Case report: Familial case with autism spectrum and bipolar disorder showing a 20q11.21 microduplication including TM9SF4.

Autism spectrum disorder (ASD) is characterized by multifactorial etiology and high heritability but can be challenging to be diagnosed, especially in cases presenting subthreshold symptoms with no cognitive or language impairment, which may not be identified until adulthood but may occur in family members of subjects with ASD. This study explores the possible correlation between a genomic imbalance and clinical phenotypes in a family case of a proband with ASD, with subjects presenting full-blown or subthreshold ASD and/or mood disorders. Clinical assessments were carried out by means of the Structured Clinical Interview for DSM-5 (SCID-5) disorders, Autism Spectrum Quotient (AQ), Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule Module 2 (ADOS-2), and Adult Autism Subthreshold Spectrum (AdAS Spectrum). The genetic evaluation included array comparative genomic hybridization (array-CGH). The proband was diagnosed with ASD and bipolar disorder type I (BD-I), her twin brothers with ASD and intellectual disability (ID), and her father and sister with BD type II (BD-II) and autism traits. The proband, her father, twin brothers, and older sister showed a microduplication of 350 kb in 20q11.21. In contrast, the proband's mother did not present the microduplication or any mental disorder. This study reports a microduplication that segregates with family members affected by ASD or autistic traits comorbid in some cases with bipolar disorder, and that has never been reported in healthy subjects. Among the genes harbored in this region, the TM9SF4 gene has been recently implicated in risk for ASD.

Depression and Pseudodementia: Decoding the Intricate Bonds in an Italian Outpatient Setting.

In spite of the uncertainties of its diagnostic framework, pseudodementia may be conceptualized as a condition characterized by depressive symptoms and cognitive impairment in the absence of dementia. Given the controversies on this topic, the aim of the present study was to assess neurological and cognitive dysfunctions in a sample of elderly depressed subjects, and the eventual relationship between cognitive impairment and depressive symptoms. Fifty-seven elderly depressed outpatients of both sexes were included in the study. A series of rating scales were used to assess diagnoses, depressive and cognitive impairment. Comparisons for continuous variables were performed with the independent-sample Student's t-test. Comparisons for categorical variables were conducted by the χ2 test (or Fisher's exact test when appropriate). The correlations between between socio-demographic characteristics and clinical features, as well as between cognitive impairment and depressive symptoms were explored by Pearson's correlation coefficient or Spearman's rank correlation. Our data showed the presence of a mild-moderate depression and of a mild cognitive impairment that was only partially related to the severity of depression. These dysfunctions became more evident when analyzing behavioral responses, besides cognitive functions. A high educational qualification seemed to protect against cognitive decline, but not against depression. Single individuals were more prone to cognitive disturbance but were similar to married subjects in terms of the severity of depressive symptoms. Previous depressive episodes had no impact on the severity of depression or cognitive functioning. Although data are needed to draw firm conclusions, our findings strengthen the notion that pseudodementia represents a borderline condition between depression and cognitive decline that should be rapidly identified and adequately treated.

Effects of exogenous melatonin on sleep and circadian rhythm parameters in bipolar disorder with comorbid delayed sleep-wake phase disorder: An actigraphic study.

The present study evaluates the effect of exogenous melatonin (exo-MEL) on sleep and circadian parameters in patients with bipolar disorder (BD) and delayed sleep-wake phase disorder (DSWPD). BD euthymic patients (n = 83, mean age = 45.13 ± 13.68, males 56%) were evaluated for chronotype (reduced Morningness-Eveningness Questionnaire [rMEQ]), sleep quality (Pittsburgh Sleep Quality Index), sleep and circadian parameters (actigraphic monitoring). Patients that fulfilled criteria for DSWPD (n = 25) were treated for three months with exo-MEL 2 mg administered approximately 4 h before the sleep onset time (SOT) actigraphically-determined at baseline. Sleep and circadian parameters at baseline (T0) and after the exo-MEL treatment (T1) were compared using paired Wilcoxon test. In patients that completed the treatment (n = 19), the rMEQ score increased between T0 (median = 8.0 [IQR = 7.0, 11.0]) and T1 (median = 13.5 [IQR = 9.3, 15.0], p-value = 0.006), the SOT was advanced between T0 (median = 00:55 [IQR = 00:25, 01:39] and T1 (median = 00:09 [IQR = 23:41, 01:04], p-value = 0.039), the sleep efficiency and total sleep time increased (T0: median = 84.4 [IQR = 81.3, 89.4]; T1 (median = 90.3 [IQR = 85.5, 92.9] %, p-value = 0.01, and T0: median = 7.20 [IQR = 6.15, 8.15]; T1: median = 7.7 [IQR = 7.0, 9.3] hours, p-value = 0.04, respectively). These results indicate that in BD with comorbid DSWPD, the self-reported chronotype, the sleep onset time, and sleep efficiency and duration were modified after a personalized treatment with exo-MEL, suggesting its potential efficacy in improving sleep patterns in BD. The absence of proper control groups and of treatment randomization constitute limitations of our study and further randomized controlled trials are required to confirm our results.

Obsessive-Compulsive Disorder, PANDAS, and Tourette Syndrome: Immuno-inflammatory Disorders.

In the last years, much focus has been given to the possible role of inflammatory and immunologic alterations in the pathophysiology of obsessive-compulsive disorder (OCD) and some related conditions, such as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) and Tourette syndrome (TS). Although the matter is intriguing, the available data are still controversial and/or limited. Therefore, the aim of this chapter was at reviewing and commenting on the literature on possible dysfunctions of inflammatory and immune system processes in OCD, PANDAS, and TS.This narrative review was carried out through searching PubMed and Google Scholar for English language papers from January 1985 to December 31, 2021.The data gathered up to now would suggest that the mechanisms involved might be heterogeneous according to the age of the patients and the disorder examined. Indeed, PANDAS seem more related to infections triggering autoimmunity not necessarily following group A beta-hemolytic streptococcal (GABHS) infection, as supposed in the past. Autoimmunity seems also important in TS, if coupled with an individual vulnerability that can be genetic and/or environmental. The data in adult OCD, albeit scattered and sometimes obtained in small samples of patients, would indicate that immune system and inflammatory processes are involved in the pathophysiology of the disorder. However, it is still unclear to conclude whether they are primary or secondary phenomena.In conclusion, taken together, the current findings pave that way towards novel and promising domains to explore the pathophysiology of OCD and related disorders, as well towards the development of innovative therapeutic strategy beyond current pharmacological paradigms.

Prescribing Tamoxifen in Patients With Mood Disorders: A Systematic Review of Potential Antimanic Versus Depressive Effects.

PURPOSE/BACKGROUND: Tamoxifen is a selective estrogen receptor modulator widely used for treatment and prevention of estrogenic receptor-positive breast cancer. Tamoxifen is an object of growing interest in psychopharmacology as an antimanic drug, because it inhibits the protein kinase C, a molecular target of bipolar disorder. Consistently, the potential depressive effect of tamoxifen has been repeatedly reported. METHODS/PROCEDURES: This article systematically reviews studies examining tamoxifen impact on mood, exploring either its potential therapeutic use as antimanic agent or its potential depressive effect. FINDINGS: Eight studies explored tamoxifen antimanic properties, all, but one, reported a rapid and efficacious antimanic action. As to the depressive effect, 9 cohort studies emerged among which 4 pointed out an increased risk of depression. Seven case reports described the onset or exacerbation of depressive episodes besides 1 case series study reported a high rate of depressive symptoms. In addition, 1 case report study described a tamoxifen-induced manic episode. IMPLICATIONS/CONCLUSIONS: The present review highlights tamoxifen treatment as a possible trigger of mood symptoms onset or exacerbation in vulnerable patients. Accordingly, patients with a history of mood disorders may require a close clinical surveillance during tamoxifen use. At the same time, the use of tamoxifen as an antimanic agent in psychiatric settings requires caution, as available evidence came from small-sample studies with short observation time. More studies are needed to define how long-term tamoxifen use may affect the course of bipolar disorder.

Suicidality and Illness Course Worsening in a Male Patient with Bipolar Disorder during Tamoxifen Treatment for ER+/HER2+ Breast Cancer.

PURPOSE: Tamoxifen is a selective estrogenic receptor modulator (SERM) drug. In addition to its common use in breast cancer ER+, Tamoxifen has been object of growing interest in psychiatry as antimanic drug. At the same time, clinical concerns about Tamoxifen's depressogenic effect have been repeatedly raised even without reaching univocal conclusions. We discuss the case of a 45-year-old-male with a diagnosis of Bipolar Disorder type II, treated with Tamoxifen as relapse prevention treatment after surgery for a ER+/HER2+ breast cancer. The patient required two psychiatric admissions in a few-month time span since he showed a progressive worsening of both depressive and anxiety symptoms, with the onset of delusional ideas of hopelessness and failure up to suicidal thoughts. The clinical picture showed poor response to treatment trials based on various associations of mood-stabilising, antidepressants, and antipsychotic drugs. During the second hospitalization, after a multidisciplinary evaluation, the oncologists agreed on Tamoxifen discontinuation upon the severity of the psychiatric condition. The patient underwent a close oncological and psychiatric follow-up during the following 12 months. METHODS: Psychiatric assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Depression Scale (HAM-D), the Columbia Suicide Severity Rating Scale (C-SSRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). All questionnaires were administered at the time of the second hospitalization and in a one-year follow-up. RESULTS: Suicidal ideation fully remitted and depressive symptoms markedly and rapidly improved in the aftermath of Tamoxifen discontinuation. The symptomatological improvement remained stable across one-year follow-up. CONCLUSIONS: Male patients with a mood disorder history constitute a high-risk group as to Tamoxifen psychiatric side effects. The onset or worsening of depressive symptoms or suicidality should be carefully addressed and promptly treated, and clinicians should be encouraged to consider the possibility of discontinue or reduce Tamoxifen therapy after a multidisciplinary evaluation.

Obsessive-Compulsive and Depressive Symptoms in Professional Tennis Players.

Objective: A moderate sport activity is considered beneficial for both physical and mental health. On the contrary, different studies have shown that professional players may be more vulnerable to suffer from psychological and/or psychiatric disorders. Given the limited information available, the present study aimed to investigate the possible presence of depressive and obsessive-compulsive symptoms or disorders in a group of professional tennis players. Method: Twenty-five current or former professional tennis players (18 men and 7 women; mean age ± SD: 42.32 ± 13.45 years), were recruited within the Italian Tennis Federation during an international competition and during a master meeting of coaches. They were compared with a control group, recruited from university students, doctors and nurses. All of them underwent a psychiatric interview with a structured scale and a psychopathological assessment carried out with the Mini-International Neuropsychiatric Interview (MINI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Self Assessment Scale for Depression (SAD). Results: The Y-BOCS total and subscale scores were significantly higher in both current and past athletes than controls. Current athletes showed higher scores at Y-BOCS total, subscales and some items. The majority of the current athletes also showed superstitions and magical thinking. Conclusions: The present study demonstrated that professional tennis players show a relevant increase of obsessive-compulsive symptoms and supertistions than controls. Interestingly, current athletes resulted more severe than past ones. Taken together, our findings support the notion that agonistic sport activities of high level require intensive training and compliance to strict daily routines that might represent a sort of vulnerability toward the onset of full-blown obsessive-compulsive disorder (as well as other disorders) in more fragile individuals. Not suprisingly, sport psychological support experts are increasingly needed.

The increasing challenge of the possible impact of ethnicity on psychopharmacology.

Ethnic differences may significantly influence the outcome of psychopharmacological treatment, in terms of prescription, adherence, clinical response, emergence of side effects, as well as pharmacokinetics and pharmacodynamics. The purpose of this review was to explore the available literature in order to provide general suggestions to help clinicians in choosing the best therapeutic option for patients, taking into account ethnicity. Although findings are sometimes controversial, the overall published studies suggest that ethnicities other than Caucasians tend to show a lower response to antidepressants and a reduced compliance. Africans tend to be more prescribed with antipsychotics, probably due to cultural stereotypes, except with clozapine, probably for their chronic benign neutropenia. Asians usually require less antipsychotic dosages than Caucasians. The differential response and side effect profile of antidepressants and antipsychotics have been related to individual intrinsic factors, to genetic make-up, but also to cultural and contextual variables. Interestingly, albeit limited data suggest ethnic-related genetic heterogeneity at the level of the serotonin transporters, the cytochromes and some neuroreceptors. Taken together, no conclusive findings are available about the role and impact of ethnicity in psychopharmacology. One of the main problems is that the majority of the studies in psychopharmacology have been conducted on Caucasians, so that there is an urgent need to have data in other populations. Furthermore, in the era of precision medicine, the role of ethnicity may be also supported by genetic analysis.

Psychopharmacology and ethnicity: A comparative study on Senegalese and Italian men.

Objectives: Ethnicity represents a crucial factor in influencing response to psychotropic drugs. Some data indicate that functional polymorphisms of two candidate genes of the serotonin (5-HT) transporter (SERT) may affect the response to selective 5-HT reuptake inhibitors (SSRIs). The present study aimed to compare the platelet SERT, through the specific [3H]paroxetine ([3H]Par) binding, and plasma oxytocin (OT) levels in 20 Senegalese and in 20 Italian men.Methods: No subjects had family or personal history of any major psychiatric disorder, or had ever regularly taken psychotropic drugs, or were suffering from any physical illness.Results: Senegalese men showed statistically significant higher density (Bmax, fmol/mg protein, mean ± SD) of [3H]Par binding sites (2105.00 ± 473.15 vs 1139.85 ± 213.58, P < 0.001), as well as more elevated plasma OT levels (pg/ml, mean ± SD) (OT: 18.08 ± 4.46 vs 6.62 ± 2.91) than Italian men.Conclusions: These differences, possibly due to genetic or dietary reasons, or even to gender, might affect the response to psychopharmacological compounds. Our findings would suggest specific caution when administering psychotropic compounds to non-European individuals, and the need of further studies in this emerging field of neuropsychopharmacology.

QT and QTc in Male Patients with Psychotic Disorders Treated with Atypical Neuroleptics.

OBJECTIVE: We explored the potential association between antipsychotics and QT/QTc duration changes in hospitalized male patients with psychotic disorders. METHODS: The chart review was conducted on 184 male patients hospitalized between 2013 and 2015 at the Psychiatric Clinic of Pisa, Italy. Patients who were treated with one atypical antipsychotic at the time of the ECG recording were 109/184 (59.2%). QT/QTc were compared considering the atypical antipsychotic received. RESULTS: 96.3% (n = 105/109) of the sample showed QTc values ≤ 430 ms; 4 patients (3.7%) had QTc values between 430 and 450 msec (2 with paliperidone, 1 with risperidone, and 1 with olanzapine). The mean QT duration of the overall sample was 368.0 ± 28.0 and the mean QTc 400.1 ± 17.8. QTc values did not reveal statistically significant differences. QT values were significantly different (chi-square = 17.3; df = 5; p = .004). Statistically significant differences between aripiprazole and paliperidone (349.0 ± 28.3 versus 390.5 ± 29.8; p = .002) and between clozapine and paliperidone (361.1 ± 22.43 versus 390.5 ± 29.8; p = .033) were found. CONCLUSIONS: Aripiprazole was the least interfering neuroleptic with QT/QTc. Paliperidone was the atypical neuroleptic with the most relevant difference with aripiprazole, but only on QT.

Pharmacological Hypotension as a Cause of Delirious Mania in a Patient with Bipolar Disorder.

Delirious mania is a severe but often underrecognized syndrome characterized by rapid onset of delirium, mania, and psychosis, not associated with a prior toxicity, physical illness, or mental disorder. We discuss the case of a delirious mania potentially triggered and maintained by a systemic hypotension induced by antihypertensive drugs. Symptoms recovered completely after the discontinuation of antihypertensive medications and the normalization of blood pressure levels.

DSM-5 PTSD and posttraumatic stress spectrum in Italian emergency personnel: correlations with work and social adjustment.

The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) has recently recognized a particular risk for posttraumatic stress disorder (PTSD) among first responders (criterion A4), acknowledging emergency units as stressful places of employment. Little data is yet available on DSM-5 among emergency health operators. The aim of this study was to assess DSM-5 symptomatological PTSD and posttraumatic stress spectrum, as well as their impact on work and social functioning, in the emergency staff of a major university hospital in Italy. One hundred and ten subjects (doctors, nurses, and health-care assistants) were recruited at the Emergency Unit of the Azienda Ospedaliero-Universitaria Pisana (Italy) and assessed by the Trauma and Loss Spectrum-Self Report (TALS-SR) and Work and Social Adjustment Scale (WSAS). A 15.7% DSM-5 symptomatological PTSD prevalence rate was found. Nongraduated persons reported significantly higher TALS-SR Domain IV (reaction to loss or traumatic events) scores and a significantly higher proportion of individuals presenting at least one maladaptive behavior (TALS-SR Domain VII), with respect to graduate ones. Women reported significantly higher WSAS scores. Significant correlations emerged between PTSD symptoms and WSAS total scores among health-care assistants, nongraduates and women. Our results showed emergency workers to be at risk for posttraumatic stress spectrum and related work and social impairment, particularly among women and nongraduated subjects.

Lifetime autism spectrum features in a patient with a psychotic mixed episode who attempted suicide.

We present a case report of a young man who attempted suicide during a mixed episode with psychotic symptoms. The patient's history revealed the lifetime presence of signs and features belonging to the autism spectrum realm that had been completely overlooked. We believe that this case is representative of an important and barely researched topic: what happens to children with nondiagnosed and nontreated subthreshold forms of autism when they grow old. The issue of early recognition of autism spectrum signs and symptoms is discussed, raising questions on the diagnostic boundaries between autism and childhood onset psychotic spectrums among patients who subsequently develop a full-blown psychotic disorder.

Measured and expected resting energy expenditure in patients with bipolar disorder on maintenance treatment.

OBJECTIVES: Patients with bipolar disorder (BD) on long-term maintenance treatment represent a clinical population with peculiar characteristics, for which available equations to estimate resting energy expenditure (REE) are not suitable. The aim of this study was to measure REE by means of indirect calorimetry in bipolar patients on maintenance treatment and in controls, and to estimate the agreement between measured and predicted REE in both groups. METHODS: Patients diagnosed with BD I and healthy controls were assessed for height, weight and body mass index (BMI). Predicted REE was calculated using Harris-Benedict, Schofield, Recommended Nutrients Assumption Levels (LARN), and OUR equations; measurements of REE were performed using a portable indirect calorimeter. RESULTS: Results for our sample show the most commonly used formulas give a systematic overestimation of REE with respect to measured basal metabolic rate in the patient group. The mean bias was considerably greater for bipolar subjects than for controls. CONCLUSIONS: These results suggest that patients with severe mental illness on long-term psychopharmacologic treatment may have reduced basal energy expenditure that may be a cause of weight gain.

Effects of an educational intervention on weight gain in patients treated with antipsychotics.

BACKGROUND: Increasing numbers of reports have raised concerns about significant increases in weight and adiposity over both short- and long-term treatment in patients treated with antipsychotics (APs). The management of overweight and obesity in patients treated with APs has included pharmacological interventions, dietary suggestions, and behavioral strategies. Nevertheless, current evidence does not support the use of pharmacological management of this specific type of obesity, and only a limited number of studies have been published regarding prevention and treatment of weight gain with other strategies. OBJECTIVE: The aim of this study was to evaluate the effectiveness of an educational intervention (EI) that combines low-calorie diet with increased physical activity to prevent and treat weight gain in patients treated with APs. METHOD: Data were from 53 subjects whose body mass index (BMI) had increased by more than 7% after starting an AP therapy and who consented to participate in a 12-week educational intervention study aimed at preventing further weight gain and, when possible, at inducing a weight loss. Weight and BMI were measured at baseline (at each of the monthly follow-up visits) and at study completion 12 weeks from entry in the study. RESULTS: Twenty-six patients completed the 12-week program. Completers showed a significant mean body weight decrease of 3.15 kg, with a mean BMI reduction of 1.2 (kg/m) at the end of the 3-month period. CONCLUSIONS: Educational intervention can be an important tool for the management of weight increase in patients treated with APs. A larger prospective and controlled study is now needed to confirm our findings.