Psychobiology and Psychosocial Functioning of Schizoaffective Disorder
Christoph U. Correll, MD
Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, and the Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, New York
Schizoaffective disorder is a diagnostic entity derived from clinical observation of co-occurring psychotic and affective symptoms. Data from neurobiologic and psychosocial outcomes research suggest that, phenomenologically, clinically, and neurobiologically, patients with schizoaffective disorder occupy an intermediate position between more severely disturbed schizophrenia patients and similarly or less severely impaired affective disorder patients (AV 1).1 However, additional research is needed to further elucidate the etiology of schizoaffective disorder.
Psychobiology of Schizoaffective Disorder
Biologic-genetic overlap. Several models of the nosologic overlap between schizophrenia, schizoaffective disorder, and mood disorders have been proposed. One model presents 6 levels of possible etiologic relationships along a schizophrenia–bipolar disorder axis. The levels progress from the simplest relationship—ie, that all psychotic and mood disorders are elements of a single disorder, for which risk is influenced by many genes with no degree of specificity—to the most complex, which is a phenotypically structured continuum (AV 2).2 Two of these relationships (the unstructured, single psychosis and 2 nonoverlapping disease processes) have been invalidated by available data. However, insufficient evidence exists to support or exclude the remaining 4 levels.
A clinical-functional model of psychosis has been proposed that follows the categories in the DSM-IV-TR,3 which places schizophrenia and mood disorders at opposite poles of a spectrum, with schizoaffective disorder occupying a central position. A proposed alternative of this model replaces the schizoaffective category with one called mixed psychosis, which encompasses several current diagnostic categories and, thus, includes a larger proportion of patients with prominent psychotic and affective symptoms.2
A third model is a 3-dimensional representation of the psychopathological domains of psychosis, mania, and depression. Current diagnostic categories can be mapped to different areas of the dimensional planes, and the mixture of these symptom domains might better characterize an individual patient’s illness. A fourth model is a structured continuum between psychotic and mood symptoms without clearly demarcated disease entities. As the underlying clinical phenotypes of psychopathology are better understood, these approaches will allow for increasingly complex models of the relationships between psychiatric phenotypes and biological systems.2
Genetics. A review4 of studies of the genetic architecture of schizophrenia and bipolar I disorder yielded conflicting results. However, the authors concluded that evidence increasingly suggests that schizophrenia and bipolar disorder represent a clinical continuum with partially overlapping genetic, neurophysiologic, and symptom dimensions.
Studies5,6 of first-degree family members have found indications of genetic overlap and cosegregation, which is the tendency for closely linked genes and genetic markers to be inherited together. For example, relatives of individuals with schizophrenia or bipolar disorder were found to be at an increased risk for one or both of these disorders, suggesting a common genetic cause.5 Similarly, a study6 of psychotic inpatients and their relatives found that, regardless of the proband’s diagnosis, family members were at increased risk for schizophrenia and mood disorders.
Conversely, some studies7–9 have supported genetic demarcation. For instance, a study7 of twins suggested that, while some genetic risk factors for schizophrenic and manic syndromes were shared, other genetic contributions to these 2 disorders were syndrome-specific. However, the genetic risk factors for schizoaffective disorder were entirely shared in common with those for schizophrenic and manic syndromes, supporting the view that schizoaffective disorder is an intermediary geno/phenotype between schizophrenia and mood disorders.
Genes that confer risk specifically for schizoaffective disorder have been sought in various studies.8–11 Chromosomes 1q42, 22q11, and 19p13 and the DISC1 gene; the gene encoding the GABA-A receptor β1, β3, β4, and β5 subunits; and the gene encoding BDNF appear to influence risk for schizoaffective disorder.
Neuroimaging. A review of neuroimaging studies12 found that reductions in cerebral volume in the temporal and frontal regions (including both gray and white matter) that are similar to those found in schizophrenia and bipolar disorder are associated with schizoaffective disorder. Another review13 concluded that temporal volume reductions may be greater in schizophrenia than in schizoaffective disorder. Additionally, in schizophrenia and schizoaffective disorder, white matter abnormalities may worsen over time.14
Electrophysiology. In electrophysiologic studies,12,13 patients with schizoaffective disorder have been found to have abnormal event-related potentials, localization of sensory-evoked magnetic fields, and eye movements. More similarities seem to exist in these abnormalities between schizoaffective disorder and psychotic bipolar disorder than between schizoaffective disorder and schizophrenia.12
Neuroendocrine functioning. Neuroendocrine functioning in patients with schizoaffective disorder has been examined using growth hormone response to clonidine, apomorphine, or methylphenidate challenge.12 Findings suggested that neuroendocrine disturbances may be more closely related to dysfunction in either the emotional regulation domain or the information processing domain, or both, than to categorical psychiatric diagnosis.
Neurochemistry. A review17 reported that individuals with schizophrenia and schizoaffective disorder share some patterns of neurochemical abnormalities not seen in those with affective disorders, but those with schizoaffective disorder and affective disorders share certain abnormalities not seen in those with schizophrenia. These inconclusive neurochemical abnormalities included patterns in cerebrospinal fluid norepinephrine and platelet serotonin levels. Another review12 found that neurotransmitter abnormalities correlate less with particular disorders than with symptom severity, especially psychosis, and outcome measures such as duration of hospitalization.
Neuropsychology. Neuropsychological studies18,19 suggest that similar patterns of cognitive impairment occur in schizophrenia, schizoaffective disorder, and psychotic mood disorders, including psychotic depression, but the greatest impairment seems to occur in patients with schizophrenia. Some cognitive impairments appear to be shared across disorders (eg, working memory deficits), while others are associated with particular symptoms (eg, perseverative errors are influenced by severe mood symptoms).
Treatment status may influence cognition in schizoaffective disorder. A review13 examined cognitive studies of patients who were symptomatic as well as those in which patients had been stabilized. In patients with acute schizoaffective disorder or acute schizophrenia, few differences were found in neurocognitive performance. However, among stabilized patients, those with schizoaffective disorder tended to have deficits that were milder than those in schizophrenia and more similar to those in psychotic bipolar disorder. Cognitive deficits appear to persist, despite stabilization, in patients with schizophrenia.19
Levels of premorbid adjustment and psychosocial functioning appear to differ between those with schizoaffective disorder and schizophrenia. When functioning at different periods of life was examined using the Premorbid Adjustment Scale (PAS), patients with schizoaffective disorder, as of late adolescence, showed significantly better premorbid adjustment than patients with schizophrenia (AV 3).21 For example, scholastic performance and peer relationships were more impaired in patients with schizophrenia than in those with schizoaffective disorder. Another study22 found that, compared with patients with schizophrenia, patients with schizoaffective disorder had better premorbid adjustment in the academic domain, but a significant difference was not found in the social domain. Having fewer negative symptoms was associated with having better academic and social functioning. For example, Bellack and colleagues23 found that patients with schizophrenia without negative symptoms had levels of social disability similar to those of patients with schizoaffective disorder or bipolar disorder. Those with negative symptoms were more impaired than patients in the other groups on most measures of social disability, even when duration and severity of illness were comparable.
In Cheniaux and colleagues’ review,1 premorbid social adaptation was lowest in patients with schizophrenia, was higher in those with schizoaffective disorder, and was highest in those with mood disorders. Cognitive deficits, which can result in psychosocial repercussions such as unemployment, low self-esteem, and reduced independence and social activities, were greatest in patients with schizophrenia, followed by those with schizoaffective disorder and then mood disorders.
For Clinical Use
- Neurobiologic and psychosocial functioning data suggest that schizoaffective disorder occupies a central position between schizophrenia and affective disorders
- Several models of the biologic-genetic relationship between schizoaffective disorder, schizophrenia, and mood disorders have been proposed, but additional research on the biomarkers of the illness is needed to further elucidate the etiology of schizoaffective disorder
- Some biologic-genetic abnormalities are shared between these disorders while others are specific to particular symptoms
- Premorbid functioning, especially in academic areas, is better in patients with schizoaffective disorder than schizophrenia, but negative symptoms and cognitive deficits are influential and should be addressed to improve psychosocial outcomes
apomorphine (Apokyn), clonidine (Duraclon, Catapres, and others), methylphenidate (Ritalin, Concerta, and others)
BDNF = brain-derived neurotrophic factor
DISC1 = disrupted in schizophrenia 1
DSM-IV-TR = Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision
GABA = γ-aminobutyric acid
- Cheniaux E, Landiera-Fernandez J, Telles LL, et al. Does schizoaffective disorder really exist? a systematic review of the studies that compared schizoaffective disorder with schizophrenia or mood disorders. J Affect Disord. 2008;106(3):209–217.
- Craddock N, O'Donovan MC, Owen MJ. Psychosis genetics: modeling the relationship between schizophrenia, bipolar disorder, and mixed (or "schizoaffective") psychoses. Schizophr Bull. 2009;35(3):482–490.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.
- Ivleva EI, Morris DW, Moates AF, et al. Genetics and intermediate phenotypes of the schizophrenia-bipolar disorder boundary. Neurosci Biobehav Rev. 2010;34(6):897–921.
- Lichtenstein P, Yip BH, Björk C, et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009;373(9659):234–239.
- Peralta V, Cuesta MJ. The relationship between syndromes of the psychotic illness and familial liability to schizophrenia and major mood disorders. Schizophr Res. 2007;91(1–3):200–209.
- Cardno AG, Rijsdijk FV, Sham PC, et al. A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry. 2002;159(4):539–545.
- Hamshere ML, Bennett P, Williams N, et al. Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13. Arch Gen Psychiatry. 2005;62(10):1081–1088.
- Nabi MO, Mirabzadeh A, Feizzadeh G, et al. Novel mutations in the calreticulin gene core promoter and coding sequence in schizoaffective disorder. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(2):706–709.
- Craddock N, Jones L, Jones IR, et al. Strong genetic evidence for a selective influence of GABAA receptors on a component of the bipolar disorder phenotype. Mol Psychiatry. 2010;15(2):146–153.
- Lencz T, Lipsky RH, DeRosse P, et al. Molecular differentiation of schizoaffective disorder from schizophrenia using BDNF haplotypes. Br J Psychiatry. 2009;194(4):313–318.
- Abrams DJ, Rojas DC, Arciniegas DB. Is schizoaffective disorder a distinct categorical diagnosis? a critical review of the literature. Neuropsychiatr Dis Treat. 2008;4(6):1089–1109.
- Bora E, Yucel M, Fornito A, et al. Major psychoses with mixed psychotic and mood symptoms: are mixed psychoses associated with different neurobiological markers? Acta Psychiatr Scand. 2008;118(3):172–187.
- Szeszko PR, Ardekani BA, Ashtari M, et al. White matter abnormalities in first-episode schizophrenia or schizoaffective disorder: a diffusion tensor imaging study. Am J Psychiatry. 2005;162(3):602–605.
- Heng S, Song AW, Sim K. White matter abnormalities in bipolar disorder: insights from diffusion tensor imaging studies. J Neural Transm. 2010;117(5):639–654.
- Sussmann JE, Lymer GK, McKirdy J, et al. White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging. Bipolar Disord. 2009;11(1):11–18.
- Meltzer HY, Arora RC, Metz J. Biological studies of schizoaffective disorders. Schizophr Bull. 1984;10(1):49–70.
- Barch DM, Keefe RS. Anticipating DSM-V: opportunities and challenges for cognition and psychosis. Schizophr Bull. 2010;36(1):43–47.
- Hill SK, Harris MS, Herbener ES, et al. Neurocognitive allied phenotypes for schizophrenia and bipolar disorder. Schizophr Bull. 2008;34(4):743–759.
- Bora E, Yucel M, Pantelis C. Cognitive functioning in schizophrenia, schizoaffective disorder and affective psychoses: meta-analytic study. Br J Psychiatry. 2009;195(6):475–482.
- Saracco-Alvarez R, Rodríguez-Verdugo S, García-Anaya M, et al. Premorbid adjustment in schizophrenia and schizoaffective disorder. Psychiatry Res. 2009;165(3):234–240.
- Norman RM, Malla AK, Manchanda R, et al. Premorbid adjustment in first episode schizophrenia and schizoaffective disorders: a comparison of social and academic domains. Acta Psychiatr Scand. 2005;112(1):30–39.
- Bellack AS, Morrison RL, Mueser KT, et al. Social competence in schizoaffective disorder, bipolar disorder, and negative and non-negative schizophrenia. Schizophr Res. 1989;2(4–5):391–401.