Who is at risk for weight gain after weight-gain associated treatment with antipsychotics, antidepressants, and mood stabilizers: A machine learning approach.

BACKGROUND: Weight gain is a common side effect in psychopharmacology; however, targeted therapeutic interventions and prevention strategies are currently absent in day-to-day clinical practice. To promote the development of such strategies, the identification of factors indicative of patients at risk is essential. METHODS: In this study, we developed a transdiagnostic model using and comparing decision tree classifiers, logistic regression, XGboost, and a support vector machine to predict weight gain of ≥5% of body weight during the first 4 weeks of treatment with psychotropic drugs associated with weight gain in 103 psychiatric inpatients. We included established variables from the literature as well as an extended set with additional clinical variables and questionnaires. RESULTS: Baseline BMI, premorbid BMI, and age are known risk factors and were confirmed by our models. Additionally, waist circumference has emerged as a new and significant risk factor. Eating behavior next to blood glucose were found as additional potential predictor that may underlie therapeutic interventions and could be used for preventive strategies in a cohort at risk for psychotropics induced weight gain (PIWG). CONCLUSION: Our models validate existing findings and further uncover previously unknown modifiable factors, such as eating behavior and blood glucose, which can be used as targets for preventive strategies. These findings underscore the imperative for continued research in this domain to establish effective preventive measures for individuals undergoing psychotropic drug treatments.

Altered amygdalar emotion space in borderline personality disorder normalizes following dialectical behaviour therapy.

BACKGROUND: Borderline personality disorder (BPD) is a mental health condition characterized by an inability to regulate emotions or accurately process the emotional states of others. Previous neuroimaging studies using classical univariate analyses have tied such emotion dysregulation to aberrant activity levels in the amygdala of patients with BPD. However, multivariate analyses have not yet been used to investigate how representational spaces of emotion information may be systematically altered in patients with BPD. METHODS: Patients with BPD performed an emotional face matching task while undergoing MRI before and after a 10-week inpatient program of dialectical behavioural therapy. Representational similarity analysis (RSA) was applied to activity patterns (evoked by angry, fearful, neutral and surprised faces) in the amygdala and temporo-occipital fusiform gyrus of patients with BPD and in the amygdala of healthy controls. RESULTS: We recruited 15 patients with BPD (8 females, 6 males, 1 transgender male) to participate in the study, and we obtained a neuroimaging data set for 25 healthy controls for a comparative analysis. The RSA of the amygdala revealed a negative bias in the underlying affective space (in that activity patterns evoked by angry, fearful and neutral faces were more similar to each other than to patterns evoked by surprised faces), which normalized after therapy. This bias-to-normalization effect was present neither in activity patterns of the temporo-occipital fusiform gyrus of patients nor in amygdalar activity patterns of healthy controls. LIMITATIONS: Larger samples and additional questionnaires would help to better characterize the association between specific aspects of therapy and changes in the neural representational space. CONCLUSION: Our findings suggest a more refined role for the amygdala in the pathological processing of perceived emotions and may provide new diagnostic and prognostic imaging-based markers of emotion dysregulation and personality disorders.Clinical trial registration: DRKS00019821, German Clinical Trials Register (Deutsches Register Klinischer Studien).

Lifestyle behaviors, metabolic disturbances, and weight gain in psychiatric inpatients treated with weight gain-associated medication.

Many psychiatric patients suffer from overweight/obesity and subsequent metabolic disturbances, where psychotropic medication is one of the main contributors. However, the magnitude of weight gain ranges individually, which leads to questioning the role of other contributors like lifestyle factors. The present study investigated several lifestyle factors among psychiatric inpatients, their relation to biological factors, and their predictive capability for weight gain during treatment. Using a naturalistic observational study design, psychiatric inpatients of all diagnoses were followed for 4 weeks from the start of treatment with weight gain-associated medication. N = 163 participants entered the study. Lifestyle factors were assessed by patient self-report questionnaires. Body weight change over time was calculated relative to baseline body weight. Our study provides three main findings: (1) Obesity and/or metabolic syndrome (metSy) were associated with emotional eating (disinhibition), craving for fast food and sweets, and weight cycling. (2) Patients without metSy and normal BMI experienced increased sweets craving (also for women), a more positive attitude towards drugs, and an improvement of affect (also for men). (3) Sex, presence of metSy and/or drug dosage interacted with disinhibition change, sweets craving change (trend), and fast food craving change to predict weight change over time. Furthermore, drug attitude change interacted with BMI, drug dosage, and presence of metSy to predict weight change. Lifestyle factors, especially eating behaviors, are related to metabolic disturbances and predict weight gain in interaction with clinical parameters.

Deconstructing depression by machine learning: the POKAL-PSY study.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

A factor analytic comparison of three commonly used depression scales (HAMD, MADRS, BDI) in a large sample of depressed inpatients.

BACKGROUND: Quantifying depression mainly relies on the use of depression scales, and understanding their factor structure is crucial for evaluating their validity. METHODS: This post-hoc analysis utilized prospectively collected data from a naturalistic study of 1014 inpatients with major depression. Confirmatory and exploratory factor analyses were performed to test the psychometric abilities of the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the self-rated Beck Depression Inventory. A combined factor analysis was also conducted including all items of all scales. RESULTS: All three scales showed good to very good internal consistency. The HAMD-17 had four factors: an "anxiety" factor, a "depression" factor, an "insomnia" factor, and a "somatic" factor. The MADRS also had four factors: a "sadness" factor, a neurovegetative factor, a "detachment" factor and a "negative thoughts" factor, while the BDI had three factors: a "negative attitude towards self" factor, a "performance impairment" factor, and a "somatic" factor. The combined factor analysis suggested that self-ratings might reflect a distinct illness dimension within major depression. CONCLUSIONS: The factors obtained in this study are comparable to those found in previous research. Self and clinician ratings are complementary and not redundant, highlighting the importance of using multiple measures to quantify depression.

Assessing the links between childhood trauma, C-reactive protein and response to antidepressant treatment in patients with affective disorders.

Adverse Childhood Experiences (ACE) are a well-known risk-factor for depression. Additionally, (high-sensitive) C-reactive Protein (hsCRP) is elevated in subgroups of depressed patients and high following ACE. In this context the literature considers hsCRP and ACE to be associated with treatment resistant depression. With the data being heterogenous, this study aimed to explore the associations of ACE, hsCRP levels and response to antidepressant treatment in uni- and bipolar depression. N = 76 patients diagnosed with uni- or bipolar depression and N = 53 healthy controls were included. Treatment was over 6 weeks in an inpatient psychiatric setting within an observatory study design. Depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), ACE were assessed by the Childhood Trauma Questionnaire (CTQ); the body-mass-index (BMI) and hsCRP were measured. HsCRP levels did not differ between the study population and the healthy controls. While the depressive symptoms decreased, the hsCRP levels increased. Sexual abuse was associated with significant higher and emotional abuse with lower levels of hsCRP after 6 weeks. The baseline hsCRP levels and the ACE subgroups did not show significant associations with the treatment response in unipolar depressed patients. The long-lasting effects of specific forms of ACE may have relevant impact on inflammation, supporting hsCRP to be a suitable biomarker. With ACE and hsCRP not showing any significant associations with treatment response in the unipolar depressed subgroup, a more differentiate research concerning biomarkers and treatment regimens is needed when talking about treatment response.

Review and Consensus on Pharmacogenomic Testing in Psychiatry.

The implementation of pharmacogenomic (PGx) testing in psychiatry remains modest, in part due to divergent perceptions of the quality and completeness of the evidence base and diverse perspectives on the clinical utility of PGx testing among psychiatrists and other healthcare providers. Recognizing the current lack of consensus within the field, the International Society of Psychiatric Genetics assembled a group of experts to conduct a narrative synthesis of the PGx literature, prescribing guidelines, and product labels related to psychotropic medications as well as the key considerations and limitations related to the use of PGx testing in psychiatry. The group concluded that to inform medication selection and dosing of several commonly-used antidepressant and antipsychotic medications, current published evidence, prescribing guidelines, and product labels support the use of PGx testing for 2 cytochrome P450 genes (CYP2D6, CYP2C19). In addition, the evidence supports testing for human leukocyte antigen genes when using the mood stabilizers carbamazepine (HLA-A and HLA-B), oxcarbazepine (HLA-B), and phenytoin (CYP2C9, HLA-B). For valproate, screening for variants in certain genes (POLG, OTC, CSP1) is recommended when a mitochondrial disorder or a urea cycle disorder is suspected. Although barriers to implementing PGx testing remain to be fully resolved, the current trajectory of discovery and innovation in the field suggests these barriers will be overcome and testing will become an important tool in psychiatry.

Prevalence of obesity, metabolic syndrome, diabetes and risk of cardiovascular disease in a psychiatric inpatient sample: results of the Metabolism in Psychiatry (MiP) Study.

The information on prevalence of obesity, diabetes, metabolic syndrome (MetS) and cardiovascular risk (CVR) and on sociodemographic variables available in patients with psychiatric diseases about to be treated with weight gain-associated medication (e.g., clozapine, mirtazapine, quetiapine) is limited. In a naturalistic study, psychiatric inpatients (age: 18-75) of all F diagnoses according to ICD-10, who were about to be treated with weight gain-associated medication, were included. Demographic variables were assessed as well as biological parameters to calculate the Body Mass Index (BMI), MetS, diabetes and CVR. A total of 163 inpatients were included (60.1% male; mean age: 39.8 (± 15.1, 18-75 years). The three most common disorders were depression (46.0%), bipolar disorder (20.9%) and drug addiction (20.2%). The three most common pharmacotherapeutic agents prescribed were quetiapine (29.4%), mirtazapine (20.9%) and risperidone (12.9%). Of the included inpatients 30.1% were overweight, 17.2% obese, and 26.9% and 22.4% fulfilled the criteria for a MetS according to the International Diabetes Federation (IDF) and the National Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (NCEP ATP III), respectively, 3.8% had (pre)diabetes and 8.3% had a moderate and 1.9% a high CVR according to the Prospective Cardiovascular Münster (PROCAM) score. Detailed information is reported on all assessed parameters as well as on subgroup analyses concerning sociodemographic variables. The results suggest that psychiatric patients suffer from multiple metabolic disturbances in comparison to the general population. Monitoring weight, waist circumference, blood pressure and cholesterol regularly is, therefore, highly relevant.

Polygenic analysis suggests the involvement of calcium signaling in executive function in schizophrenia patients.

Cognitive deficits are increasingly recognized as a core dimension rather than a consequence of schizophrenia (SCZ). The previous evidence supports the hypothesis of shared genetic factors between SCZ and cognitive ability. The objective of this study was to test whether and to what extent the variation of disease-relevant neurocognitive function in a sample of SCZ patients from the previous clinical interventional studies can be explained by SCZ polygenic risk scores (PRSs) or by hypothesis-driven and biomedical PRSs. The previous studies have described associations of the SNAP25 gene with cognition in SCZ. Likewise, the enrichment of several calcium signaling-related gene sets has been reported by genome-wide association studies (GWAS) in SCZ. Hypothesis-driven PRSs were calculated on the basis of the SNAP-25 interactome and also for genes regulated by phorbol myristate acetate (PMA), an activator of the signal transduction of protein kinase C (PKC) enzymes. In a cohort of 127 SCZ patients who had completed a comprehensive neurocognitive test battery as part of the previous antipsychotic intervention studies, we investigated the association between neurocognitive dimensions and PRSs. The PRS for SCZ and SNAP-25-associated genes could not explain the variance of neurocognition in this cohort. At a p value threshold of 0.05, the PRS for PMA was able to explain 2% of the variance in executive function (p = 0.05, uncorrected). The correlation between the PRS for PMA-regulated genes and cognition can give hints for further patient-derived cellular assays. In conclusion, incorporating biological information into PRSs and other en masse genetic analyses may help to close the gap between genetic vulnerability and the biological processes underlying neuropsychiatric diseases such as SCZ.

The vicious circle of social exclusion and psychopathology: a systematic review of experimental ostracism research in psychiatric disorders.

Social exclusion (ostracism) is a major psychosocial factor contributing to the development and persistence of psychiatric disorders and is also related to their social stigma. However, its specific role in different disorders is not evident, and comprehensive social psychology research on ostracism has rather focused on healthy individuals and less on psychiatric patients. Here, we systematically review experimental studies investigating psychological and physiological reactions to ostracism in different responses of psychiatric disorders. Moreover, we propose a theoretical model of the interplay between psychiatric symptoms and ostracism. A systematic MEDLINE and PsycINFO search was conducted including 52 relevant studies in various disorders (some of which evaluated more than one disorder): borderline personality disorder (21 studies); major depressive disorder (11 studies); anxiety (7 studies); autism spectrum disorder (6 studies); schizophrenia (6 studies); substance use disorders (4 studies); and eating disorders (2 studies). Psychological and physiological effects of ostracism were assessed with various experimental paradigms: e.g., virtual real-time interactions (Cyberball), social feedback and imagined scenarios. We critically review the main results of these studies and propose the overall concept of a vicious cycle where psychiatric symptoms increase the chance of being ostracized, and ostracism consolidates or even aggravates psychopathology. However, the specificity and stability of reactions to ostracism, their neurobiological underpinnings, determinants, and moderators (e.g., attachment style, childhood trauma, and rejection sensitivity) remain elusive.

What happens with schizophrenia patients after their discharge from hospital? Results on outcome and treatment from a "real-world" 2-year follow-up trial.

Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.

Comparing Schizophrenia Patients With a Predicted High/Low Risk of Nonresponse Receiving Treatment with Ziprasidone and Haloperidol: A Randomized-Controlled Study.

INTRODUCTION: The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. METHODS: One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). RESULTS: Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). DISCUSSION: An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.

[Patients with tic disorders: widely known, yet underserved]. / Patienten mit Tic-Störungen: weit bekannt, doch unterversorgt.

Tic disorders typically start in early childhood and can be classified into provisional tic disorder (tics last <12 months) and chronic tic disorders (tics last > 12 months). The widely known chronic tic disorder Tourette's syndrome is featuring multiple motor and vocal tics. Tics are typically waxing and waning in frequency and intensity. Concentration and relaxation might decrease tics, whereas stress and excitement might increase tics. Psychiatric comorbidities, like obsessive-compulsive disorder, ADHD, depression and anxiety are common. The etiology is multifactorial with genetic and environmental interactions leading to a dysregulation of cortico-striato-pallido-thalamo-cortical networks.A correct diagnosis and psychoeducation are essential for patients as well as their relatives. Additional therapies are needed for patients with severe tics that cause physical impairment or great psychosocial stress. It is crucial to also treat psychiatric comorbidities. Psychotherapeutic interventions for tics include progressive muscle relaxation, habit reversal training, exposure and response prevention and comprehensive behavioral intervention for tics. First-line psychopharmacological treatment in Europe contains aripiprazole, tiapride and risperidone, which are all used off-label for tic disorders. Haloperidol remains the only approved medication for the pharmacotherapy of tics in Germany, but is rarely used due to its side effects. Cannabinoids gain interest as a new pharmacological option, but are mainly offered within the frame of studies.

QTc prolongation in short-term treatment of schizophrenia patients: effects of different antipsychotics and genetic factors.

Antipsychotics are effective in treating schizophrenia but may lead to a higher cardiovascular risk due to QTc prolongation. Besides drugs, genetic and clinical factors may contribute to QTc prolongation. The aim of this study is to examine the effect of candidate genes known for QTc prolongation and their interaction with common antipsychotics. Thus, 199 patients were genotyped for nine polymorphisms in KCNQ1, KCNH2, SCN5A, LOC10537879, LOC101927066, NOS1AP and NUBPL. QTc interval duration was measured before treatment and weekly for 5 weeks while being treated with risperidone, quetiapine, olanzapine, amisulpride, aripiprazole and haloperidol in monotherapy. Antipsychotics used in this study showed a different potential to affect the QTc interval. We found no association between KCNH2, KCNQ1, LOC10537879, LOC101927066, NOS1AP and NUBPL polymorphisms and QTc duration at baseline and during antipsychotic treatment. Mixed general models showed a significant overall influence of SCN5A (H558R) on QTc duration but no significant interaction with antipsychotic treatment. Our results do not provide evidence for an involvement of candidate genes for QTc duration in the pathophysiology of QTc prolongation by antipsychotics during short-term treatment. Further association studies are needed to confirm our findings. With a better understanding of these interactions the cardiovascular risk of patients may be decreased.

Validity of remission and recovery criteria for schizophrenia and major depression: comparison of the results of two one-year follow-up naturalistic studies.

The objective of the present study was the application and comparison of common remission and recovery criteria between patients with the diagnosis of schizophrenia and major depressive disorder (MDD) under inclusion of other outcome parameters. Patients with schizophrenia and MDD who were treated as inpatients at the beginning of the study were examined within two naturalistic follow-up trials from admission to discharge of an inpatient treatment period and the one-year follow-up assessment. PANSS criteria of the Remission in Schizophrenia Working Group (RSWG) for schizophrenia and HAMD criteria of the ACNP Task Force in MDD for depressive patients as well as the Clinical Global Impression-Severity Scale (CGI-S) were applied as symptomatic outcome measures additionally to functional outcome parameters. Data of 153 schizophrenia patients and 231 patients with a MDD episode have been included in the analysis. More depressive than schizophrenia patients reached a threshold score of ≤3 on the CGI-S, indicating symptomatic remission at discharge and at the one-year follow-up. In contrast similar proportions of patients reaching symptomatic remission at discharge from inpatient treatment and at the one-year follow-up in the schizophrenia and in the MDD group were found when disease-related consensus criteria (RSWG vs. ACNP Task Force) were used. Functional remission and recovery rates were significantly lower in schizophrenia than in depressive patients at the one-year follow-up visit. Common outcome criteria for remission and recovery in schizophrenia and major depression were not directly comparable. However, our results indicated a significantly poorer outcome in schizophrenia than in depressive patients according to terms of remission and recovery.

Add-on Antidepressants in the Naturalistic Treatment of Schizophrenia Spectrum Disorder - When, Who, and How?

The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25% improvement (p=0.2623), a 50% improvement (p=0.3946), remission (p=0.0552), or remission of depressive (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found. Add-on with antidepressants is common. A final recommendation in terms of this strategy's efficacy cannot be given.

Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment.

INTRODUCTION: NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics. METHODS: Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index. RESULTS: 167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed. CONCLUSIONS: Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial.

The aim of this study was to evaluate residual symptoms in patients achieving remission according to the consensus criteria and to analyze their potential influence on the patient's outcome one year after discharge. In total, 399 patients suffering from a schizophrenia spectrum disorder were evaluated within a naturalistic study. Remission status was examined using the consensus criteria. Residual symptoms were defined as any symptom present at the time-point of remission following analogous analyses performed in depressed patients. Therefore, a PANSS item with a symptom severity of >1 (= at least borderline mentally ill) was defined to be a residual symptom. Remitters with and without residual symptoms were compared regarding psychopathology, functioning and side effects. In total, 236 patients (59%) were remitters at discharge with 94% of them suffering from at least one residual symptom. The most common residual symptoms were blunted affect (49%), conceptual disorganization (42%) and social withdrawal (40%). A significant association was found between the presence of residual symptoms and the severity of side effects (p < 0.0001) and functioning (p = 0.0003) at discharge as well as between residual symptoms and the risk of relapse and chance of remission one year after discharge. Residual symptoms were highly prevalent in remitted schizophrenia inpatients following the suggested definition. Most residual symptoms were persistent baseline symptoms suggesting an ongoing illness severity. Also, the necessity to re-evaluate the consensus criteria questioning the status of remission in these patients is also pointed out.

Three-Year long-term outcome of 458 naturalistically treated inpatients with major depressive episode: severe relapse rates and risk factors.

In randomized controlled trials, maintenance treatment for relapse prevention has been proven to be efficacious in patients responding in acute treatment, its efficacy in long-term outcome in "real-world patients" has yet to be proven. Three-year long-term data from a large naturalistic multisite follow-up were presented. Severe relapse was defined as suicide, severe suicide attempt, or rehospitalization. Next to relapse rates, possible risk factors including antidepressant medication were identified using univariate generalized log-rank tests and multivariate Cox proportional hazards model for time to severe relapse. Overall data of 458 patients were available for analysis. Of all patients, 155 (33.6%) experienced at least one severe relapse during the 3-year follow-up. The following variables were associated with a shorter time to a severe relapse in univariate and multivariate analyses: multiple hospitalizations, presence of avoidant personality disorder, continuing antipsychotic medication, and no further antidepressant treatment. In comparison with other studies, the observed rate of severe relapse during 3-year period is rather low. This is one of the first reports demonstrating a beneficial effect of long-term antidepressant medication on severe relapse rates in naturalistic patients. Concomitant antipsychotic medication may be a proxy marker for treatment resistant and psychotic depression.