peptide angiotensin II (Ang II) on the memory processes, as well as on oxidative stress status is not completely understood. The purpose of the present work was to evaluate the effects of central Ang II administration, as well as the effects of Ang II inhibition with either AT1 and AT 2 receptor specific blockers (losartan and PD-123177, respectively) or an angiotensin-converting enzyme (ACE) inhibitor (captopril). These effects were studied on the short-term memory (assessed through Y-maze) or long-term memory (as determined in passive avoidance) and on the oxidative stress status of the hippocampus. Our results demonstrate memory deficits induced by the administration of Ang II, as showed by the significant decrease of the spontaneous alternation in Y-maze (p=0.015) and latency-time in passive avoidance task (p=0.001) when compared to saline. On the other side, the administration of all the aforementioned Ang II blockers significantly improved the spontaneous alternation in Y-maze task, while losartan also increased the latency time as compared to saline in step-through passive avoidance (p=0.042). Also, increased oxidative stress status was induced in the hippocampus by the administration of Ang II, as demonstrated by increased levels of lipid peroxidation markers (malondialdehyde-MDA concentration) (p<0.0001) and a decrease in both antioxidant enzymes determined: superoxide dismutase-SOD (p<0.0001) and glutathione peroxidase-GPX (p=0.01), as compared to saline. Additionally, the administration of captopril resulted in an increase of both antioxidant enzymes and decreased levels of lipid peroxidation (p=0.001), while PD-123177 significantly decreased MDA concentration (p>0.0001) vs. saline. Moreover, significant correlations were found between all of the memory related behavioral parameters and the main oxidative stress markers from the hippocampus, which is known for its implication in the processes of memory and also where RAS components are well expressed. This could be relevant for the complex interactions between Ang II, behavioral processes and neuronal oxidative stress, and could generate important therapeutic approaches.

The relevance of oxidative stress status in first episode and recurrent depression.

Oxidative and nitrosative stress (O&NS) could play an important role in the pathophysiology of major depression (MDD). The aim of the present work was to evaluate the specific activity of the main peripheral antioxidant defences (superoxide dismutase--SOD and glutathione peroxidase--GPX) and the level of malondialdehyde--MDA (a lipid peroxidation maker), in depressed patients, as compared to an age-matched control group. Also, we were interested to see if there are any differences between first episode vs. recurrent depression groups, in terms of oxidative stress markers. Additionally, we want it to investigate the effects of different antidepressant medication (mirtazapine, venlafaxine, tianeptine and escitalopram) on oxidative status of depressed patients. Our results showed an increased oxidative stress status in the serum of patients with MDD, expressed by a significant decrease of both SOD and GPX specific activities and a significant increase of the lipid peroxidation marker MDA, as compared to the control group. When we analyzed the oxidative stress status in depressed patients based on chronicity we observed significant decrease of SOD and GPX specific activities in recurrent depression group, as compared to the first episode group. Moreover, a very significant increase in MDA concentration was observed in recurrent depression patients, as compared to the first episode group. Our work provides additional evidences of increased oxidative stress in MDD, expressed by altered antioxidant enzyme activity and increased levels of lipid peroxidation. Also, it seems that sub-classifying depression into different subtypes, based on chronicity, can predict differences in the levels of some various oxidative stress markers.

Evaluation of antioxidant enzymes activities and lipid peroxidation in schizophrenic patients treated with typical and atypical antipsychotics.

Studies performed in schizophrenia patients have generally suggested the presence of a compromised antioxidant system, but this is not always consistent with specific observed parameters, which on the whole, show evidences of dysregulation. There are also controversies regarding the oxidative stress status in patients treated with typical vs. atypical antipsychotics. In this context, the aim of the present work was to evaluate the specific activity of some peripheral antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX) and the level of a lipid peroxidation maker (malondialdehyde-MDA), in schizophrenic patients treated with typical (haloperidol) or atypical (olanzapine, quetiapine and risperidone) antipsychotics, compared with age-matched healthy subjects. We found a significant decrease in GPX specific activity and also a significant increase of MDA levels in schizophrenic patients, compared to age-matched control group, regardless of their type of treatment. Additionally, an increase in SOD specific activity was observed, mainly in the patients treated with haloperidol and quetiapine. Further research is necessary in order to elucidate the effects of different antipsychotic agents on antioxidant enzymes and lipid peroxidation or possible interventions at the oxidative stress level in schizophrenic patients.

Changes of some oxidative stress markers in the serum of patients with mild cognitive impairment and Alzheimer's disease.

Mild cognitive impairment (MCI) is a nosological entity proposed as an intermediate state between normal aging and dementia. MCI seems to represent an early stage of Alzheimer's disease (AD) and there is a great interest in the relationship between MCI and the progression to AD. Some studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment. The aim of the present work was to evaluate the serum levels of some enzymatic antioxidant defences like superoxide dismutase (SOD) and glutathione peroxidase (GPX), as well as lipid peroxidation markers like MDA (malondialdehyde), in MCI and AD patients, compared with age-matched healthy controls. The subjects of this study (45 patients) consisted of 15 individuals with mild cognitive impairment (MCI), 15 with Alzheimer's disease (AD) and 15 healthy age-matched controls. Biochemical analyses showed a similar decrease of the main enzymatic antioxidant defences (SOD and GPX) and increased production of lipid peroxidation marker (MDA) in the serum of the MCI and AD patients, compared to age-matched control group. This study clearly demonstrates that oxidative stress damage occurs in patients with MCI and AD. Moreover, some enzymatic markers of oxidative stress are similar in MCI and AD patients, suggesting that oxidative damage could be one important aspect for the onset of AD.