Sexual Dysfunction in Schizophrenia: A Systematic Review and Meta-Analysis.

Importance: In individuals with schizophrenia, antipsychotic-induced dysfunctions are frequent but often underexplored in clinical practice. Objective: To synthetize the data of observational studies exploring the prevalence of sexual dysfunction in individuals with schizophrenia-spectrum disorders as well as associated factors. Data Sources: A systematic literature search without language or time restrictions was conducted in Google, Google Scholar, PubMed/MEDLINE, Science Direct, and Université Sorbonne Paris Cité for studies published up to June 8, 2022. Study Selection: All observational studies reporting a prevalence of sexual dysfunction in schizophrenia-spectrum disorder were included. Data Extraction and Synthesis: The MOOSE guidelines with independent extraction by 2 observers and random-effects models were used. Main Outcomes and Measures: The prevalence of sexual dysfunction and each specific dysfunction. Results: A total of 72 of 1119 studies from 33 countries on 6 continents published from inception to June 2022 were included with a total of 21 076 participants with schizophrenia. The pooled global prevalence of sexual dysfunctions was 56.4% (95% CI, 50.5-62.2), with a prevalence of 55.7% (95% CI, 48.1-63.1) for men and 60.0% (95% CI, 48.0-70.8) for women. The most frequent sexual dysfunction was erectile dysfunction in men (44%; 95% CI, 33.5-55.2), followed by loss of libido in men (41%; 95% CI, 30.7-51.4), ejaculation dysfunction in men (39%; 95% CI, 26.8-51.8), orgasm dysfunction in women (28%; 95% CI, 18.4-40.2), and amenorrhea in women (25%; 95% CI, 17.3-35.0). Factors associated with heterogeneity were study design, time and location, sociodemographic data, alcohol use disorder, psychiatric diagnosis, illness severity, and the use of antidepressants and anxiolytics. Sexual dysfunctions were more frequent in schizophrenia vs schizoaffective disorders, and erectile disorders were less frequent in individuals with longer illness duration. Antidepressant and mood stabilizer prescriptions were associated with lower rates of erection disorders (ß, -6.30; 95% CI, -10.82 to -1.78); P = .006 and -13.21; 95% CI, -17.59 to -8.83; P < .001, respectively) and ejaculation disorders (ß, -6.10; 95% CI, -10.68 to -1.53; P = .009 and ß, -11.57; 95% CI, -16.34 to -6.80; P < .001, respectively). No obvious improvements in the rates of sexual dysfunction at other times were found, and there were conflicting results regarding antipsychotic classes. Conclusions and Relevance: This systematic review and meta-analysis found a high prevalence of sexual dysfunction among individuals with schizophrenia, with considerable heterogeneity in associated factors. The findings also suggest that some dysfunctions may be explained by schizophrenia. The association between lower rates of dysfunction and antidepressant use suggests that treating comorbid depression could be an effective strategy to improve sexual health. A lack of data on metabolic parameters and physical health in general was also noted, while these issues are frequent in the care of schizophrenia.

Long-term benzodiazepine prescription in treatment-resistant depression: A national FACE-TRD prospective study.

BACKGROUND: Benzodiazepine long-term use (BLTU) is a public health challenge. We lack data on the consequences of LBTU on the trajectory of treatment-resistant depression (TRD). OBJECTIVE: To determine the prevalence of BLTU in a nationwide non-selected population of patients with TRD, to determine the rate of patients succeeding at withdrawing benzodiazepines at one year and to determine if persistent BLTU is associated with poorer mental health outcomes. METHOD: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at one year. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at one year. RESULTS: At baseline, 45.2% of the patients were classified in the BLTU group. In multivariate analysis, compared to patients without BLTU, patients with BLTU were more frequently classified in the "low physical activity" group (adjusted odds ratio (aOR) = 1.885, p = 0.036), and had higher primary healthcare consumption (B = 0.158, p = 0.031) independently of age, sex and antipsychotic consumption. We found no significant difference for personality traits, suicidal ideation, impulsivity, childhood trauma exposure, earlier age at first major depressive episode, anxiety and sleep disorders (all p > 0.05). Despite recommendations for withdrawal, <5% of BLTU patients withdraw benzodiazepines during the one-year follow-up. Persistent BLTU at one-year was associated with higher depression severity (B = 0.189, p = 0.029), higher clinical global severity (B = 0.210, p = 0.016), higher state-anxiety (B = 0.266, p = 0.003), impaired sleep quality (B = 0.249, p = 0.008), increased peripheral inflammation (B = 0.241, p = 0.027), lower functioning level (B = -0.240, p = 0.006), decreased processing speed (B = -0.195, p = 0.020) and verbal episodic memory (B = -0.178, p = 0.048), higher absenteeism and productivity loss (B = 0.595, p = 0.016) and lower subjective global health status (B = -0.198, p = 0.028). CONCLUSION: Benzodiazepines are over-prescribed in TRD (in almost a half of the patients). Despite recommendations for withdrawal and psychiatric follow-up, <5% of patients successfully stopped taking benzodiazepines at one-year. Maintaining BLTU may contribute to the worsening of clinical and cognitive symptoms and of daily functioning in TRD patients. Progressive and planed withdrawal of benzodiazepines seems therefore strongly recommended in TRD patients with BLTU. Pharmacological and non-pharmacological alternatives should be promoted when possible.

The Validity of the SQoL-18 in Patients with Bipolar and Depressive Disorders: A Psychometric Study from the PREMIUM Project.

The S-QoL 18 is a self-administered questionnaire that assesses quality of life (QoL) among individuals with schizophrenia. This study aims to validate the S-QoL 18 in bipolar and depressive disorders for a more widespread use in psychiatric settings. This study was conducted in a non-selected sample of individuals with bipolar and depressive disorders in the day hospital of a regional psychiatric academic hospital. Two-hundred and seventy-two stable outpatients with bipolar (n = 73) and recurrent and persistent depressive (n = 199) disorders were recruited over a 12 month-period. The S-QoL 18 was tested for construct validity, reliability, and external validity. The eight-factor structure of the S-QoL 18 was confirmed by confirmatory factor analysis (RMSEA = 0.075 (0.064-0.086), CFI = 0.972, TLI = 0.961). Internal consistency and reliability were satisfactory. External validity was confirmed via correlations between S-QoL 18 dimension scores, symptomatology, and functioning. The percentage of missing data for the eight dimensions did not exceed 5%. INFIT statistics were ranged from 0.7 to 1.2, ensuring that all items of the scale measured the same QoL concept. In conclusion, the S-QoL 18 appears to be a valid and reliable instrument for measuring QoL in patients with bipolar and depressive disorders. The S-QoL 18 may be used by healthcare professionals in clinical settings to accurately assess QoL in individuals with bipolar and depressive disorders, as well as in schizophrenia.

Precision-medicine findings from the FACE-SZ cohort to develop motivation-enhancing programs in real-world schizophrenia.

BACKGROUND: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. AIM: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life. METHODS: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits. RESULTS: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235 (41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR = 2.141, p = 0.021), severe nicotine dependence (aOR = 2.906, p < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR = 2.297, p = 0.001), positive symptoms (aOR = 1.052, p = 0.006), current major depressive episode (aOR = 2.627, p < 0.001), sleep disorders (aOR = 1.474, p = 0.024) and lower medication adherence (aOR = 0.836, p = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder. INTERPRETATION: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia.

Peripheral inflammation is associated with brain SPECT perfusion changes in schizophrenia.

PURPOSE: Peripheral inflammation is frequent in schizophrenia and could play a role in the pathophysiology, prognosis, and persistence of psychotic symptomatology under treatment. We seek to determine the relationship between peripheral inflammation and brain SPECT perfusion in stabilized antipsychotic-treated outpatients with schizophrenia, and to determine whether such perfusion changes are correlated with persistent symptoms. METHODS: Highly sensitive C-reactive protein blood level (hs-CRP) and brain SPECT perfusion were assessed in 137 stabilized outpatients with schizophrenia. Whole-brain voxel-based associations were searched with SPM between SPECT perfusion and hs-CRP (correlation analysis to quantitative levels and between-group analysis according to a threshold of 3 mg/L). The identified clusters were secondarily correlated with clinical symptoms. RESULTS: After adjustment for age, sex, educational level, illness duration, antidepressant use, chlorpromazine equivalent dose, tobacco smoking and obesity, a negative correlation was found between hs-CRP level and the perfusion of 4 brain areas: the right inferior frontal gyrus, the right middle/superior temporal gyrus, the left superior parietal lobe, and the right postcentral/transverse temporal gyrus (p-voxel < 0.001, k > 80, uncorrected). Increased perfusion of the left amygdala was found in patients with hs-CRP ≥ 3 mg/L compared to those with hs-CRP levels < 3 mg/L. A negative correlation was found between perfusion of the right inferior frontal gyrus and the persistence of positive, negative, and excitement symptoms under antipsychotic treatment. CONCLUSION: In stabilized patients with schizophrenia, peripheral inflammation is associated with brain perfusion changes that are correlated with the persistence of psychotic symptomatology.

Recommendations of the treatment-resistant depression expert center network for promoting tobacco smoking cessation based on the results from the real-world FACE-TRD national cohort.

BACKGROUND: Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. OBJECTIVE: To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. METHOD: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. RESULTS: 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. INTERPRETATION: Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed.

Toward a transdiagnostic tool to evaluate depressive symptoms across mental disorders: Validation of the Calgary depression rating scale in patients with major depressive disorder.

The severity of depressive symptoms across two discrete mental disorders should be evaluated with the same psychometrically validated tools. In patients with schizophrenia the Calgary Depression Rating Scale (CDSS) is recommended for evaluating depressive symptoms. The aim of this study was to validate the CDSS in patients with major depressive disorder. The CDSS exhibit satisfactory psychometric properties for evaluating depressive symptoms in major depressive disorder. Clinicians and researchers now have a validated scale at their disposal to evaluate depressive symptoms in various mental disorders using a transdiagnostic approach.

Sensory gating deficits and impaired quality of life in patients with schizophrenia: A preliminary study.

BACKGROUND: New determinants of quality of life in schizophrenia need to be identified. As sensory gating deficit is core impairment in schizophrenia, the present study hypothesized that sensory gating deficit is a determinant of impaired quality of life in schizophrenia. This study therefore investigated the relationship between sensory gating deficit and quality of life in patients with schizophrenia after adjusting for key confounding factors. SUBJECTS AND METHODS: Sensory gating was assessed with the auditory event-related potential method by measuring P50 amplitude changes in a double-click conditioning-testing procedure, perceptual impairments related to sensory gating deficit was assessed with the SGI questionnaire and quality of life was assessed with the SQoL 18 questionnaire in 39 patients with schizophrenia. RESULTS: Patients with sensory gating deficit (n=14) had a lower subjective quality of life on the psychological well-being dimension evaluated with SQoL 18 questionnaire (p=0.008) compared to those without it (n=25). This result remained significant (B=-0.45, Wald=4.84, p=0.02) after taking into account 7 potential confounding factors (gender, age, level of education, duration of disorder, positive symptoms, depressive symptoms and anxiety symptoms). Poorer psychological well-being was related to a higher score on the SGI (rho=-0.40, p=0.01), in particular on the Distractibility dimension (rho=-0.47, p=0.001). CONCLUSIONS: These findings suggest that sensory gating deficit may be a determinant of impaired quality of life in schizophrenia. Further studies are needed to address the causal relationship between sensory gating deficit, perceptual impairments, attentional deficit and impaired quality of life in schizophrenia in order to act more efficiently on the quality of life of patients with this disorder.

A structural equation modelling approach to explore the determinants of quality of life in schizophrenia.

OBJECTIVE: This study aimed to analyse the relationships among psychotic symptoms, depression, neurocognition and functioning as determinants of quality of life (QoL) in patients with schizophrenia. METHODS: In this cross-sectional study, we evaluated QoL with the Schizophrenia Quality of Life 18-item scale (S-QoL 18), neurocognition with multiple tests exploring memory, attention and executive functions, the severity of psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS), depression with the Calgary Depression Scale for Schizophrenia (CDSS) and functioning using the Functional Remission Of General Schizophrenia (FROGS) scale. We used Structural Equation Modelling (SEM) to describe the relationships among the severity of psychotic symptoms, depression, neurocognition, functioning and QoL. RESULTS: Two hundred and seventy-one outpatients with schizophrenia participated in our study. SEM showed good fit with χ(2)/df=1.97, root mean square error of approximation=0.06, comparative fit index=0.93 and standardized root mean square residuals=0.05. This model revealed that depression was the most important feature associated with QoL, mainly for the self-esteem, autonomy and resilience dimensions (direct path coefficient=-0.46). The direct path between functioning and QoL was also significant (path coefficient=0.26). The severity of psychotic symptoms and neurocognitive impairment were weakly and indirectly associated with QoL via functioning (path coefficients=-0.18 and 0.04, respectively). CONCLUSIONS: This study contributes to a better understanding of the determinants of QoL in schizophrenia. Our findings should be considered in developing effective strategies for improving QoL among this population.

Association of metabolic syndrome with sensory gating deficits in patients with chronic schizophrenia.

Metabolic syndrome is more prevalent in schizophrenia than in the general population and is associated with an increased rate of morbidity. It has been associated with cognitive impairments in schizophrenia, which are a core deficit in patients with chronic schizophrenia. Sensory gating deficit is also a core deficit in schizophrenia. The principal objective of this study was to investigate the relationship between sensory gating deficit and metabolic syndrome in patients with schizophrenia, after adjusting for key confounding factors. We hypothesized that patients with metabolic syndrome exhibit a higher rate of sensory gating deficit compared to those without metabolic syndrome. This study investigated sensory gating with the auditory event-related potential method by measuring P50 amplitude changes in a double click conditioning-testing procedure in 51 patients with schizophrenia. Patients with metabolic syndrome (n = 14) had a higher rate of sensory gating deficit (P50 suppression <50%) (p < 0.001) compared to those without metabolic syndrome (n = 37). This result remained significant (B = 2.94, Wald = 8.32, p = 0.004) after taking into account 5 potential confounding factors (age, gender, duration of disorder, Fagerström test, presence of clozapine or olanzapine). In patients without metabolic syndrome, sensory gating deficit was linked to a poorer attentional performance (rho = -0.371, p = 0.05). In patients with metabolic syndrome, sensory gating deficit was linked to poorer memory performance (rho = -0.635, p = 0.02). These findings suggest that metabolic syndrome may be linked to sensory gating deficit in patients with schizophrenia and that the relationship between neurocognitive function and sensory gating deficit could be affected by the metabolic status of the patients. Further studies are needed to address the causal relationship between sensory gating deficit related to schizophrenia, cognitive impairments and metabolic syndrome.

Elevated C-reactive protein is associated with sensory gating deficit in schizophrenia.

Sensory and cognitive impairments and inflammatory processes are contributing factors to the pathogenesis of schizophrenia. A previous study found that an elevated CRP level (≥5mg/L) was associated with higher cognitive impairments in schizophrenia. We aimed to investigate the association between an elevated CRP level and sensory impairments defined by a sensory gating deficit (abnormal P50 suppression) in 55 outpatients. Fifteen patients (27.3%) had an elevated CRP level that was associated with higher rate of sensory gating deficit (60% vs. 12.5%, p<0.001). This is the first study suggesting a relationship between sensory gating deficit and inflammatory processes in schizophrenia.

Determinants of patient satisfaction with hospital health care in psychiatry: results based on the SATISPSY-22 questionnaire.

BACKGROUND: The aim of our study was to identify patient- and care-related factors that are associated with patients' satisfaction with psychiatric hospital care, using a specific, self-administered questionnaire based exclusively on the patient's point of view: the Satisfaction with Psychiatry Care Questionnaire-22 (SATISPSY-22). METHODS: This cross-sectional study was conducted in the psychiatric departments of two French public university teaching hospitals. The data collected included sociodemographic information, clinical characteristics, care characteristics, and the SATISPSY-22. A multivariate analysis using multiple linear regressions was performed to determine the variables potentially associated with satisfaction levels. RESULTS: Two hundred seventy patients were enrolled in our study. Only one moderate association was found between satisfaction and sociodemographic characteristics: the personal experience dimension with age (ß=0.15). Clinical improvement was moderately associated with higher global satisfaction (ß=-0.15), higher satisfaction with quality of care (ß=-0.19), and higher satisfaction with food (ß=-0.18). Stronger associations with satisfaction were found for care characteristics, particularly the therapeutic alliance with all of the satisfaction dimensions (ß, 0.20-0.43) except food, and for seclusion with global satisfaction (ß=-0.33) and personal experience (ß=-0.32). Patients with previous hospitalization also had a higher level of satisfaction with quality of care compared with patients who were admitted for the first time (ß=-0.15). CONCLUSION: This study has identified a number of potential determinants of satisfaction. The therapeutic relationship and seclusion were the most important features associated with a patient's satisfaction. These factors might be amenable through intervention, which, in turn, might be expected to improve satisfaction, patients' management, and health outcomes in psychiatric hospitals.

Validation of the French sensory gating inventory: a confirmatory factor analysis.

The Sensory Gating Inventory (SGI) is an instrument investigating daily experiences of sensory gating deficit developed for English speaking schizophrenia patients. The purpose of this study is to design and validate a French version of the SGI. A forward-backward translation of the SGI was performed. The psychometric properties of the French SGI version were analyzed. A confirmatory factor analysis (CFA) was carried out to determine whether factor structure of the French version is similar to the original English version. In a sample of 363 healthy subjects (mean age=31.8 years, S.D.=12.2 years) the validation process revealed satisfactory psychometric properties: the internal consistency reliability was confirmed for each dimension; each item achieved the 0.40 standard threshold for item-internal consistency; each item was more highly correlated with its contributive dimension than with the other dimensions; and based on a CFA, we found a 4-factor structure for the French version of the SGI similar to the original instrument. Test-retest reliability was not determined. The French version of the SGI is a psychometrically sound self-report for measuring phenomenological sensory gating experiences.

Do schizophrenia patients with low P50-suppression report more perceptual anomalies with the sensory gating inventory?

BACKGROUND: P50 amplitude changes in dual click conditioning-testing procedure might be a neurophysiological marker of deficient sensory gating in schizophrenia. However, the relationship between abnormalities in the neurophysiological and phenomenological dimensions of sensory gating in schizophrenia remains unclear. The aim of the present study was to determine if patients with low P50-suppression (below 50%) report more perceptual anomalies. METHODS: Three groups were compared: twenty-nine schizophrenia patients with high P50-suppression (above 50% amplitude suppression), twenty-three schizophrenia patients with low P50-suppression (below 50%) and twenty-six healthy subjects. The Sensory Gating Inventory (SGI), a four-factor self-report questionnaire, was used to measure perceptual anomalies related to sensory gating. A comparison of demographic and clinical data was also carried out. RESULTS: Patients with low P50-suppression presented: i) significantly higher scores on the SGI (for the overall SGI score and for each of the 4 factors) and ii) significantly larger P50 amplitude at the second click, than both patients with high P50-suppression and healthy subjects. There were no group differences in the most of demographic and clinical data. DISCUSSION: The finding offers support for conceptual models wherein abnormal neurophysiologic responses to repetitive stimuli give rise to clinically relevant perceptions of being inundated and overwhelmed by external sensory stimuli. Further studies are needed to explore the contributions of clinical symptoms, medication and neuropsychological functions to the relationship between P50-suppression and the SGI, and the role of sensory "gating in" versus "gating out".

Natural speech comprehension in bipolar disorders: an event-related brain potential study among manic patients.

BACKGROUND: Thought and language disturbances are crucial clinical features in Bipolar Disorders (BD), and constitute a fundamental basis for social cognition. In BD, clinical manifestations such as disorganization and formal thought disorders may play a role in communication disturbances. However, only few studies have explored language disturbances in BD at a neurophysiological level. Two main Event-Related brain Potentials (ERPs) have been used in language comprehension research: the N400 component, elicited by incongruous word with the preceding semantic context, and the Late Positive Component (LPC), associated with non-specifically semantic and more general cognitive processes. Previous studies provided contradictory results regarding N400 in mood disorders, showing either preserved N400 in depression or dysthymia, or altered N400 in BD during semantic priming paradigm. The aim of our study was to explore N400 and LPC among patients with BD in natural speech conditions. METHODS: ERPs from 19 bipolar type I patients with manic or hypomanic symptomatology and 19 healthy controls were recorded. Participants were asked to listen to congruous and incongruous complete sentences and to judge the match between the final word and the sentence context. Behavioral results and ERPs data were analyzed. RESULTS: At the behavioral level, patients with BD show worst performances than healthy participants. At the electrophysiological level, our results show preserved N400 component in BD. LPC elicited under natural speech conditions shows preserved amplitude but delayed latency in difference waves. LIMITATIONS: Small size of samples, absence of schizophrenic group and medication status. CONCLUSIONS: In contrast with the only previous N400 study in BD that uses written semantic priming, our results show a preserved N400 component in ecological and natural speech conditions among patients with BD. Possible implications in terms of clinical specificity are discussed.