Does Biology Transcend the Symptom-based Boundaries of Psychosis?

Abstract

Synopsis Psychotic disorders, as defined by clinical features alone, overlap considerably in terms of symptoms, familial patterns, risk genes, outcome and treatment response. As a result, numerous neurobiological measurements also fail to distinguish patients with the most prevalent classic psychotic syndromes (schizophrenia, schizo-affective and bipolar with psychosis). Statistical methods applied to such biological measurements in large numbers of psychosis patients yield novel categories, that cut across traditional diagnostic boundaries, called “Biotypes”, i.e. biologically-defined presumptive disease entities. Such new classification approaches within psychosis hopefully represent an opportunity to transcend clinical phenomenologically-defined syndromes in psychiatry with neurobiologically-defined diseases that can advance drug discovery and support precision medicine approaches in psychiatry.

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

“…Schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar disorder with psychosis (BPP) have overlapping clinical symptoms, familial co-occurrence and shared genetic risk (Cardno and Owen, 2014; Cosgrove and Suppes, 2013; Pearlson, et al, 2016). SZ is a psychotic disorder characterized by persistent psychotic symptoms (e.g., delusions and hallucinations) and decreased function.…”

“…Considering the difficulty of differential diagnosis and lack of consensus, biological, in addition to symptomatic, measurements may be useful for differentiating these clinical syndromes. So far, most biological measures also fail to uniquely differentiate the psychoses, suggesting that more work is needed to understand the relationships between these clinical syndromes and neurobiology (Clementz, et al, 2015; Clementz, et al, 2016; Pearlson, et al, 2016). …”

Functional outcome and service engagement in major depressive disorder with psychotic features: comparisons with schizophrenia, schizoaffective disorder and bipolar disorder in a 6‐year follow‐up of the Cavan‐Monaghan First Episode Psychosis Study (CAMFEPS)

“…There is increasing opinion and evidence that diagnostic categories such as SZ, SA, and BD reflect not discrete entities but, rather, domains characterized by certain psychopathological dimensions, pathobiological processes, and functional characteristics, the boundaries of which are likely arbitrary and in continuity or intersection with other domains of mental illness, through to the limits of “normal” human experience and functioning . That the long‐term outcome of MDDP differed quantitatively but not qualitatively from that of SZ, SA, or BD in terms of psychopathology, functionality, QoL, and service engagement suggests that MDDP should join SZ, SA, BD, and likely other arbitrary diagnostic categories in what is, in reality, a milieu of psychosis.…”

“…Functionality and quality of life are well recognized as critical indices of outcome in all medical conditions and have been widely studied in relation to psychotic illness. However, this literature derives primarily from studies on the diagnostic category of schizophrenia (SZ), while contemporary research is increasingly involving broader, dimensional concepts of psychosis . To the forefront of such research is the nosological, clinical, and biological relationship between SZ and bipolar I disorder (BD), with the long‐standing conundrum of schizoaffective disorder (SA) continuing to receive consideration in this context .…”

Emerging and evolving concepts in the pathobiology and treatment of psychosis

“…These insights are now seen to be of 2 types: Those evolving increase our understanding incrementally along established lines with which we feel comfortable, for example, genome‐wide association studies of genetic risk, neuroimaging studies of brain structure and function, and antipsychotic drug development, as they relate to specific psychotic diagnoses, most typically schizophrenia. Those emerging are more radical and challenge these “comfort zones,” for example, recent evidence that: psychotic ideation and associated psychopathology can be present in young persons across the general population; early intervention for features associated with “clinical high risk” and at the first psychotic episode may, respectively, ameliorate the emergence of diagnostic psychotic symptoms and improve long‐term outcome; schizophrenia‐related psychopathology, pathobiology and risk genes are disrespectful to conventional diagnostic boundaries …”