Clozapine for the treatment of aggressiveness and agitation in advanced dementia.

BACKGROUND: Distressing behavioural symptoms, particularly agitation and aggressiveness, remain a difficult problem in everyday clinical practice in the treatment of multimorbid patients with dementia. Clozapine may be an effective therapeutic alternative in this context. METHODS: In a retrospective study, patients who had a diagnosis of dementia and had been treated in a specialized geriatric psychiatry unit with clozapine between August 2018 and February 2022 were included, and medical records were systematically reviewed. The Clinical Global Impressions Scale was used to assess improvement, and the Pittsburgh Agitation Scale for symptom reduction. In addition, side effects and clinical features were documented in detail. RESULTS: A total of 31 patients (median age 82 years) were identified with a mean clozapine dose of 47.2 (SD 35.6) mg. A total of 13 patients tolerated clozapine very well, 10 showed tolerable side effects, and in 10 patients side effects were the reason for stopping clozapine. Behavioural symptoms improved significantly, as indicated by the assessment scores. CONCLUSIONS: In summary, clozapine was effective and well tolerated in 23 patients, suggesting that low-dose clozapine may help to alleviate the suffering of difficult-to-treat multimorbid patients with advanced dementia and their caregivers. However, particular attention should be paid to adverse drug reactions, especially in patients with cardiovascular and pulmonary impairment.

New determinants of mental health: the role of noise pollution. A narrative review.

Urbanisation processes and anthropogenic actions led to a significant increase in pollution levels, with relevant consequences on global health. In particular, noise pollution demonstrated an association with cardiovascular, metabolic, and respiratory diseases. Furthermore, increasing evidence underlined the possible role of air and noise pollution in the development of psychiatric disorders. In this narrative review, evidence concerning the relationship between noise pollution and the emergence of psychiatric symptoms or psychiatric disorders is summarised. After the literature search process was completed, 40 papers were included in the present review. The exposure to road-, rail-, and air- traffic represented a risk factor for the emergence of affective disorders. This could also be mediated by the occurrence of circadian rhythms disturbances or by noise annoyance and noise sensitivity, both influencing psychological well-being and health-related quality of life. Fewer studies concentrated on special populations, particularly pregnant women and children, for whom noise pollution was confirmed as a risk factor for psychopathology. The better clarification of the complex interaction between noise pollution and mental health may help to identify subjects at risk and targeting specific prevention and intervention strategies in the urban environment.

Ludwig van Beethoven-a psychiatric perspective.

Biographical accounts of famous artists usually try to relate the life story to the works (and vice versa). This gives the work a special "colour", often the context for understanding for today's recipients. This interrelation is complex and often judgmental, sometimes manipulative. Thus, medical (including psychiatric), characterological and psychodynamic assessments and interpretations must be made with great caution. Primary sources may be scanty and diagnostic concepts may have changed (Mozart died of hitzigem Frieselfieber [prickly heat fever]; in Hölderlin's lifetime, schizophrenia or bipolar disorder did not yet "exist"). The attempt at a diagnostic classification often says more about the author and his time than about the artist (for example, the assessment of Robert Schumann's or Friedrich Hölderlin's mental illness). Against this background, elements of Ludwig van Beethoven's biography are presented from a psychiatric perspective. In summary, Beethoven can be diagnosed with an alcohol use disorder. A pronounced hyperthymic temperament is likely to have had a clearly positive influence on the course of the disorder. In particular, no influence of the alcohol use disorder on the musical quality of the work can be proven. A clear episodic course of affective symptoms as in bipolar disorder is not demonstrable. The deafness caused a severe reduction in quality of life.

Challenging predictions between affective temperaments, depression and anxiety in a Kosovo student community sample.

OBJECTIVE: The relationship between temperament and mental health problems is seen very important as we hope to explain the trajectory of this interaction. The aim of this study was to test the validity of affective temperaments for predicting psychiatric morbidity, by explaining the relationships between temperament, anxiety and depression in a community sample. METHODS: This was a cross-sectional study. The present sample consisted of 960 participants (347 male, 622 female) with a mean age of M = 28.4 (SD = 10) randomly recruited. Affective temperaments were measured by the brief version of TEMPS-A, depression and anxiety measured with Beck Depression Inventory and Beck Anxiety Inventory. RESULTS: The Cronbach alpha reliability coefficients for affective temperaments were between .72 and .81, for BDI and BAI, were .88 and .90. The study found significant gender differences on depressive [t(959) = -4.2, p<.001], cyclothymic [t(957) = -4.6, p < .001] and anxious temperament [t(957) = -8.2, p < .001], females having higher scores than males, and reverse results on hyperthermic temperament [t(958) = 2.1, p < .045], males having higher scores than females. No gender difference is found in irritable temperament [t(955) = -.581, p < .561]. Affective temperaments were found significant predictors for depression and anxiety. The combination of the depressive temperament and cyclothymic temperament explained the 32% variance of depression and the 25% variance of anxiety. CONCLUSIONS: Study findings are consistent with some other studies and stress the importance of screening for effective temperament in order to early identify depression and anxiety. Further investigation is needed to understand what are other factors that influence the relationship between affective temperaments with depression and anxiety.

Negative symptoms and social cognition as mediators of the relationship between neurocognition and functional outcome in schizophrenia.

Introduction: In this study we assessed the contribution of psychopathology, including the two domains of negative symptoms (motivational deficit and expressive deficit), processing speed as an index of neurocognition, and emotion recognition, as an index of social cognition, to poor functional outcomes in people with schizophrenia. Methods: The Positive and Negative Syndrome Scale was used to evaluate positive symptoms and disorganization and the Brief Negative Symptom Scale to assess negative symptoms. The Symbol Coding and the Trail Making Test A and B were used to rate processing speed and the Facial Emotion Identification Test to assess emotion recognition. Functional outcome was assessed with the Personal and Social Performance Scale (PSP). Regression analyses were performed to identify predictors of functional outcome. Mediation analyses was used to investigate whether social cognition and negative symptom domains fully or partially mediated the impact of processing speed on functional outcome. Results: One hundred and fifty subjects from 8 different European centers were recruited. Our data showed that the expressive deficit predicted global functioning and together with motivational deficit fully mediated the effects of neurocognition on it. Motivational deficit was a predictor of personal and social functioning and fully mediated neurocognitive impairment effects on the same outcome. Both motivational deficit and neurocognitive impairment predicted socially useful activities, and the emotion recognition domain of social cognition partially mediated the impact of neurocognitive deficits on this outcome. Conclusions: Our results indicate that pathways to functional outcomes are specific for different domains of real-life functioning and that negative symptoms and social cognition mediate the impact of neurocognitive deficits on different domains of functioning. Our results suggest that both negative symptoms and social cognition should be targeted by psychosocial interventions to enhance the functional impact of neurocognitive remediation.

Controversies regarding lithium-associated weight gain: case-control study of real-world drug safety data.

BACKGROUND: The impact of long-term lithium treatment on weight gain has been a controversial topic with conflicting evidence. We aim to assess reporting of weight gain associated with lithium and other mood stabilizers compared to lamotrigine which is considered free of metabolic adverse drug reactions (ADRs). METHODS: We conducted a case/non-case pharmacovigilance study using data from the AMSP project (German: "Arzneimittelsicherheit in der Psychiatrie"; i.e., Drug Safety in Psychiatry), which collects data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of weight gain (> 10% of baseline body weight) calculating reporting odds ratio (ROR). We compared aripiprazole, carbamazepine, lithium, olanzapine, quetiapine, risperidone, and valproate to lamotrigine. Additional analyses related to different mood stabilizers as reference medication were performed. We also assessed sex and age distributions of weight-gain reports. RESULTS: We identified a total of 527 cases of severe drug-induced weight gain representing 7.4% of all severe ADRs. The ROR for lithium was 2.1 (95%CI 0.9-5.1, p > 0.05), which did not reach statistical significance. Statistically significant disproportionate reporting of weight gain was reported for olanzapine (ROR: 11.5, 95%CI 4.7-28.3, p < 0.001), quetiapine (ROR: 3.4, 95%CI 1.3-8.4, p < 0.01), and valproate (ROR: 2.4, 95%CI 1.1-5.0, p = 0.03) compared to lamotrigine. Severe weight gain was more prevalent in non-elderly (< 65 years) than in elderly patients, with an ROR of 7.6 (p < 0.01) in those treated with lithium, and an ROR of 14.7 (p < 0.01) in those not treated with lithium. CONCLUSIONS: Our findings suggest that lithium is associated with more reports of severe weight gain than lamotrigine, although this difference did not reach statistical significance. However, lithium use led to fewer reports of severe weight gain than some alternative drugs for long-term medication (olanzapine, quetiapine, and valproate), which is consistent with recent studies. Monitoring of weight gain and metabolic parameters remains essential with lithium and its alternatives.

No amygdala attenuation in schizophrenic patients treated with atypical antipsychotics.

Functional magnetic resonance (fMRI) imaging was used to measure amygdala activation in an emotional valence discrimination task in clinically stable patients with schizophrenia treated with atypical antipsychotics and healthy controls. No difference was detected between patients with schizophrenia and controls.

An fMRI study of cognitive remediation in drug-naïve subjects diagnosed with first episode schizophrenia.

OBJECTIVE: The purpose of our functional magnetic resonance imaging (fMRI) study was to examine brain activity using a "1-back" paradigm as working memory task in drug-naïve subjects with first episode schizophrenia before and after cognitive remediation training. METHODS: In this study 15 drug-naïve first episode subjects who met DSM-IV criteria for schizophrenia were randomized to receive either atypical antipsychotics (AP, n = 8) or atypical antipsychotics in combination with cognitive remediation therapy (AP + CR, n = 7), 11 subjects had a follow-up fMRI examination after therapy (AP, n = 5; AP + CR, n = 6). RESULTS: In 4 of the 6 AP + CR subjects the number of activation clusters increased, whereas in 4 out of the 5 AP subjects the number of clusters decreased (mean number of clusters: AP + CR = 5.53, SD 12.79, AP = -5.8, SD 6.9). CONCLUSION: In this randomized study the number of activation clusters during a working memory task increased after cognitive remediation training. Our data show that neurobiological effects of cognitive remediation can be identified in the very early course of schizophrenia.

Dimensionality analysis of the German version of the Screen for Cognitive Impairment in Psychiatry (SCIP-G).

Background: Psychiatric disorders, especially schizophrenia, are characterised by cognitive impairment. The rapid detection of cognitive dysfunction - also in the course of the disease - is of great importance. The Screen for Cognitive Impairment in Psychiatry (SCIP) was developed to provide screening of psychiatric patients in clinical practice and is available in several languages. Prior psychometric investigations into the dimensionality of the SCIP have produced two different models: a one-factor model assumes that the five subscales of the SCIP load together, whereas an alternative model suggests that the subscales load on two factors, namely verbal memory and processing speed. We carried out a confirmatory factor analysis of the German version of the SCIP (SCIP-G). Methods: 323 patients with psychotic, bipolar affective, and depressive disorders were studied. Results: The one-factor approach did not yield an acceptable model fit (chi-squared test: χ2 = 109.5, df = 5, p < 0.001, χ2/df = 21.9). A two-factor solution, with the subtests Verbal Learning Test-Immediate Recall, Delayed Recall Test of the VLT, and Working Memory Test loading on the first factor, whereas the subtests Verbal Fluency Test and Psychomotor Speed Test loading on the second factor, obtained a good model fit (χ2 = 6.7, df = 3, p = 0.08, χ2/df = 2.2). Conclusions: These data show that a good model fit can be achieved with a two-factor solution for the SCIP. This study is the first to conduct a confirmatory factor analysis using the German SCIP version and to test its dimensional structure using a hypothesis-testing approach.

Pain sensitivity is modulated by affective temperament: Results from the population-based CHRIS Affective Disorder (CHRIS-AD) study.

BACKGROUND: Nociceptive pain modulation is related to psychological and psychiatric conditions. Evidence from clinical studies backs innate temperaments as potential precursors of mood symptoms and disorders, and pain sensitivity. Our study examines the modulation effect of affective temperaments on pain sensitivity in a general population adult sample, accounting for possible intervening mood symptoms, lifetime anxiety and depression, and pain treatments. METHODS: The sample is part of the CHRIS-AD study, Italy. Primary outcomes were the pain sensitivity questionnaire PSQ-total intensity score and the experimental pressure pain threshold (PPT). Affective temperaments were evaluated with the TEMPS-M. Lifetime depression, anxiety, current mood disorders, and treatments were self-reported via rating-scales. Directed acyclic graphs theory guided linear and mixed linear regression model analyses. RESULTS: Among 3804 participants (aged 18-65; response rate 78.4 %, females 53.3 %, mean age 38.4 years) for any given temperament, both the PSQ-total and the PPT were associated with temperament. The TEMPS-M four cyclothymic-related temperaments aligned on the pain-sensitive pole and the hyperthymic on the pain-resilient pole. The inclusion of current or lifetime mood symptoms, or pain drug use, as possible intervening pathways only partly diluted these associations, with stronger evidence for an effect of trait anxiety. LIMITATIONS: The main limitations were the lack of experimental measures of suprathreshold pain intensity perception, and detailed information on affective disorders in the study population. CONCLUSIONS: These findings support the hypothesis of a biological dichotomous diathesis of affective temperaments towards pain sensitivity; hyperthymic suggesting protection, whereas cyclothymic suggesting predisposition.

European Psychiatric Association guidance on assessment of cognitive impairment in schizophrenia.

BACKGROUND: Impairment in a wide range of cognitive abilities has been consistently reported in individuals with schizophrenia. Both neurocognitive and social cognitive deficits are thought to underlie severe functional disabilities associated with schizophrenia. Despite the key role in schizophrenia outcome, cognition is still poorly assessed in both research and clinical settings. METHODS: In this guidance paper, we provide a systematic review of the scientific literature and elaborate several recommendations for the assessment of cognitive functions in schizophrenia both in research settings and in real-world clinical practice. RESULTS: Expert consensus and systematic reviews provided guidance for the optimal assessment of cognitive functions in schizophrenia. Based on the reviewed evidence, we recommend a comprehensive and systematic assessment of neurocognitive and social cognitive domains in schizophrenia, in all phases of the disorder, as well as in subjects at risk to develop psychosis. This European Psychiatric Association guidance recommends not only the use of observer reports but also self-reports and interview-based cognitive assessment tools. The guidance also provides a systematic review of the state of the art of assessment in the first episode of psychosis patients and in individuals at risk for psychosis. CONCLUSION: The comprehensive review of the evidence and the recommendations might contribute to advance the field, allowing a better cognitive assessment, and avoiding overlaps with other psychopathological dimensions. The dissemination of this guidance paper may promote the development of shared guidelines concerning the assessment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to obtain recovery.

European Validation of the Self-Evaluation of Negative Symptoms (SNS): A Large Multinational and Multicenter Study.

BACKGROUND: Negative symptoms are usually evaluated with scales based on observer ratings and up to now self-assessments have been overlooked. The aim of this paper was to validate the Self-evaluation of Negative Symptoms (SNS) in a large European sample coming from 12 countries. We wanted to demonstrate: (1) good convergent and divergent validities; (2) relationships between SNS scores and patients' functional outcome; (3) the capacity of the SNS compared to the Brief Negative Symptom Scale (BNSS) to detect negative symptoms; and (4) a five-domain construct in relation to the 5 consensus domains (social withdrawal, anhedonia, alogia, avolition, blunted affect) as the best latent structure of SNS. METHODS: Two hundred forty-five subjects with a DSM-IV diagnosis of schizophrenia completed the SNS, the Positive and Negative Syndrome Scale (PANSS), the BNSS, the Calgary Depression Scale for Schizophrenia (CDSS), and the Personal and Social Performance (PSP) scale. Spearman's Rho correlations, confirmatory factor analysis investigating 4 models of the latent structure of SNS and stepwise multiple regression were performed. RESULTS: Significant positive correlations were observed between the total score of the SNS and the total scores of the PANSS negative subscale (r = 0.37; P < 0.0001) and the BNSS (r = 0.43; p < 0.0001). SNS scores did not correlate with the level of insight, parkinsonism, or the total score of the PANSS positive subscale. A positive correlation was found between SNS and CDSS (r = 0.35; p < 0.0001). Among the 5 SNS subscores, only avolition subscores entered the regression equation explaining a lower functional outcome. The 1-factor and 2-factor models provided poor fit, while the 5-factor model and the hierarchical model provided the best fit, with a small advantage of the 5-factor model. The frequency of each negative dimension was systematically higher using the BNSS and the SNS vs. the PANSS and was higher for alogia and avolition using SNS vs. BNSS. CONCLUSION: In a large European multicentric sample, this study demonstrated that the SNS has: (1) good psychometric properties with good convergent and divergent validities; (2) a five-factor latent structure; (3) an association with patients' functional outcome; and (4) the capacity to identify subjects with negative symptoms that is close to the BNSS and superior to the PANSS negative subscale.

Screening for cognitive impairment in schizophrenia: Psychometric properties of the German version of the Screen for Cognitive Impairment in Psychiatry (SCIP-G).

BACKGROUND: The Screen for Cognitive Impairment in Psychiatry (SCIP) is a brief scale designed for detecting cognitive deficits in patients with psychiatric disorders including schizophrenia. In this preliminary study the psychometric properties of the German version of the SCIP are examined in a sample of patients with schizophrenia and schizoaffective psychosis (DSM-IV) as well as in healthy controls. METHODS: Thirty patients and thirty matched controls were asked to complete two versions of the SCIP separated by two-week intervals in addition to psychiatric and neurocognitive instruments including assessments to measure psychosocial functioning. Feasibility, reliability and validity of the SCIP were examined in order to determine parallel reliability. The convergent validity was assessed by the BACS (Brief Assessment of Cognition in Schizophrenia) and the MMSE (Mini-Mental-State-Examination). RESULTS: Significant differences in cognitive performance between patients and healthy controls were detected in both versions of the SCIP. The SCIP effectively discriminated between patients and the control sample. The reliability of the parallel versions of the SCIP was supported by high correlations between the alternate forms, and by the high internal consistency of SCIP subtests within the patient sample. Construct validity of the SCIP was supported by high correlations between the SCIP and the BACS total scores, and by high correlations with common cognitive domain scores from the two tests. CONCLUSIONS: Our data show that the German version of the SCIP (SCIP-G) is a brief, valid and reliable assessment tool for the detection of cognitive impairment in patients with schizophrenia or schizoaffective psychosis.

Pulmonary Embolism and Acute Psychosis, a Case Report of an Outpatient with a Mild Course of COVID-19.

The increased risk for thromboembolism in hospitalized COVID-19 patients has been communicated extensively. The fact that home quarantined patients can develop pulmonary embolism, however, has so far not been reported. Furthermore, attention should be brought to psychotic developments in COVID-19 patients. We report a 46-year-old previously healthy patient with a mild course of COVID-19, who developed a massive pulmonary embolism with right heart strain while being home quarantined. He was hospitalized and anticoagulant therapy was started. Nine days after admission, the patient appeared increasingly psychotic and suffered from hallucinations as well as paranoid thoughts. After treatment with risperidone and valproate, the patient's condition improved. At a follow-up 1 month after discharge, he was completely recovered regarding the respiratory, cardiac, and psychic situation. SARS-CoV-2 infection can not only increase the prevalence of thromboembolism in hospitalized patients but also in outpatients. COVID-19 also increases the risk of developing psychiatric reactions.

Predictors of Functional Outcome in Patients With Bipolar Disorder: Effects of Cognitive Psychoeducational Group Therapy After 12 Months.

Background: Cognitive deficits are known as a core feature in bipolar disorder. Persisting neurocognitive impairment is associated with low psychosocial functioning. The aim of this study was to identify potential cognitive, clinical and treatment-dependent predictors for functional impairment, symptom severity and early recurrence in bipolar patients, as well as to analyze neurocognitive performance compared to healthy controls. Methods: Forty three remitted bipolar patients and 40 healthy controls were assessed with a neurocognitive battery testing specifically attention, memory, verbal fluency and executive functions. In a randomized controlled trial, remitted patients were assigned to two treatment conditions as add-on to state-of-the-art pharmacotherapy: cognitive psychoeducational group therapy over 14 weeks or treatment-as-usual. At 12 months after therapy, functional impairment and severity of symptoms were assessed. Results: Compared to healthy controls, bipolar patients showed lower performance in executive function (perseverative errors p < 0.01, categories correct p < 0.001), sustained attention (total hits p < 0.001), verbal learning (delayed recall p < 0.001) and verbal fluency (p-words p < 0.002). Cognitive psychoeducational group therapy and attention predicted occupational functioning with a hit ratio of 87.5%. Verbal memory recall was found to be a predictor for symptom severity (hit ratio 86.8%). Recurrence in the follow-up period was predicted by premorbid IQ and by years of education (hit ratio 77.8%). Limitations: Limitations of the present study result mainly from a small sample size. The extent of cognitive impairment appears to impact occupational disability, clinical outcome as well as recurrence rate. This result must be interpreted with caution because statistical analysis failed to show higher significance. Conclusions: Bipolar patients benefit from cognitive psychoeducational group therapy in the domain of occupational life. Deficits in sustained attention have an impact on occupational impairment. Implications for treatment strategies are discussed. Further evaluation in larger studies is needed.

Affective temperaments (TEMPS-A) in panic disorder and healthy probands: Genetic modulation by 5-HTT variation.

OBJECTIVES: Temperamental traits as ascertained by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto-Questionnaire (TEMPS-A) have been suggested as promising intermediate phenotypes of mental disorders. In anxiety disorders, however, TEMPS scales and their genetic underpinnings are still understudied. METHODS: TEMPS-A scores in 109 patients with panic disorder (PD) were compared to a sample of 536 healthy probands. All participants were genotyped for serotonin transporter gene variation (5-HTTLPR/rs25531). RESULTS: PD patients displayed significantly increased scores on the dysthymic, cyclothymic, irritable and anxious subscales, and lower scores on the hyperthymic subscale, respectively (all ps < 0.001) compared to healthy probands. In the total sample, the less active 5-HTTLPR/rs25531 S/LG alleles were associated with higher scores on the dysthymic, cyclothymic, irritable and anxious temperaments (all ps < 0.01), but not the hyperthymic subscale. Mediation analyses revealed anxious temperament in particular to mediate the relationship between 5-HTT genotype and PD. CONCLUSIONS: Dysthymic, cyclothymic, irritable and notably anxious temperament could serve as valuable intermediate phenotypes in efforts to unravel neurobiological, particularly serotonin system related genetic pathomechanisms associated with PD and potentially contribute to a panel of vulnerability markers guiding early targeted preventive interventions.

An investigation of temperamental traits in patients with somatoform disorder: do they belong in the affective spectrum?

BACKGROUND: About 10% of the general population report multiple and persisting physical symptoms resulting in extensive screening but with no organic explanation found. OBJECTIVE: The authors sought to determine whether these somatoform-disorder patients show characteristics of the affective disorder spectrum, with the cyclothymic temperament likely showing the highest specificity for somatoform disorder. METHOD: This study examined temperamental traits and current mood states of 44 general-hospital inpatients diagnosed with somatoform disorder. RESULTS: There was a higher prevalence of abnormal temperamental traits in patients with somatoform disorder. CONCLUSION: Based on the idea of a continuum between temperament and affective disorders, the results should trigger further research on this issue possibly leading to novel treatment options in the future.

Elevated metabolites within dorsolateral prefrontal cortex in rapid cycling bipolar disorder.

Metabolites within the left dorsolateral prefrontal cortex (DLPFC) of six inpatients with bipolar II rapid cycling (RC) during various mood states (depressed, hypomanic, and euthymic), six depressed inpatients with non-RC bipolar disorder (BIPD), and six healthy controls (HC) were assessed by proton magnetic resonance spectroscopy (MRS). We hypothesized that glutamate/glutamine levels should be altered in RC compared with HC. Patients with RC in contrast to BIPD and HC exhibited elevated levels of N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and glutamate/glutamine (Glx) during all mood states. The Glx levels of BIPD compared with HC did not differ significantly; the other metabolites were increased, though less than in RC patients. Our findings of elevated metabolites in patients with RC, especially Glx as a possible marker of cortical activity, indicate that increased neuronal activity may constitute an important neurobiological feature of RC.