Background: Major depressive disorder (MDD) is a complex psychiatric condition significantly impacted by environmental stress and inflammation. Previous research suggests that stress-induced alterations in the blood-brain barrier (BBB) may allow pro-inflammatory cytokines like interleukin-6 (IL-6) to enter the brain, contributing to depression. Tumor necrosis factor-alpha (TNF-α) is another prominent cytokine implicated in depression, but its role in the context of BBB integrity and stress-mediated depression remains unclear.

Objectives: This study aimed to investigate whether TNF-α plays a similar role as IL-6 in the development of depression through interactions with environmental stress and BBB integrity. Specifically, we examined the interaction between environmental stress, genetic variants of CLDN5 (the gene of the Claudin-5, a protein critical for BBB integrity), and TNF (the gene encoding the TNF-α protein) genetic variants on depressive symptoms.

Methods: We utilized data from the UK Biobank, comprising genetic, health, and lifestyle information from approximately 500,000 participants aged 40 to 69. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and a composite Current Depressive Symptoms (CDS) score based on self-reported questionnaire items. Environmental stress was quantified through participants’ reports of significant life events in the past two years. Genetic analysis focused on 15 single nucleotide polymorphisms (SNPs) within the TNF gene (after linkage disequilibrium pruning) and a functional polymorphism in CLDN5 (rs885985). Linear regression models were used to assess main effects, gene-gene interactions, gene-environment interactions, and three-way interactions on depressive symptoms, adjusting for covariates and applying Bonferroni correction for multiple testing.

Results: No significant associations were found between TNF genetic variants and depressive symptoms after correcting for multiple testing. While some TNF SNPs showed nominal significance in interaction models – most notably rs3093546, which showed nominal significance in both depressive phenotypes – the findings were not robust enough to confirm a significant role. Unlike previous findings with IL6, TNF did not exhibit significant interactions with environmental stress and CLDN5 variants affecting depression risk.

Conclusions: The study does not support a significant role for TNF genetic variants interacting with environmental stress and BBB integrity in influencing depression risk. These findings suggest that IL-6 and BBB integrity may be more critical targets for understanding and treating stress-related depression, highlighting the complexity of depression’s pathophysiology.

(Neuropsychopharmacol Hung 2024; 26(4): 197–203)

Keywords: major depression, TNF-alpha, IL-6, blood-brain-barrier, CLDN5, stress, genetic interaction, proinflammatory citoknes, depression symptoms

Background/Objective: Behavioural Parent Training (BPT) is an evidence-based psychosocial intervention for attention-deficit/hyperactivity disorder (ADHD) in children. The use of online technologies significantly increases the accessibility of these interventions. This study aimed to assess the relative efficacy of face-to-face and online training in the use of parenting strategies taught. We also explored the impact of parental ADHD symptom levels.

Method: A massive open online course (MOOC) version of a BPT program was designed and evaluated. A total of ninety parents of children diagnosed with ADHD were recruited. Randomisation was not employed; parents gave their preferences in choosing between face-to-face and online training formats. One month after the completion of the training and at a three-month follow-up, parents were queried regarding the implementation and frequency of use of the parenting strategies taught. The two groups were compared along these variables. The Adult ADHD Rating Scale (ASRS-A) was employed to screen parental ADHD symptoms, with the two groups (positively/negatively screened) subsequently compared in terms of their choice of training format and the use of the parenting strategies. The psychopathological symptoms of the child were evaluated using the Strengths and Difficulties Questionnaire (SDQ).

Results: Thirty parents elected to participate in the face- to-face training, while sixty parents registered for the online programme. The drop-out rate was high, data from 21 and 39 parents was included in the analysis from the two groups, respectively. The two groups did not differ in the ASRS-A screening outcome. The only difference was the implementation of the reward system, which was reported by more parents in the face-to-face group than in the online group. The only difference between the groups that screened positive and negative in the ASRS-A was found in the use of proactive parenting strategies. We found no significant differences between the two time points in the use of most parenting strategies.

Discussion: Our results suggest that the online format may be similarly effective in teaching parenting techniques as the face-to-face parenting training. The level of parental ADHD symptoms had little effect; the difficulties regarding proactive strategies may be due to deficits in executive functioning. Parent training delivered through telemedicine can significantly improve access and is cost-effective; therefore, we recommend its use in the treatment of ADHD in children. Nevertheless, this necessitates appropriate regulation and funding of telemedicine.

(Neuropsychopharmacol Hung 2024; 26(4): 204–217)

Keywords: attention-deficit/hyperactivity disorder, ADHD, psychosocial interventions, parent training, internet, telemedicine

Aims: Autism spectrum disorder and schizophrenia are traditionally viewed as distinct diagnostic categories. However, evidence increasingly suggests overlapping pathological functioning at various levels, starting from brain circuitry to behaviour. Notably, both disorders are characterized by anomalous minimal self-experience (altered body ownership and agency), which is a trait-like, phenomenological distortion. We propose a conceptual framework that unites multiple levels, from neural mechanisms to cognitive and phenomenological correlates, for understanding minimal self-disturbance across diagnostic boundaries.

Methods: A comprehensive review of existing literature was conducted, examining phenomenological, neurocognitive, and neural correlates of minimal self-disturbance in both schizophrenia and autism spectrum disorder. Assessment tools and scales such as the Examination of Anomalous Self-Experience Scale, as well as experimental neurocognitive paradigms like the Rubber-Hand Illusion and self-relevant stimuli tasks, were examined for their relevance in evaluating self-experience in both conditions.

Results: Minimal self-disturbances were found to be a prominent feature of both schizophrenia and autism, albeit with different manifestations. Patients with schizophrenia showed heightened susceptibility to body ownership alterations, while individuals with autism exhibited decreased susceptibility. Neural markers, particularly within the default mode network and thalamocortical connectivity, were implicated in self-disturbance in both disorders, suggesting a shared neurobiological basis.

Conclusion: The minimal self- disturbance appears to be a transdiagnostic feature of both schizophrenia and autism spectrum disorder, indicating that these conditions may represent points along a shared psychopathological continuum. The proposed model integrates neurobiological, cognitive, and phenomenological aspects of self-disturbance, offering a comprehensive framework for understanding and assessing disruptions in self-experience across these conditions. This approach promotes a shift away from rigid diagnostic classifications towards approaches that highlight the importance of atypical self-experience.

(Neuropsychopharmacol Hung 2024; 26(4): 218–226)

Keywords: minimal self, schizophrenia, autism spectrum disorder, neurophenomenology

The discovery of the functioning of intra- and extracellular ion compartments and cell membranes’ operation opened the possibility of extending Claude Bernard’s theory to intracellular ions. In contrast, by underestimating the role of ions, many misconceptions have prevailed. The author points out that maintaining the constancy of carbon dioxide is especially important. CO2 is one of the most decisive signalling molecules, a mediator connecting the body and the soul. It interacts with intracellular pH, Ca2+, H2PO4- and HPO42- ions, but the intracellular ion pattern, as a whole, also has a primary signalling function. Chronic stress changes the intracellular ion patterns, increasing or decreasing the pCO2 level, an increase in the HCO3-/Cl- ratio leads to Metabolic Syndrome. The HCO3-/Cl- ratio decrease due to chronic hypocapnia results in hyperarousal mental disorders, which seem reversible for decades. The organism starts to get exhausted around 50, and it is not excluded that respiratory alkalosis could turn into metabolic acidosis, making the kidneys reactor organs. (The hypothesis still needs to be verified.) The background of stress-caused age-related diseases is the threat of intracellular acidosis and the organism’s fighting against it. With chronic hypo- vs hypercapnia, the humoral counter-regulation cannot fulfil its function and can result in (e.g.) salt-sensitive vs salt-resistant hypertension, respectively. Preserving the original ion pattern is essential but impossible without euventilation. We could control ventilation and stress by administering H2PO4- and HPO42- ion salts. The life span correlates with the Body Cell Mass (BCM); we should preserve it as long as possible.

(Neuropsychopharmacol Hung 2024; 26(4): 227–242)

Keywords: age-related disorders, carbon dioxide signalling, chronic stress, ion pattern signalling, metabolic syndrome.

Objective: Benzodiazepines, particularly lorazepam, are good options for acute catatonia treatment. Published catatonia literature on benzodiazepine maintenance treatment and benzodiazepine tolerance is limited.

Methods: This is a chart review covering 30 years of clinical experience in the state of Kentucky, (United States of America), where there was no easy access to electroconvulsive therapy. Nine patients with prolonged catatonia requiring benzodiazepine maintenance treatment were selected for review.

Results: Three cases were switched from oral lorazepam to oral clonazepam, but relapses happened in 2 of them. Two patients lost their response to lorazepam and clonazepam. One with periodic catatonia needed ECT added to maintenance lorazepam. The other patient had 3 episodes of catatonia secondary to sudden clozapine withdrawal and required a restart of clozapine. Four patients were treated only with lorazepam. Two of them had relapses due to non-adherence or taper and needed indefinite lorazepam maintenance with no known relapses. One case initially responded to 1.5 mg/day of oral lorazepam but the dosage had to be increased to 18 mg/day to keep the response. Chronic tolerance requiring higher doses was present in 4 of the 9 patients and 2 of them were catatonic for many months.

Conclusions: Some patients may need to continue benzodiazepines indefinitely for maintenance treatment of catatonia following failed attempts at tapering. Sudden benzodiazepine discontinuation or non-adherence can lead to loss of benzodiazepine response or need for higher doses. A cross-taper from lorazepam to clonazepam can be accomplished, but is challenging and may result in relapse.

(Neuropsychopharmacol Hung 2024; 26(4): 243–260)

Keywords: benzodiazepines/therapeutic use; benzodiazepines/administration and dosage; catatonia; catatonia/drug therapy; clonazepam; lorazepam