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This is a multi-disciplinary project maintained by the members of Johns Hopkins iMIND. There are two major goals in this project, such as:

 

  1. Cross-diagnostic assessment of a major phenotype of neuropsychiatric conditions (psychosis) to discover novel biomarkers and underlying biological mechanisms.  
     

  2. Discovery of biomarkers and underlying biological mechanisms in early stages of psychotic conditions that tend to be chronic and devasting so that we may slow down, block, or even ideally prevent the pathological conditions. 

 

Current diagnosis of psychiatric disorders relies on clinical interviews according to the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) or the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10).

 

Such diagnostic manuals emphasize clinical utility and reliability, but do not address the biological validity of these classifications. Thus, biological tests using validated biomarkers that are able to 

objectively identify  neuropsychiatric conditions and re-stratify the currently available diagnostic categorizations are truly important.

 

We also need to understand the disease mechanisms based on the re-stratified groups of patients, which is important for discovering and establishing mechanism-guided, biology-relevant treatment strategies.

 

This strategy will improve our clinical performance, not only in a medicine-based approach, but also in a non-medicine-based approach [such as brain stimulation and cognitive behavioral therapy (CBT)].  

 

The concept of intervening with key biological processes before the full and chronic expression of an illness has many precedents in non-brain disorders, including those in cardiovascular disease and diabetes. Moreover, recent studies have suggested that interventions during earlier stages of the disease, such as mild cognitive impairment (MCI), are important to develop effective therapeutic targets for Alzheimer’s disease.

 

Likewise, many researchers have begun to pay more attention to first episode psychosis (FEP) to study schizophrenia and related psychotic disorders. To this end, longitudinal studies of FEP patients are crucial in understanding the pathophysiology of psychotic disorders and exploring mechanism-based biomarkers and possibly therapeutic targets.  

 

Based on the backgrounds and major aims described above, we established a cohort of FEP patients 

that has been maintained in a longitudinal fashion. We have data in three-arms from the study participants: clinical arm, brain imaging arm, and molecular/cellular arm. In addition to dimensional assessment of symptoms and cognitive changes, we conduct olfactory functional study in the clinical arm. Olfactory functional deficits are key features that can be observed in very early stages of the diseases.

 

Importantly, our study may also contribute to post-pandemic psychiatric manifestations elicited by COVID-19 in which olfactory deficits are included in early signs of the infection. In the brain imaging 

arm, we use the technologies of magnetic resonance imaging (MRI) to study changes in the structure, functional neuron connectivity, and molecular dispositions associated with the disease conditions. This arm also utilizes positron emission tomography (PET) to dissect molecular dynamics in the brain.

 

Lastly, in the molecular/cellular arm, we first conduct multiple tissue biopsies, including those for the olfactory neurons, skin fibroblasts, blood, and cerebrospinal fluid. These bio-resources are carefully maintained and used for molecular and cellular analysis, including multiple types of next generation sequencing (genetics, epigenetics, expression profiles) and metabolomic analysis. Altogether, our uniqueness is to approach the disease conditions by integrating the information of these three distinct arms. Accordingly, the use of the frontline methodologies of deep learning and artificial intelligence is within our research repertoire.