This pain drives me crazy: Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic, abdominal, and/or pelvic pain. Although the term cystitis suggests an inflammatory or infectious origin, no definite cause has been identified. It occurs in both sexes, but women are twice as much affected. AIM: To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS. METHODS: Hypothesizing that particular psychological characteristics could underpin IC/BPS, we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy: ("interstitial cystitis" OR "bladder pain syndrome") AND ("mood disorder" OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk). RESULTS: On September 27, 2023, the PubMed search produced 223 articles, CINAHL 62, and the combined PsycLIT/ PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36. Search on ClinicalTrials.gov produced 14 studies, of which none had available data. Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS, i.e. 63 articles spanning from 2000 to October 2023. These studies identified depression and anxiety problems in the IC/BPS population, along with sleep problems and the tendency to catastrophizing. CONCLUSION: Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS. Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

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.

Type of cycle, temperament and childhood trauma are associated with lithium response in patients with bipolar disorders.

BACKGROUND: Lithium stands as the gold standard in treating bipolar disorders (BD). Despite numerous clinical factors being associated with a favorable response to lithium, comprehensive studies examining the collective influence of clinical variables alongside psychopathological dimensions are lacking. Our study aims to enhance comprehension of lithium response in individuals with BD by integrating clinical variables with psychopathological traits and early adverse events. METHODS: We assessed 201 patients with BD for clinical characteristics, childhood trauma, temperament traits, impulsivity, and aggression. Lithium response was evaluated using the gold standard Alda scale, and predictors of lithium response were estimated through a multivariate model. RESULTS: On the total sample, 61 (30.3%) patients were lithium responders according to the Alda scale. Comparatively, lithium responders, in contrast to non-responders, demonstrated a higher prevalence of the mania-depression-interval (MDI) cycle, a more frequent diagnosis of BD type I, and reported an earlier age of onset. They also exhibited less lifetime substance abuse, emotional, physical, and sexual abuse, while scoring higher on hyperthymic and irritable temperament scales. In multivariate analyses, only the MDI cycle (OR,3.47; 95%CI,1.61-7.50) hyperthymic (OR,1.20; 95%CI,1.02-1.41) and irritable temperament (OR,1.28; 95%CI,1.08-1.52) persisted as significant predictors of a positive response to lithium treatment, while emotional (OR,0.87; 95%CI,0.76-0.98) and physical abuse (OR,0.83; 95%CI,0.70-0.98) were predictors of non-response. CONCLUSIONS: In evaluating lithium response in BD, our study highlights the importance of considering clinical variables alongside temperament and childhood adversities. The assessment of hyperthymic and irritable temperament, emotional and physical abuse together with the type of cycle is of particular importance. Furthermore, our findings underscore the significance of systematically assessing the type of cycle in patients with BD through the use of life charts.

Dopaminergic dysfunction in the left putamen of patients with major depressive disorder.

INTRODUCTION: Dopaminergic transmission impairment has been identified as one of the main neurobiological correlates of both depression and clinical symptoms commonly associated with its spectrum such as anhedonia and psychomotor retardation. OBJECTIVES: We examined the relationship between dopaminergic deficit in the striatum, as measured by 123I-FP-CIT SPECT imaging, and specific psychopathological dimensions in patients with major depressive disorder. METHODS: To our knowledge this is the first study with a sample of >120 subjects. After check for inclusion and exclusion criteria, 121 (67 females, 54 males) patients were chosen retrospectively from an extensive 1106 patients database of 123I-FP-CIT SPECT scans obtained at the Nuclear Medicine Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS in Rome. These individuals had undergone striatal dopamine transporter (DAT) assessments based on the recommendation of their referring clinicians, who were either neurologists or psychiatrists. At the time of SPECT imaging, each participant underwent psychiatric and psychometric evaluations. We used the following psychometric scales: Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Snaith Hamilton Pleasure Scale, and Depression Retardation Rating Scale. RESULTS: We found a negative correlation between levels of depression (p = 0.007), anxiety (p = 0.035), anhedonia (p = 0.028) and psychomotor retardation (p = 0.014) and DAT availability in the left putamen. We further stratified the sample and found that DAT availability in the left putamen was lower in seriously depressed patients (p = 0.027) and in patients with significant psychomotor retardation (p = 0.048). CONCLUSION: To our knowledge this is the first study to have such a high number of sample. Our study reveals a pivotal role of dopaminergic dysfunction in patients with major depressive disorder. Elevated levels of depression, anxiety, anhedonia, and psychomotor retardation appear to be associated with reduced DAT availability specifically in the left putamen.

Novel Advancements in COVID-19 and Neuroscience.

From an initial cluster of cases reported in Wuhan, the SARS-Cov-2 infection has since spread globally, causing a pandemic that began on 11 March 2020 [...].

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.

Psychological factors and barriers to donating and receiving milk from human milk banks: A review.

Human milk banks (HMBs), established in the early 20th century, aimed to provide safe breast milk for infants with challenges obtaining it. The spread of infections since the 1980s resulted in strict regulations and screening in HMBs, to ensure the safety of donated milk. Several social and personal factors discourage mothers from practicing breastfeeding, making donated milk a viable alternative because of its protective and immunity-enhancing properties. However, psychological barriers can affect the decision to donate or receive donated milk. To identify psychological factors related to donating and receiving human milk from HMBs, we searched PubMed to identify studies reporting psychological factors in donating and receiving milk and excluding studies not reporting psychological factors. The search identified 28 articles meeting the inclusion criteria. Eligible studies from various countries spanned from 1995 to 2023 and focused on psychological factors influencing milk donation and receiving. Most studies were descriptive-qualitative. Factors facilitating or hindering milk donation and reception included perceptions, psychological aspects, and previous experiences. Positive factors for donors included the desire to help other mothers, support from health care professionals, and personal well-being. Negative factors included breast milk exclusivity and discomfort caused by health checks. For recipients, awareness of donated milk benefits was a positive factor, whereas fear regarding safety was negative. The altruistic motivation to help other mothers drove many women to donate. Proper awareness and support from health care professionals and families can help women understand the value of milk donation and support their personal and identity reintegration, especially in cases of the loss of a child.

Resting-State Functional Connectivity of the Anterior Cingulate Cortex Among Persons With Mood Disorders and Suicidal Behaviors.

OBJECTIVE: To assess whether anterior cingulate cortex (ACC) abnormalities contribute to suicide risk in major depressive disorder and bipolar disorder, the investigators compared resting-state functional connectivity (rsFC) of ACC subdivisions between individuals with major depressive or bipolar disorder with and without a lifetime history of suicidal behavior. METHODS: Forty-two inpatients with and 26 inpatients without a history of suicidal behavior (SB+ and SB-, respectively) associated with major depressive or bipolar disorder and 40 healthy control (HC) participants underwent rsFC neuroimaging. RsFC of the subgenual, perigenual, rostral, dorsal, and caudal subdivisions of the ACC was calculated. Possible confounders, such as psychosis and severity of depression, were controlled for, seed-to-voxel and post hoc region of interest (ROI)-to-ROI analyses were performed, and the accuracy of rsFC in classifying suicidal behavior was studied. RESULTS: Compared with individuals in the SB- and HC groups, patients in the SB+ group had higher rsFC between the left rostral and right dorsal ACC seeds and visual cortex clusters. Conversely, rsFC between the left rostral and right dorsal ACC seeds and cingulate and frontal clusters was lower in the SB+ group than in the HC group. Left rostral ACC to left Brodmann's area 18 connectivity showed up to 75% discriminative accuracy in distinguishing SB+ from SB- patients. CONCLUSIONS: A history of suicidal behavior among individuals with major depressive disorder or bipolar disorder was associated with altered rsFC of the rostral and caudal ACC, regions involved in conflict detection and error monitoring. Replication of these findings is needed to further explore the involvement of the ACC in the neurobiology of suicidal behavior and suicidal ideation.

Childhood Trauma and Self-harm in Youths with Bipolar Disorders.

BACKGROUND: Bipolar disorders (BD) in youth are associated with a high risk of self-harm behaviors. Childhood trauma (CT) is a relevant environmental stressor that is related to both BD diagnosis and self-harm in adulthood. It is not yet established whether CT may impact self-harm risk in youth. Therefore, the aim of this study was to investigate the distribution patterns of CT in youth BD with and without self-harm. METHODS: We assessed 273 participants (aged 13-25 years), 96 youths with BD according to DSM-5 criteria and 177 healthy controls (HC). History of CT was obtained using the Childhood Trauma Questionnaire (CTQ). The association between CT and self-harm was tested using multivariate statistical models. RESULTS: Over 45% of participants with BD reported lifetime self-harm. The BD Self-harm group reported more emotional abuse, emotional neglect, sexual abuse, and physical abuse than HC. The BD No-Self-harm group reported more emotional abuse than HC. The BD Self-harm group reported more emotional abuse and neglect than the BD No-Self-harm group. The BD Self-harm group also reported separated parents, hospitalizations, smoking, use of antiepileptics, antipsychotics and lithium. Emotional abuse was an independent predictor of self-harm in youths with BD. CONCLUSION: Findings support the importance of assessing CT, in particular emotional abuse, in youth with BD at risk for self-harm.

Primary emotional systems, childhood trauma, and suicidal ideation in youths with bipolar disorders.

BACKGROUND: Bipolar disorders (BD) in youths are strongly associated with suicidal ideation. Childhood trauma is a prominent environmental stressor associated with both BD diagnosis and suicide. Primary emotional systems are altered in adult BD and may contribute to suicide risk in youths. OBJECTIVE: The aim of this study was to investigate primary emotional systems distribution patterns and childhood trauma in youths' BD with and without suicidal ideation (BD-IS, BD-NIS). PARTICIPANTS AND SETTING: We assessed 289 participants, 103 youths with DSM-5 BD and 186 healthy controls (HCs). METHODS: Primary emotional systems were obtained with Panksepp's Affective Neuroscience Personality Scale (ANPS), and history of childhood trauma using the Childhood Trauma Questionnaire (CTQ). Suicidal ideation was assessed through the Columbia Suicide Scale for the Rating of Suicide Severity (C-SSRS). The associations with suicidal ideation were tested using two different multivariate models. RESULTS: Over 48 % of participants reported lifetime suicidal ideation and differed on clinical variables from BD-NIS. According to the first model (Wilk's Lambda = 0.72, p < 0.0001), BD-IS scored higher on Panksepp's ANGER and lower on PLAY and CARE than BD-NIS. Both BD-SI and BD-NSI scored higher on ANGER and SEEK and lower on PLAY and CARE than HCs. BD-IS reported more emotional abuse than BD-NIS. They also reported more emotional, sexual, and physical abuse, and emotional neglect than HCs. Only ANGER (OR = 1.13, 95 % CI = 1.01-1.26, Wald = 5.72) and CTQ-Emotional abuse (OR = 1.26, 95 % C.I. = 1.04-1.52, Wald = 5.72) independently predicted suicidal ideation. CONCLUSIONS: Findings support the importance of assessing primary emotional systems and childhood trauma, in particular emotional abuse, in youths with BD at risk for suicide.

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.

Reduction in Cognitive Symptoms Following Intranasal Esketamine Administration in Patients With Chronic Treatment-resistant Depression: A 12-Week Case Series.

BACKGROUND: Cognitive symptoms are a core feature of depressive disorders, interfere with full functional recovery and are prominent in patients with treatment-resistant depression (TRD), particularly in severe chronic cases. Intranasal (IN) esketamine was recently approved for the treatment of TRD; however, its effects on cognitive symptoms are unclear. In this article, we describe cognitive changes in 8 patients with chronic TRD who were treated with IN administration of esketamine. METHODS: Eight outpatients with chronic TRD received IN esketamine over 3 months and were assessed at baseline and after 4, 8, and 12 weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Digit Symbol Substitution Test (DSST), the Trail Making Test-B (TMT-B), the Patient Deficits Questionnaire for Depression 5-item (PDQ-D5), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impressions Scale (CGI). FINDINGS: We observed reductions in cognitive symptoms according to DSST, TMT-B, and PDQ-D5 scores within the first 2 months of treatment with IN esketamine. These improvements were observed before patients achieved clinical response (≥50% decrease in baseline MADRS scores), and they also occurred earlier than reductions in HARS scores. CONCLUSIONS: A clinical response to IN esketamine was detected in severely ill patients with chronic TRD after 3 months of treatment. Interestingly, improvements on measures of cognitive symptoms were observed before patients achieved antidepressant response. These preliminary observations suggest an additional value to the antidepressant properties of IN esketamine. Clinical studies specifically investigating cognition as a primary outcome measure of IN esketamine in TRD are warranted.

Mixed Depression in the Post-COVID-19 Syndrome: Correlation between Excitatory Symptoms in Depression and Physical Burden after COVID-19.

The relationship between depression and post-COVID-19 disease syndrome (post-COVID-19 syndrome) is established. Nevertheless, few studies have investigated the association between post-COVID-19 syndrome and mixed depression, i.e., a specific sub-form of depression characterized by high level of excitatory symptoms. Aims of the present study are: (a) to compare the post-COVID-19 syndrome's burden in depressed and non-depressed patients, and (b) to investigate the correlation between post-COVID-19 syndrome's burden and the severity of mixed depression. One thousand and forty six (n = 1460) subjects with post-COVID-19 syndrome were assessed. Subjects were divided into those with (DEP) or without (CONT) depression. Sociodemographically, post-COVID-19 syndrome's symptoms number and type were compared. In DEP, association between levels of excitatory symptoms and the presence of post-COVID-19 syndrome's symptoms were additionally assessed. DEP showed greater percentages of family history of psychiatric disorders than CONT. DEP showed higher percentages of post-COVID-19 symptoms than CONT. A greater level of excitatory symptoms were associated to higher frequencies of post-COVID-19 syndrome' symptoms. Higher levels of post-COVID-19 syndrome's symptoms in DEP corroborate the evidence of a common pathway between these two syndromes. Presence of excitatory symptoms seem to additionally add a greater illness burden. Such findings might help clinicians choose the appropriate treatment for such states. More specifically, therapies aimed to treat excitatory symptoms, such as antipsychotics and mood stabilizers, might help reduce the illness burden in post-COVID-19 patients with mixed depression.

Effect of affective temperament on illness characteristics of subjects with bipolar disorder and major depressive disorder.

BACKGROUND: Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder (BD) or major depressive disorder (MDD) has been described. However, the strength of such relationship should be tested while considering other factors influencing the diagnosis of BD/MDD. Literature also lacks a comprehensive description of the interplay between affective temperament and characteristics of mood disorders. The aim of the present study is to address these issues. METHODS: This is a multicentric observational study including 7 Italian university sites. Five-hundred-fifty-five euthymic subjects with BD/MDD were enrolled and further divided in those with hyperthymic (Hyper, N = 143), cyclothymic (Cyclo, N = 133), irritable (Irr, N = 49), dysthymic (Dysth, N = 155), and anxious (Anx N = 76) temperaments. Linear, binary, ordinal and logistic regressions were performed to assess the association between affective temperaments and i) diagnosis of BD/MDD; ii) characteristics of illness severity and course. RESULTS: Hyper, Cyclo and Irr were more likely to be associated with BD, together with earlier age of onset and presence of a first-degree relative with BD. Anx and Dysth were more associated with MDD. Differences in association between affective temperaments and characteristics of BD/MDD were observed for hospital admissions, phase-related psychotic symptoms, length and type of depression, comorbidity and pharmacological intake. LIMITATIONS: Small sample size, cross-sectional design, recall biases. CONCLUSION: Specific affective temperaments were associated to certain characteristics of illness severity and course of BD or MDD. Evaluation of affective temperaments might help a deeper understanding of mood disorders.

Neuroanatomical Correlates of the Late Positive Potential in Youth with Pediatric Bipolar Disorder.

BACKGROUND: The late positive potential (LPP) could be a marker of emotion dysregulation in youth with pediatric bipolar disorder (PBD). However, the neuroanatomical correlates of the LPP are still not clarified. OBJECTIVE: To provide cortical and deep gray matter correlates of the LPP in youth, specifically, youth with PBD. METHODS: Twenty-four 7 to 17 years-old children with PBD and 28 healthy controls (HC) underwent cortical thickness and deep gray matter volumes measurements through magnetic resonance imaging and LPP measurement elicited by passively viewing emotional faces through electroencephalography. T-tests compared group differences in LPP, cortical thickness, and deep gray matter volumes. Linear regressions tested the relationship between LPP amplitude and cortical thickness/deep gray matter volumes. RESULTS: PBD had a more pronounced LPP amplitude for happy faces and a thinner cortex in prefrontal areas than HC. While considering both groups, a higher LPP amplitude was associated with a thicker cortex across occipital and frontal lobes, and with a smaller right globus pallidus volume. In addition, a higher LPP amplitude for happy faces was associated with smaller left caudate and left globus pallidus volumes across both groups. Finally, the LPP amplitude correlated negatively with right precentral gyrus thickness across youth with PBD, but positively across HC. CONCLUSION: Neural correlates of LPP in youth included fronto-occipital areas that have been associated also with emotion processing and control. The opposite relationship between BPD and HC of LPP amplitude and right precentral gyrus thickness might explain the inefficacy of the emotional control system in PBD.

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.

Functional Movement Disorders during COVID-19: Psychological Distress, Affective Temperament and Emotional Dysregulation.

Background and objective: Functional movement disorders (FMD) represent a spectrum of psychosomatic symptoms particularly sensitive to stress. The COVID-19 pandemic has increased psychological distress worldwide and may have worsened FMD. The study aimed to confirm this hypothesis and to test whether in FMD there is a relationship between affective temperament, emotional dysregulation and psychological distress due to the pandemic. Methods: We recruited individuals with FMD, diagnosed them according to validated criteria and matched them with healthy controls (HC). Psychological distress and temperament were obtained using the Kessler-10 and the Temperament Evaluation of Memphis, Pisa and San Diego Autoquestionnaire, respectively. We used bootstrapped mediation analysis to test the mediator role of emotional dysregulation on the effect of temperament on psychological distress. Results: The sample consisted of 96 individuals. During the pandemic, 31.3% of the patients reported the need for urgent neurological care, and 40.6% reported a subjective worsening neurological condition. Patients with FMD presented with more psychological distress during the COVID-19 pandemic (F = 30.15, df = 1, p ≤ 0.001) than HC. They also reported more emotional dysregulation (F = 15.80, df = 1, p ≤ 0.001) and more cyclothymic traits (F = 14.84, df = 1, p ≤ 0.001). Cyclothymic temperament showed an indirect effect on COVID-19-related psychological distress, mediated by deficits in emotion regulation mechanisms (Bootstrapped LLCI = 0.41, ULCI = 2.41). Conclusion: Our results suggest that emotional dysregulation may represent a dimension mediating cyclotimic temperament response to the stressful effect of the pandemic and provide insight for developing intervention policies.

Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes.

Major Depressive Episodes (MDE) following COVID-19 are frequent, can have a characteristic clinical picture, and are associated with immune-inflammatory changes. Vortioxetine is known to improve physical and cognitive performance in patients with depression and shows anti-inflammatory and anti-oxidative activities. This study aimed to retrospectively evaluate the effects of vortioxetine after 1 and 3 months of treatment in 80 patients (44.4% males, 54±17.2 years) with post-COVID-19 MDE. The primary outcome was improvement in physical and cognitive symptoms measured by specific items of Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Short Form-36 Health Survey Questionnaire (SF-36), Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire for Depression (PDQ-D5). Changes in mood, anxiety, anhedonia, sleep, and quality of life were also investigated, as well as the underlying inflammatory status. Results show that, alongside reduction of depressive symptoms (HDRS, p<0.001), vortioxetine (mean dose: 10.1±4.1 mg/day) significantly improved physical features (all measurements p<0.001) and cognitive functioning (DDST, p=0.02; PDQ-D5, p<0.001) throughout treatment. We also observed significant reductions in inflammatory indexes. Therefore, vortioxetine might be a favorable therapeutic choice in post-COVID-19 patients with MDE because of its beneficial effects on physical complaints and cognition, features that appear to be specifically affected in relation to SARS-CoV-2 infection, and its good safety/tolerability profile. High prevalence and clinical and socioeconomic implications of COVID-19 consequences are a major public health concern and developing tailored, safe interventions is crucial to promote full functional recovery.