Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.

Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.

Effects of electroconvulsive therapy on cortical thickness in depression: a systematic review.

OBJECTIVE: Electroconvulsive therapy (ECT) is one of the most studied and validated available treatments for severe or treatment-resistant depression. However, little is known about the neural mechanisms underlying ECT. This systematic review aims to critically review all structural magnetic resonance imaging studies investigating longitudinal cortical thickness (CT) changes after ECT in patients with unipolar or bipolar depression. METHODS: We performed a search on PubMed, Medline, and Embase to identify all available studies published before April 20, 2023. A total of 10 studies were included. RESULTS: The investigations showed widespread increases in CT after ECT in depressed patients, involving mainly the temporal, insular, and frontal regions. In five studies, CT increases in a non-overlapping set of brain areas correlated with the clinical efficacy of ECT. The small sample size, heterogeneity in terms of populations, comorbidities, and ECT protocols, and the lack of a control group in some investigations limit the generalisability of the results. CONCLUSIONS: Our findings support the idea that ECT can increase CT in patients with unipolar and bipolar depression. It remains unclear whether these changes are related to the clinical response. Future larger studies with longer follow-up are warranted to thoroughly address the potential role of CT as a biomarker of clinical response after ECT.

Vagus Nerve Stimulation in Treatment-Resistant Depression: A Case Series of Long-Term Follow-up.

OBJECTIVES: Vagus nerve stimulation (VNS) has been shown to be effective for treatment-resistant depression (TRD). However, long-term (>5 years) studies on the efficacy and tolerability of this treatment have been lacking. Here, we report a long-term clinical follow-up of 5 patients with severe and long-standing TRD, who received a VNS implant. METHODS: Of the initial 6 patients with TRD implanted with VNS at our center, 5 of them were followed for 6 to 12 years after implantation. Primary efficacy outcomes were clinical response and improved functioning at follow-up visits. The primary safety outcome was all-cause discontinuation, and the secondary safety outcomes were the number and the severity of adverse events. RESULTS: The VNS implant was associated with a sustained response (>10 years) in terms of clinical response and social, occupational, and psychological functioning in 3 patients. Two patients dropped out after 6 and 7 years of treatment, respectively. Vagus nerve stimulation was well tolerated by all patients, who reported only mild adverse effects. One patient, who discontinued concomitant drug treatment, had a hypomanic episode in the 10th year of treatment. The parameters of the VNS device were fine-tuned when life stressors or symptom exacerbation occurred. CONCLUSIONS: Our case series showed that VNS can have long-term and durable effectiveness in patients with severe multiepisode chronic depression, and this could be associated with its neuroplastic effects in the hippocampus. In light of good general tolerability, our findings support VNS as a viable treatment option for TRD.

Treatment persistence with aripiprazole once monthly: a 4-year follow-up.

OBJECTIVES: Treatment persistence refers to the act of continuing a treatment as prescribed and reflects the patient's or doctor's judgment about efficacy, tolerability, and acceptability. In patients with schizophrenia, antipsychotic persistence is often poor, because of issues such as lack or loss of efficacy, side effects, and poor adherence, which is often related to the degree to which patients find the medication and overall intervention to be helpful, tolerable, fair, reasonable, appropriate, and consistent with expectations of treatment. Despite the poor antipsychotic persistence that has been reported to date in patients with schizophrenia, we previously observed a relatively high (86%) 6 months persistence with aripiprazole once-monthly (AOM) in a group of patients with schizophrenia, treated in the real world Italian clinical practice. The present study explores the longer term persistence with AOM, over a mean follow-up period of 48 months. METHODS: This was a multicenter, retrospective, non-interventional follow-up study, aimed at evaluating the longer term persistence with AOM in a group of patients with schizophrenia who had already shown persistence over a period of at least 6 months. The study included 161 individuals who had participated in our previous study, where 86% of participating individuals had shown persistence with AOM for at least 6 months. Non-persistence was defined as discontinuing the medication for any reason. Baseline demographic and clinical characteristics of patients who continued AOM were then compared to those of patients who discontinued the medication. RESULTS: Study subjects were predominantly male (64.4%) and their mean age was 39.7 (SD: 12.24). Treatment persistence with AOM was 69.6% and 112 out of 161 patients were still receiving AOM treatment at the last follow-up visit. The mean duration of AOM treatment until the last recorded observation was 55.87 months (median 56.17, SD6.23) for the 112 persistent patients and 32.23 (median 28.68.SD 15.09) months for the 49 non-persistent individuals. The mean observation period for all patients (persistent and non-persistent) was 48.78 months (median 52.54, SD 14.64). For non-persistent subjects, the observation period ended with the discontinuation of AOM. Subjects treated with AOM at 400 mg presented a 69.6% lower risk of all-cause treatment discontinuation when compared with patients treated with 300 mg (HR: 0.314; 95% confidence interval [CI] 0.162-0.608; P = 0.001). The main reasons for discontinuation were lack of efficacy (30.6%), patient/caregiver choice (18.4%), physician's choice (16.3%), non-adherence (12.2%) and inconvenience (6.1%). Only 3 patients (6.1%) discontinued AOM for tolerability issues. CONCLUSIONS: In subjects with schizophrenia, who had already shown a 6 months persistence with AOM, a high number of patients (69.6%) continued to be persistent over a 4-year follow-up period. This may reflect a favourable profile of efficacy, tolerability, and acceptability. Larger and prospective studies are warranted to confirm our observations.

Longitudinal Course of Depressive, Anxiety, and Posttraumatic Stress Disorder Symptoms After Heart Surgery: A Meta-Analysis of 94 Studies.

OBJECTIVE: This study aimed to analyze the longitudinal course of depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms in patients with cardiac disease after heart surgery (HS). METHODS: We conducted a systematic review and random-effects meta-analysis of cohort studies in patients undergoing HS, measuring anxiety, depressive, and PTSD symptoms before and at least 30 days thereafter. Subgroup and meta-regression analyses, investigation of publication bias, and quality assessment were undertaken. RESULTS: We included 94 studies relating to 15,561 patients. HS included coronary artery bypass graft surgery, valve replacement, implantable cardioverter-defibrillator placement, left ventricular assist device placement, heart transplantation, and other types of HS. Across studies, symptoms of depression (g = 0.32; 95% confidence interval [CI] = 0.25 to 0.39; p < .001) and anxiety improved after HS (g = 0.52; 95% CI = 0.43 to 0.62; p < .001), whereas PTSD symptoms worsened (g = -0.42; 95% CI = -0.80 to -0.04; p = .032). The reduction of depression and anxiety levels was more pronounced for patients with underlying coronary artery disease and heart failure and persisted for 1 year after HS, whereas the increase in PTSD symptoms returned to baseline after 6 months. Depression improvement was inversely associated with older age, diabetes, hypertension, and dyslipidemia and positively with baseline heart failure. No additional clinical or demographic variables were associated with the course of anxiety symptoms. Quality of included studies was low overall. Publication bias was nonsignificant. CONCLUSIONS: Depressive and anxiety symptoms improve for 1 year after HS, whereas PTSD symptoms might worsen. Older patients and those with metabolic comorbidities, valve disease, or ventricular arrhythmias are at higher risk for continued depressive and anxiety symptoms and should be monitored closely.

Hippocampal Gray Volumes Increase in Treatment-Resistant Depression Responding to Vagus Nerve Stimulation.

BACKGROUND: Changes in hippocampal gray matter volumes are proposed to be involved in pathogenesis, course, and treatment response of major depressive disorder. Converging evidence suggests that reduced neurogenesis may occur in treatment-resistant depression (TRD). Vagus nerve stimulation (VNS) is a well-defined, long-term brain stimulation treatment for TRD. However, its in vivo positive effect on hippocampal modulation as mechanism of action has never been investigated before in clinical studies. In this study, we intended to explore hippocampal volumetric changes and clinical antidepressant responses in patients with TRD after 6 and 12 months of treatment with VNS. METHODS: The TRD outpatients were evaluated for VNS implantation. Right and left hippocampal volumes in 6 TRD patients, who met the criteria for VNS treatment, were measured at baseline before the implantation and after 6 and 12 months. The patients were assessed using Beck Depression Inventory and Hamilton Depression Rating Scale at baseline and at follow-up visits. RESULTS: There was a statistically significant and progressive increase in right and left hippocampal volumes during the follow up (P < 0.05). Furthermore, patients showed a significant improvement on Hamilton Depression Rating Scale and Beck Depression Inventory scores (P < 0.05). CONCLUSIONS: Our data suggest a VNS modulatory effect on hippocampal plasticity as measured by hippocampal gray volume increase in TRD patients. These preliminary findings indicate the fundamental role of hippocampal remodeling as a marker of response to VNS in TRD.

Electroconvulsive Therapy in a Patient With Chronic Catatonia: Clinical Outcomes and Cerebral 18[F]Fludeoxyglucose Positron Emission Tomography Findings.

Catatonia is a psychomotor syndrome that can be associated with both psychiatric diseases (mainly mood disorders, but also psychotic disorders) and medical conditions. Lorazepam (6-21 mg/day, occasionally up to 30 md/day) is the first choice treatment and electroconvulsive therapy (ECT) is the second line, regardless of the underlying clinical condition. There are some evidences also for effectiveness of other medications. Patients treated acutely usually show rapid and full therapeutic response but even longstanding catatonia can improve. However, some authors suggested that chronic catatonia in the context of schizophrenia is phenomenologically different and less responsive to lorazepam and ECT, especially if associated with echophenomena. We present here the case of a patient with longstanding catatonic schizophrenia treated with antipsychotics who significantly improved after ECT. Improvement regarded mainly catatonia, but also negative symptoms, cognition and psychosocial functioning. A slight amelioration in prefrontal metabolism (Brain[F]FDG PET) one month following the ECT course was also noted.

Data-driven analysis of regional brain metabolism in behavioral frontotemporal dementia and late-onset primary psychiatric diseases with frontal lobe syndrome: A PET/MRI study.

Late-onset primary psychiatric disease (PPD) and behavioral frontotemporal dementia (bvFTD) present with a similar frontal lobe syndrome. We compare brain glucose metabolism in bvFTD and late-onset PPD and investigate the metabolic correlates of cognitive and behavioral disturbances through FDG-PET/MRI. We studied 37 bvFTD and 20 late-onset PPD with a mean clinical follow-up of three years. At baseline evaluation, metabolism of the dorsolateral, ventrolateral, orbitofrontal regions and caudate could classify the patients with a diagnostic accuracy of 91% (95% CI: 0.81-0.98%). 45% of PPD showed low-grade hypometabolism in the anterior cingulate and/or parietal regions. Frontal lobe metabolism was normal in 32% of genetic bvFTD and bvFTD with motor neuron signs. Hypometabolism of the frontal and caudate regions could help in distinguishing bvFTD from PPD, except in cases with motor neuron signs and/or genetic bvFTD for which brain metabolism may be less informative.

Neural stem/progenitor cells from olfactory neuroepithelium collected by nasal brushing as a cell model reflecting molecular and cellular dysfunctions in schizophrenia.

OBJECTIVES: Neural stem/progenitor cells derived from olfactory neuroepithelium (hereafter olfactory neural stem/progenitor cells, ONSPCs) are emerging as a potential tool in the exploration of psychiatric disorders. The present study intended to assess whether ONSPCs could help discern individuals with schizophrenia (SZ) from non-schizophrenic (NS) subjects by exploring specific cellular and molecular features. METHODS: ONSPCs were collected from 19 in-patients diagnosed with SZ and 31 NS individuals and propagated in basal medium. Mitochondrial ATP production, expression of ß-catenin and cell proliferation, which are described to be altered in SZ, were examined in freshly isolated or newly thawed ONSPCs after a few culture passages. RESULTS: SZ-ONSPCs exhibited a lower mitochondrial ATP production and insensitivity to agents capable of positively or negatively affecting ß-catenin expression with respect to NS-ONSPCs. As to proliferation, it declined in SZ-ONSPCs as the number of culture passages increased compared to a steady level of growth shown by NS-ONSPCs. CONCLUSIONS: The ease and safety of sample collection as well as the differences observed between NS- and SZ-ONSPCs, may lay the groundwork for a new approach to obtain biological material from a large number of living individuals and gain a better understanding of the mechanisms underlying SZ pathophysiology.

Prevalence and Risk Factors for QTc Prolongation in Acute Psychiatric Hospitalization.

Objective: Prolongation of corrected QT (QTc) interval increases the risk of severe ventricular arrhythmias, in particular torsades de pointes. Patients with severe mental illness (SMI) represent a vulnerable population. This study aimed to measure the prevalence of QTc prolongation in inpatients with SMI and to identify risk factors for QTc prolongation.Methods: Demographic, clinical, anthropometric, laboratory, and electrocardiographic information was extracted from the electronic records of a cohort of patients hospitalized in a psychiatry inpatient unit between July 1, 2017, and July 22, 2019. The primary outcome was the estimation of prevalence of QTc prolongation. The secondary outcome was the identification of risk factors for QTc prolongation.Results: A total of 597 admissions were included. Only 1.4% had a QTc > 500 msec, while 11.6% had a QTc > 460 msec. The proportion of women with a QTc > 470 msec was 3.6% and men with a QTc > 450 msec was 7.3%. Several risk factors were individually associated with QTc prolongation. In the multivariate model explaining almost one-third of QTc variance, female sex (P = .04), older age (P = .011), heart rate (P < .001), systolic blood pressure (P = .042), potassium (P = .012), hemoglobin (P = .006), number of antipsychotics (P = .026), and treatment with clotiapine (P = .012) and clozapine (P = .003) were associated with QTc length. Several factors beyond pharmacologic treatment identify subjects at risk for QTc prolongation, and polypharmacotherapy does not seem to increase the risk of QTc prolongation.Conclusions: QTc prolongation was rare in this cohort of SMI inpatients. Most of the risk factors involved in QTc prolongation are unchangeable elements or linked to general medical conditions, and only a few are modifiable factors, including psychotropic treatment.

Validation of the Italian version of the Northoff Catatonia Rating Scale.

PURPOSE: Catatonia is a psychomotor syndrome characterized by heterogeneous motor, behavioral and affective alterations, and, in some cases, neurovegetative abnormalities that can be life-threatening. Although the prevalence estimates of catatonia are 10-20% of the hospitalized population, its clinical recognition remains a challenge for most clinicians. Differently from other catatonia rating scales, the Northoff Catatonia Rating Scale (NCRS) also evaluates the affective alterations that patients experience during catatonia and thus provides a more inclusive assessment of the alterations associated with this condition. To provide clinicians with a valuable tool for diagnosis, we translated the NCRS in Italian and validated it on a sample of 52 hospitalized patients with psychiatric disorders. METHODS: An Italian version of the NCRS was prepared using the forward-backwards translation from English and administered to a sample of 52 in-patients (age 46.9±2.37 years). The inter-rater reliability, score correlations, internal coherence and decision statistics were computed. RESULTS: The inter-rater agreement was higher for the motor subscale (100% agreement) than for the behavioral (94%) or affective subscales (92.3%). The inter-rater agreement was 100% for the diagnosis of catatonia. The NCRS correctly identified all patients with catatonia according to DSM-5 (sensitivity= 100%) and had a specificity of 88.9%, and its subscale scores were highly inter-correlated. CONCLUSIONS: This validation shows that the NCRS yields a good accuracy in diagnosing catatonia and high inter-rater reliability. Moreover, the high correlation between its subscales supports the view that catatonia is a multi-faceted truly psycho-motor syndrome. In conclusion, the validation and Italian translation of the NCRS provides the clinicians with a helpful tool for diagnosing catatonia which is easy to use and assesses the full psychomotor complexity of the syndrome.

Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review.

BACKGROUND: The degree of efficacy, safety, quality, and certainty of meta-analytic evidence of biological non-pharmacological treatments in mental disorders is unclear. METHODS: We conducted an umbrella review (PubMed/Cochrane Library/PsycINFO-04-Jul-2021, PROSPERO/CRD42020158827) for meta-analyses of randomized controlled trials (RCTs) on deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electro-convulsive therapy (ECT), and others. Co-primary outcomes were standardized mean differences (SMD) of disease-specific symptoms, and acceptability (for all-cause discontinuation). Evidence was assessed with AMSTAR/AMSTAR-Content/GRADE. RESULTS: We selected 102 meta-analyses. Effective interventions compared to sham were in depressive disorders: ECT (SMD=0.91/GRADE=moderate), TMS (SMD=0.51/GRADE=moderate), tDCS (SMD=0.46/GRADE=low), DBS (SMD=0.42/GRADE=very low), light therapy (SMD=0.41/GRADE=low); schizophrenia: ECT (SMD=0.88/GRADE=moderate), tDCS (SMD=0.45/GRADE=very low), TMS (prefrontal theta-burst, SMD=0.58/GRADE=low; left-temporoparietal, SMD=0.42/GRADE=low); substance use disorder: TMS (high frequency-dorsolateral-prefrontal-deep (SMD=1.16/GRADE=moderate), high frequency-left dorsolateral-prefrontal (SMD=0.77/GRADE=very low); OCD: DBS (SMD=0.89/GRADE=moderate), TMS (SMD=0.64/GRADE=very low); PTSD: TMS (SMD=0.46/GRADE=moderate); generalized anxiety disorder: TMS (SMD=0.68/GRADE=low); ADHD: tDCS (SMD=0.23/GRADE=moderate); autism: tDCS (SMD=0.97/GRADE=very low). No significant differences for acceptability emerged. Median AMSTAR/AMSTAR-Content was 8/2 (suggesting high-quality meta-analyses/low-quality RCTs), GRADE low. DISCUSSION: Despite limited certainty, biological non-pharmacological interventions are effective and safe for numerous mental conditions. Results inform future research, and guidelines. FUNDING: None.

Neuropsychological and Pet Study of Depersonalization and Derealization: A Single Case Report.

The present work depicts the case of a young man suffering from a depersonalization and derealization (DD) disorder, which mainly affects his own body. When the symptoms concern something else, they almost exclusively affect living beings. Neuropsychological and neuropsychiatric studies, as well as functional neuroanatomy studies, have led to hypothesize possible relationships among cognitive-neurofunctional alterations and symptoms of depersonalization and derealization. The present study suggests that a malfunction of the left frontal and prefrontal cortex causes deficits of working memory, producing some of the symptoms of DD.

How can we improve antidepressant adherence in the management of depression? A targeted review and 10 clinical recommendations.

Adherence to antidepressants is crucial for optimal treatment outcomes when treating depressive disorders. However, poor adherence is common among patients prescribed antidepressants. This targeted review summarizes the main factors associated with poor adherence, interventions that promote antidepressant adherence, pharmacological aspects related to antidepressant adherence, and formulates 10 clinical recommendations to optimize antidepressant adherence. Patient-related factors associated with antidepressant non-adherence include younger age, psychiatric and medical comorbidities, cognitive impairment, and substance use disorders. Prescriber behavior-related factors include neglecting medical and family histories, selecting poorly tolerated antidepressants, or complex antidepressant regimens. Multi-disciplinary interventions targeting both patient and prescriber, aimed at improving antidepressant adherence, include psychoeducation and providing the patient with clear behavioral interventions to prevent/minimize poor adherence. Regarding antidepressant choice, agents with individually tailored tolerability profile should be chosen. Ten clinical recommendations include four points focusing on the patient (therapeutic alliance, adequate history taking, measurement of depressive symptoms, and adverse effects improved access to clinical care), three focusing on prescribing practice (psychoeducation, individually tailored antidepressant choice, simplified regimen), two focusing on mental health services (improved access to mental health care, incentivized adherence promotion and monitoring), and one relating to adherence measurement (adherence measurement with scales and/or therapeutic drug monitoring).

Reduced right posterior hippocampal volume in women with recurrent familial pure depressive disorder.

Volumetric changes in mood-relevant distributed limbic/paralimbic structures have been reported in the recent literature on the course of mood disorders. Patients with unipolar and bipolar disorders have been found to have smaller hippocampal and anterior cingulate volumes. We examined hippocampal, amygdalar and anterior cingulate cortex (ACC) volumes in female patients with recurrent familial pure depressive disorder (rFPDD). We used semi-automated software for magnetic resonance imaging (MRI) to measure the volumes of the hippocampus, amygdala, ACC and subgenual prefrontal cortex (SGPFC) in 15 female patients with familial recurrent major depression (MD) and 15 healthy female subjects. Analysis of covariance, with whole brain volume as covariate, was used to compare volumetric measurements in the two groups. Volumes of the right hippocampal body and tail were significantly smaller in female patients with familial depressive disorder than in healthy subjects. Our data provide evidence of structural lateralized hippocampal body and tail abnormalities in women with familial history and recurrent episodes of depression. Although global reduction of hippocampal volume has been widely reported, data on lateralized regional reductions in familial recurrent depression had not been previously reported. Reduced volume of the right posterior hippocampus could be a structural endophenotype for recurrent depressive disorders in women.

Prevalence of Extrapyramidal Symptoms in In-Patients With Severe Mental Illnesses: Focus on Parkinsonism.

Patients with severe mental illnesses may present extrapyramidal symptoms as part of a concomitant neurological disorder or secondary to medications. Extrapyramidal symptoms are frequently unrecognized, have negative consequences for adherence to treatment, negatively affect quality of life and can induce stigma. We estimated and correlated with demographic and clinical variables prevalence of extrapyramidal symptoms in in-patients with severe mental illnesses. Additionally we evaluated 123I-FP-CIT SPECT binding to striatal dopamine transporter in subjects with clinical manifestations suggestive of Parkinson's Disease and recorded therapeutic management and clinical evolution for 6-months. Extrapyramidal symptoms were present in 144 out of 285 patients (50.5%), mainly tremor (94 patients, 33%). There were 38 patients (13.3%) with parkinsonism and they had older age, more medical comorbidities and medical treatments. In 15/38 patients striatal dopamine transporter binding was abnormal resulting in dose reduction or change of psychotropic drugs as well as combination with antiparkinson therapy. Our study confirmed the clinical and epidemiological relevance of extrapyramidal symptoms among inpatients with severe mental illnesses. A small percentage of patients with extrapyramidal symptoms had features compatible with possible diagnosis of Parkinson's Disease. 123I-FP-CIT SPECT was useful to identify dopaminergic dysfunction and initiate dopamine replacement therapy.

Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders.

The literature on non-genetic peripheral biomarkers for major mental disorders is broad, with conflicting results. An umbrella review of meta-analyses of non-genetic peripheral biomarkers for Alzheimer's disease, autism spectrum disorder, bipolar disorder (BD), major depressive disorder, and schizophrenia, including first-episode psychosis. We included meta-analyses that compared alterations in peripheral biomarkers between participants with mental disorders to controls (i.e., between-group meta-analyses) and that assessed biomarkers after treatment (i.e., within-group meta-analyses). Evidence for association was hierarchically graded using a priori defined criteria against several biases. The Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to investigate study quality. 1161 references were screened. 110 met inclusion criteria, relating to 359 meta-analytic estimates and 733,316 measurements, on 162 different biomarkers. Only two estimates met a priori defined criteria for convincing evidence (elevated awakening cortisol levels in euthymic BD participants relative to controls and decreased pyridoxal levels in participants with schizophrenia relative to controls). Of 42 estimates which met criteria for highly suggestive evidence only five biomarker aberrations occurred in more than one disorder. Only 15 meta-analyses had a power >0.8 to detect a small effect size, and most (81.9%) meta-analyses had high heterogeneity. Although some associations met criteria for either convincing or highly suggestive evidence, overall the vast literature of peripheral biomarkers for major mental disorders is affected by bias and is underpowered. No convincing evidence supported the existence of a trans-diagnostic biomarker. Adequately powered and methodologically sound future large collaborative studies are warranted.

[A naturalistic study comparing two initial duloxetine dosing strategies in a clinical "real world" setting]. / Studio naturalistico di confronto tra due strategie di dosaggio iniziale di duloxetina in un contesto clinico "real world".

UNLABELLED: AIMS. To compare, in a "real world" setting, the efficacy and tolerability of two initial duloxetine starting doses: 30 mg once daily (q.d.) for 1 week, followed by escalation to 60 mg q.d. versus 60 mg q.d. without titolation, evaluating expecially the effects on sexual dysfunction. METHODS: The sample is constituted by outpatients meeting diagnostic criteria for mild-severe (HAMD17 > or =24 and CGI-S > or =4) Major Depressive Episode as defined by DSM-IV-TR (Diagnostic and Statistic Manual for Mental Disorder, Fourth Edition-Text Revision), based on the Structured Clinical Interview for DSM-IV-TR (Mini International Neuropsychiatric Interview, MINI). The study design planned an initial evaluation and 4 follow-up visits; at each visit the following scales were administered: Hamilton Rating Scale for Depression (HAMD17) and Anxiety (HAMA), Clinical Global Impression Severity Scale (CGI-S) for severity evaluation and Arizona Sexual Experience Scale (ASEX) for sexual disfunction evaluation. RESULTS: Both of the groups showed 90% of response (> or = 50% reduction in a patient's HAMD17 total score from baseline) within 2 months of follow-up. 50% of patients receiving a 30 mg q.d. starting dose achieved a HAMD17 total score < or =7 versus 40% of 60 mg q.d. treating group. None showed relapses during the study. After the first treatment month, the 60 mg q.d. receiving group showed a statistical significative amelioration of sexual function (Mann-Whitney test: p=0,02). CONCLUSIONS: Our naturalistic "real world" study results confirm previous duloxetine tolerability and efficacy findings suggesting a 60 mg q.d. after meal duloxetine somministration without titolation.

Psychiatric Phenocopy Syndrome of Behavioral Frontotemporal Dementia: Behavioral and Cognitive Fingerprint.

Behavioral and cognitive variables predicting behavioral frontotemporal dementia (bvFTD) versus primary psychiatric disorders mimicking bvFTD (phenocopy syndrome: bvFTD-PS) were studied. Forty-one probable/definite bvFTD and 16 bvFTD-PS patients were evaluated with cognitive battery, Neuropsychiatric Inventory, and Stereotypic and Ritualistic Behavior-revised questionnaires. Twenty-seven healthy subjects served as control. Severity of cognitive impairment/behavioral symptoms and profile of cognitive deficits were similar, with bvFTD-PS showing impaired executive abilities and memory. However, phonemic fluency was impaired only in bvFTD (p < 0.001). Depression was worse in bvFTD-PS, while apathy, disinhibition, and dietary changes characterized bvFTD. Phonemic fluency and depression accounted for the best predictive diagnostic model. A structured psychiatric screening of bvFTD mimickers may often yield a psychiatric diagnosis with predominant depressive symptoms and therefore a potentially treatable condition.

Olfactory neuroepithelium alterations and cognitive correlates in schizophrenia.

BACKGROUND: Few studies have investigated alterations of olfactory neuroepithelium (ONE) as a biomarker of schizophrenia, and none its association with cognitive functioning. METHOD: Fresh ONE cells from twelve patients with schizophrenia and thirteen healthy controls were collected by nasal brushing, cultured in proper media and passed twelve times. Markers of cell proliferation (BrdU incorporation, Cyclin-D1 and p21 protein level) were quantified.Cognitive function was measured using Brief Neuropsychological Examination-2. PRIMARY OUTCOME: proliferation of ONE cells from schizophrenic patients at passage 3. Secondary outcome: association between alteration of cell proliferation and cognitive function. RESULTS: Fresh ONE cells from patients showed a faster cell proliferation than those from healthy controls at passage 3. An opposite trend was observed at passage 9, ONE cells of patients with schizophrenia showing slower cell proliferation as compared to healthy controls. In schizophrenia, overall cognitive function (Spearman's rho -0.657, p < 0.01), verbal memory - immediate recall, with interference at 10 s and 30 s (Spearman's rho from -0.676 to 0.697, all p < 0.01) were inversely associated with cell proliferation at passage 3. CONCLUSION: Fresh ONE cells collected by nasal brushing might eventually represent a tool for diagnosing schizophrenia based upon markers of cell proliferation, which can be easily implemented as single-layer culture. Cell proliferation at passage 3 can be regarded as a promising proxy of cognitive functioning in schizophrenia. Future studies should replicate these findings, and may assess whether ONE alterations are there before onset of psychosis, serving as an early sign in patients with at risk mental state.