INTRODUCTION:Bipolar Disorder (BD) presents with heterogeneous longitudinal cycling patterns, including Manic-Depressive-free Interval (MDI), Depressive-Manic-free Interval (DMI), and Irregular (IRR) cycles. Studies investigating how these cycle types affect clinical course remain limited. This study aimed to examine a large, well-characterised sample of patients with BD types I (BD-I) and II (BD-II). METHODS:Life charts were used to determine the type of cycle, collecting information on first affective episode type, hospitalisations (presence or absence), suicidal ideation/attempts, psychiatric family history, seasonality, agitated depression, predominant polarity, and diagnostic subtype (BD-I vs. BD-II). The impact of cycle type on clinical course was analysed through univariate and multivariate models. RESULTS:Of 378 BD patients, 140 (37.0%) had MDI cycles, 92 (24.3%) had DMI cycles, and 146 (38.6%) had IRR cycles. Multivariate analyses showed MDI patients were more likely to have a manic onset compared to DMI and IRR (p < 0.001). They also showed a higher likelihood of hypomanic onset compared to DMI (p < 0.001). Conversely, DMI was associated with a depressive onset relative to MDI and IRR (p < 0.001). Seasonality was more frequent in patients with regular cycles (MDI and DMI) compared to IRR (p < 0.001). Hospitalisations were more frequent in MDI and DMI cycles compared to IRR, but the association survived only for MDI in multivariate analysis. MDI patients had a higher prevalence of manic predominant polarity and lower rates of depressive predominant polarity compared to both DMI and IRR (p < 0.001). A BD-II diagnosis was significantly more frequent in DMI and IRR (p < 0.001), and a BD-I diagnosis was more prevalent in MDI (p < 0.001). DISCUSSION:Cycle type affected the BD clinical course, with MDI tending to show more frequent hospitalisations, BD-I diagnosis, and manic predominant polarity, while DMI and IRR patients had more BD-II diagnoses. CONCLUSION:Findings underscore the importance of classifying BD based on cycle patterns and suggest that taking into account these patterns may support more personalised treatment planning and improve clinical outcomes.

BACKGROUND:Many reports associate particular phases of the human reproductive cycle with psychiatric symptoms including depression, although details of associations of morbidity of depressive, bipolar, and anxiety disorders with pre-, peri-, and post-menopausal phases require further clarification. This naturalistic study evaluated the timing of onset and morbidity of mood and anxiety disorders in women during these menopausal phases. METHODS:Women (N = 928) with a primary diagnosis of BD type I or II (BD1 or BD2), major depressive disorder (MDD) or an anxiety disorder were clinically evaluated after menopause to determine the onset of affective illness during the pre, peri-, or post-menopausal phases. Psychometric scales were used to assess affective illness and multivariable regression modeling was used to compare menopausal phases. RESULTS:Many descriptive and clinical measures differed significantly with illnesses starting in the three menstrual phases. Women with onset of affective illness in the perimenopause phase spent 1.33 more time ill than those starting in the premenopausal phase and 1.46 more time ill than women with postmenopausal onset, with corresponding differences in illness episodes/year as well as suicidal risks. CONCLUSIONS:Study findings are consistent with the view that onset in the peri-menopausal phase may be associated with an excess of affective morbidity in both MDD and BD and that the post-menopausal phase may involve less morbidity.

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.

Objectives: There are reports of mental health worsening during the COVID-19 pandemic. We aimed to assess whether this occurred in women who were pregnant at baseline (late 2019) and unaware of the pandemic, and who delivered after the implementation of COVID-19 restrictions and threat (March–April 2020). To compare the pandemic period with the pre-pandemic, we capitalized on a retrospective 2014–2015 perinatal sample which had had affective symptoms assessed. Methods: The COVID sample were administered the Postnatal Depression Scale (EPDS), Zung Self-Rating Anxiety Scale (SAS), Hypomania Checklist-32 (HCL-32), Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS) at T0 (pregnancy) and T1 (post-delivery). The Non-COVID sample had completed EPDS and HCL-32 at the same timepoints. Results: The COVID sample included 72 women, aged 21–46 years (mean = 33.25 years ± 4.69), and the Non-COVID sample included 68 perinatal women, aged 21–46 years (mean = 34.01 years ± 4.68). Our study showed greater levels of mild depression in T1 among the COVID sample compared to the Non-COVID sample. No significant differences in terms of major depression and suicidal ideation were found. The levels of hypomania were significantly different between the two groups at T1, with the COVID sample scoring higher than the Non-COVID sample. This may be related to the high levels of perceived stress we found during the postpartum evaluation in the COVID sample. Limitations: There was a relatively small sample size. Conclusions: New mothers responded to the pandemic with less mental health impairment than expected, differently from the general population. Women delivering amidst the pandemic did not differ in depressive and anxiety symptoms from their pre-pandemic scores and from pre-pandemic women. Because stress responses have high energy costs, it is optimal for maternal animals to minimize such high metabolic costs during motherhood. Evidence suggests that reproductive experience alters the female brain in adaptive ways. This maternal brain plasticity facilitates a higher purpose, the continuation of the species. This may point to the recruitment of motherhood-related resources, for potentially overcoming the effects of the pandemic on mental health.

Background. Sleep disorders are common in perinatal women and may underlie or trigger anxiety and depression. We aimed to translate and validate and evaluate the psychometric properties of the Italian version of the Insomnia Symptom Questionnaire (ISQ), in a sample of women during late pregnancy and 6-months postpartum according to the DSM-5 criteria. Methods. The ISQ was administered to 292 women prenatally along with other measures of sleep quality, depression, and anxiety, to examine its construct and convergent validity. Women were readministered the ISQ six months postdelivery to assess test–retest reliability. Women were divided into DSM-5 No-Insomnia (N = 253) and Insomnia (N = 39) groups. Results. The insomnia group had received more psychopharmacotherapy, had more psychiatric family history, increased rates of medically assisted reproduction, of past perinatal psychiatric disorders, and scored higher on almost all TEMPS-A dimensions, on the EPDS, HCL-32, PSQI, and on ISQ prenatally and postnatally. ISQ scores correlated with all scales, indicating adequate convergent and discriminant validity; furthermore, it showed antenatal–postnatal test–retest reliability, 97.5% diagnostic accuracy, 79.5% sensitivity, 94.9% specificity, 70.5% positive predictive power, and 92.8% negative predictive power. Conclusions. The ISQ is useful, valid, and reliable for assessing perinatal insomnia in Italian women. The Italian version showed equivalent properties to the original version.

Literature stressed the importance of using valid, reliable measures to assess anxiety in the perinatal period, like the self-rated Perinatal Anxiety Screening Scale (PASS). We aimed to examine the psychometric properties of the Italian PASS version in a sample of Italian women undergoing mental health screening during their third trimester of pregnancy and its diagnostic accuracy in a control perinatal sample of psychiatric outpatients. Sample comprised 289 women aged 33.17 ± 5.08, range 19–46 years, undergoing fetal monitoring during their third trimester of pregnancy, with 49 of them retested 6 months postpartum. Controls were 60 antenatal or postnatal psychiatric outpatients aged 35.71 ± 5.02, range 22–50 years. Groups were assessed through identical self- and clinician-rating scales. Confirmatory Factor Analysis (CFA), Principal Component Analysis (PCA), Pearson's correlations and receiver operating characteristic were conducted for PASS. PCA and CPA confirmed four-factor structure with slight differences from the original version. Construct validity and test-retest reliability were supported. Cut-off was 26. The PASS correlated with principal anxiety scales. Despite small sample size, findings confirm reliability and validity of the Italian PASS version in assessing anxiety symptoms in the perinatal period. Its incorporation in perinatal care will improve future mother and child psychological health.

Background: Women taking advantage of medically assisted reproduction (MAR) techniques may differ from spontaneously conceiving women (nonMAR) in risk of depression and/or anxiety. We aimed to investigate possible differences between MAR and nonMAR through the use of the Edinburgh Postnatal Depression Scale in a sample of Italian-speaking women at their third trimester of pregnancy. Methods: We administered the Edinburgh Postnatal Depression Scale (EPDS) to two groups of pregnant women, MAR and nonMAR, at the third trimester of pregnancy (T0), one month after delivery (T1), and three months after delivery (T2) from February 2013 to December 2019. EPDS total scores cutoffs were ≥9 for risk of depression, 9–11 mild depression, ≥12 major depression, and the EPDS-3A cluster ≥4 was a proxy for anxiety. Results: Included were 1303 nonMAR women and 92 MAR, an expected disproportion. NonMAR and MAR women did not differ on depression or anxiety at any assessment timepoint. MAR women were older than nonMAR, consumed more alcohol and medical drugs, and displayed more complications during pregnancy. Scoring over the threshold on depression risk was associated with foreign nationality, unemployment, psychiatric history of the patient, family or partner, psychiatric problems in past pregnancies, hyperemesis, premenstrual syndrome (PMS), and stressful life events in the last year at baseline, and, for some of them, at other timepoints. In contrast, MAR past or current was associated with having suprathreshold depression at the first-month postpartum follow-up. Conclusions: Taken together, our data show that women opting for MAR do not differ from spontaneously conceiving women regarding psychiatric outcomes but do differ on some sociodemographic and clinical variables.

Mixed states in patients with a perinatal mood episode is seldom encountered. Lack of appropriate assessment tools could be partly responsible for this observation. The authors conducted a selective review of studies dealing with the reporting of mixed symptoms in women during the perinatal period with the intention to quantify the phenomenon. In many instances of reported postpartum depression, either a first onset or an onset in the context of bipolar disorder, mixed states were identifiable. However, the strict application of the Diagnostic and Statistical Manual of Mental Disorders , 5th edition, mixed features specifier to these episodes risks misdiagnosis.

Childhood trauma (CT) Is strongly associated with bipolar disorder, possibly through emotional hyperreactivity (EH). Mixed symptoms/states (MSs) are associated with Increased illness severity. The authors tested through a systematic review the association between CT and MSs. The authors systematically looked for studies exploring associations between MSs and CT, CT and EH, and EH and MSs. Most literature agrees that MSs are associated with CT; the latter was found to be associated to EH, which is in turn associated with MSs. The literature supports an association between CT and later development of MSs, possibly mediated through EH.

BACKGROUND:There are different ways to define stabilization and currently, the main standpoint regards it as no-depression/no-mania. Furthermore, each person is physiologically different from childhood to adulthood, and in old age, thus the meaning of stabilization should take into account both growth and maturity. We aimed to review systematically studies focusing on mood stabilization in all phases of bipolar disorder (BD) and across all life phases, including pregnancy and the perinatal period, which is still a different phase in women's life cycles.METHODS:We carried out a PubMed search focusing on studies of bipolar disorder treated with drugs and aimed at stabilization with the following search strategy stabiliz*[ti] OR stabilis*[ti] OR stable[ti] OR stability[ti]) AND mood[ti] AND bipolar. In conducting our review, we followed the PRISMA statement. Agreement on inclusion was reached by consensus of all authors through a Delphi rounds procedure.RESULTS:The above search strategy produced 509 records on January 25, 2020. Of them, 58 fitted our inclusion criteria and were discussed. The eligible studies spanned from September 1983 to July 6, 2019.CONCLUSIONS:No clear-cut indications could be drawn due to a number of limitations involving sample inconsistency and different methods of assessing mood stabilization. The evidence collected so far does not allow recommended treatments for Adolescents, pregnant or perinatal women, and aged patients. However, adults, not within these groups, better focused upon. For their manic/mixed phases, second generation antipsychotic drugs may be useful in the short-to-medium run, alone or combined with mood stabilizers (MSs). However, MSs, and especially lithium, continue to be pivotal in chronic treatment. Bipolar depression should rely on MSs, but an antidepressant may be added on and can prove to be helpful. However, there are concerns with the tendency of antidepressants to induce the opposite polarity or mood instability, rendering the need for concurrent MS prescription mandatory.

Background: Mixed symptoms in depression may underlie bipolar diathesis rather than unipolarity. Uncovering mixed depression (MxD) is crucial for appropriate management, especially in the perinatal period, as it may affect treatment planning and impact future child development. We used a scale specific for identifying MxD and tested its validity in pregnant and postpartum women with depression. Methods: Women developing a major depressive episode (MDE) during their perinatal period extending from pregnancy to one year postpartum from November-2012 through June-2019 were assessed with BPRS-18, EPDS, CGI-S, GAF, HAM-A, HAM-D, Koukopoulos' Mixed Depression Rating Scale (KMDRS), TEMPS, and YMRS. They were classified, based on KMDRS criteria, as with mixed (MxD) or without (nonMxD) mixed symptoms. We conducted ROC analysis and performed factor analysis of the KMDRS. Results: Of 45 included, MxD (N = 19) were biased towards diagnosis of bipolar disorder and nonMxD (N = 26) towards major depressive disorder. Other sociodemographic variables did not differ significantly between MxD and nonMxD. MxD scored higher on total YMRS, BPRS, and KMDRS, and on KMDRS-6 Subjective Feelings of Irritability and KMDRS-12 Suicidal Impulsiveness items. The KMDRS correlated in the entire sample, in MxD and nonMxD, with the YMRS and the BPRS, while correlating with the HAM-D in nonMxD only. The KMDRS showed acceptable AUC distribution, with a 68% sensitivity and 58% specificity. Best-fit was three-factor-structure, explaining 54.66% of cumulative variance. Limitations: Small sample and cross-sectional design. Conclusions: The KMDRS is fit for investigating MxD along with the YMRS and the BPRS in perinatal women with a MDE.

BACKGROUND:The construct of mixed depression (MxD), namely the simultaneous presence of excitatory symptoms during a depressive episode, has gained increased interest in the recent years. The Koukopoulos Mixed Depression Rating Scale (KMDRS) has been recently validated for the diagnosis and assessment of MxD. The aim of this study was to validate the Italian version of the KMDRS.METHODS:Patients with a major depressive episode (MDE) (N=396, age, mean=44.73 years, SD=15.93) were recruited at Lucio Bini Center, Rome, Italy. All participants were administered the Italian version of the KMDRS, the Montgomery-Åsberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Clinical Global Impressions (CGI), and the Global Assessment of Functioning (GAF). We calculated predictive validity, and performed Receiver Operator Curve (ROC) analysis, Cronbach's alpha, and inter-rater reliability.RESULTS:Predictive validity (C-statistic= 0.80; IC 95%: 0.75, 0.85) and capacity [OR=1.25±.03 (SE); 95% CI: 1.18, 1.32; p<.001] were good, matching those of the original version, whereas internal consistency (Cronbach's alpha = .70, IC 95%: 0.65, 0.75) and interrater reliability (Cohen's kappa= 0.74) were adequate.CONCLUSIONS:The agreement of results with those of the original version point to the validity of the Italian version of KMDRS in assessing MxD.

BACKGROUND The construct of mixed depression (MxD), namely the simultaneous presence of excitatory symptoms during a depressive episode, has gained increased interest in the recent years. The Koukopoulos Mixed Depression Rating Scale (KMDRS) has been recently validated for the diagnosis and assessment of MxD. The aim of this study was to validate the Italian version of the KMDRS. METHODS Patients with a major depressive episode (MDE) (N=396, age, mean=44.73 years, SD=15.93) were recruited at Lucio Bini Center, Rome, Italy. All participants were administered the Italian version of the KMDRS, the Montgomery-Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Clinical Global Impressions (CGI), and the Global Assessment of Functioning (GAF). We calculated predictive validity, and performed Receiver Operator Curve (ROC) analysis, Cronbach's alpha, and inter-rater reliability. RESULTS Predictive validity (C-statistic= 0.80; IC 95%: 0.75, 0.85) and capacity [OR=1.25±.03 (SE); 95% CI: 1.18, 1.32; p<.001] were good, matching those of the original version, whereas internal consistency (Cronbach's alpha = .70, IC 95%: 0.65, 0.75) and interrater reliability (Cohen's kappa= 0.74) were adequate. CONCLUSIONS The agreement of results with those of the original version point to the validity of the Italian version of KMDRS in assessing MxD.

Background: Placebo response appears to be increasing in antidepressant, antipsychotic and various internal medicine trials. A similar trend has been reported for OCD during 1989-1999. Placebo response is generally considered as the extent to which placebo treatment is associated with core symptom improvement. In this analysis, we used Joinpoint regression to assess the time trend of both placebo response and placebo responder rates according to the year of publication with no time restriction in OM drug trials. Methods: We included drug and/or psychotherapy trials vs. placebo from PubMed, Embase, CINAHL, and PsycINFO retrieved through the search (placebo OR sham) AND (obsessive* OR OCD). We included studies through investigator consensus. We then performed on data of included studies log-linear joinpoint segmented regression models using a p<0.05 cutoff. Results: We included 113 studies from 112 published papers. Placebo mean annual response rates in OCD studies significantly increased from 1991 to 2017 with an annual percent change (APC) of 0.66%, while placebo mean annual responder rates also significantly increased from 2010 to 2017, with an APC of 5.45%. Drug mean annual response rates in OCD studies significantly increased from 1987 to 2012 with an APC of 0.72%, while the corresponding responder rates did not show statistically significant APC changes between 1984 and 2017. Conclusion: We observed a tendency for placebo to increase both measures of response in OCD clinical drug trials through the years that tend to approximate the responses shown by drugs. Changes in the type of study (moving from classical head to head comparisons to add-on studies in treatment-resistant populations) and countries involved in experimentation may partially account for some portion of these results. It appears that placebo effects are becoming more elusive and out of control.