Neurophysiological biomarkers support bipolar-spectrum disorders within psychosis cluster

Abstract

IntroductionA current topic of controversy in psychiatry is whether or not bipolar-spectrum disorders should be considered as part of the psychosis cluster in the upcoming DSM-V. Currently, bipolarspectrum disorders are classified as mood disorders in line with the Kraeplinian dichotomy; however, recent literature suggests that there may be more overlap in the underlying neurobiology in these major psychiatric illnesses than once thought.1 It is not unusual for patients with similar pheno typic presentation and common symptomatology to receive a diagnosis of either a bipolar-spectrum or a schizophrenia-spectrum disorder, particularly in the early stages of illness. Thus, investigation of the underlying neurobiology of these 2 major psychi atric groups is crucial to our understanding of their pathophysiological overlap. Shared genetic vulnerabilities in individuals with bipolar disorder and schizophrenia have been documented and describe how some symptoms overlap and how some are unique. [2][3][4][5] In support of the shared genetic basis of these disorders, there is evidence that first-degree relatives of probands with bipolar disorder or schizophrenia are at increased risk for either disorder, irrespective of the phenotype present in their relative. Background: Mismatch negativity (MMN) and P3a are event-related potentials that index deviance detection and the orienting response, respectively. We have previously shown that the MMN/P3a complex is impaired in patients with schizophrenia and affective spectrum psychoses, which suggests that it may index a common pathophysiology and argues against the purported specificity in schizo phrenia. Further research is warranted to determine whether patients with bipolar-spectrum disorders show similar impairments in these biomarkers. Methods: We assessed patients aged 15-30 years with early schizophrenia-spectrum disorders (schizophrenia, schizoaffective disorder, schizophreniform disorder), early bipolar-spectrum disorders (bipolar I or II, with and without psychotic features) and healthy, matched controls. We acquired MMN/P3a amplitudes during a 2-tone, auditory paradigm with 8% duration deviants. Clinical, psychosocial and neuro psychological assessments were also undertaken. Results: We included 20 patients with schizophrenia-spectrum disorders, 20 with bipolar-spectrum disorders and 20 controls in our study. Both patient groups showed significantly reduced frontocentral MMN and central P3a amplitudes. The schizophrenia-spectrum group had additional impairments in left temporal MMN and frontal P3a. Both patient groups performed worse than controls across psychosocial and clinical measures; however, only the schizophrenia-spectrum group performed significantly worse than controls for cognitive measures. Correlational analyses between patient groups revealed associations between frontocentral or left temporal MMN and psychiatric symptomatology or quality of life measures. Limitations: Limitations to our study include the modest sample size and the lack of control with r...

Equivalent mismatch negativity deficits across deviant types in early illness schizophrenia-spectrum patients

“…No correlations between MMN amplitude and symptom ratings were present, which is consistent with a number of previous studies in schizophrenia patients (Umbricht & Krljes, 2005), but not other studies showing relationships with negative symptoms (Catts et al, 1995; Javitt, Shelley, & Ritter, 2000a; Kasai et al, 2002) positive symptoms (Kaur et al, 2012a; Thonnessen et al, 2008), or hallucinations in particular (Fisher et al, 2008; Youn, Park, Kim, Kim, & Kwon, 2003). This type of variability may, in part, be due to small sample sizes, difficulty getting valid reports from patients during clinical interviews, and/or symptom attenuation following treatment with antipsychotic medication (Mathalon & Ford, 2012).…”

Clinical significance of auditory target P300 subcomponents in psychosis: Differential diagnosis, symptom profiles, and course

“…The few studies that compared schizophrenia with other psychotic disorders on auditory target P300 amplitude have yielded mixed results (Iwanami et al, 1994; Hermens et al, 2010; Kaur et al, 2012; Kaur et al, 2011; Salisbury et al, 1998; Salisbury et al, 1999; Ethridge et al, 2012; Mathalon et al, 2010). Consequently, it is unclear whether P300 amplitude reduction is best conceptualized as a unique characteristic of schizophrenia or a transdiagnostic indicator of psychosis.…”

“…In particular, many patients diagnosed initially with other psychoses were reclassified with schizophrenia at follow-up. Prior studies comparing P300 amplitude between schizophrenia and other psychotic disorders may have been subject to misclassification confounds due to a focus on recent-onset psychosis and/or lack of longer-term follow-up (Iwanami et al, 1994; Hermens et al, 2010; Kaur et al, 2012; Kaur et al, 2011; Salisbury et al, 1998; Salisbury et al, 1999; Ethridge et al, 2012; Mathalon et al, 2010). Thus, very little is known about auditory target P300 in psychotic disorders with diagnoses ascertained longitudinally to minimize misclassification.…”

“…Past studies used different tasks that elicit these subcomponents to different degrees. For example, a mismatch negativity task (i.e., Kaur et al, 2012) elicits a P3a, whereas a two-stimulus oddball task (Salisbury et al, 1999) elicits both P3a and P3b. Thus, it is not clear to what extent auditory target P3a, P3b, or both distinguish schizophrenia from other psychotic disorders because prior studies did not attempt to differentiate these components.…”

Alcohol use in bipolar disorder: A neurobiological model to help predict susceptibility, select treatments and attenuate cortical insult

“…However, recent evidence suggests that MMN impairments also exist in BD (Andersson et al, 2008;Jahshan et al, 2012;Kaur et al, 2012;Shimano et al, 2014), which was corroborated by our meta-analysis of the seven available studies suggesting that overall, frontal MMN amplitude is moderately impaired in BD (Chitty et al, 2013b). It is noteworthy however, that the calculated effect size was considerably smaller than that reported in a schizophrenia MMN metaanalysis (Umbricht et al, 2005), which may suggest that the impairments in BD are not as pronounced, or may reflect the substantially lower number of available studies in BD.…”