Physical and cognitive correlates, inflammatory levels, and treatment response in post-COVID-19 first-onset vs. recurrent depressive episodes.

Psychiatric symptoms have been frequently reported in patients affected by COVID-19, both as new occurring and recurrences of pre-existing diseases. Depressive symptoms are estimated to affect at least 30% of patients following infection, with specific physical and cognitive features and relevant immune-inflammatory alterations. This study aimed to retrospectively characterize post-COVID-19 first-onset and recurrent major depressive episodes (MDE) and to evaluate the effects of antidepressants on physical and cognitive correlates of depression, in addition to mood, anxiety, and underlying inflammatory status. We evaluated 116 patients (44.8% males, 51.1 ± 17 years) with post-COVID-19 first-onset (38.8%) and recurrent (61.2%) MDE at baseline and after one- and three-month treatment with antidepressants (31% SSRIs, 25.9% SNRIs, 43.1% others). We assessed sociodemographic and clinical features and psychopathological dimensions through: Hamilton Depression and Anxiety Rating Scales; Short Form-36 Health Survey Questionnaire; Perceived Deficits Questionnaire-Depression 5-items. The systemic immune-inflammatory index was calculated to measure inflammation levels. Alongside the reduction of depression and anxiety (p < 0.001), physical and cognitive symptoms improved (p < 0.001) and inflammatory levels decreased (p < 0.001) throughout treatment in both groups. Post-COVID-19 recurrent MDE showed a significantly more severe course of physical and cognitive symptoms and persistently higher levels of inflammation than first-onset episodes. Antidepressants proved to be effective in both post-COVID-19 first-onset and recurrent MDE. However, a sustained inflammatory status might blunt treatment response in patients with recurrent depression in terms of physical correlates and cognition. Therefore, personalized approaches, possibly involving combinations with anti-inflammatory compounds, could promote better outcomes in this clinical population.

Effect of Anti-Interleukin-6 Agents on Psychopathology in a Sample of Patients with Post-COVID-19 Syndrome: An Observational Study.

Interleukin 6 (IL-6) receptor inhibitors tocilizumab and sarilumab have recently been approved for severe coronavirus disease 2019 (COVID-19). They also affect mood, even though their effect on the post-COVID-19 syndrome-related psychopathology still has to be investigated. The aim of this study was to investigate their effect on psychopathology in a sample of patients with post-COVID-19 syndrome. We included 246 patients (34% female, 66% male) aged 18-75 years who had been hospitalized for COVID. Patients were split into those who received anti-IL-6 receptor agents (Anti-IL-6-R, N = 88) and those who did not (Ctrl, N = 158). The former group was further split into those receiving tocilizumab (TOC, N = 67) and those receiving sarilumab (SAR, N = 21). Groups were compared based on clinical characteristics before and during COVID-19 as well as on physical and psychiatric symptoms after COVID-19. Ctrl had less psychiatric and physical symptoms during hospitalization and more post-COVID-19 diarrhea, headache, cough, and dyspnea upon exertion than those receiving IL-6-receptor inhibitors. Ctrl also showed greater difficulties in emotion regulation. These differences were driven by TOC vs. Ctrl, whereas differences between SAR and Ctrl or TOC did not reach significance. IL-6 receptor inhibitors are related to a lower post-COVID-19 illness burden and seem to be effective in emotion regulation. Further research is needed to confirm these findings.

Is Antipsychotic Drug Use During Pregnancy Associated with Increased Malformation Rates and Worsening of Maternal and Infant Outcomes? A Systematic Review.

There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR "birth defect*" OR "congenital abnormality" OR "congenital abnormalities" OR "brain changes" OR "behavioral abnormalities" OR "behavioral abnormalities") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics, especially the second-generation antipsychotics, were devoid of teratogenic potential, while few studies were inconclusive and recommended replication. Most authoritative articles were from the Boston area, where large databases were implemented to study the malformation potential of psychiatric drugs. Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics are no more related to malformations than the disorders themselves; most studies recommend that there are no reasons to discontinue antipsychotic medications in pregnancy.

Association of Delirium and Depression with Respiratory and Outcome Measures in COVID-19 Inpatients.

Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, we enrolled 100 inpatients from COVID-19 units of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Participants were divided into those with DEL, DEP, or absence of either delirium or depression (CONT). Delirium severity was assessed with the Neelson and Champagne Confusion Scale (NEECHAM). Psychopathology was assessed with the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), and the Brief Psychiatric Rating Scale (BPRS). Dependent variables include: (a) respiratory parameters, i.e., partial pressure of oxygen in arterial blood (PaO2), oxygen saturation (SpO2), ratio between arterial partial pressure of oxygen (PaO2), and fraction of inspired oxygen (PaO2/FiO2); (b) outcome parameters, i.e., duration of hospitalization and number of pharmacological treatments used during the hospitalization. We investigated between-group differences and the relationships between severity of delirium/depression and the dependent variables. Duration of hospitalization was longer for DEL than for either DEP or CONT and for DEP compared to CONT. NEECHAM and HAM-D scores predicted lower PaO2 and PaO2/FiO2 levels in the DEL and DEP groups, respectively. In DEP, BPRS scores positively correlated with duration of hospitalization. Delirium impacted the course of COVID-19 more severely than depression. The mechanisms by which delirium and depression worsen respiratory parameters differ.

Are the Post-COVID-19 Posttraumatic Stress Disorder (PTSD) Symptoms Justified by the Effects of COVID-19 on Brain Structure? A Systematic Review.

COVID-19 affects brain function, as deduced by the "brain fog" that is often encountered in COVID-19 patients and some cognitive impairment that is observed in many a patient in the post-COVID-19 period. Approximately one-third of patients, even when they have recovered from the acute somatic disease, continue to show posttraumatic stress disorder (PTSD) symptoms. We hypothesized that the persistent changes induced by COVID-19 on brain structure would overlap with those associated with PTSD. We performed a thorough PubMed search on 25 April 2023 using the following strategy: ((posttraumatic OR PTSD) AND COVID-19 AND (neuroimaging OR voxel OR VBM OR freesurfer OR structural OR ROI OR whole-brain OR hippocamp* OR amygd* OR "deep gray matter" OR "cortical thickness" OR caudate OR striatum OR accumbens OR putamen OR "regions of interest" OR subcortical)) OR (COVID-19 AND brain AND (voxel[ti] OR VBM[ti] OR magnetic[ti] OR resonance[ti] OR imaging[ti] OR neuroimaging[ti] OR neuroimage[ti] OR positron[ti] OR photon*[ti] OR PET[ti] OR SPET[ti] OR SPECT[ti] OR spectroscop*[ti] OR MRS[ti])), which produced 486 records and two additional records from other sources, of which 36 were found to be eligible. Alterations were identified and described and plotted against the ordinary PTSD imaging findings. Common elements were hypometabolism in the insula and caudate nucleus, reduced hippocampal volumes, and subarachnoid hemorrhages, while white matter hyperintensities were widespread in both PTSD and post-COVID-19 brain infection. The comparison partly supported our initial hypothesis. These data may contribute to further investigation of the effects of long COVID on brain structure and function.

The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies.

There is increasing interest in the involvement of antioxidative systems in protecting from depression. Among these, Nrf2 occupies a central place. We aimed to review the role of Nrf2 in depression. For this reason, we conducted a PubMed search using as search strategy (psychiatr*[ti] OR schizo*[ti] OR psychot*[ti] OR psychos*[ti] OR depress*[ti] OR MDD[ti] OR BD[ti] OR bipolar[ti] OR Anxiety[ti] OR antidepress*[ti] OR panic[ti] OR obsess*[ti] OR compulsio*[ti] OR "mood disord*"[ti] OR phobi*[ti] OR agoraphob*[ti] OR anorex*[ti] OR anorect*[ti] OR bulimi*[ti] OR "eating disorder*"[ti] OR neurodevelopm*[ti] OR retardation[ti] OR autism[ti] OR autistic[ti] OR ASM[ti] OR adhd[ti] OR "attention-deficit"[ti]) AND nrf2, which on the 9th of March produced 208 results of which 89 were eligible for our purposes. Eligible articles were studies reporting data of Nrf2 manipulations or content by any treatment in human patients or animals with any animal model of depression. Most studies were on mice only (N = 58), 20 on rats only, and three on both rats and mice. There were two studies on cell lines (in vitro) and one each on nematodes and fish. Only four studies were conducted in humans, one of which was post mortem. Most studies were conducted on male animals; however, human studies were carried out on both men and women. The results indicate that Nrf2 is lower in depression and that antidepressant methods (drugs or other methods) increase it. Antioxidant systems and plasticity-promoting molecules, such as those in the Nrf2-HO-1, BDNF-TrkB, and cyclic AMP-CREB pathways, could protect from depression, while glycogen synthase kinase-3ß and nuclear factor κB oppose these actions, thus increasing depressive-like behaviours. Since Nrf2 is also endowed with tumorigenic and atherogenic potential, the balance between benefits and harms must be taken into account in designing novel drugs aiming at increasing the intracellular content of Nrf2.