Habenular structural-functional dysconnectivity in bipolar disorder: evidence from multimodal imaging and transcriptomic integration.

A prodrome refers to a subthreshold state that precedes the onset of a diagnosable psychiatric disorder [–]. With growing emphasis on early detection and prevention of major mental illnesses, increasing efforts have focused on delineating prodromal phases and developing reliable diagnostic instruments [–]. The most well-established example is the clinical high-risk for psychosis (CHR-P). CHR-P is defined by psychotic symptoms that do not meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases (ICD) diagnostic thresholds in duration or severity []. The most widely used assessment tools for CHR-P include the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Structured Interview for Psychosis-Risk Syndromes (SIPS) [, ]. The criteria for CHR-P are primarily based on the presence of attenuated positive symptoms, such as unusual thought content or delusional thinking, persecutory ideas, grandiosity, hallucinations, and disorganized communication [, ]. Similarly, the clinical high-risk for bipolar disorder (CHR-BD), also referred to as the bipolar prodrome, has been proposed. It is characterized by episodic mood fluctuations that are typically subthreshold in intensity and potentially prodromal, with or without additional risk factors or symptomatology []. Subthreshold manic symptoms, mood swings, and depressive episodes in individuals with a family history of bipolar disorder are considered strong indicators [–]. The Bipolar Prodrome Symptom Interview and Scale (BPSS) was developed to characterize CHR-BD. This tool includes mania, depression, and general symptom indices []. CHR-P is defined by attenuated positive psychotic symptoms and is assessed using the SIPS or CAARMS, whereas CHR-BD is characterized by episodic subthreshold mood symptoms and is evaluated using the BPSS. Nevertheless, both constructs share a common framework: they identify individuals with subthreshold psychopathology who experience functional distress but have not yet met criteria for a full psychiatric diagnosis.