This challenge is particularly evident along the psychosis spectrum disorders (PSD) where there is notable shared symptom variation across distinct DSM diagnostic categories, including schizophrenia (SZP), schizo-affective (SADP), bipolar disorder with psychosis (BPP). Consequently, the current diagnosis system cannot optimally map onto patient-specific brain-behavioral alterations. the Diagnostic and Statistical Manual of Mental Disorders (DSM) ) were built to aid clinical consensus, but were not designed to guide quantitative mapping of symptoms onto neural alterations ( Phillips et al., 2008 Gillihan and Parens, 2011). This goal is particularly challenging because neuropsychiatric diagnoses and consequently drug development still operate under ‘legacy’ categorical constraints, which were not quantitatively informed by neural data.Ĭritically, diagnostic systems in psychiatry (e.g. A key step toward developing more effective therapies for specific psychiatric symptoms is reliably mapping them onto underlying neural targets. Mental health conditions cause profound disability, yet most treatments offer limited efficacy across psychiatric symptoms ( Tohen et al., 2003 McEvoy et al., 2007 aan het Rot et al., 2010 Cipriani et al., 2018). Collectively, these results highlight a stable and data-driven BBS mapping across PSD, which offers an actionable path that can be iteratively optimized for personalized clinical biomarker endpoints. Finally, we show a proof-of-principle framework for relating personalized BBS metrics with molecular targets via serotonin and glutamate receptor manipulations and neural gene expression maps derived from the Allen Human Brain Atlas. However, we show that a univariate brain-behavioral space (BBS) can resolve stable individualized prediction. canonical correlation analysis) do not produce stable results with current sample sizes. Critically, we found that multivariate brain-behavior mapping techniques (e.g.

In turn, these symptom axes mapped onto distinct, reproducible brain maps. Here, in a sample of 436 PSD patients spanning several diagnoses, we derived and replicated a dimensionality-reduced symptom space across hallmark psychopathology symptoms and cognitive deficits. This gap is particularly acute for psychosis-spectrum disorders (PSD). Difficulties in advancing effective patient-specific therapies for psychiatric disorders highlight a need to develop a stable neurobiologically grounded mapping between neural and symptom variation.

Human brain mapping 2018