The relation of "acute and transient psychotic disorder" (ICD-10 F23) to bipolar schizoaffective disorder

The aim of this work is to investigate differences between acute and transient psychotic disorders (ATPD; F23 of ICD-10) and bipolar schizoaffective disorders (BSAD). In a controlled prospective and longitudinal study, we compared all inpatients with ATPD treated at Halle university hospital during a 5-year period with matched controls with BSAD. Sociobiographical data were collected using a semi-structured interview. Follow-up investigations were performed at a mean of 2.2-3.3 years after the index episode or 8.2-16.1 years after the first episode by means of standardized instruments. ATPD differs significantly from BSAD on various relevant levels, such as gender (more female), age at onset (older), development of the full symptomatology (more rapid), duration of the symptomatology (shorter), acuteness of onset (more acute), preceding stressful life-events (more frequent) and long-term prognosis (better). It is concluded that ATPD and BSAD are different nosological entities.     

Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

Objective:  Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders.
Methods:  We assayed 276 publicly available 'tag' single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS).
Results:  Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders ( NPAS2 : rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL .
Conclusions:  Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.     

Cognitive impairment in schizoaffective disorder: a comparison with non-psychotic bipolar and healthy subjects

Objective: Only a few studies have examined specifically the neuropsychological performance of schizoaffective patients. Method: The sample consisted of 34 euthymic DSM‐IV schizoaffective patients, who were compared with 41 euthymic bipolar patients without history of psychotic symptoms and 35 healthy controls. Euthymia was defined by a score of 6 or less at the Young Mania Rating Scale and a score of 8 or less at the Hamilton Depression Rating Scale for at least 6 months. Patients were compared with several clinical, occupational, and neuropsychological variables such as executive function, attention, verbal and visual memory and the two groups were contrasted with 35 healthy controls on cognitive performance. The three groups were compared using mancova after checking the potential role of several co‐variables. Results: Schizoaffective patients showed greater impairment than controls and bipolar patients, in several domains, including verbal memory, executive function, and attentional measures. Bipolar patients without history of psychosis performed similar to the controls except for verbal fluency. Conclusion: Schizoaffective disorder carries more neurocognitive impairment than non‐psychotic bipolar disorder and more occupational difficulties.     

Syndrome shift in the long-term course of schizoaffective disorders

Summary Seventy-two patients diagnosed as having schizoaffective disorders (Cologne study) were investigated with regard to syndrome shift. During long-term follow-up (mean 25.6 years) they had 400 episodes (the duration of an episode being defined as the time between the beginning and end of inpatient or inpatient-like treatment). A total of 61% of the patients had a polymorphous course, i.e. displayed more than one type of episode. The first syndrome shift was found in the early stages of the course (in 61% of the cases as early as the second episode, in 84% at latest by the third episode). Using diagnostic criteria considering the longitudinal approach, 88% of schizoaffective disorders could be definitively diagnosed as such at the latest by the second episode. The only difference in the course between polymorphous and monomorphous (with only one type of episode) schizoaffective disorders was that the former relapsed more frequently. On the basis of the findings of the present study we suggest a longitudinally based dichotomy of schizoaffective disorders into bipolar and unipolar.Supported by German Research Association (Deutsche Forschungsgemeinschaft) grants Ma 915-1/1 and Ma 915-1/2     

Diagnostic stability of first-episode psychosis and predictors of diagnostic shift from non-affective psychosis to bipolar disorder: a retrospective evaluation after recurrence

Diagnostic changes during follow-up are not uncommon with a first-episode psychosis (FEP). This study aimed to evaluate the diagnostic stability of the FEP and to identify factors associated with a diagnostic shift from non-affective psychosis to bipolar disorder. Considering that the diagnosis of FEP is frequently more definite after recurrence in many clinical settings, a retrospective evaluation after recurrence was preformed. Subjects were 150 patients with psychotic disorders who had been admitted to a psychiatric ward both for first episode and recurrence of their psychosis. Consensus diagnosis was made for each episode through a review of hospital records. Patients diagnosed with non-affective psychoses at the first episode were included in the analysis of predictive factors of a diagnostic shift to bipolar disorder. First-episode diagnoses were revised upon recurrence in 20.7% of patients. The most common change was to bipolar disorder accounting for more than half of all diagnostic changes. Schizophrenia exhibited the highest prospective and retrospective diagnostic consistencies. Female gender, short duration of untreated psychosis, high level of premorbid functioning, and several symptoms including lability, mood elation, hyperactivity, and delusions with religious or grandiose nature were identified as predictive factors for a diagnostic shift from non-affective psychosis to bipolar disorder. Clinical features of psychoses seem to evolve during the disease course resulting in diagnostic changes upon recurrence in a significant portion of FEP. Special consideration on a diagnostic shift to bipolar disorder is required in patients exhibiting the predictive factors identified in the current study.     

Rates and clinical correlates of treatment non-adherence in schizoaffective bipolar patients

Murru A, Pacchiarotti I, Nivoli AMA, Bonnin CM, Patrizi B, Amann B, Vieta E, Colom F. Rates and clinical correlates of treatment non‐adherence in schizoaffective bipolar patients. Objective: To analyze demographical, clinical, and therapeutic variables that may be associated with pharmacological non‐adherence in a sample of schizoaffective patients, bipolar type. Method: Adherence to treatment and its clinical correlates were assessed at the end of a 10‐year follow‐up in 76 patients meeting DSM‐IV‐TR diagnosis of schizoaffective disorder, bipolar type. Adherent and poorly adherent patients were compared regarding clinical and therapeutic variables. Results: The rate of poorly adherent patients was 32/76 (41.2%) of the sample. Adherent patients were more likely to have presented an affective episode at illness onset and to have fewer purely – non‐affective – psychotic episodes. Demographic or other clinical variables were not found to be associated to treatment adherence. Family history for psychiatric disorders or suicide did not correlate either, and neither did any specific pharmacological agent. Conclusion: Rates of non‐adherence in schizoaffective disorder are high. Adherence seems to be associated to a more affective course of illness (affective first episode and fewer purely psychotic episodes). Patients with more prominent schizophrenia‐like characteristics could be at higher risk for poor adherence and need to be closely followed and monitored. Even when properly treated, schizoaffective disorder is a disabling and severe disorder with high risk for recurrences.     

Course of adolescent psychotic disorder with schizoaffective episodes

This study examines educational/occupational outcome and social functioning of adolescents treated for psychosis (mean onset age 16.1 yrs±1.3). In a sample of 157 subjects, 26 patients with schizoaffective episodes (defined as any episode meeting ICD-9 criteria for schizoaffective psychosis, occurring at any time during the course of illness) were compared to 101 patients with schizophrenia, and to 30 affective disordered patients, all without schizoaffective episodes. Follow-up information (mean interval 7.3 yrs ±4.3) was obtained on 130 subjects. The three groups did not differ concerning sex, duration of first inpatient treatment, symptoms and social competence at discharge, nor at follow-up. At the time of outcome subjects with schizoaffective episodes showed greater similarities to schizophrenic than to severe affective disorder. Educational and occupational impairment was found in 72% of the schizoaffective group (schizophrenic group 79%, affective group 40%), obvious or more severe social disability in 86% of the schizoaffective group (schizophrenic 79%, affective 40%). Disabilities regarding performance of specific social roles and specific downward educational and occupational drifts were found to be more marked in schizoaffective than in affective disorder. Implications for further research and clinical practice are discussed.     

Identifying dynamic functional connectivity biomarkers using GIG‐ICA: Application to schizophrenia,schizoaffective disorder,and psychotic bipolar disorder

Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here, we aim to explore DFC across a spectrum of symptomatically‐related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD), and schizophrenia (SZ). We introduce a group information guided independent component analysis procedure to estimate both group‐level and subject‐specific connectivity states from DFC. Using resting‐state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD, and 113 SZ patients, we identified measures differentiating groups from the whole‐brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis‐related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post‐central, frontal, and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD‐unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis. Hum Brain Mapp 38:2683–2708, 2017. © 2017 Wiley Periodicals, Inc.     

Towards a blood-based diagnostic panel for bipolar disorder

BackgroundBipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD.Methods and findingsWe performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies.We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC) ⩾ 0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel.ConclusionsAn early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.     

Variations in the Hoffmann reflex recovery curve related to clinical manifestations of schizoaffective disorder

Recovery curves of the Hoffmann reflex (H reflex) were measured in both legs of 10 unmedicated inpatients with schizoaffective disorder, depressed type. Neither recovery curve height of the right leg nor that of the left leg was significantly correlated with clinical psychopathology, although a consistent negative relation was noted between recovery curve height of the left leg and psychopathology. Right-left differences in recovery curve height significantly correlated with both Brief Psychiatric Rating Scale and Hamilton Rating Scale for Depression ratings of psychopathology, such that relative elevation of the recovery curve of the right leg or relative lowering of the recovery curve of the left leg correlated with symptom severity. Three patients who later developed psychotic symptoms when treated with bupropion, a dopaminergic agent, had lower recovery curves, indicative of increased central dopaminergic activity. Relatively lower left-sided recovery curves may reflect increased dopaminergic activity on the right side of the brain in schizoaffective disorder, compared to the left in schizophrenia.     

Antipsychotic switching in schizoaffective disorder: A systematic review

Objectives. To systematically review the evidence about the switching of antipsychotics in SZA in acute and maintenance treatment. Methods. A systematic review following the PRISMA statement identifying studies specifically conducted on, or including, SZA patients. Results. One analysis considered uniquely a SZA population, 13 more studies including an adequate SZA subsample were considered. Most of the studies were aimed at switching antipsychotic treatments to improve tolerability issues. Despite the absolute lack of trials specifically conducted on SZA populations, we found limited evidence on the use of aripiprazole, lurasidone, and, to a lesser extent, risperidone and ziprasidone as possible agents to substitute previous treatments whereas efficacy or, more frequently, tolerability issues arise. Evidence supports also the switch to risperidone long-acting injectable when the adherence to oral treatment may be a concern. Conclusions. Antipsychotic switching in SZA is a neglected topic that would need better profiling. Clinicians should keep in mind the receptor binding characteristics of drugs in order to optimize transitions. Evidence supports the switch to aripiprazole and lurasidone, less strongly to risperidone and ziprasidone. The switch to risperidone long-acting injectable is supported, especially in patients with limited treatment adherence to oral therapy.