Mood disorder with psychotic features,schizoaffective disorder,and schizophrenia with mood features: Trouble at the borders

Psychiatry has long struggled with the problem of how to understand the relationship between psychotic symptoms and mood symptoms. In the past, these debates were over conceptualizations of categories based on syndromal definitions of mental illnesses. Ample data now exists that provide insight into the biologic basis for syndromal distinctions. We examine the syndromes of mood disorder with psychotic features, schizoaffective disorder, and schizophrenia with mood features, reviewing their classification, clinical features, course, and treatment. We provide evidence that, clinically, mood disorders and schizophrenia do not separate neatly. We will also review data arising from studies in brain imaging, molecular neurobiology, and genetics. Evidence is accumulating that overlap across diagnostic boundaries for both pathologic and etiologic factors exist, along with disorder-specific factors. The nosology that will carve the reality of psychotic illness at the joints awaits further advances in genetics and neurobiology. Or, alternatively, carving out categories may turn out to be less useful for some purposes than considering dimensions.     

Diagnostic specificity of poor premorbid adjustment: Comparison of schizophrenia, schizoaffective disorder, and mood disorder with psychotic features

Individuals with schizophrenia have significant deficits in premorbid social and academic adjustment compared to individuals with non-psychotic diagnoses. However, it is unclear how severity and developmental trajectory of premorbid maladjustment compare across psychotic disorders. This study examined the association between premorbid functioning (in childhood, early adolescence, and late adolescence) and psychotic disorder diagnosis in a first-episode sample of 105 individuals: schizophrenia (n=68), schizoaffective disorder (n=22), and mood disorder with psychotic features (n=15). Social and academic maladjustment was assessed using the Cannon-Spoor Premorbid Adjustment Scale. Worse social functioning in late adolescence was associated with higher odds of schizophrenia compared to odds of either schizoaffective disorder or mood disorder with psychotic features, independently of child and early adolescent maladjustment. Greater social dysfunction in childhood was associated with higher odds of schizoaffective disorder compared to odds of schizophrenia. Premorbid decline in academic adjustment was observed for all groups, but did not predict diagnosis at any stage of development. Results suggest that social functioning is disrupted in the premorbid phase of both schizophrenia and schizoaffective disorder, but remains fairly stable in mood disorders with psychotic features. Disparities in the onset and time course of social dysfunction suggest important developmental differences between schizophrenia and schizoaffective disorder.     

Prospective study of adolescents with subsyndromal psychosis: characteristics and outcome

OBJECTIVE: The aim of this study was to examine the characteristics and outcome of adolescents with psychotic disorder not otherwise specified (PsyNOS) and brief psychotic disorder (BrPsy), two neglected subsyndromal diagnostic entities. METHODS: As part of an ongoing, naturalistic study investigating adolescents considered to be prodromal for schizophrenia, 29 youngsters (mean age, 16.2 +/- 2.7 years) with PsyNOS or BrPsy were identified as theoretically at highest risk for schizophrenia and followed for over 6 (mean, 22.8 +/- 19.4) months. RESULTS: Contrary to our expectations, only 7 of the 26 individuals (27.0%) with follow-up data developed schizophrenia or schizoaffective disorder, and only 2 subjects (7.7%) retained their diagnosis of BrPsy/PsyNOS. The most frequent other diagnoses at follow-up were mood disorders (34.6%), personality disorders (11.5%), and obsessive-compulsive disorder (7.7%). Regarding severity of outcome, 38.5% of the patients progressed to a syndromal psychotic disorder, 23.1% continued to have attenuated positive symptoms, and 38.4% improved to having attenuated negative symptoms only, or no positive or negative symptoms. BrPsy was associated with lower maximum levels of negative symptoms (p = 0.02) and higher likelihood of symptom remission (p = 0.02). CONCLUSIONS: This study indicates that psychotic symptoms not fulfilling criteria for schizophrenia or a psychotic mood disorder are unreliable predictors of a syndromal psychotic disorder outcome at 2 years. Long-term studies of PsyNOS and BrPsy are needed to clarify where these disorders fall in the developmental course of schizophrenia.     

精神分裂症与心境障碍诊断变更的特征比较

目的:探讨精神分裂症和心境障碍诊断相互变更的特征。方法:从10年间住院2次的786例病例中筛查出交替出现过心境障碍和精神分裂症诊断的患者93例,对其人口学资料和临床表现进行比较。结果:女性、家族史阴性、起病较早、首次病程短及心境障碍伴精神病性症状者较易变更诊断;起病年龄较大的首次诊断为精神分裂症患者,再次住院时易变更诊断为心境障碍。结论:精神分裂症的诊断并非固定不变,与心境障碍二者间可相互变更。     

Cross-sectional similarities and differences between schizophrenia, schizoaffective disorder and mania or mixed mania with mood-incongruent psychotic features.

BACKGROUND: The cross-sectional clinical differentiation of schizophrenia or schizoaffective disorder from mood-incongruent psychotic mania or mixed mania is difficult, since pathognomonic symptoms are lacking in these conditions. AIMS OF THE STUDY: To compare a series of clinical variables related to mood and cognition in patient groups with DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, mood-incongruent psychotic mania and mood-incongruent psychotic mixed mania. METHODS: One hundred and fifty-one consecutive patients were evaluated in the week prior to discharge by using the structured clinical interview for DSM-III-R-patient edition (SCID-P). Severity of psychopathology was assessed by the 18-item version of the brief psychiatric rating scale (BPRS) and negative symptoms by the scale for assessment of negative symptoms (SANS). Level of insight was assessed with the scale to assess unawareness of mental disorders (SUMD). RESULTS: There were no differences in rates of specific types of delusions and hallucinations between subjects with schizophrenia, schizoaffective disorder, psychotic mania and psychotic mixed mania. SANS factors scores were significantly higher in patients with schizophrenia than in the bipolar groups. Patients with mixed state scored significantly higher on depression and excitement compared to schizophrenia group and, to a lesser extent, to schizoaffective group. Subjects with schizophrenia showed highest scores on the SUMD indicating that they were much more compromised on the insight dimension than subjects with psychotic mania or mixed mania. CONCLUSION: Negative rather than affective symptomatology may be a useful construct to differentiate between schizophrenia or schizoaffective disorders from mood-incongruent psychotic mania or mixed mania.     

Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia

BACKGROUND: Although growing research indicates that the atypical antipsychotic agent clozapine is effective in patients with schizophrenia, little is known about the efficacy of clozapine in patients with schizoaffective disorder or psychotic mood disorders. The purpose of this study was to assess whether or not clozapine is effective in some patients with schizoaffective disorder or psychotic mood disorders. METHOD: By surveying treating clinicians and chart data, we assessed treatment response in 85 consecutive patients, including 39 with schizophrenia, 25 with schizoaffective disorder, and 14 with bipolar disorder with psychotic features, who received clozapine for at least 6 weeks at our center. RESULTS: All patients were either inadequately responsive to or unable to tolerate standard somatic therapies. Compared to patients with schizophrenia, patients with schizoaffective disorder and bipolar disorder with psychotic features displayed significantly higher response rates to clozapine. CONCLUSION: Clozapine may be a useful drug in the treatment of patients with schizoaffective disorder or psychotic mood disorders who are treatment resistant or intolerant of side effects.     

The genetics of psychotic bipolar disorder

Psychotic features, defined as delusions or hallucinations, commonly occur in bipolar disorder (BP) and may be indicative of a more homogeneous form of the illness, with possible etiologic ties to schizophrenia. Several studies have shown that psychotic features aggregate in bipolar families, and increased interest in the molecular genetics of psychotic BP is emerging. Although preliminary, linkage studies of psychotic BP show replicated evidence for suggestive genome-wide linkage to chromosomes 8p and 13q, which have been implicated in prior linkage studies of schizophrenia and BP. Association studies of psychotic BP and sub-types such as mood-incongruent psychotic BP have uncovered modest positive results for several candidate schizophrenia susceptibility genes, including dysbindin, DAOA/G30, Disrupted-in-Schizophrenia-1, and neuregulin 1. These tentative results are consistent with the hypothesis that the subphenotype of psychotic BP may represent a clinical manifestation of “overlap” genes between schizophrenia and mood disorder syndromes.     

Schizophreniform disorder,delusional disorder and psychotic disorder not otherwise specified: clinical features,outcome and familial psychopathology

The relationship between DSM-III-R schizophreniform disorder, delusional disorder (DD) and psychotic disorder not otherwise specified (PD-NOS) and schizophrenia and affective illness (AI) remains uncertain. We explore this question in the Roscommon Family Study by examining symptoms, outcome and patterns of psychopathology in relatives. Probands were selected from a population-based case registry in the west of Ireland with an ICD-9 diagnosis of schizophrenia or AI. Personal interviews were conducted with 88% of traceable, living probands, a mean of 16 years after onset, and 86% of traceable, living first-degree relatives. Best-estimate diagnoses were made at follow-up. Schizophreniform disorder, DD and PD-NOS constituted 6.4%, 2.8% and 7.5%, respectively, of all probands with a registry diagnosis of schizophrenia. Probands with schizophreniform disorder had prominent positive psychotic symptoms, negligible negative symptoms and a good outcome, comparable to that seen in AI probands. Their relatives had an excess risk of schizophrenia spectrum illness but not AI. Probands with DD had prominent delusions but no other psychotic symptoms, few negative symptoms, fair to good outcome and an increased risk in relatives for alcoholism. Probands with PD-NOS had both moderate positive and negative psychotic symptoms, a poor to fair outcome and a substantially elevated risk in relatives of schizophrenia and schizophrenia spectrum disorders but not AI. These results suggest that i) DSM-III-R criteria for schizophreniform disorder define a good outcome disorder with prominent positive psychotic symptoms that probably has a familial relationship to schizophrenia, but not AI; ii) DD is a rare, monosymptomatic psychosis that may have a modest etiologic relationship with alcoholism, but probably not with schizophrenia or AI and iii) PD-NOS is probably heterogeneous but, of these 3 disorders, most closely resembles schizophrenia with respect to symptoms, outcome and familial psychopathology. These results should be seen as tentative given the small number of probands and relatives evaluated.     

Insight into illness in schizophrenia, schizoaffective disorder, and mood disorders with psychotic features

OBJECTIVE: Deficits in insight have been found in one study to be more common and severe in patients with schizophrenia than in patients with schizoaffective and major depression with and without psychosis but not more severe than they are in patients with bipolar disorder. The goals of this study were to replicate this finding independently and to clarify whether patients with schizophrenia differ from patients with bipolar disorder in a larger study group. METHOD: Using the Scale to Assess Unawareness of Mental Disorder, the authors evaluated 29 inpatients with schizophrenia, 24 with schizoaffective disorder, and 183 with mood disorders with psychotic features (153 with bipolar disorder and 30 with unipolar depression). RESULTS: Patients with schizophrenia had poorer insight than patients with schizoaffective disorder and patients with psychotic unipolar depression but did not differ from patients with bipolar disorder. CONCLUSIONS: The lack of significant differences between patients with schizophrenia and patients with bipolar disorder was not a result of low statistical power. This replication and more detailed examination of diagnostic group differences in insight have clinical, theoretical, and nosological implications.     

Schizoaffective disorders are psychotic mood disorders; there are no schizoaffective disorders

Schizoaffective disorder (SA D/O), introduced in 1933 by Dr. Jacob Kasanin, represented a first, modest change in our concept about the diagnoses of psychotic patients away from the beliefs of E. Bleuler, i.e., that hallucinations and delusions define schizophrenia, and toward the recognition of a significant role for mood disorders. SA D/O established a connection between schizophrenia and mood disorders, traditionally considered mutually exclusive, a connection that has strengthened progressively toward the diagnostic unity of all three disorders. A basic tenet of medicine holds that if discrepant symptoms can be explained by one disease instead of two or more, it is likely there is only one disease. The scientific justification for SA D/O and schizophrenia as disorders distinct from a psychotic mood disorder has been questioned. The "schizo" prefix in SA D/O rests upon the presumption that the diagnostic symptoms for schizophrenia are disease specific. They are not, since patients with severe mood disorders can evince any or all of the "schizophrenic" symptoms. "Schizophrenic" symptoms mean "psychotic" and not any specific disease. These data and a very low interrater reliability for SA D/O suggest that the concepts of SA D/O and schizophrenia as valid diagnoses are flawed. Clinically SA D/O remains popular because it encompasses both schizophrenia and psychotic mood disorder when there is a diagnostic question. We present a review of the literature in table form based on an assignment of each article assigned to one of five categories that describe the possible relationships between SA D/O, schizophrenia and psychotic mood disorders. We conclude that the data overall are compatible with the hypothesis that a single disease, a mood disorder, with a broad spectrum of severity, rather than three different disorders, accounts for the functional psychoses.     

Hypothesis: grandiosity and guilt cause paranoia; paranoid schizophrenia is a psychotic mood disorder; a review

Delusional paranoia has been associated with severe mental illness for over a century. Kraepelin introduced a disorder called "paranoid depression," but "paranoid" became linked to schizophrenia, not to mood disorders. Paranoid remains the most common subtype of schizophrenia, but some of these cases, as Kraepelin initially implied, may be unrecognized psychotic mood disorders, so the relationship of paranoid schizophrenia to psychotic bipolar disorder warrants reevaluation. To address whether paranoia associates more with schizophrenia or mood disorders, a selected literature is reviewed and 11 cases are summarized. Comparative clinical and recent molecular genetic data find phenotypic and genotypic commonalities between patients diagnosed with schizophrenia and psychotic bipolar disorder lending support to the idea that paranoid schizophrenia could be the same disorder as psychotic bipolar disorder. A selected clinical literature finds no symptom, course, or characteristic traditionally considered diagnostic of schizophrenia that cannot be accounted for by psychotic bipolar disorder patients. For example, it is hypothesized here that 2 common mood-based symptoms, grandiosity and guilt, may underlie functional paranoia. Mania explains paranoia when there are grandiose delusions that one's possessions are so valuable that others will kill for them. Similarly, depression explains paranoia when delusional guilt convinces patients that they deserve punishment. In both cases, fear becomes the overwhelming emotion but patient and physician focus on the paranoia rather than on underlying mood symptoms can cause misdiagnoses. This study uses a clinical, case-based, hypothesis generation approach that warrants follow-up with a larger representative sample of psychotic patients followed prospectively to determine the degree to which the clinical course observed herein is typical of all such patients. Differential diagnoses, nomenclature, and treatment implications are discussed because bipolar patients misdiagnosed with schizophrenia are severely misserved.     

Schizoaffective disorder merges schizophrenia and bipolar disorders as one disease--there is no schizoaffective disorder

PURPOSE OF REVIEW: Schizoaffective disorder was named as a compromise diagnosis in 1933, and remains popular as judged by its place in the International Classification of Diseases and the Diagnostic and Statistical Manual of Mental Disorders, its frequent use in clinical practice, and its extensive discussion in the literature. Some, however, have questioned the validity of schizoaffective disorder as separate from psychotic mood disorder. We examined the literature to assess the rationale for the continuation of schizoaffective disorder as a legitimate diagnostic category. RECENT FINDINGS: The diagnosis of schizoaffective disorder depends on the disease specificity of the diagnostic criteria for schizophrenia; however, the psychotic symptoms for schizophrenia, traditionally held as specific, can be accounted for by psychotic bipolar. Further, the interrater reliability for diagnosing schizoaffective disorder is very low. A recent and expanding body of comparative evidence from a wide range of clinical and basic science studies, especially genetic, reveals multiple similarities between schizoaffective disorder, schizophrenia and psychotic bipolar. SUMMARY: Schizoaffective disorder unifies schizophrenia and bipolar, blurring the zones of rarity between them and suggesting that schizoaffective disorder is not a separate, 'bona-fide' disease. Patients diagnosed with schizoaffective disorder likely suffer from a psychotic mood disorder. The diagnosis of schizoaffective disorder, which can result in substandard treatment, should be eliminated from the diagnostic nomenclature.     

精神分裂症与分裂情感性障碍的核心特征与治疗

精神分裂症是一种严重的精神障碍,在普通人群中的患病率为0.5%~1.0%,在住院患者中,其比例更高。由于精神分裂症的不同亚型在治疗上并无区别,并且容易给临床诊断造成混乱,因此,DSM-5去除了精神分裂症的亚型。分裂情感性障碍的患病率约为精神分裂症的一半。其症状相当于既有精神分裂症的A组症状,同时又有心境症状,例如重性抑郁或躁狂。诊断此障碍必须符合两个关键标准:(1)在半数以上的病程中,除了存在精神分裂症诊断标准A的症状以外,还伴有重性抑郁发作或躁狂发作;(2)在没有心境发作至少2周(抑郁或躁狂)的情况下,存在持续的妄想或幻觉,即证明这些精神病性症状并非由心境发作所致。     

Remission of mood disorder with psychotic features after treatment with mirtazapine

The antidepressant mirtazapine enhances both noradrenergic and serotonergic transmission by blocking α_2-adrenergic presynaptic auto- and heteroreceptors, respectively. We here report on three patients with mood disorders with psychotic features (two cases with depressive and one with bipolar disorder). Treatment with mirtazapine significantly improved not only their depression, but also their delusions. Depressive symptoms were only partially responsive and delusions unresponsive in all three patients to previous antidepressive and/or antipsychotic treatment, and only mirtazapine induced persistent improvement. These clinical cases suggest that mirtazapine can be a valid alternative for patients with depression with psychotic features and partial treatment-resistance.     

Toward convergence in the medication treatment of bipolar disorder and schizophrenia

Reaching a correct differential diagnosis among patients with psychotic symptoms was especially important during the era of first-generation antipsychotics, when treatments for the different disorders varied in terms of adverse events and likelihood of response. The historical "overdiagnosis" of schizophrenia and "underdiagnosis" of bipolar disorder in the United States was blamed for an increased exposure to neuroleptics among patients who might have benefited from lithium. With the recognition that second-generation antipsychotics are useful in the treatment of both schizophrenia and bipolar mania, and that combining them with classic mood stabilizers such as valproate may results in increased efficacy, the field is witnessing a convergence of pharmacological approaches to the treatment of schizophrenia and bipolar disorder. Substantially more data is available regarding combination treatments for bipolar disorder than for schizophrenia, and appropriate diagnosis remains important in predicting prognosis, but until the precise pathophysiology of psychotic disorders can be elucidated, and specific targeted treatments crafted, we will continue to see similar blended treatments for these two disease states.     

Psychotic features in chronic posttraumatic stress disorder and schizophrenia: comparative severity

Psychotic features are frequent in combat veterans with chronic posttraumatic stress disorder (PTSD), may correlate with severity of PTSD symptoms, and may reflect a distinct subtype of the disorder. These psychotic features include auditory and visual hallucinations and delusional thinking that is usually paranoid in nature. Psychotic features may be under-recognized in chronic PTSD because patients are reluctant to report these symptoms and because they may not have overt changes in affect or bizarre delusions characteristic of other psychoses, e.g., schizophrenia. To further assess these phenomena, we compared clinical ratings on the Positive and Negative Syndrome Scale (PANSS) and other assessments, including the Clinical Global Impression Scale and the Structured Clinical Interview with Psychotic Screen, in veterans meeting DSM-IV criteria for chronic PTSD with well-defined comorbid psychotic features (N = 40) or chronic schizophrenia (N = 40). The patients with schizophrenia had modestly higher composite PANSS scores and positive symptom scores although average scores in both groups were moderate to severe in intensity. Negative symptom and general psychopathology subscale scores were comparable in both groups. Regarding specific positive symptoms, hallucinations were comparable between groups in severity; however, schizophrenia patients had slightly more intense delusions and conceptual disorganization. These data further validate the occurrence of positive as well as negative symptoms of psychosis in chronic PTSD in a range of severity that may approach that of patients with schizophrenia. Although meeting DSM-IV criteria for two different major psychiatric disorders, these two patient populations were remarkably similar with respect to not only positive but also negative symptoms.     

Relational memory in psychotic bipolar disorder

Sheffield JM, Williams LE, Cohen N, Heckers S. Relational memory in psychotic bipolar disorder.
Bipolar Disord 2012: 14: 537–546. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Recent research has highlighted the phenotypic and genetic overlap of bipolar disorder and schizophrenia. Cognitive deficits in bipolar disorder parallel those seen in schizophrenia, particularly for bipolar disorder patients with a history of psychotic features. Here we explored whether relational memory deficits, which are prominent in schizophrenia, are also present in patients with psychotic bipolar disorder. Methods: We tested 25 patients with psychotic bipolar disorder on a relational memory paradigm previously employed to quantify deficits in schizophrenia. During the training, participants learned to associate a set of faces and background scenes. During the testing, participants viewed a single background overlaid by three trained faces and were asked to recall the matching face, which was either present (Match trials) or absent (Non‐Match trials). Explicit recognition and eye‐movement data were collected and compared to those for 28 schizophrenia patients and 27 healthy subjects from a previously published dataset. Results: Contrary to our prediction, we found psychotic bipolar disorder patients were less impaired in relational memory than schizophrenia subjects. Bipolar disorder subjects showed eye‐movement behavior similar to healthy controls, whereas schizophrenia subjects were impaired relative to both groups. However, bipolar disorder patients with current delusions and/or hallucinations were more impaired than bipolar disorder patients not currently experiencing these symptoms. Conclusions: We found that patients with psychotic bipolar disorder had better relational memory performance than schizophrenia patients, indicating that a history of psychotic symptoms does not lead to a significant relational memory deficit.     

Suggestive linkage to chromosomal regions 13q31 and 22q12 in families with psychotic bipolar disorder

OBJECTIVE: Linkage studies of bipolar disorder and schizophrenia have found overlapping evidence for susceptibility genes in four chromosomal regions-10p12-14, 13q32, 18p11.2, and 22q12-13. The authors previously demonstrated familial clustering of psychotic symptoms-defined as hallucinations and/or delusions-in some bipolar disorder pedigrees. In this study they used stratified linkage analysis to test the hypothesis that those bipolar disorder pedigrees most enriched for psychotic symptoms would show greater evidence of linkage to the regions of previous bipolar disorder/schizophrenia linkage overlap. METHOD: Nonparametric linkage analyses using GENEHUNTER and ASPEX were performed on 65 bipolar disorder families. Family subsets were defined by the number of family members with psychotic mood disorder. RESULTS: The 10 families in which three or more members had psychotic mood disorder showed suggestive evidence of linkage to 13q31 (nonparametric linkage score=3.56; LOD score=2.52) and 22q12 (nonparametric linkage score=3.32; LOD score=3.06). These results differed significantly from those for the entire study group of 65 families, which showed little or no linkage evidence in the two regions. The 10 families with three or more psychotic members did not show evidence of linkage to 10p12-14 or 18p11.2. The 95% confidence interval on 22q12 spanned 4.3 centimorgans (2.6 megabases) and was congruent with previous findings. CONCLUSIONS: Bipolar disorder families in which psychotic symptoms cluster may carry susceptibility genes on chromosomal regions 13q31 and 22q12. Replication should be attempted in similar families and perhaps in schizophrenia families in which mood symptoms cluster because these overlapping phenotypes may correlate most closely with the putative susceptibility genes. The localization of the 22q12 finding particularly encourages further study of this region.