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The re-emergence (i.e. ‘breakthrough’) of depressive symptoms despite maintenance treatment of depression with antidepressant drugs is a complex clinical phenomenon referred to as tolerance. Herein we critically appraise evidence from both pre-clinical and clinical studies, focusing on putative mechanisms as well as clinical correlates and implications of the emergence tolerance during antidepressant treatment for major depressive disorder (MDD). It is firstly unclear to what extent this phenotype reflects a pharmacological effect of an antidepressant, is driven by non-adherence, is a marker of latent bipolarity or another comorbidity, a marker of neuroprogression of the underlying disorder or the intrusion of the impact of psychosocial variables into the clinical course. The operational definitions of tolerance and its related phenomena have also been largely inconsistent. Several protective clinical indicators have been proposed, including a rapid-cycling course and comorbid chronic anxiety, whilst poor treatment adherence, proneness to emotional blunting and sub-threshold bipolarity have been identified as possible correlates of tolerance to antidepressant treatment in MDD. Putative neurobiological underpinnings include adaptations in the hypothalamic–pituitary–adrenal (HPA) axis and the serotonergic system. Due to the clinical and diagnostic challenges imposed by the emergence of tolerance to antidepressants, there is an urgent need for upcoming international guidelines to reach a consensus on operational definitions for this complex clinical phenomenon, thus enabling a more precise appreciation of the incidence and correlates of tolerance to antidepressants. Taken together, the present review underscores the need to cautiously weight benefits and risks prior to considering long-term antidepressant treatment for patients with MDD as tolerance may emerge in a subset of patients. © 2018 Elsevier Ltd

The prediction of acute and maintenance lithium treatment response carries major clinical and neurobiological implications, warranting systematic review. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant review searched major electronic databases from inception until December 2017 for studies documenting a clinical diagnosis of bipolar disorder (BD) made according to the mainstream diagnostic manuals and confirmed by a structured interview. Eligible studies allowed a quantitative comparison of endpoint vs baseline mean values of a given biomarker, regardless of the mood phase of patients with BD, and the disorder was assessed for severity using validated rating tool(s). Owing to the purposely applied stringent selection criteria, 16 acute and 12 maintenance studies could be included. The anticipated publication bias limited the chances of reportable generalizable findings, hindering a side-by-side comparison of different records across varying biomarkers and subsequent meta-analyses. The PRISMA approach was nonetheless preferred; it aimed at enhancing the homogeneity of the included results and minimizing the chances of “apples and oranges” with respect to the present research theme. The present critical review confirms the need for future research to specifically assess either pretreatment and/or posttreatment putative biomarkers of patients with BD and treated with lithium. © 2018 Elsevier B.V.

Major depressive disorder carries a significant burden and a high risk for suicide. The need for more effective, safer, and faster-acting drugs is, therefore, compelling. The present chapter briefly assesses the most promising agents, focusing on non-monoamine-targeting compounds, namely, the glutamate antagonist ketamine and its enantiomer esketamine. A critical overview of the evidence and the pitfalls associated with current antidepressant drug development is likewise provided in the following text.

Lithium represents a cornerstone treatment for bipolar disorder (BD), and its putative mechanisms of action represent a potential avenue toward the neurobiological understanding of the illness. The predictive value of varying course specifiers of BD seems suboptimal. Therefore the assessment and integration of biomarkers of various modalities (e.g., neuroimaging, peripheral biomarkers, and proteomic, metabolomic, and genomic biomarkers) have the potential to predict therapeutic response to lithium and also to unravel novel pathophysiological mechanisms of BD. This chapter provides a critical summary of potential biomarkers and biosignatures of lithium response with the ultimate goal of promoting a more patient-tailored approach toward the lithium treatment of BD.

Major depressive disorder carries a significant burden and a high risk for suicide. The need for more effective, safer, and faster-acting drugs is, therefore, compelling. The present chapter briefly assesses the most promising agents, focusing on non-monoamine-targeting compounds, namely, the glutamate antagonist ketamine and its enantiomer esketamine. A critical overview of the evidence and the pitfalls associated with current antidepressant drug development is likewise provided in the following text.

Drop-out from follow-up visits carries significant burden for people diagnosed with depression. The present study assesses multiple clinical moderators of drop-out among depressed outpatients. We retrospectively followed-up 131 outpatients over 6 months: 78 major depressive disorder (MDD), and 53 bipolar disorder (BD-I = 24; BD-II = 29) patients diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Participants were assessed with standard rating scales administered by experienced psychiatrists. Upon descriptive and Cox regression analyses, 17/53 BDs (32%) dropped-out; the overall survival time until drop-out was 57.94 ± 17.79 days. BD drop-outs were younger, had an earlier age at onset, shorter illness duration, lower rates of lifetime obsessive-compulsive disorder/suicidal behavior, higher rates of substance use disorder (SUD), anxious and mixed features of depression compared to BDs attending up to six months. Among MDD patients, 10/78 cases (13%) dropped-out by month-6 with an average survival of 42.40 ± 16.45 days. Earlier age of onset, younger age, positive family history for mood disorders, lower rates of lifetime generalized anxiety disorder were significantly more frequent among drop-outs than completers, as opposite to SUD, and lifetime recurrent depression. Older age predicted lower drop-out among BDs and MDDs, although with almost null hazard ratio (HR) = 0.928, p < 0.01 vs. HR = 0.941, p < 0.01, respectively. Higher rates of lifetime SUD predicted higher drop-out rates by month-6 among MDDs (HR = 5.477, p = 0.02). Limitations of the study: retrospective design, small sample size, lack of objective measures of treatment-adherence/mood rating during follow-up. Drop-out is common in the real-world setting, warranting specific interventions since the beginning of the treatment.

Background There are scarce and discrepant data about the prevalence and correlates of co-occurring eating disorders (EDs) among people with a primary diagnosis of bipolar disorder (BD), and vice-versa, compelling a systematic review and meta-analysis on the matter. Methods MEDLINE/PsycINFO databases were systematically searched for original studies documenting BD⇌ED comorbidity across the lifespan, from inception up until April 20th, 2020. Random-effects meta-analysis and meta-regression analyses were conducted, accounting for multiple moderators. Results Thirty-six studies involved 15,084 primary BD patients. Eleven studies encompassed 15,146 people with primary EDs. Binge eating disorder (BED) occurred in 12.5% (95%C.I.=9.4-16.6%, I2=93.48%) of BDs, while 9.1% (95%C.I.=3.3-22.6%) of BEDs endorsed BD. Bulimia Nervosa (BN) occurred in 7.4% (95%C.I.=6-10%) of people with BD, whereas 6.7% (95%C.I.=12-29.2%) of subjects with BN had a diagnosis of BD. Anorexia Nervosa (AN) occurred in 3.8% (95%C.I.=2-6%) of people with BDs; 2% (95%C.I.=1-2%) of BD patients had a diagnosis of AN. Overall, BD patients with EDs had higher odds of being female vs. non-ED controls. Several moderators yielded statistically significant differences both within- and between different types of BDs and EDs. Limitations Scant longitudinal studies, especially across different EDs and pediatric samples. High heterogeneity despite subgroup comparisons. Limited discrimination of the quality of the evidence. Conclusions The rates of BD⇌ED comorbidity vary across different diagnostic groups, more than they do according to the “direction” of BD⇌ED. Further primary studies should focus on the risks, chronology, clinical impact, and management of the onset of intertwined BD⇌ED across different ages, promoting a continuum approach.

BackgroundThe elderly population and numbers of nursing homes residents are growing at a rapid pace globally. Uncertainty exists regarding the actual rates of major depressive disorder (MDD), bipolar disorder and schizophrenia as previous evidence documenting high rates relies on suboptimal methodology.AimsTo carry out a systematic review and meta-analysis on the prevalence and correlates of MDD, bipolar disorder and schizophrenia spectrum disorder among nursing homes residents without dementia.MethodMajor electronic databases were systematically searched from 1980 to July 2017 for original studies reporting on the prevalence and correlates of MDD among nursing homes residents without dementia. The prevalence of MDD in this population was meta-analysed through random-effects modelling and potential sources of heterogeneity were examined through subgroup/meta-regression analyses.ResultsAcross 32 observational studies encompassing 13 394 nursing homes residents, 2110 people were diagnosed with MDD, resulting in a pooled prevalence rate of 18.9% (95% CI 14.8–23.8). Heterogeneity was high (I2 = 97%, P≤0.001); no evidence of publication bias was observed. Sensitivity analysis indicated the highest rates of MDD among North American residents (25.4%, 95% CI 18–34.5, P≤0.001). Prevalence of either bipolar disorder or schizophrenia spectrum disorder could not be reliably pooled because of the paucity of data.ConclusionsMDD is highly prevalent among nursing homes residents without dementia. Efforts towards prevention, early recognition and management of MDD in this population are warranted.

Objective: Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of treatment of major depressive disorder (MDD). However, non-response is common, often necessitating combination strategies. The present study assessed the efficacy of vortioxetine as an add-on therapy in patients with SSRI-resistant MDD. Methods: The charts of 36 adult outpatients with DSM-IV-TR MDD who had not achieved a response after at least 8 weeks of treatment with an SSRI were reviewed retrospectively. Subjects were treated with vortioxetine (5-20 mg/day) for 8 weeks added to the current SSRI. The main outcome measures were change from baseline in total Hamilton Scale for Depression (HAM-D) score and the rate of response (a 50% or greater reduction in HAM-D score and a Clinical Global Impression ‐ Improvement module [CGI-I] score of 1 or 2 at endpoint). HAM-D scores ≤ 7 were considered as remission. Additional outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Scale for Suicide Ideation (SSI). Results: 32 patients completed the 8 weeks of treatment. At 8 weeks, a significant reduction in HAM-D score was observed (p ≤ 0.001), with response obtained by 41.7% and remission by 33.3% of patients. Significant reductions in SHAPS and SSI were also observed (p ≤ 0.001 for both scales). Conclusions: Adjunctive vortioxetine may be useful and well-tolerated in stage I treatment-resistant depression. However, the limitations of this study (such as small sample size, absence of randomization and control group, retrospective design, etc.) must be considered.

Background: The definitions of treatment-resistant bipolar disorder (TRBD) have varied across studies. Additionally, its management is clinically challenging. An updated synthesis and appraisal of the available evidence is needed. Methods: A systematic search of major electronic databases from inception up to May 25th, 2020, was conducted to identify randomized controlled trials (RCTs) of pharmacological and non-pharmacological interventions for the management of TRBD. When sufficient evidence was available, a meta-analysis was conducted. Results: Seventeen studies (n = 928 patients) were included in the qualitative synthesis. Fourteen studies (n = 803) assessed treatment-resistant acute bipolar depression (TRBD-De), including five neuromodulatory and nine pharmacological trials. Rapid- vs. standard up-titration of clozapine showed promising efficacy for TRBD mania, without significant adverse events. Electroconvulsive therapy (ECT) was confirmed to be similarly effective for TRBD-De as for treatment-resistant unipolar depression: odd ratio, OR = 0.919 (95%C.I. = 0.44–1.917), I2 = 13.98, p = .822. TRBD-De patients exposed to ketamine at day one post-infusion had high odds of response: OR = 10.682 (95%C.I. = 2.142–53.272), I2 = 0, p =

Objective: The present exploratory study aimed to investigate relationships between alexithymia, suicide ideation, affective temperaments and homocysteine levels among drug-naïve adult outpatients with Post-Traumatic Stress Disorder (PTSD) in an everyday ‘real world’ clinical setting. Method: Sixty-four adult outpatients with PTSD were evaluated using the Davidson Trauma Scale (DTS), the Toronto Alexithymia Scale (TAS–20), the Scale of Suicide Ideation (SSI), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire. As well, homocysteine levels were measured. Results: Alexithymic subjects showed higher values on all scales but not homocysteine levels. Partial correlations showed that almost all studied variables were correlated with each other, except homocysteine levels. Regression analysis showed that higher disorder severity as measured by DTS and TAS-20 ‘Difficulty in Identifying Feelings’ dimension was associated with higher SSI scores. Conclusions: In conclusion, alexithymic PTSD outpatients may be characterised by higher disorder severity and difficulty in identifying feelings that may be linked to increased suicide ideation, regardless of affective temperaments or homocysteine levels. Homocysteine levels were not related to any studied variable. However, study limitations are discussed and must be considered. Keypoints Patients with alexithymia showed increased PTSD severity, a higher score on TEMPS-A subscales, and more severe suicide ideation. The Difficulty in Identifying Feelings (DIF) dimension of TAS-20 was associated with suicide ideation in patients with PTSD. Homocysteine did not correlate with any studied variables. This study was exploratory and cross-sectional: further larger and prospective studies are needed.

OBJECTIVE: Uncertainty surrounds the risks of lithium use during pregnancy in women with bipolar disorder. The authors sought to provide a critical appraisal of the evidence related to the efficacy and safety of lithium treatment during the peripartum period, focusing on women with bipolar disorder and their offspring. METHODS: The authors conducted a systematic review and random-effects meta-analysis assessing case-control, cohort, and interventional studies reporting on the safety (primary outcome, any congenital anomaly) or efficacy (primary outcome, mood relapse prevention) of lithium treatment during pregnancy and the postpartum period. The Newcastle-Ottawa Scale and the Cochrane risk of bias tools were used to assess the quality of available PubMed and Scopus records through October 2018. RESULTS: Twenty-nine studies were included in the analyses (20 studies were of good quality, and six were of poor quality; one study had an unclear risk of bias, and two had a high risk of bias). Thirteen of the 29 studies could be included in the quantitative analysis. Lithium prescribed during pregnancy was associated with higher odds of any congenital anomaly (N=23,300, k=11; prevalence=4.1%, k=11; odds ratio=1.81, 95% CI=1.35-2.41; number needed to harm (NNH)=33, 95% CI=22-77) and of cardiac anomalies (N=1,348,475, k=12; prevalence=1.2%, k=9; odds ratio=1.86, 95% CI=1.16-2.96; NNH=71, 95% CI=48-167). Lithium exposure during the first trimester was associated with higher odds of spontaneous abortion (N=1,289, k=3, prevalence=8.1%; odds ratio=3.77, 95% CI=1.15-12.39; NNH=15, 95% CI=8-111). Comparing lithium-exposed with unexposed pregnancies, significance remained for any malformation (exposure during any pregnancy period or the first trimester) and cardiac malformations (exposure during the first trimester), but not for spontaneous abortion (exposure during the first trimester) and cardiac malformations (exposure during any pregnancy period). Lithium was more effective than no lithium in preventing postpartum relapse (N=48, k=2; odds ratio=0.16, 95% CI=0.03-0.89; number needed to treat=3, 95% CI=1-12). The qualitative synthesis showed that mothers with serum lithium levels

Background Hospitalization accounts for significant health care resource utilization for treatment-resistant Bipolar Disorder (BD), especially among frequent users of acute inpatient psychiatric units. Appraisal of the clinical features and predictive role of selected variables is therefore crucial in such population, representing the aim of the present research. Methods A hundred and nineteen BD inpatients with an established history of pharmacological treatment resistance for either mania or bipolar depression were classified as long hospitalization cases (LOS+) and their controls and compared against each other for a number of demographic, clinical, and psychopathological features. Results Overall, female sex, current second-generation atypical antipsychotic (SGA)/mood stabilizer other than lithium as well as antidepressant treatment at the admission occurred statistically more frequently among LOS+ cases, concordant with higher scores at the Hamilton scales for depression and anxiety. Lithium utilization at the time of hospitalization did not differ between cases and controls (LOS-, n = 81/119), as predominant affective temperament and other psychopathological rating did not. Overall, the time of admission, use of SGA, anticonvulsant (other than lithium), antidepressant, lifetime alcohol dependence, and BD Type (-I or -II), but not current mood polarity at the time of hospitalization, correctly predicted LOS+ grouping 68.2% of the times: Exp(B) = 3.151, p042. Limitations Post-hoc, cross-sectional study, relatively small sample size, recall and selection bias on some diagnoses. Conclusions Overall, LOS+ treatment-resistant BD inpatients characterize for higher severity and greater pharmaco-utilization use, which warrants replication studies to include additional predictors to shed further light on the matter.

Introduction: Bipolar disorder (BD) is a considerable burden to the affected individual. The need for novel drug targets and improved drug design (DD) in BD is therefore clear. Areas covered: The following article provides a brief, narrative, clinician-oriented overview of the most promising novel pharmacological targets for BD along with a concise overview regarding the general DD process and the unmet needs relevant to BD. Expert opinion: A number of novel potential drug targets have been investigated. With the notable exception of the kynurenine pathway, available evidence is too scarce to highlight a definitive roadmap for forthcoming DD in BD. BD itself may present with different facets, as it is a polymorphic clinical spectrum. Therefore, promoting clinical-case stratification should be based on precision medicine, rather than on novel biological targets. Furthermore, the full release of raw study data to the scientific community and the development of uniform clinical trial standards (including more realistic outcomes) should be promoted to facilitate the DD process in BD.

Introduction:Treatment-resistant depression (TRD), seldom interchangeably referred to as 'depression inadequately responding to the standard antidepressant drug,' carries a significant burden. The atypical antipsychotics represent a popular augmentation strategy for antidepressant-resistant depression, although their efficacy/safety profiles vary across different agents and presentations of depression. Areas covered: This review appraises the evidence supporting the use of brexpiprazole augmentation for major depressive disorder (MDD) adults showing an inadequate response to standard antidepressants, covering the related regulatory affairs, and essential pharmacology. Expert opinion: Brexpiprazole is a 'third-generation' antipsychotic featuring dopaminergic D2 and serotonergic 5-HT1A partial agonism approved by the U.S. Food and Drug Administration for the treatment of MDD, besides schizophrenia in adults. The clinical trials leading to the extended approval of brexpiprazole rely on the definition of 'inadequate response' to antidepressants, which seems to poorly represent the most severe cases of TRD seen in clinical practice. TRD definitions appraised in the literature are likewise inconsistent and questionable from a clinical-standpoint. Compared to aripiprazole, brexpiprazole has lower D2 intrinsic activity, although the latter features a more potent serotonergic 5-HT2A antagonism. The actual propensity of brexpiprazole to induce akathisia and tardive dyskinesia warrants assessment by ad-hoc designed long-term, controlled trials.

Schizophrenia is a chronic and debilitating illness affecting about 0.5% of the population. Antipsychotics are the mainstay of the pharmacological treatment of such burdensome condition, although documented that roughly 20% up to 60% of the patients with schizophrenia do not respond sufficiently to conventional treatments. These patients may have a good response when clozapine is introduced with a great efficacy often seen in everyday clinical practice. However, it has been estimated that around 40–70% of patients with ascertained treatment-resistant schizophrenia receiving clozapine may have an incomplete remission and are referred to as “ultra-resistant” or “refractory.” Clozapine-resistant schizophrenia represents a challenge for the clinician and a misfortune for the patients, and several strategies have been proposed to overcome this problem, yet, to date, it remains high-bar goal. The aim of this chapter was to provide an overview of the managing strategies of clozapine-resistant schizophrenia with a particular focus on augmentation strategies aimed to improve efficacy on schizophrenia symptoms.

Aripiprazole is an atypical antipsychotic drug with a polypharmacological mechanism of action and a favorable tolerability profile. Its major indications are schizophrenia and mania in adults and adolescents. Here we present the case of a 43-year-old Caucasian man with schizophrenia who developed atrial fibrillation (AF) after starting aripiprazole treatment. Prior to this treatment, he had never received any antipsychotic drugs. On admission to our inpatient unit, he showed severe psychotic symptoms and was started on aripiprazole with a rapid titration regimen (15 mg on the first day and then 15 mg twice daily thereafter) in combination with lorazepam (2.5 mg thrice a day). On the third day, the patient exhibited vomiting and an irregular pulse. An electrocardiogram (ECG) revealed new-onset AF with rapid ventricular response. Aripiprazole was discontinued and cardioversion was obtained with intravenous amiodarone. A different antipsychotic treatment was thus started (perphenazine 12 mg/d), which led to symptom remission without any relevant adverse effects. During the 2-year follow-up observation, neither psychotic symptoms nor ECG abnormalities were detected. Besides aripiprazole, other co-occurring factors might have contributed to the onset of AF in our patient, namely hypertension, low-grade diastolic dysfunction, chronic inflammatory disease, CYP2D6 polymorphism, corticosteroid and antiulcer treatment, and a family loading for myocardial infarction. In conclusion, our case study suggests that although aripiprazole has fewer cardiovascular effects than other antipsychotic drugs, in the presence of concomitant risk factors, high dose, and rapid titration regimen, regular monitoring of clinical parameters and ECG is highly recommended. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Background Treatment-emergent affective switch (TEAS), including treatment-emergent mania (TEM), carry significant burden in the clinical management of bipolar depression, whereas the use of antidepressants raises both efficacy, safety and tolerability concerns. The present study assesses the prevalence and clinical correlates of TEM in selected sample of Bipolar Disorder (BD) Type-II (BD-II) acute depression outpatients. Methods Post-hoc analysis of the clinical and psychopathological features associated with TEM among 91 BD-II depressed outpatients exposed to antidepressants. Results Second-generation antipsychotics (SGA) (p = .005), lithium (≤ .001), cyclothymic/irritable/hyperthymic temperaments (p = ≤ .001; p = .001; p = .003, respectively), rapid-cycling (p = .005) and depressive mixed features (p = .003) differed between TEM+ cases vs. TEM− controls. Upon multinomial logistic regression, the accounted psychopathological features correctly classified as much as 88.6% of TEM+ cases (35/91 overall sample, or 38.46% of the sample), yet not statistically significantly [Exp(B) = .032; p = ns]. Specifically, lithium [B = − 2.385; p = .001], SGAs [B = − 2.354; p = .002] predicted lower rates of TEM+ in contrast to the number of lifetime previous psychiatric hospitalizations [B = 2.380; p = .002], whereas mixed features did not [B = 1.267; p = ns]. Limitations Post-hoc analysis. Lack of systematic pharmacological history record; chance of recall bias and Berkson's biases. Permissive operational criterion for TEM. Relatively small sample size. Conclusions Cyclothymic temperament and mixed depression discriminated TEM+ between TEM− cases, although only lithium and the SGAs reliably predicted TEM+/− grouping. Larger-sampled/powered longitudinal replication studies are warranted to allow firm conclusions on the matter, ideally contributing to the identification of clear-cut sub-phenotypes of BD towards patient-tailored-pharmacotherapy.

Background: Treatment-emergent mania (TEM) represents a common phenomenon inconsistently reported across primary studies, warranting further assessment. Methods: A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were conducted. Major electronic databases were searched from inception to May 2017 to assess the incidence and prevalence rates and clinical features associated with manic switch among bipolar depressed patients receiving antidepressants, using meta-regression and subgroup analysis. Results: Overall, 10098 depressed patients with bipolar disorder (BD) across 51 studies/arms were included in the quantitative analysis. The cumulative incidence of cases (TEM+) among 4767 patients with BD over 15 retrospective studies was 30.9% (95% confidence interval [CI] 19.6-45.0%, I2=97.9%). The cumulative incidence of TEM+ among 1929 patients with BD over 12 prospective open studies was 14.4% (95% CI 7.4-26.1%, I2=93.7%). The cumulative incidence of TEM+ among 1316 patients with BD over 20 randomized controlled trials (RCTs) was 11.8% (95% CI 8.4-16.34%, I2=73.46%). The pooled prevalence of TEM+ among 2086 patients with BD over four cross-sectional studies was 30.9% (95% CI 18.1-47.4%, I2=95.6%). Overall, concurrent lithium therapy predicted the lowest TEM rates. Inconsistent operational definitions of TEM were recorded, and the lack of information about age, sex, co-occurring anxiety, and other clinically relevant moderators precluded further stratification of the results. Conclusions: Rates of TEM vary primarily depending on study setting, which is concordant with the high degree of heterogeneity of the included records. Forthcoming RCT studies should adopt consistent operational definitions of TEM and broaden the number of moderators, in order to contribute most effectively to the identification of clear-cut sub-phenotypes of BD and patient-tailored pharmacotherapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Background Presupplementary motor area (pre-SMA) hyperactivity has been detected in obsessive–compulsive disorder (OCD) patients. However, it is not understood whether this is a putative primary cause or a compensatory mechanism in OCD pathophysiology. Considering the polarity-dependent effects on cortical excitability of transcranial direct current stimulation (tDCS), we applied cathodal and/or anodal tDCS to the pre-SMA of OCD patients to test which current polarity might better improve symptoms. Methods Twelve OCD patients received initially 10 anodal (n = 6) or cathodal (n = 6) daily consecutive 2 mA/20 min tDCS sessions with the active electrode placed bilaterally on the pre-SMA. In case of improvement or no change in symptoms severity, the subjects were maintained on the same current polarity for 10 more sessions. In case of symptoms worsening after the first 10 sessions they were switched to the other polarity for 10 more sessions to test the hypothesis of a polarity-dependent effect. Therefore, each subject received 20 tDCS sessions. The Yale-Brown Obsessive–Compulsive Scale (Y-BOCS) and the Sheehan Disability Scale (SDS) were administered biweekly to assess changes in symptoms severity. Results After 10 sessions, 50% of patients who initially received anodal stimulation were switched to cathodal, while 100% of patients initially assigned to cathodal stimulation continued on the same polarity. At the end of the study, a statistically significant decrease was observed in the mean Y-BOCS scores of those patients who underwent cathodal tDCS. No pre–post difference was found in the scores of patients following anodal tDCS. Conclusions Cathodal but not anodal tDCS over the pre-SMA significantly improved OCD symptoms.

Annalisa Anastasia,1 Chiara Colletti,1 Valentina Cuoco,1 Adele Quartini,1 Stefania Urso,2 Raffaella Rinaldi,2 Giuseppe Bersani1 1Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, 2Department of Anatomical, Istological, Forensic and Locomotor System Sciences, Sapienza University of Rome, Rome, Italy Introduction: Although adjustment disorder (AD) is considered as residual diagnosis and receives little attention in research, it plays an important role in clinical practice and also assumes an increasingly important role in the field of legal medicine, where the majority of diagnostic frameworks (eg, mobbing) often refer to AD. Our study aimed to look for specific stressor differences among demographic and clinical variables in a naturalistic setting of patients with AD.Methods: A restrospective statistical analysis of the data of patients diagnosed with AD from November 2009 to September 2012, identified via manual search from the archive of the outpatient setting at the University Unit of Psychiatry “A. Fiorini” Hospital, Terracina (Latina, Italy), was performed.Results: The sample consisted of 93 patients (46 males and 47 females), aged between 26 and 85, with medium–high educational level who were mainly employed. In most cases (54.80%), a diagnosis of AD with mixed anxiety and depressed mood was made. In all, 72% of the sample reported a negative family history for psychiatric disorders. In 22.60%, a previous history of psychopathology, especially mood disorders (76.19%), was reported. The main stressors linked to the development of AD were represented by working problems (32.30%), family problems (23.70%), and/or somatic disease (22.60%) with significant differences with respect to age and sex. Half of the patients were subjected to a single first examination; 24.47% requested a copy of medical records.Conclusion: Confirming previous data from previous reports, our results suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications. Keywords: adjustment disorder, diagnostic criteria, stressor, mobbing, medicolegal

Shared psychotic disorder (folie à deux) is a rare condition characterized by the transmission of delusional aspects from a patient (the "dominant partner") to another (the "submissive partner") linked to the first by a close relationship. We report the case of two Moroccan sisters who have experienced a combined delusional episode diagnosed as shared psychotic disorder. In these circumstances, assessment of symptoms from a cross-cultural perspective is a key factor for proper diagnostic evaluation.

Over the past twenty years, in Italy there has been an intense debate that has focused on the function, and overcoming the limits of the institution Judicial Psychiatric Hospital (ospedale psichiatrico giudiziario - OPG). Although the contribution of legislative proposals, conferences and workshops on the OPG subject has received significant, the interest focused on the development and elaboration of criminological and epidemiological research on a national scale has been proportionately less impetum. In this study a survey aimed to explore the socio-demographic, clinical and criminological features of patients discharged from the OPG and admitted to neuropsychiatric clinic, under the restriction of freedom, has been performed.The information was gathered at the time of entry in the clinical management, by means of the first clinical interview and during subsequent interviews. During hospitalization, patients were administered the Mini-Mental State Examination (MMSE) and K Axis (Axis V of Kennedy) questionaires.23 patients from forensic hospitals of Aversa, Secondigliano and Castiglione delle Stiviere were included in the study. The main characteristics investigated delineate a profile of an individual with an average age of about 49 years, unmarried, from a low socio-economic context, unemployed at the time of internment. About the diagnosis, schizophrenic spectrum disorders prevail, there is history of substance abuse in 35% of cases, history of previous admission to psychiatric facilities in 87% of these subjects. The type of committed crimes regards crimes against the person. About 40% of individuals have exhausted the danger to society correlate at the time of admission.Despite the small sample size, the data from this study are consistent with those reported in few studies in the literature. The specificity of clinical care needs of mentally ill offenders requires greater definition that could be achieved through the development of this research area.

Giuseppe Bersani,1 Francesco Saverio Bersani,1,2 Giuseppe Valeriani,1 Maddalena Robiony,1 Annalisa Anastasia,1 Chiara Colletti,1,3 Damien Liberati,1 Enrico Capra,2 Adele Quartini,1 Elisa Polli11Department of Medical-Surgical Sciences and Biotechnologies, 2Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, 3Department of Neuroscience and Behaviour, Section of Psychiatry, Federico II University of Naples, Naples, ItalyBackground: Research shows that impairment in the expression and recognition of emotion exists in multiple psychiatric disorders. The objective of the current study was to evaluate the way that patients with schizophrenia and those with obsessive-compulsive disorder experience and display emotions in relation to specific emotional stimuli using the Facial Action Coding System (FACS).Methods: Thirty individuals participated in the study, comprising 10 patients with schizophrenia, 10 with obsessive-compulsive disorder, and 10 healthy controls. All participants underwent clinical sessions to evaluate their symptoms and watched emotion-eliciting video clips while facial activity was videotaped. Congruent/incongruent feeling of emotions and facial expression in reaction to emotions were evaluated.Results: Patients with schizophrenia and obsessive-compulsive disorder presented similarly incongruent emotive feelings and facial expressions (significantly worse than healthy participants). Correlations between the severity of psychopathological condition (in particular the severity of affective flattening) and impairment in recognition and expression of emotions were found.Discussion: Patients with obsessive-compulsive disorder and schizophrenia seem to present a similarly relevant impairment in both experiencing and displaying of emotions; this impairment may be seen as a chronic consequence of the same neurodevelopmental origin of the two diseases. Mimic expression could be seen as a behavioral indicator of affective flattening. The FACS could be used as an objective way to evaluate clinical evolution in patients.Keywords: schizophrenia, obsessive-compulsive disorder, facial expression, Facial Action Coding System

Affective flattening and the consequent anomalous expression of emotions are considered as key elements of the negative symptoms of schizophrenia. The purpose of this work is to assess how a survey instrument based on objective evaluation of emotional facial expressiveness (FACS) and a method of elicitation of emotions (film clips) can provide psychopathological manifestations about schizophrenia.Relevant literature was identified through a search of Medline, PsychInfo and PubMed. Search terms included: "elicitation of emotions", "facial action coding system" and "schizophrenia". The research was limited to English-language publications and studies conducted exclusively in humans.The overall evaluation of the studies analyzed in this work show that the FACS is a useful tool to highlight specific clinical characteristics of schizophrenic patients with significant deficits in the expression and recognition of emotions, such as the status of hospitalization, the age of onset, the treatment with antipsychotic drugs, the SANS, SAPS and BPRS scores.Even if we have preliminary and incomplete data, the FACS and the elicitation of emotions through film clips can give an original contribution to the development of knowledge on pathophysiological events and interpretive models of schizophrenia.