Rethinking ketamine and esketamine action: Are they antidepressants with mood-stabilizing properties?

Ketamine and esketamine, the S-enantiomer of the racemic mixture, have recently generated considerable interest as potential therapeutic agents for Treatment-Resistant Depression (TRD), a complex disorder that includes various psychopathological dimensions and distinct clinical profiles (e.g., comorbid personality disorder, bipolar spectrum, dysthymic disorder). This perspective article provides a comprehensive overview of the action of ketamine/esketamine from a dimensional point of view, taking into account the high prevalence of bipolarity in TRD and the evidence of the efficacy of these substances on mixed features, anxiety, dysphoric mood, and, generally, bipolar traits. Additionally, the article underscores the complexity of the pharmacodynamic mechanisms of action of ketamine/esketamine, which goes beyond the non-competitive antagonism of NMDA-R. The need for further research and evidence is highlighted, mainly to evaluate the efficacy of esketamine nasal spray in bipolar depression, the presence of bipolar elements as a predictor of response, and the potential role of these substances as mood stabilizers. The article implies that, in the future, ketamine/esketamine could be used with fewer limitations, not only as antidepressants for the most severe form of depression but also as valuable tools to stabilize subjects with mixed symptoms or bipolar spectrum.

[Neurobiological correlates of EMDR therapy]. / Substrato neurobiologico della terapia con EMDR.

The EEGs in a group of ten subjects with major psychological trauma treated with EMDR and in ten controls have been registered both during the listening of the autobiographical narrative of the index trauma (script) and during a whole EMDR session. The EEGs have been performed again during the last EMDR session when patients were free of symptoms. During script listening a prevalent activation of the limbic regions corresponding to prefrontal and orbitofrontal cortex has been registered, being explained as the emotional arousal during trauma reliving at the symptomatic phase. The significant decrease of such activations during the late asymptomatic phase represents the neurobiological correlate of recovery. Moreover, the evidence of significant cortical activation in the parietal-temporo-occipital areas, during the last session, suggests a switch of the dominant electrical signal towards cortical areas with a prevalent cognitive function.

Stressful Life Events and Resilience During the COVID-19 Lockdown Measures in Italy: Association With Mental Health Outcomes and Age.

Background: The COVID-19 pandemic, due to its disproportionated higher morbidity and mortality rates in the older age, has been considered to be a "geropandemic." Several studies, however, have found that older age is associated with lower psychological distress in relation to the COVID-19 outbreak and related lockdown measures. Aim: To explore the role of Resilience as a mediator between stressful COVID-19 related life events and depressive and, anxiety symptoms and perceived stress, and to ascertain the role of age as a moderator of the mediator's effect. Methods: An on-line survey was spread through social networks during the first lockdown in Italy. Depressive and anxiety symptoms and perceived stress were measured using the Italian version of the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder Questionnaire-7 (GAD-7) and the Perceived Stress Scale (PSS). Resilience was measured using the Italian version of the Resilience Scale for Adults (RSA). Stressful COVID-19 related life events were explored using a checklist of events derived from the International Adjustment Disorder Questionnaire (IADQ). After a preliminary panel of linear regressions, mediation was tested using Structural Equation Modeling and inspecting the bootstrapped indirect effects. Afterwards, age was introduced as a mediator of the indirect effect in a moderated mediation analysis. Results: Twenty one thousand three hundred and thirty four subjects completed the questionnaire, 17,178 (80.52%) were female, 748 (3.5%) were >60 years old. In the whole sample, the presence of any stressful event was associated with depressive and anxiety symptoms and perceived stress. Resilience mediated the effects of stressful COVID-19-related events on depressive and anxiety symptoms and perceived stress. The moderated mediation analysis revealed that age moderated the mediation effect of Resilience between the presence of a stressful event and the selected outcomes. Conclusion: Taken together, our results show that age moderates the mediating effect of Resilience in the relationship between COVID-19-related stressful events and depressive and anxiety symptoms and perceived stress. Older adults' Resilience was less influenced by stressful events, and this could be one of the reasons accounting for the better mental health outcomes observed in the older age.

High Frequency of Undiagnosed Psychiatric Disorders in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD) are associated with comorbid depressive and anxiety disorders, but a significant proportion of IBD patients with psychiatric disorders (PsychD) remain undiagnosed and untreated. The aim of this study was to assess the frequency and type of undiagnosed PsychD in IBD patients. Two hundred and thirty-seven adult IBD (136 Crohn's disease (CD) and 101 ulcerative colitis (UC)) outpatients were consecutively recruited at a single university hospital centre between January 2018 and June 2019. After a scheduled follow-up visit for IBD clinical evaluation, participants underwent a semi-structured interview with a trained psychiatrist. One hundred and fourteen (48%) IBD patients had at least one PsychD, and in 67 (59%) of them, a diagnosis was made for the first time during the study. The remaining 47 (41%) patients had received a previous psychiatric diagnosis, but in only six cases was it consistent with the diagnosis made during the study. PsychD were equally distributed in CD (72/136, 53%) and UC (42/101, 42%), and mostly represented by mood disorders (54/114, 47%) and anxiety (27/114, 24%) disorders. PsychD were not related to the disease severity, phenotype or localisation of IBD, even though having three or more concomitant PsychD was associated with more severe disease in CD. Our data indicate that undiagnosed PsychD are common in IBD and highlight the importance of considering psychiatric evaluation in the management of IBD patients.

[Critical evaluation of current diagnostic classification systems in psychiatry: the case of DSM-5]. / Critiche e prospettive degli attuali sistemi di classificazione in psichiatria: il caso del DSM-5.

Since its first edition, the Diagnostic and Statistical manual of Mental disorders (DSM) has had a great impact on the scientific community and the public opinion as well. In 2013, the American Psychiatric Association released the fifth edition of the manual and - as for the previous versions - several criticisms raised. In particular, the persistence of the categorical approach to mental disorders represents one of the main debated topics, as well as the introduction of new diagnostic syndromes, which are not based on an adequate evidences. Moreover, the threshold of diagnostic criteria for many mental disorders has been lowered, with the consequence that the boundaries between "normality" and "pathology" is not so clear. In this paper, we will: 1) report the historical development of the DSM from the publication of its first edition; 2) describe the main changes introduced in the DSM-5; 3) discuss critical elements in the DSM-5. The current debate regarding the validity of diagnostic manuals and its criteria is threatening the psychiatric discipline, but a possible solution should be represented by the integration of diagnostic criteria with the in-depth description of patient's psychopathological experiences.

Predictors of poor adherence to treatment in inpatients with bipolar and psychotic spectrum disorders.

AIM: The aim of this study was to assess possible predictors of poor adherence in patients with a diagnosis of schizophrenia-spectrum disorders (SD) or bipolar disorder (BD) and to evaluate the roles of attachment style and caregivers as predictive factors of adherence. METHODS: The sample was composed of 178 voluntarily hospitalized inpatients: 89 diagnosed with BD (I, II), 89 with SD and other schizophrenia-spectrum disorders. All patients enrolled in the study were assessed for adherence, psychopathology, attachment style, presence of caregiver, subjective well-being during pharmacological treatment with neuroleptics, side effects following therapy, subjective attitude towards drugs, global functioning and quality of life. RESULTS: In patients with SD, non-adherence was associated with the absence of a caregiver, fewer years of treatment, poor insight and attitude towards drugs and fearful dimensions of attachment. In patients with BD, poor insight, anxious and social avoidant temperament traits, together with a high sense of self efficacy, were related to non-adherence. Diagnosis, type of medication and side effects were not predictive factors of adherence in either group. Interestingly, some temperament traits and dimensions of attachment predict non-adherence, indicating differences between patients with SD and BD. CONCLUSION: Considering these predictors of non-adherence and assessing adherence at the time of admission for relapse could be useful to plan an early and tailored "treatment adherence", along with other therapeutic strategies, for patients using these predictive factors. The role of caregiver proved particularly important in relation to the therapeutic alliance. Attachment style may play a key role in predicting adherence through the therapeutic alliance with both patients and caregivers.

Subcutaneous sumatriptan induces changes in frequency pattern in cluster headache patients.

OBJECTIVES: To document the relationship between the use of subcutaneous (SQ) sumatriptan (sum) and a change in frequency pattern of cluster headache (CH) in six patients. To discuss the clinical and pathophysiological implications of this observation in the context of available literature. BACKGROUND: Treatment with SQ sum may cause an increase in attack frequency of CH but data from literature are scant and controversial. METHODS: Six CH sum-naïve patients (three episodic and three chronic according to the International Headache Society (IHS) criteria) are described. RESULTS: All six patients had very fast relief from pain and accompanying symptoms from the drug but they developed an increase in attack frequency soon after using SQ sum. In all patients, the CH returned to its usual frequency within a few days after SQ sum was withdrawn or replaced with other drugs. Five patients were not taking any prophylactic treatment and SQ sum was the only drug prescribed to treat their headache. CONCLUSIONS: Physicians should recognize the possibility that treatment of CH with SQ sum may be associated with an increased frequency of headache attacks.