Havaki-Kontaxaki BJ, Ferentinos PP, Kontaxakis VP, Kontaxaki M-I V, Geronikola X, Armeniakos I, Papadimitriou GN. Low-dose clozapine monotherapy for recurring episodes of depression, hypersomnia and behavioural disturbances: a case report.

Case Report: We present a 27-year-old woman who manifested recurrent episodes of hypersomnia, compulsive hyperphagia, hypersexuality, impulsive behaviours, irritability and depressive mood since the age of 13 after a viral febrile infection. She had 3–4 episodes/year lasting from a few days to 2–3 weeks which were managed with various psychotropics. During her last episode, she was admitted because of persistent behavioural disturbances. Brain 99m-Tc-ethyl cysteinate dimer single-photon emission computed tomography scans showed bilateral mesiotemporal and thalamic hypoperfusion, more significant in the right hemisphere. While hospitalised, she developed neuroleptic malignant syndrome following haloperidol administration. She was discharged on clozapine 100 mg/day. Over the following 30 months, she remained symptom free on clozapine 50–100 mg/day.

Discussion: Differential diagnosis included either an atypical recurrent mood disorder with hypersomnia and behavioural disturbances or Kleine–Levin syndrome.

Conclusion: Low-dose clozapine monotherapy may worth being further investigated for the management of recurring episodes of depression, hypersomnia and behavioural disturbances.

Coronavirus disease, one of the most disastrous epidemics, has caused a worldwide crisis, and the containment measures applied to decelerate the progression of the pandemic can increase the risk of obsessive-compulsive disorder (OCD). Identifying vulnerable groups in this area can lead us to better resource expenditure, and therefore, this systematic review aims to make a comparison between males and females to determine which of the two groups was most affected by the COVID-19 pandemic regarding OCD. Also, a meta-analysis was designed to investigate the prevalence of OCD during the COVID-19 pandemic. A comprehensive search was conducted among three databases (Medline, Scopus, Web of Science) until August 2021 which resulted in 197 articles, and 24 articles met our inclusion criteria. Overall, more than half of the articles stated the role of gender in OCD during the COVID-19 pandemic. Several articles emphasized the role of the female gender, and some others the role of the male gender. The meta-analysis revealed a 41.2% overall prevalence of OCD during the COVID pandemic and 47.1% and 39.1% OCD prevalence for female and male genders respectively. However, the difference between the two genders was not statistically significant. Generally, it seems that females are at greater risk of OCD during the COVID-19 pandemic. In the following groups, the female gender may have acted as a risk factor: under-18 years students, hospital staff, and the studies in the Middle East. In none of the categories, male gender was clearly identified as a risk factor.

Though commonly used to model affective disorders, zebrafish display notable differences in terms of the structure and function of the brain serotonin system, including responses to pharmacological interventions, as compared to mammals. For example, elevation of brain serotonin following acute administration of serotonin reuptake inhibitors (SRIs) generally has anxiogenic effects, both in the clinical situation and in rodent models of anxiety, but previous research has indicated the opposite in zebrafish. However, several issues remain unresolved. We conducted a systematic review of SRI effects in zebrafish models of anxiety and, on the basis of these results, performed a series of experiments further investigating the influence of serotonin-releasing agents on anxiety-like behaviour in zebrafish, with sex-segregated wild-type animals being administered either escitalopram, or the serotonin releaser fenfluramine, in the light-dark test. In the systematic review, we find that the available literature indicates an anxiolytic-like effect of SRIs in the novel-tank diving test. Regarding the light-dark test, most studies reported no behavioural effects of SRIs, although the few that did generally saw anxiolytic-like responses. In the experimental studies, consistent anxiolytic-like effects were observed with neither sex nor habituation influencing treatment response. We find that the general effect of acute SRI administration in zebrafish indeed appears to be anxiolytic-like, indicating, at least partly, differences in the functioning of the serotonin system as compared to mammals and that caution is advised when using zebrafish to model affective disorders.

Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N6 (m6A) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that m6A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt’s test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered ex vivo catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m6A methylation has potential for neuropsychiatric drug development.

The analysis of motivational systems underlying temporal organisation in animal behaviour has relied primarily on two conceptual functional frameworks: Homeostasis and biological clocks. Homeostasis is one of the most general and influential concepts in physiology. Walter Cannon introduced homeostasis as a universal regulatory principle which animals employ to maintain constancy of their ‘internal milieu’ in the face of challenges and perturbations from the external environment. Cannon spoke of “The Wisdom of the Body”, the collective of responses designed to defend the ideal internal state against those perturbations.

It is now generally agreed that healthy individuals are characterized by cognitive decline during the later decades of adult life. The acquisition of new information becomes less efficient, which, coupled with a diminished retention of this information for later use, results in substantially poorer memory performance. The ability to plan new activities, solve problems and make complex decisions, as well as cognitive flexibility is noticeably diminished. In addition, attentional processes appear to be invariably poorer in old subjects than in young subjects (for review). While it is quite clearly established that elderly subjects (i.e. after 65 years of age) show a deterioration of cognitive functioning, there is also evidence that this deterioration may start in middle age (40 years). There is large individual variance in age groups; for instance, some old individuals perform on many neurocognitive tests as well as young individuals do. Rowe and Kahn proposed in their influential article to discern between successful aging and usual aging. Successful aging would be due to the effect of chronological age, whereas additional factors would be responsible for usual aging. An important point is the nature of the borderland between usual cognitive aging and pathological conditions such as dementia. Various health-related factors are thought to be important in this respect. They may be a determinant for the transition between successful aging to normal aging and into the borderland with dementia. The Brain & Behavior Research Institute in Maastricht investigates the determinants of successful and pathological aging in a number of related and multidisciplinary projects. This paper describes some major findings of this research programme and gives a theory on the interaction of vulnerability factors and protective factors in their effect on cognitive aging.

Verhoeven WMA, Bon BV, Egger JIM, Hoischen A, Doelman JC. An adult female patient with ring chromosome 21: behavioural phenotype and results of high-resolution molecular characterisation.