Associations between immune biomarkers and symptoms of anxiety, depression, and insomnia in paediatric inflammatory bowel disease: A preliminary longitudinal analysis.

Innate immunity may influence the onset of affective symptoms and alter sleep patterns in chronic inflammatory conditions. Here, we tested the prospective associations between baseline serum C-reactive protein (CRP), albumin, and CRP/albumin ratio (CAR, i.e., an emerging biomarker of disease activity), and self-reported symptoms of anxiety, depression, and insomnia at 1-year follow up in paediatric inflammatory bowel disease (n = 17). After controlling for baseline values, CAR (ρ = 0.591, p = 0.026) predicted anxiety symptoms, while albumin predicted both anxiety (ρ = -0.687, p = 0.007) and insomnia symptoms (ρ = -0.648, p = 0.012). Current findings preliminarily suggest that inflammation may influence anxiety and sleep disturbance in paediatric IBD.

Psychological Distress Affects Performance during Exercise-Based Cardiac Rehabilitation.

BACKGROUND: It is known that psychosocial distress affects the morbidity and mortality of patients with cardiovascular disease of every age. The aim of this study was to produce novel information on how psychological distress can influence cardiovascular performance in patients after cardiac surgery undergoing multidisciplinary cardiac rehabilitation. METHODS: Patients (n = 57) admitted after cardiac surgery for valvular or coronary disease underwent, within 5 days of admission, the Symptom Checklist-90-Revised (SCL-90-R) self-report questionnaire to measure psychiatric symptoms and the 12-item General Health Questionnaire (GHQ-12) to assess the level of psychological distress. The Positive Symptom Distress Index (PSDI) was measured to indicate the amplitude of symptom distress. Cardiovascular performance was assessed by a 6 min walking test (6MWT) at admission and discharge, and oxygen consumption (VO2 max) was derived. RESULTS: Within the SCL-90-R score, somatic symptoms (47.4%), depressive and anxiety symptoms (36.8% and 33.3%, respectively), symptoms of phobic anxiety (21.1%), and psychoticism (24.6%) were over-represented. As for the GHQ-12, 75.4% of the sample reported an abnormally negative perception of their health status. An inverse correlation was shown between the variation in 6MWT and SCL depression (p = 0.048), PSDI (p = 0.022), and the GHQ-12 (p = 0.040). Similarly, an inverse correlation was shown between the variation in the VO2 max, GHQ-12 (p = 0.041), and the PSDI (p = 0.023). CONCLUSIONS: Post-cardiac surgery cardiac rehabilitation was associated with increased symptoms of psychological discomfort, as compared with the general population. The amplitude of psychological distress, depression, and hostility are associated with limited improvement in performance. These data strengthen the need for psychological support during cardiac rehabilitation programs.

The impact of COVID-19 on menstrual cycle's alterations, in relation to depression and sleep disturbances: a prospective observational study in a population of medical students.

BACKGROUND: The sars-Cov-2 pandemic has determined psychological stress, particularly in the young population of medical students. We studied the impact of the pandemic on menstrual cycle alteration in relation to psychological stress, presence of depression, sleep disturbances and post-traumatic stress, on a population of medical students. METHODS: 293 female students at the Faculty of Medicine and Psychology of the Sapienza University of Rome (23.08 years old ± 3.8) were enrolled. In March 2021, one year after quarantine, a personal data sheet on menstrual cycle, examining the quality of the menstrual cycle during the pandemic, compared to the previous period. Concomitantly, the Beck Depression Inventory and the Impact of Event Scale have been administered. A Pearson chi-square test was assessed to evaluate the difference between the characteristics of the menstrual cycle and the scores obtained with the questionnaires. RESULTS: A statistically significant association between menstrual alterations and stress during pandemic had been found. The onset of depressive symptoms and sleep disturbances was observed in 57.1% and in 58.1% of young women with cycle's alterations, respectively. Amenorrhea was three times more common in female students with depressive symptoms, premenstrual syndrome had a significant correlation with both depression and sleep disturbances. The pandemic has been related to menstrual alterations, with depressive symptoms and sleep disorders. Amenorrhea is connected to depression, as observed on the functional hypothalamic amenorrhea. CONCLUSIONS: The pandemic affected the menstrual cycle as well as the depressive symptoms and sleep. Practical implications of the study lead to the development of strategies for psychological intervention during the pandemic experience, in order to help medical trainees, with specific attention to women's needs. Future studies should analyze the impact of other types of social stress events, on sleep, depression and the menstrual cycle beside the pandemic.

The Newborn's Reaction to Light as the Determinant of the Brain's Activation at Human Birth.

Developmental neuroscience research has not yet fully unveiled the dynamics involved in human birth. The trigger of the first breath, often assumed to be the marker of human life, has not been characterized nor has the process entailing brain modification and activation at birth been clarified yet. To date, few researchers only have investigated the impact of the extrauterine environment, with its strong stimuli, on birth. This 'hypothesis and theory' article assumes the role of a specific stimulus activating the central nervous system (CNS) at human birth. This stimulus must have specific features though, such as novelty, efficacy, ubiquity, and immediacy. We propose light as a robust candidate for the CNS activation via the retina. Available data on fetal and neonatal neurodevelopment, in particular with reference to retinal light-responsive pathways, will be examined together with the GABA functional switch, and the subplate disappearance, which, at an experimental level, differentiate the neonatal brain from the fetal brain. In this study, we assume how a very rapid activation of retinal photoreceptors at birth initiates a sudden brain shift from the prenatal pattern of functions to the neonatal setup. Our assumption implies the presence of a photoreceptor capable of capturing and transducing light/photon stimulus, transforming it into an effective signal for the activation of new brain functions at birth. Opsin photoreception or, more specifically, melanopsin-dependent photoreception, which is provided by intrinsically photosensitive retinal ganglion cells (ipRGCs), is considered as a valid candidate. Although what is assumed herein cannot be verified in humans based on knowledge available so far, proposing an important and novel function can trigger a broad range of diversified research in different domains, from neurophysiology to neurology and psychiatry.

Psychological disorders, adverse childhood experiences and parental psychiatric disorders in children affected by headache: A systematic review.

BACKGROUND: Pediatric headaches have been linked to adverse life events or psychological factors in children and their families, with a complex and bidirectional association. Moreover, it is well-known that psychological stress can trigger headaches. METHODS: We searched three databases for studies focusing on headaches and adverse events or psychological factors in children up to 12 years old or in their caregivers. RESULTS: We included 28 studies. Child psychological factors, including internal and external symptoms, were commonly associated with all types of headaches. Sleep disturbances showed a positive association with headaches in 3 out of 5 studies. Family conflict and unhappiness were frequently found in children suffering with headaches, while single-parent families and divorce were not associated. Stressful environments and adverse life events, particularly bullying, were also found to be linked with headaches. CONCLUSIONS: Childhood headaches represent an alarm bell for clinicians to investigate and treat psychological or psychiatric disorders in children and their family. Further studies are needed to elucidate the role of early-life adverse events in children and their families.

Something must happen before first breath.

BACKGROUND: Definition and concept of the 'beginning of human life' are weakened by co-existing contrasting hypotheses based on humanistic or religious beliefs rather than scientific foundations. This plethora of conceptually distant views have important common concerns in different fields of science and shape, in turn, several societal aspects including laws related, for instance, to inheritance eligibility or abortion, end-of-life care and euthanasia, and reproductive technology. Also, they are fundamental to evaluate opportunity for resuscitation vs. palliative care in extremely preterm infants. In this article, we address one of the most common tenets in medicine: the acceptance that human life starts with first breath, even though several events are well-documented to take place before its occurrence. MAIN TEXT: Several studies show how pivotal physiological events take place before first breath. Evidence of a number of neurological events occurring before first breath opens the way to the primacy of the Central Nervous System, given its immediate extra-uterine activation at birth. This activation eventually sets specific physiological conditions that allow the complex sequence of events determining the muscle activity associated with the influx of air in the lung and the settling of a continuous and successful extra-uterine respiration. We would like to invite the scientific community to endorse a clear-cut position against the paradigm of 'first breath' as the beginning of life. Herein, we also assume how, a still undefined, yet possibly specific quid in the external environment triggers further physiological response in newborns. Better understanding of the critical events that occur at the beginning of human life is likely to cause great concern and expectations in scientists, researchers and physicians working in the domain of brain, and its physiology, and mental health. CONCLUSIONS: The comparison between beliefs and evidence-based observations generates confusion, misperceptions and false expectations in society, hence, in the scientific and medical community. Different and more solid alternatives about the carachterization of the 'beginning of human life' are indeed available and require to be explored and defined.

Treatment-Resistant to Antipsychotics: A Resistance to Everything? Psychotherapy in Treatment-Resistant Schizophrenia and Nonaffective Psychosis: A 25-Year Systematic Review and Exploratory Meta-Analysis.

Background: Roughly 30% of schizophrenia patients fail to respond to at least two antipsychotic trials. Psychosis has been traditionally considered to be poorly sensitive to psychotherapy. Nevertheless, there is increasing evidence that psychological interventions could be considered in treatment-resistant psychosis (TRP). Despite the relevance of the issue and the emerging neurobiological underpinnings, no systematic reviews have been published. Here, we show a systematic review of psychotherapy interventions in TRP patients of the last 25 years. Methods: The MEDLINE/PubMed, ISI WEB of Knowledge, and Scopus databases were inquired from January 1, 1993, to August 1, 2018, for reports documenting augmentation or substitution with psychotherapy for treatment-resistant schizophrenia (TRS) and TRP patients. Quantitative data fetched by Randomized Controlled Trials (RCTs) were pooled for explorative meta-analysis. Results: Forty-two articles have been found. Cognitive behavioral therapy (CBT) was the most frequently recommended psychotherapy intervention for TRS (studies, n = 32, 76.2%), showing efficacy for general psychopathology and positive symptoms as documented by most of the studies, but with uncertain efficacy on negative symptoms. Other interventions showed similar results. The usefulness of group therapy was supported by the obtained evidence. Few studies focused on negative symptoms. Promising results were also reported for resistant early psychosis. Limitations: Measurement and publication bias due to the intrinsic limitations of the appraised original studies. Conclusions: CBT, psychosocial intervention, supportive counseling, psychodynamic psychotherapy, and other psychological interventions can be recommended for clinical practice. More studies are needed, especially for non-CBT interventions and for all psychotherapies on negative symptoms.

Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life.

Ketamine-related expression of glutamatergic postsynaptic density genes: possible implications in psychosis.

Systemic administration of ketamine, a non-competitive antagonist of the N-methyl-d-aspartate receptor (NMDA-R), produces a condition of NMDA-R hypofunction, which is considered one of the putative molecular mechanisms involved in psychosis. In this study, we evaluated the effect of ketamine on glutamatergic markers of the postsynaptic density (PSD), a pivotal site for dopamine-glutamate interaction. We assessed gene expression of Homer1a, alpha and betaCaMKII, and dopamine transporter (DAT) by two different doses of ketamine. These genes were chosen because of their impact on signal transduction and dopamine-glutamate interplay in postsynaptic density. Moreover, Homer1a is modulated by antipsychotics and represents a candidate gene for schizophrenia. Male Sprague-Dawley rats were injected with saline, 12mg/kg ketamine or 50mg/kg ketamine, and sacrificed 90 minutes after injections. In situ hybridization histochemistry was used to quantitate the rate of gene expression in rat forebrain. Homer1a was induced by 50mg/kg ketamine in ventral striatum and by both 50 and 12mg/kg ketamine in nucleus accumbens, whereas gene expression was not affected in dorsal striatum. alphaCaMKII was increased by 12mg/kg ketamine against saline in almost all subregions assessed. betaCaMKII was not affected by ketamine. DAT was increased by both doses of ketamine in the ventro-tegmental area and substantia nigra pars compacta. We suggest that these changes may represent molecular adaptations to the perturbation in glutamatergic transmission induced by ketamine blockade of NMDA receptors and may be implicated in molecular alterations occurring in schizophrenia.

Worldwide access to evidence-based mental health literature: how useful is PubMed in Anglo-Saxon and non-Anglo-Saxon countries?

The aim of this study was to verify the presence of cultural variety among the psychiatric journals available on PubMed, the major online tool for accessing literature. Data for analysis were taken from a survey of the world psychiatric journals indexed in Index Medicus 1999 (IM), the alphabetical list used by PubMed, and from the mean impact factor (IF) values of the journals. Approximately 80% of international psychiatric literature available on PubMed is published in Anglo-Saxon countries, especially in the USA (59.8% of the total). The widespread use of the English language (94.9% of all the journals) further stresses the dominance of the Anglo-Saxon cultural model, as do the mean IF values of Anglo-Saxon journals compared to non-Anglo-Saxon publications (3.252 vs. 1.693; P=0.0079). The under-representation of non-Anglo-Saxon cultural models on PubMed plays a negative role for bringing about a truly multicultural literature in psychiatry.

Homer 1a gene expression modulation by antipsychotic drugs: involvement of the glutamate metabotropic system and effects of D-cycloserine.

N-methyl-D-aspartate receptor hypofunction has been suggested to play a role in the pathophysiology of schizophrenia. New glutamatergic mechanisms involving metabotropic receptors have been recently proposed to further expand this hypothesis. "Homer" is a family of postsynaptic density proteins functionally and physically attached to glutamate metabotropic receptors. We investigated the activation of the early gene form of Homer after acute treatment with typical or atypical antipsychotic drugs alone or with the adjunction of D-cycloserine. This activation was compared with that of c-fos, considered a putative molecular marker of brain regions activated by antipsychotics. Male Sprague-Dawley rats were treated intraperitoneally with haloperidol (0.8 mg/Kg) or clozapine (15 mg/Kg) alone or with the adjunction of D-cycloserine (20 mg/Kg). Rats were sacrificed ninety minutes after injection and the brains were processed for quantitative in situ hybridization histochemistry. Haloperidol induced a statistically significant increase of Homer both in caudate-putamen and nucleus accumbens compared with controls; clozapine induced Homer significantly only in the accumbens. The adjunction of D-cycloserine attenuated the haloperidol-induced increase of Homer expression in caudate-putamen and nucleus accumbens and attenuated the clozapine-induced increase in the accumbens. The c-fos gene expression was potently induced by haloperidol in caudate-putamen and nucleus accumbens, and by clozapine only in the accumbens. The adjunction of D-cycloserine enhanced c-fos expression only for clozapine in both regions of the forebrain. These results demonstrate a differential involvement of glutamatergic metabotropic system in gene expression modulation induced by typical or atypical antipsychotic drugs and may suggest new molecular basis for the augmentation strategy by a glycine site partial agonist.