Self-esteem in stabilized individuals with chronic schizophrenia: association with residual symptoms and cognitive functioning.

Low self-esteem is regarded as a barrier to recovery from schizophrenia and the identification of factors affecting this psychological characteristic may help to implement effective therapeutic interventions. To this end, the present study aimed to assess whether residual symptoms of the disorder and performance on a comprehensive neuropsychological test battery might differently impact self-esteem among 70 stabilized outpatients with chronic schizophrenia from public outpatient mental health services. Self-esteem inter-correlated with the severity of overall symptomatology, affective and negative symptoms, with premorbid intelligence, and with performance in the domains of verbal learning and memory, visual memory, working memory, and verbal fluency. Residual affective symptoms, premorbid intelligence, and female sex predicted poorer self-esteem in multiple linear regression analysis. The findings of this study implicate that next to psychological interventions therapeutic strategies that specifically target affective symptoms of schizophrenia may have a beneficial impact on patients' self-esteem.

Driving fitness in clinically stable outpatients with chronic schizophrenia.

INTRODUCTION: Driving motorized vehicles is an integral part of individual mobility and a key parameter for employment and social integration. This naturalistic, cross-sectional study investigated the associations between driving fitness, residual symptomatology, olanzapine equivalent, and extrapyramidal symptoms (EPS) in long term stable outpatients with schizophrenia. METHODS: Beside sociodemographic data, and driving habits, residual symptoms, and EPS were assessed using the Positive and Negative Syndrome Scale (PANSS), and the Modified Simpson Angus Scale (MSAS). PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. MSAS cut-off scores ≥3 were defined as positive for EPS. Driving skills were assessed using the Vienna Test System and an expert evaluation. RESULTS: 50 patients were included into the study. Mean PANSS total scores indicated mild residual symptomatology and EPS were not present in 48% of study participants. 44% passed the driving fitness assessment and were considered as competent to drive, 20% were judged to be partially competent and 36% to be incompetent to drive. With the exception of disorganization (r = -0·287, p = 0·048) residual symptoms of schizophrenia did not correlate with driving fitness. However, moderate negative correlations were detected between driving fitness and the severity of EPS (r = -0·554, p = 0·000), age (r = -0·413, p = 0·003) as well as olanzapine equivalent doses (r = -0·432, p = 0·002). These results were not corrected for multiple comparison. DISCUSSION: The present findings indicate that up to two thirds of clinically stable outpatients with chronic schizophrenia may be (partially) competent to drive. Both the presence of EPS as well as the dosage of antipsychotic medication seem to be of particular relevance in this regard.

Combined Processing of Facial and Vocal Emotion in Remitted Patients With Bipolar I Disorder.

OBJECTIVES: Bipolar disorder (BD) is associated with impairments in facial emotion and emotional prosody perception during both mood episodes and periods of remission. To expand on previous research, the current study investigated cross-modal emotion perception, that is, matching of facial emotion and emotional prosody in remitted BD patients. METHODS: Fifty-nine outpatients with BD and 45 healthy volunteers were included into a cross-sectional study. Cross-modal emotion perception was investigated by using two subtests out of the Comprehensive Affective Testing System (CATS). RESULTS: Compared to control subjects patients were impaired in matching sad (p < .001) and angry emotional prosody (p = .034) to one of five emotional faces exhibiting the corresponding emotion and significantly more frequently matched sad emotional prosody to happy faces (p < .001) and angry emotional prosody to neutral faces (p = .017). In addition, patients were impaired in matching neutral emotional faces to the emotional prosody of one of three sentences (p = .006) and significantly more often matched neutral faces to sad emotional prosody (p = .014). CONCLUSIONS: These findings demonstrate that, even during periods of symptomatic remission, patients suffering from BD are impaired in matching facial emotion and emotional prosody. As this type of emotion processing is relevant in everyday life, our results point to the necessity to provide specific training programs to improve psychosocial outcomes. (JINS, 2019, 25, 336-342).

Prescribing Practice in Inpatients Versus Outpatients With Schizophrenia Initiating Treatment With Second-Generation Antipsychotics: A Naturalistic Follow-Up Study.

OBJECTIVE: The primary objective of this study was to investigate whether the choice and dosage of antipsychotic medication differ between patients with schizophrenia starting treatment in an inpatient or outpatient unit. In addition, we investigated whether the reason for the introduction of new antipsychotic medication had an impact on the treatment setting and whether the use of benzodiazepines differed between inpatients and outpatients. METHOD: From October 1997 to September 2010, patients with a schizophrenia spectrum disorder according to the International Classification of Diseases, Tenth Revision aged between 18 and 65 years were allocated to a naturalistic drug-monitoring program when starting treatment with a second-generation antipsychotic drug. Psychopathological symptoms were rated at baseline and after 1, 2, 4, and 8 weeks of treatment using the Positive and Negative Syndrome Scale. Inpatients and outpatients were compared with regard to the use of antipsychotics and benzodiazepines. To compare different drugs, chlorpromazine and diazepam equivalents were calculated. RESULTS: Lack of efficacy and side effects were the main reasons for initiating new antipsychotic medication. Combined evaluation of all antipsychotic compounds by meta-analysis resulted in a significant effect of the treatment setting, with inpatients receiving higher doses than outpatients. In addition, inpatients were prescribed benzodiazepines more often and in higher doses than outpatients. CONCLUSIONS: Both antipsychotics and benzodiazepines were prescribed at higher doses in an inpatient setting. Moreover, benzodiazepines were prescribed more frequently to inpatients. Accordingly, the treatment setting needs to be taken into consideration in treatment recommendations for schizophrenia spectrum disorders.

Psychotic disorders in DSM-5 and ICD-11.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was published by the American Psychiatric Association (APA) in 2013, and the Work Group on the Classification of Psychotic disorders (WGPD), installed by the World Health Organization (WHO), is expected to publish the new chapter about schizophrenia and other primary psychotic disorders in 2017. We reviewed the available literature to summarize the major changes, innovations, and developments of both manuals. If available and possible, we outline the theoretical background behind these changes. Due to the fact that the development of ICD-11 has not yet been completed, the details about ICD-11 are still proposals under ongoing revision. In this ongoing process, they may be revised and therefore have to be seen as proposals. DSM-5 has eliminated schizophrenia subtypes and replaced them with a dimensional approach based on symptom assessments. ICD-11 will most likely go in a similar direction, as both manuals are planned to be more harmonized, although some differences will remain in details and the conceptual orientation. Next to these modifications, ICD-11 will provide a transsectional diagnostic criterion for schizoaffective disorders and a reorganization of acute and transient psychotic and delusional disorders. In this manuscript, we will compare the 2 classification systems.

Changes in psychopathology in schizophrenia patients starting treatment with new-generation antipsychotics: therapeutic drug monitoring in a naturalistic treatment setting.

Previous studies on the relationship between plasma levels of new-generation antipsychotics (NGAs) and clinical response did not account for inter- and intra-individual variability in drug levels. Therefore, the present study calculated the ratio of observed versus expected NGA plasma levels and investigated its relationship with changes in the Positive and Negative Syndrome Scale (PANSS). Data of patients starting monotherapy with a NGA were collected 2, 4, 8, and 12 weeks after initiation of treatment. Next to the assessment of changes in psychopathology (PANSS) the ratio of observed versus expected plasma level was calculated. A total number of 221 ratios were eligible for analysis. About half of them ranged from 0.5-2 and were considered "normal", whereas the others were considered either "too low" or "too high". Psychopathological symptoms improved over the course of treatment, but changes in PANSS from baseline did not correlate significantly with the ratios of observed versus expected plasma levels at any assessment. The lack of linear correlation can be explained by the fact that 92% of the observed NGA plasma levels were at ≥ 50% of the lower limit of the therapeutic reference range, i.e., within the asymptote of the logistic plasma level-effect relationship. Accordingly, our findings indicate that the great majority of patients were treated with NGA doses that led to optimal plasma levels, based on the clinical impression of the treating psychiatrist only. Thus, calculating the ratio of observed versus expected plasma level may not be necessary in a routine clinical setting.

Prosodic and semantic affect perception in remitted patients with bipolar I disorder.

OBJECTIVE: Bipolar disorder is associated with impairments in emotion processing that are present during both mood episodes and periods of remission. In this context, most previous studies have investigated facial emotion recognition abilities. In contrast, the current study focused on the perception of prosodic and semantic affect. METHOD: The present study directly contrasted the perception of prosodic and semantic affect in 58 remitted patients meeting DSM-IV criteria for bipolar I disorder and 45 healthy volunteers by using 2 subtests of the Comprehensive Affective Testing System (CATS) and investigated the relationship of prosodic and semantic affect perception with patients' outcomes. Participants were investigated from June 2011 until May 2013. RESULTS: Patients and controls did not differ regarding the recognition of the vocal emotion while ignoring the affective meaning of test trials (CATS 1), but patients significantly more often misinterpreted sad as happy prosody (P = .039). In addition, patients were impaired in recognizing the affective meaning of test trials while ignoring the vocal emotion (CATS 2; P = .052). Again, they significantly more often misinterpreted a sad affective meaning as a happy one (P = .025). However, the findings on misinterpretations did not withstand Bonferroni correction for multiple testing. CATS 1 test performance was negatively correlated with depression scores, whereas a positive association was found between performance on both tests and patients' functioning. Patients indicated a significantly lower quality of life (P < .001); however, multiple mediation analysis revealed that this finding was not mediated by differences in prosodic and/or semantic affect perception between the 2 groups. CONCLUSIONS: Even during periods of remission, patients with bipolar disorder may be impaired in semantic but not prosodic affect perception. Notably, they may frequently misinterpret sadly expressed emotions as happy ones. Our findings underscore the relevance of these deficits in the psychosocial context.

Measuring adherence to medication in schizophrenia: the relationship between attitudes toward drug therapy and plasma levels of new-generation antipsychotics.

BACKGROUND: Nonadherence to medication is still a major problem in the treatment of schizophrenia. The current longitudinal study investigated whether the patients' attitudes toward treatment correlated with the ratio of observed vs expected plasma levels of antipsychotic drugs as an objective measurement of adherence. METHODS: Data of patients starting monotherapy with a new-generation antipsychotic were collected 2, 4, and 12 weeks after the initiation of treatment. Next to the assessment of patients' attitudes toward medication by means of the Drug Attitude Inventory, the ratio of the observed vs expected plasma level was calculated. Antipsychotic-induced side effects were evaluated by means of the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. RESULTS: A total of 93 patients were eligible for statistical analysis. About one-half of the ratios of observed vs expected plasma levels ranged from 0.5 to 2 and were considered normal, whereas the other ratios were considered either too low (<0.5) or too high (>2). No consistent correlation between patients' attitude toward drug therapy and the individual ratios of observed vs expected plasma levels of medication was detected. This finding was not affected by side effects. CONCLUSIONS: Our results highlight the importance of recognizing the complex nature of adherence to medication in schizophrenia patients. Importantly, we found no consistent correlation between subjective and objective measures of medication adherence. Therefore, monitoring adherence to medication remains a challenge in clinical practice.

Affective prosody perception in symptomatically remitted patients with schizophrenia and bipolar disorder.

Affect perception has frequently been shown to be impaired in patients suffering from schizophrenia or bipolar disorder (BD), but it remains unclear whether these impairments exist during symptomatic remission and whether the two disorders differ from each other in this regard. Most previous studies have investigated facial affect recognition, but not the ability to decode mental states from emotional tone of voice, i.e. affective prosody perception (APP). Accordingly, the present study directly compared APP in symptomatically remitted patients with schizophrenia or BD and healthy control subjects and investigated its relationship with residual symptomatology in patients. Patients with schizophrenia and BD showed comparable APP impairments despite being symptomatically remitted. In comparison to healthy control subjects, overall APP deficits were found in BD but not in schizophrenia patients. Both patient groups were particularly impaired in the identification of anger and confounded it with neutral prosody. In addition, schizophrenia patients frequently confused sadness with happiness, anger, or fright. There was an inverse association between the degree of residual positive symptoms and the ability to correctly recognize happiness in schizophrenia patients. Overall, these data indicate that impairments in APP represent an enduring deficit and a trait marker of both schizophrenia and BD and that the level of impairment is comparable between disorders.

Facial affect recognition in symptomatically remitted patients with schizophrenia and bipolar disorder.

Both schizophrenia and bipolar disorder (BD) have consistently been associated with deficits in facial affect recognition (FAR). These impairments have been related to various aspects of social competence and functioning and are relatively stable over time. However, individuals in remission may outperform patients experiencing an acute phase of the disorders. The present study directly contrasted FAR in symptomatically remitted patients with schizophrenia or BD and healthy volunteers and investigated its relationship with patients' outcomes. Compared to healthy control subjects, schizophrenia patients were impaired in the recognition of angry, disgusted, sad and happy facial expressions, while BD patients showed deficits only in the recognition of disgusted and happy facial expressions. When directly comparing the two patient groups individuals suffering from BD outperformed those with schizophrenia in the recognition of expressions depicting anger. There was no significant association between affect recognition abilities and symptomatic or psychosocial outcomes in schizophrenia patients. Among BD patients, relatively higher depression scores were associated with impairments in both the identification of happy faces and psychosocial functioning. Overall, our findings indicate that during periods of symptomatic remission the recognition of facial affect may be less impaired in patients with BD than in those suffering from schizophrenia. However, in the psychosocial context BD patients seem to be more sensitive to residual symptomatology.

Sibutramine in the treatment of antipsychotic-induced weight gain: a pilot study in patients with schizophrenia.

Weight gain represents a frequent side effect of antipsychotic drug treatment. The current trial investigated the effect of add-on treatment with sibutramine in schizophrenia outpatients who had gained more than 7% of weight during the course of treatment. This 24-week placebo-controlled study evaluated the effects of sibutramine added to ongoing antipsychotic treatment. Weight, waist-hip ratio, BMI, blood pressure/pulse and ECG were monitored regularly. In addition, several laboratory tests were performed. Psychopathological symptoms and side effects were assessed frequently. Fifteen patients were assigned randomly to add-on treatment with sibutramine 10 mg or placebo. The two groups did not differ in weight, sociodemographic, or clinical data. Eleven patients were considered for statistical analysis. Significant weight loss was observed in the sibutramine group (mean = -6.1 kg), whereas patients on placebo experienced a mean weight gain of 1.9 kg. A reduction in HbA1c was apparent in the sibutramine but not in the placebo group. No significant between-group differences were found in changes in psychopathology or drug safety. This pilot trial suggests that adjunctive treatment with sibutramine may be safe and effective in schizophrenic patients with antipsychotic-induced weight gain.

Theory of mind and its relevance in schizophrenia.

PURPOSE OF REVIEW: Social cognitive impairments are considered to be core features of schizophrenia and have been hypothesized to play a mediator role between basic neurocognition and patients' outcomes. In this context, theory of mind (ToM) abilities are of special relevance, and deficits in this area may represent trait markers of schizophrenia. RECENT FINDINGS: In this review, studies published since September 2010 have been summarized with a particular focus on the relationships between ToM and psychopathology, neurocognition, and psychosocial outcomes in patients with schizophrenia, as well as on ToM abilities in high-risk individuals. In addition, recent neuroimaging data as well as treatment interventions have been described. SUMMARY: The reviewed literature strengthens the hypothesis that ToM deficits have the potential to be valid markers for schizophrenia.

Combined clozapine and electroconvulsive therapy in clozapine-resistant schizophrenia: clinical and cognitive outcomes.

For treatment-refractory schizophrenia, electroconvulsive therapy (ECT) remains controversial because of its cognitive adverse effects. We report here on clinical and cognitive outcomes of a treatment-resistant schizophrenia patient treated with clozapine and right unilateral ECT.The patient was administered 300 mg of clozapine and 12 right unilateral ECT sessions. Psychopathology was rated by means of the Positive and Negative Syndrome Scale. The neurocognitive test battery included the Wisconsin Card Sorting Test, the Münchner Gedächtnis Test, an attentional performance test, the Trail Making Test, and the Hamburger-Wechsler Intelligence Test.The Positive and Negative Syndrome Scale total score decreased, and all cognitive measures improved.Electroconvulsive therapy would seem to be a safe treatment option for treatment-refractory schizophrenia patients.

Facial emotion recognition and its relationship to subjective and functional outcomes in remitted patients with bipolar I disorder.

OBJECTIVES: Outcome in bipolar disorder (BD) is multidimensional and consists of clinical and psychosocial domains. Difficulties in affect recognition and in emotional experience are a hallmark of BD, but there is little research investigating the consequences of this deficit on the psychosocial status of patients who are in remission. METHODS: This cross-sectional study examined the relationship of facial affect recognition and treatment outcomes in terms of psychopathology, quality of life, and psychosocial functioning in remitted BD patients compared to healthy volunteers. RESULTS: Altogether, 47 outpatients meeting diagnostic criteria for bipolar I disorder according to DSM-IV and 45 healthy control subjects were included in the study. Patients were particularly impaired in the recognition of facial expressions depicting disgust and happiness. For patients, the most frequently observed misidentifications included disgusted faces misrecognized as angry expressions, fearful faces misrecognized as disgusted or surprised expressions, surprised faces misrecognized as fearful expressions, and sad faces misrecognized as fearful or angry expressions. Regarding emotional experience, shame, guilt, sadness, fear, lifelessness, loneliness, and existential fear were experienced more intensely by patients. CONCLUSIONS: These findings demonstrate deficits in experiencing and recognizing emotions in BD patients who are in remission and underscore the relevance of these deficits in the psychosocial context.

Emerging drugs for schizophrenia.

INTRODUCTION: Since the development of clozapine, scores of antipsychotics have been introduced. These are, with one exception (aripiprazole), based on the pharmacological principle of 5-HT(2)/dopamine antagonism. Research on other treatment targets, which, in part, influence dopaminergic pathways directly or indirectly, is mounting. Managing psychotic symptoms is only one facet of successful treatment of schizophrenia. Effective remedies against negative symptoms and cognitive deficits are still an unmet clinical need. AREAS COVERED: With the focus on the topics mentioned above, the authors briefly review the latest clinical research organized on the basis of receptor systems and other drug targets, which are discussed to be involved in the pathophysiology of schizophrenia. EXPERT OPINION: In conclusion, although clinicians will have to have considerable patience before truly novel anti-schizophrenia treatments become obtainable, a number of interesting leads with considerable theoretical potential are being explored. As yet, it is difficult to predict which of these mechanisms will effectively augment the currently available treatments.

[Neurocognition and social cognition in patients with schizophrenia or mood disorders]. / Neurokognition und soziale Kognition bei Patienten mit schizophrenen und affektiven Störungen.

OBJECTIVE: Overview on the current knowledge regarding neurocognition and social cognition in patients with schizophrenia or mood disorders. METHODS: Selective literature research on deficits in neurocognition and social cognition intrinsic to schizophrenia and mood disorders, their occurrence and effects. RESULTS: Deficits in neurocognition and social cognition are more pronounced in patients with schizoprenia than in those with mood disorders. However, regardless of diagnosis these impairments have significant negative impact on the patients' subjective and functional outcome. CONCLUSIONS: It is important to consider cognitive deficits as an integral part of a treatment approach to achieve mental stabilization in patients with schizophrenia or mood disorders.

Antipsychotics in the early stage of development.

PURPOSE OF REVIEW: In this article, we will summarize some of the most recent pharmacological approaches by briefly reviewing the latest research results related to different neurotransmitter receptor systems but also alternative approaches that do not affect central nervous system receptors directly. RECENT FINDINGS: Although the field still struggles with the lack of major breakthroughs, some novel pharmacological leads have provided encouraging findings in proof of concept or early phase II clinical trials. Although some of these approaches are based on the modified dopamine/glutamate hypothesis of schizophrenia, others appear to have been driven by more serendipitous observations. Apart from this, more traditional routes such as compounds targeting D2/HT2 receptors are also still being pursued. Attempts to advance treatment response of negative symptoms and cognitive impairment, two areas of considerable unmet need have been an overriding theme in many studies. SUMMARY: Clinical psychopharmacologists increasingly realize that it is highly unlikely that we have a magic bullet to treat adequately all aspects of this complex disorder in the foreseeable future. Rational polypharmacy may be the trend for the next decade.