Mortality in Qatari individuals with mental illness: a retrospective cohort study.

INTRODUCTION: There is substantial evidence that people with mental illness have higher mortality rates than the general population. However, most of the studies were from Western countries, and it is not clear whether this finding also applies to Arab countries like Qatar. OBJECTIVES: We aimed to explore whether mortality in patients with mental illness in Qatar, is different from those without. METHODS: We conducted a retrospective cohort study, including all Qatari nationals deceased in 2017 and 2018, using the list of registered deaths from Hamad Medical Corporation (HMC) Mortuary. We divided the cohort of deceased people into two groups: with and without mental illness. For each of the groups, we collected the age at death, the reported cause of death as well as sociodemographic and clinical data. RESULTS: There were 602 registered deaths in 2017 and 589 deaths in 2018. The prevalence of mental illness was 20.4%. Compared to subjects without mental illness, subjects with mental illness surprisingly had higher age at death (median ± IQR = 76.5 ± 22.1 years vs. 62.7 ± 32.9 years; p < .001). This difference persisted even after we controlled for covariates. Individuals with mental illness were more likely to die of an infection (OR = 1.98[1.44;2.71]), or of chronic respiratory disease (OR = 3.53 [1.66;7.52]) but less likely to die because of accidental (OR = 0.21[0.09;0.49]) or congenital causes (OR = 0.18[0.04;0.77]). CONCLUSION: Contrary to most previous studies, we did not find that mortality was higher in Qatari individuals with mental illness. Sociocultural factors, free and easy-to-access healthcare, and an enhanced role of mental health professionals in detecting medical comorbidities may explain this finding.

Impact of the fear of Covid-19 infection on intent to breastfeed; a cross sectional survey of a perinatal population in Qatar.

OBJECTIVES: Infection control measures during the Covid-19 pandemic have focused on limiting physical contact and decontamination by observing cleaning and hygiene rituals. Breastfeeding requires close physical contact and observance of hygienic measures like handwashing. Worries around contamination increase during the perinatal period and can be expressed as increase in obsessive compulsive symptoms. These symptoms have shown to impact breastfeeding rates. This study attempts to explore any relationship between the Covid-19 pandemic and perinatal obsessive-compulsive symptomatology and whether the Covid-19 pandemic has any impact on intent to breastfeed. METHODS: A cross sectional survey of perinatal women attending largest maternity centre in Qatar was carried out during the months of October to December 2020. Socio-demographic information, intent to breastfeed and information around obsessive compulsive thoughts around Covid-19 pandemic were collected using validated tools. RESULTS: 15.7% respondents report intent to not breastfeed. 21.4% respondents reported obsessive-compulsive symptoms. 77.3% respondents believed the biggest source of infection was from others while as only 12% of the respondents believed that the source of infection was through breastfeeding and 15.7% believed the vertical transmission as the main source of risk of transmission. CONCLUSIONS: The rates of Obsessive-compulsive symptoms were increased and the rates of intent to breastfeed were decreased when compared with pre pandemic rates. The obsessive-compulsive symptoms and the intent to not breastfeed were significantly associated with fear of infection to the new-born. Obsessive-compulsive symptoms were not significantly correlated with intent to breastfeed and can be seen as adaptive strategies utilized by women to continue breastfeeding in the context of fear of infection.

Suspected Agomelatine-induced restless legs syndrome: a case report.

BACKGROUND: Restless Legs Syndrome (RLS) is a sensorimotor disorder characterized by unpleasant and distressing sensations in the lower limbs that are more pronounced in the evening, commence or worsen at rest, and show partial or complete relief following movement. It can occur as a primary disorder, secondary to medical conditions or treatment with medications including but not limited to antidepressants or antipsychotics. CASE PRESENTATION: A 32-year old man with major depressive disorder showed partial response to Escitalopram 10 mg daily. Agomelatine 25 mg at night was added to Escitalopram to treat his residual depressive symptoms, namely insomnia and tiredness. Within two days he developed restlessness and unpleasant sensations in his legs which were worse at night. Symptom severity increased over the following days, prompting an urgent consultation a week later. The patient's presentation met the criteria for RLS. Agomelatine was discontinued leaving the patient on Escitalopram alone. The patient's symptoms improved within 24 h of stopping Agomelatine, with complete resolution four days later. There was no recurrence of RLS during follow-up. The patient scored 6 on Naranjo's adverse drug reaction probability scale, indicating a probable adverse drug reaction caused by Agomelatine. CONCLUSIONS: To the best of our knowledge, this is the first case report of suspected Agomelatine-induced RLS. Clinicians need to be aware of RLS to enable prompt diagnosis and management. We suggest adding Agomelatine to the list of agents that can potentially induce RLS.

Prevalence, median time, and associated factors with the likelihood of initial antidepressant change: a cross-sectional study in Qatar.

BACKGROUND: Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4-12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. METHODS: This was a retrospective study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using several cox regression models. RESULTS: A total of 487 patients met the inclusion criteria of the study, 431 (88%) of them had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44-53%]) had their IAD changed less than or equal to 30 days. The median time to IAD change was 43 days with 95% CI [33.2-52.7]. The factors statistically associated with higher hazard of IAD change were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. CONCLUSIONS: Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. Our findings offered some clues to help clinicians identify the high-risk predictors of short survival and subsequent failure of IAD.

Quality of diabetes care in patients with schizophrenia: a case-control study in Qatar.

BACKGROUND: Patients with schizophrenia are at least twice as likely to develop diabetes mellitus compared to the general population. This is of significance in Qatar given the high prevalence of obesity and diabetes. Furthermore, the lifespan of people with schizophrenia is shortened by approximately 15 years, partly due to long-term microvascular and macrovascular complications. High quality diabetes care can significantly reduce morbidity and mortality. We assessed the level of diabetes care delivered to patients in Qatar with schizophrenia and diabetes compared to those with diabetes alone. METHODS: We performed a retrospective chart review of patients with diabetes mellitus with (n = 73) and without (n = 73) schizophrenia. Demographic information and electronic medical records were reviewed to determine adherence to American Diabetes Association standards of diabetes care in the last 6 and 12 months. Optimal diabetes care was defined as having completed glycated hemoglobin (HbA1c), lipid profile and retinal examination within 12 months. RESULTS: Optimal diabetes care was significantly lower in patients with schizophrenia and diabetes compared to diabetes alone [26.0% (n = 19/73) vs 52.1% (n = 38/73), p = 0.002]. Patients with diabetes and schizophrenia were also significantly less likely to have had body mass index recorded within 6 months (p = 0.008) and HbA1c (p = 0.006), lipid profile (p = 0.015), estimated glomerular filtration rate (eGFR) (p = 0.001) and order for retinal examination (p = 0.004) over 12 months. After adjusting for multiple comparisons, only assessment of eGFR (p = 0.01) and order for retinal examination (p = 0.04) remained significant. CONCLUSION: Patients in Qatar with schizophrenia and diabetes, receive sub-optimal diabetes care compared to those with diabetes alone.

Redeployment of psychiatrist trainees during the COVID-19 pandemic: evaluation of attitude and preparedness.

Background: The coronavirus disease-2019 (COVID-19) pandemic has imposed an unprecedented strain on healthcare systems worldwide. In response, psychiatrist trainees were redeployed from their training sites to help manage patients with COVID-19. This study aimed to examine the attitude of psychiatrist trainees toward redeployment to COVID-19 sites and their perceived preparedness for managing physical health conditions during redeployment. Methods: A cross-sectional researcher-developed online survey was administered among psychiatrist trainees in May 2020 at the Department of Psychiatry, Hamad Medical Corporation, Qatar. Results: Of the 45 psychiatrist trainees, 40 (88.9%) responded to the survey. Most trainees reported being comfortable dealing with chronic medical conditions, but less so with acute life-threatening medical conditions. Half reported feeling anxious about redeployment, and most felt the need for additional training. We found that trainees' perceived redeployment preparedness was significantly associated with their level of postgraduate training and the time since and duration of their last medical or surgical training. Conclusion: Adequate preparation and training of psychiatrist trainees is important before redeployment to COVID-19 sites to ensure that they can effectively and safely manage patients with COVID-19.

Women's mental health: acute impact of COVID-19 pandemic on domestic violence.

The coronavirus disease 2019 (COVID-19) pandemic created a situation of general distress. Although the focus has been initially more on the physical health during the pandemic, mental health concerns linked to the lockdown have quickly risen. This study aims to assess the effect of the COVID-19-related lockdown on Tunisian women's mental health and gender-based violence. An online survey was conducted, using the Depression Anxiety and Stress Scales (DASS-21) and the Facebook Bergen Addiction Scale (FBAS). We chose a female-exclusive social group on Facebook and used the snowball sampling method. A total of 751 participants originating from all the Tunisian regions completed the questionnaire. More than half of the participants (57.3%) reported extremely severe distress symptoms, as per the DASS-21. Those who had a history of mental illness and who were allegedly abused during lockdown were found to have more severe symptoms of depression, anxiety, and stress. Around 40% of women reported problematic social media use. Violence against women also reportedly increased significantly during the lockdown (from 4.4 to 14.8%; p < 0.001). Psychological abuse was the most frequent type of violence (96%). Women who had experienced abuse before the lockdown were at an increased risk of violence during lockdown (p < 0.001; OR = 19.34 [8.71-43.00]). To our knowledge, this is the first study that evaluates the acute impact of COVID-19 on mental health and violence against women in Tunisia, Africa, and the Arab world. It may be a sound basis for developing a more effective psychological intervention aimed at women in these regions.

Catatonia in adolescents: series of 12 inpatients.

BACKGROUND: Catatonia is one of the most severe psychiatric syndromes that might be caused by many medical as well as psychiatric conditions. Catatonia in adolescents is rare and largely understudied. AIMS: This papers aims to examine cases of catatonia among adolescent psychiatric inpatients, and to scrutinize both the etiologies and the management options. METHODS: A retrospective descriptive study involving all cases of catatonia among adolescents admitted to the Department of Child and Adolescent Psychiatry in Razi Hospital - Manouba - Tunisia between January 2006 and December 2013. Catatonia was confirmed by Bush-Francis Catatonia Rating Scale. Medical records were examined for gender, age, clinical presentation, medical or psychiatric diagnosis as well as management. Psychiatric diagnoses were made according to the DSM-IV criteria. RESULTS: Our series consisted of 12 cases, aged between 12 and 16 with a sex ratio male/female of 0.5. Catatonia was due to a medical condition in three cases and to a psychiatric disorder in the other nine cases. Psychiatric diagnoses included: manic episode (n=3), major depressive episode (n=2), schizophrenia (n=2), pervasive developmental disorder (n=1) and conversion disorder (n=1). CONCLUSION: Catatonia is rare yet life-threatening. Careful and thorough examination is needed to determine the etiological disorder, on which depend both treatment and prognosis.

Psychiatric disorders following the Tunisian revolution.

BACKGROUND: During the Tunisian Revolution, the constant threat of death and the feeling of insecurity brought about psychological reactions that tended to be excessive in some individuals, thus leading to genuine psychiatric disorders. OBJECTIVES: This study aimed to outline the different psychiatric disorders which occurred following the Tunisian Revolution and to determine the social, demographic and clinical features associated with these disorders. METHOD: A cross-sectional study was undertaken. We included all patients who first presented at the outpatient clinic at Razi hospital with psychiatric symptoms attributed to the Tunisian Revolution between 15 January 2011 and 15 October 2011. We used a form detailing social, demographic and clinical characteristics. Diagnoses were made on the basis of the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR) criteria. RESULTS: Our population consisted of 107 subjects: 28 women (26.2%) and 79 men (73.8%), with a mean age of 40 ± 12. The majority (66.4%) were married. Most (57.9%) patients had a secondary education level. Agents of order represented the largest occupational group accounting for 36.4% of the population. The most prevalent psychiatric disorders included major depressive disorder (30.8%), adjustment disorder (30.8%) and post-traumatic stress disorder (27.1%). CONCLUSION: This study emphasizes the diversity of psychiatric disorders that can occur following a man-made disaster.

Effectiveness of an educational program for reducing mental illness stigma targeting family medicine trainees in Tunisia: A quasi-experimental study.

Reducing stigma among mental health and health professionals has been an ultimate priority in many countries worldwide. This study aimed to evaluate the effectiveness of a four-session educational intervention for reducing stigma of mental illness targeting family medicine trainees in Tunisia. A quasi-experimental design was adopted with an intervention group (N = 51) and a control group (N = 56). Pre-intervention data were collected using an online survey. A four-session seminar series was implemented and organized. Post-intervention data were collected immediately after the end of the intervention then 2 months thereafter. Instruments included Attribution Questionnaire (AQ-27), Self-Determination Scale (SDS), Empowerment Scale (ES), and Recovery Scale (RS). Repeated measures analysis of covariance and multiple analysis of covariance tests were carried out. Results revealed that the intervention had moderate effects on the AQ-27 score and on six of its stigma factors including factors of the dangerousness model. The intervention improved SDS score, but not ES or RS scores. Positive effects were observed immediately after the intervention and 2 months thereafter. Regular implementation of educational programs in clinical practice would be beneficial. Developing other anti-stigma methods is needed to address the concepts of recovery and responsibility of patients with mental illness.

Patients with vitiligo have a distinct affective temperament profile: A cross-sectional study using Temperament Evaluation of Memphis, Paris, and San Diego Auto-Questionnaire.

Background: Vitiligo is a skin disease associated with significant psychiatric comorbidities. Affective temperaments represent the inherited foundation of personality and represent the biologically stable part of emotional reactivity. Studies assessing the temperament profile of patients with vitiligo are still scarce. Method: This was a cross-sectional study enrolling 34 patients with vitiligo and 34 age and sex-matched healthy controls. Affective temperament profile was investigated using the Temperament Evaluation of Memphis, Paris, and San Diego Auto-questionnaire. Dermatology life quality index was used to evaluate disease impact on patients' quality of life. Results: We found significant differences with vitiligo patients scoring higher in anxious (11.5 ± 4.76 vs. 9.06 ± 6.22; p = 0.036) and lower in hyperthymic (5.79 ± 3.82 vs. 7.5 ± 3.64; p = 0.027) temperaments. Vitiligo worsening reported by patients was associated with recent psychological stressors in 18 cases (52.9%) and Koebner phenomenon in 20 cases (58.8%). Koebner phenomenon was more frequently associated with the hyperthymic temperament (p = 0.035). Cyclothymic temperament was positively correlated with Dermatology life quality index (rho = 0.417, p = 0.014). Conclusions: This study demonstrated that patients with vitiligo have a distinct premorbid temperament profile. Having low hyperthymic and high anxious temperament traits seem to predispose patients to be less resilient to psychological stressors. A better understanding of the affective traits of vitiligo patients would be vital in personalising and adapting the management of this chronic skin disease.

Management of suicide and self-harm risk by the National Mental Health Helpline in the State of Qatar.

BACKGROUND: Suicide is a serious public health problem. AIMS: To investigate the sociodemographic and clinical features of callers (patients) classed by the Qatar National Mental Health Helpline (NMHH) as moderate to high priority based on the risk of self-harm or suicide during the COVID-19 pandemic. METHOD: The study design was a retrospective chart review of patients who contacted the helpline in the first 12 months, starting 1 April 2020. Data of those classed as moderate to high priority based on risk to self were collected using a specifically designed form. Absolute and relative frequencies for each of the studied categorical variables were determined. RESULTS: Four hundred and ninety-eight patients were included. More than half were female. The mean age was 32 years (range 8-85 years). Two-thirds of patients were from Arab countries and more than half of all patients had contacted mental health services for the first time. The most common symptoms elicited included suicidal thoughts, depressed mood and disturbed sleep. The most common psychiatric disorders were depression and generalised anxiety disorder. Most patients were seen within 4 h and received psychiatric interventions. Virtually all patients received non-pharmacological interventions; only 38.5% received pharmacological interventions. The majority had follow-up appointments arranged with mental health services. CONCLUSIONS: People from the Indian subcontinent and males proportionally approached services less, which may reflect stigma. The NMHH improved access to care for patients considered at risk to self and prevented hospital admissions. The NMHH offers a valuable additional choice to patients and assists in prevention and management of suicidal behaviour and other mental health difficulties.

Evaluating COVID-19 vaccination intentions and vaccine hesitancy among parents of children with autism spectrum disorder.

As the global vaccination mass campaign against COVID-19 extended to children aged 5 to 11 years, some parents remained hesitant about their children being administered the vaccine despite data supporting its safety. Parent vaccine hesitancy (PVH) may have predisposed certain groups of children, particularly those with autism spectrum disorder (ASD), to COVID-19 when other neurotypical children would have been vaccinated. We investigated the current PVH in 243 parents of children with ASD and 245 controls using the Parent Attitudes about Childhood Vaccines (PACV) scale. The study was conducted in Qatar from May to October 2022. Overall, 15.0% [95% CI 11.7%; 18.3%] of parents were vaccine-hesitant, with no difference (p = 0.054) between groups (ASD children [18.2%] vs. controls [11.7%]). The only sociodemographic factor associated with higher vaccine hesitancy was being a mother (as compared to being a father). The COVID-19 vaccine receipt rate at the time of the study did not differ between ASD (24.3%) and non-ASD groups (27.8%). Around two-thirds of parents of children with ASD refused or were unsure about vaccinating their children against COVID-19. We found that the intent to vaccinate against COVID-19 was higher in parents who were married and in those with a lower PACV total score. Continued public health efforts are needed to address vaccine hesitancy among parents.

A systematic review of the use of atomoxetine for management of comorbid anxiety disorders in children and adolescents with attention-deficit hyperactivity disorder.

BACKGROUND: Anxiety disorders are among the most common comorbid mental disorders in children and adolescents with attention-deficit hyperactivity disorder (ADHD). While the role of atomoxetine, a non-stimulant medication, is well-established in the management of ADHD symptoms since two decades, there is a dearth of evidence regarding its efficacy in the management of anxiety disorders in children and adolescents with ADHD. AIMS: We aimed to provide insights into (1) the comparative efficacy of atomoxetine in children and adolescents with comorbid ADHD and anxiety disorders, (2) change in severity of anxiety symptoms based on patients', parents', and clinicians' ratings, (3) tolerability and side effects. METHODS: We searched PubMed, EMBASE, and PsycINFO for clinical trials that addressed the efficacy of atomoxetine for anxiety symptoms in children and adolescents with ADHD. All published literature was systematically reviewed. RESULTS: We included four studies, out of which two specifically addressed comorbid ADHD and anxiety disorder. The studies suggested that atomoxetine did not exacerbate and in fact reduced anxiety symptoms in young patients with comorbid ADHD. CONCLUSIONS AND IMPLICATIONS: Overall, atomoxetine demonstrates good efficacy in improving anxiety symptoms in children and adolescents with ADHD. Further studies are needed to shed light on atomoxetine's efficacy for anxiety subtypes in ADHD.

Persisting neuropsychiatric symptoms, Alzheimer's disease, and cerebrospinal fluid cortisol and dehydroepiandrosterone sulfate.

INTRODUCTION: Neuropsychiatric symptoms are important treatment targets in the management of dementia and can be present at very early clinical stages of neurodegenerative diseases. Increased cortisol has been reported in Alzheimer's disease (AD) and has been associated with faster cognitive decline. Elevated cortisol output has been observed in relation to perceived stress, depression, and anxiety. Dehydroepiandrosterone sulfate (DHEAS) has known anti-glucocorticoid effects and may counter the effects of cortisol. OBJECTIVES: We aimed to examine whether CSF cortisol and DHEAS levels were associated with (1) neuropsychiatric symptoms at baseline, (2) changes in neuropsychiatric symptoms over 3 years, and (3) whether these associations were related to or independent of AD pathology. METHODS: One hundred and eighteen participants on a prospective study in a memory clinic setting, including patients with cognitive impairment (n = 78), i.e., mild cognitive impairment or mild dementia, and volunteers with normal cognition (n = 40), were included. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). CSF cortisol and DHEAS, as well as CSF AD biomarkers, were obtained at baseline. Neuropsychiatric symptoms were re-assessed at follow-up visits 18 and 36 months from baseline. We constructed linear regression models to examine the links between baseline neuropsychiatric symptoms, the presence of AD pathology as indicated by CSF biomarkers, and CSF cortisol and DHEAS. We used repeated-measures mixed ANCOVA models to examine the associations between the neuropsychiatric symptoms' changes over time, baseline CSF cortisol and DHEAS, and AD pathology. RESULTS: Higher CSF cortisol was associated with higher NPI-Q severity scores at baseline after controlling for covariates including AD pathology status (B = 0.085 [0.027; 0.144], p = 0.027; r = 0.277). In particular, higher CSF cortisol was associated with higher baseline scores of depression/dysphoria, anxiety, and apathy/indifference. Elevated CSF cortisol was also associated with more marked increase in NPI-Q scores over time regardless of AD status (p = 0.036, η2 = 0.207), but this association was no longer significant after controlling for BMI and the use of psychotropic medications. CSF DHEAS was associated neither with NPI-Q scores at baseline nor with their change over time. Cortisol did not mediate the association between baseline NPI-Q and changes in clinical dementia rating sum of boxes over 36 months. CONCLUSION: Higher CSF cortisol may reflect or contribute to more severe neuropsychiatric symptoms at baseline, as well as more pronounced worsening over 3 years, independently of the presence of AD pathology. Our findings also suggest that interventions targeting the HPA axis may be helpful to treat neuropsychiatric symptoms in patients with dementia.

Quetiapine-Induced Thyroid Dysfunction: A Systematic Review.

Thyroid abnormalities are documented consequences of quetiapine treatment. This may have clinical implications as changes in thyroid hormones may deteriorate a person's affective state. Yet less is known about the clinical factors and underlying mechanisms associated with thyroid hormones on quetiapine therapy. We therefore systematically reviewed the published literature of evidence of quetiapine-induced thyroid abnormalities. We searched MEDLINE, PsycINFO, Google Scholar, and EMBASE for articles in which individuals developed biochemically confirmed thyroid abnormalities (with or without clinical symptoms) while on quetiapine treatment. We included case reports, case series, observational, and experimental studies. We included 32 studies, 20 of which were observational and experimental studies. There were 10 case reports and 1 case series. All the research designs suggested an association between quetiapine and hypothyroidism. However, these findings were limited by the quality of the included studies and the general lack of either a clear temporal relationship or dose response. Quetiapine has been associated with thyroid abnormalities, mainly with hypothyroidism. Drug imputability in these abnormalities is not always clear, and the underlying pathophysiology may include immunological and nonimmunological mechanisms. Large prospective studies are required to clarify this association and to further inform the management of patients treated with quetiapine where hypothyroidism occurs.

Akathisia Among Patients Undergoing Antipsychotic Therapy: Prevalence, Associated Factors, and Psychiatric Impact.

OBJECTIVES: The prevalence of akathisia is variably reported in the literature and its psychiatric impact is little studied. The aim of this study was to establish the prevalence, the associated factors, and the psychiatric impact of akathisia among patients undergoing antipsychotic treatment. METHODS: A cross-sectional descriptive study was carried out at the Department of Psychiatry A, at Razi Hospital, in Tunis. It included patients with psychosis, undergoing antipsychotic treatment, from June 2016 to February 2017. Akathisia was diagnosed according to the Barnes Akathisia Scale. RESULTS: The prevalence of akathisia was 19.5% (n = 24, schizophrenia/schizoaffective disorder, n = 20; bipolar disorder, n = 4). The delay between the diagnosis of the disease and the onset of akathisia was 7.1 ± 8.8 years. Among the sample of patients with akathisia, 20/24 were on monotherapy of which 14 on conventional antipsychotics and six on atypical antipsychotics. Patients with akathisia were on atypical (8/24), low-potency conventional (4/24), or high-potency conventional (17/24) antipsychotics. The average dose of antipsychotics in chlorpromazine equivalent was 2294.5 ± 3037.7 mg. After adjusting for confounders, the only factor significantly positively associated with the diagnosis of akathisia was the dose of antipsychotics prescribed ( P = 0.01). The following psychiatric manifestations were reported by patients with akathisia: dysphoria/irritability (16/23), anxiety (18/24), sadness (15/24), suicidal thoughts (11/24), heteroaggressivity (8/23), sleep disturbances (16/24), and suicidal attempts (9/24). CONCLUSIONS: Despite the high psychiatric and social burden of akathisia, it remains largely underdiagnosed and undertreated, because in part of its subjective component.

Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer's Disease Pathology, and Cognitive Decline.

Introduction: Elevated cortisol levels have been reported in Alzheimer's disease (AD) and may accelerate the development of brain pathology and cognitive decline. Dehydroepiandrosterone sulfate (DHEAS) has anti-glucocorticoid effects and it may be involved in the AD pathophysiology. Objectives: To investigate associations of cerebrospinal fluid (CSF) cortisol and DHEAS levels with (1) cognitive performance at baseline; (2) CSF biomarkers of amyloid pathology (as assessed by CSF Aß levels), neuronal injury (as assessed by CSF tau), and tau hyperphosphorylation (as assessed by CSF p-tau); (3) regional brain volumes; and (4) clinical disease progression. Materials and Methods: Individuals between 49 and 88 years (n = 145) with mild cognitive impairment or dementia or with normal cognition were included. Clinical scores, AD biomarkers, brain MRI volumetry along with CSF cortisol and DHEAS were obtained at baseline. Cognitive and functional performance was re-assessed at 18 and 36 months from baseline. We also assessed the following covariates: apolipoprotein E (APOE) genotype, BMI, and education. We used linear regression and mixed models to address associations of interest. Results: Higher CSF cortisol was associated with poorer global cognitive performance and higher disease severity at baseline. Cortisol and cortisol/DHEAS ratio were positively associated with tau and p-tau CSF levels, and negatively associated with the amygdala and insula volumes at baseline. Higher CSF cortisol predicted more pronounced cognitive decline and clinical disease progression over 36 months. Higher CSF DHEAS predicted more pronounced disease progression over 36 months. Conclusion: Increased cortisol in the CNS is associated with tau pathology and neurodegeneration, and with decreased insula and amygdala volume. Both CSF cortisol and DHEAS levels predict faster clinical disease progression. These results have implications for the identification of patients at risk of rapid decline as well as for the development of interventions targeting both neurodegeneration and clinical manifestations of AD.

Proteomic Analysis of Plasma Markers in Patients Maintained on Antipsychotics: Comparison to Patients Off Antipsychotics and Normal Controls.

Background: Schizophrenia (SZ) and bipolar disorder (BD) share many features: overlap in mood and psychotic symptoms, common genetic predisposition, treatment with antipsychotics (APs), and similar metabolic comorbidities. The pathophysiology of both is still not well defined, and no biomarkers can be used clinically for diagnosis and management. This study aimed to assess the plasma proteomics profile of patients with SZ and BD maintained on APs compared to those who had been off APs for 6 months and to healthy controls (HCs). Methods: We analyzed the data using functional enrichment, random forest modeling to identify potential biomarkers, and multivariate regression for the associations with metabolic abnormalities. Results: We identified several proteins known to play roles in the differentiation of the nervous system like NTRK2, CNTN1, ROBO2, and PLXNC1, which were downregulated in AP-free SZ and BD patients but were "normalized" in those on APs. Other proteins (like NCAM1 and TNFRSF17) were "normal" in AP-free patients but downregulated in patients on APs, suggesting that these changes are related to medication's effects. We found significant enrichment of proteins involved in neuronal plasticity, mainly in SZ patients on APs. Most of the proteins associated with metabolic abnormalities were more related to APs use than having SZ or BD. The biomarkers identification showed specific and sensitive results for schizophrenia, where two proteins (PRL and MRC2) produced adequate results. Conclusions: Our results confirmed the utility of blood samples to identify protein signatures and mechanisms involved in the pathophysiology and treatment of SZ and BD.

Fatal pulmonary embolism in patients on antipsychotics: case series, systematic review and meta-analysis.

Since the 1950 s, several studies have reported that patients using first generation and/or second-generation antipsychotics had increased risk of venous thromboembolism events. These events include deep vein thrombosis and/or pulmonary embolism (PE). However, data about fatal PE in patients on antipsychotics (APs) remain scarce. Thus, the current study aimed to investigate sociodemographic, clinical and pharmacological characteristics related to psychiatric patients on APs and who died from a fatal PE. We reported a case-series, then conducted a literature review of relevant studies and performed a meta-analysis of studies with usable data. The main outcome of the study suggested a significantly high risk of fatal PE in patients using APs compared to nonusers (Odds Ratio=6.68, with 95% confidence interval 1.43-31.11). Clozapine was the most incriminated drug. Low potency first generation APs were the second most exhibited medication. Studies about the topic remain scarce with a high heterogeneity and a high probability of bias. Further studies are needed to ascertain this risk and to establish target preventive measures in this particularly vulnerable population.