Brain Circuits and Functions Across Psychiatric Disorders

Background:  Common psychiatric disorders as we now define them are not discrete diseases with specific pathophysiology, but rather broad heterogeneous syndromes with multiple overlaps in their genetics, neural system involvement and behavioral features.  Meaningful subgroups within broad syndromes have been repeatedly hard to identify using behavioral and symptom data.  This situation complicates efforts to define pathophysiological mechanisms, it slows treatment development, and it adds uncertainty and instability to clinical diagnostic practice. The long experience with these challenges in adult psychiatric disorders is now being recapitulated autism spectrum disorders, and that extensive history can inform expectations and strategies for addressing these challenges now being encountered in ASD after its boundaries were expanded. 

Objectives:  Data from the BSNIP deep phenotyping project will be reviewed to show how issues of diagnostic boundaries have been examined in psychotic disorders.  The overlap of affective and nonaffective psychotic disorders in symptom, imaging and cognition data shows how a dimensional model across disorders can offer some advantages to categorical approaches.  The neural circuitry impaired in psychotic disorders also has parallels as well as differences from those we have observed in ASD, and these will be discussed to illustrate the scale of overlap of ASD with other neuropsychiatric disorders.

Methods:  The BSNIP study involved clinical, imaging, electrophysiological and neurocognitive studies with over 2000 participants (probands, family members and controls).  Cognitive and imaging studies of ASD (n=100) will be presented and compared to findings with psychotic disorder patients. 

Results:  Similarities and differences observed across psychotic disorders will be presented.  Some measures seem to fit dimensional models across psychotic disorders, while some deficits are more disorder specific, suggesting that dimensional and categorical diagnostic approaches both have value. Overlaps and differences from ASD data will be presented.

Conclusions:  The history of diagnostic practice in heterogeneous/complex neuropsychiatric syndromes has many examples of both overlap across syndromes and difficulty defining discrete subgroups within the syndromes.  Resolving heterogeneity using molecular and systems biology approaches and dense phenotyping offer promising strategies for addressing this challenge.  There are several reasons why success may be easier in ASD than in other common neuropsychiatric disorders.