Table 3 A neuroplasticity-based perspective on near-term clinical practice and clinical research directions for psychosis spectrum illnesses.
From: Psychosis spectrum illnesses as disorders of prefrontal critical period plasticity
Mechanism of action | Phase of Illness/Illness biotype to be targeted | Potential treatment approaches |
|---|---|---|
Reduce antiplasticity factors | Likely relevant to all individuals experiencing psychosis spectrum illness May need special considerations for the subgroup of individuals characterized by neuroinflammation? | Eliminate or reduce medication-induced anticholinergic burden through all possible prescribing approaches Intervene to avoid or mitigate social deafferentiation and maintain appropriate levels of social/cognitive stimulation Vigorously address obesity and poor dietary practices/dysbiosis/systemic inflammation [183] Since both immune activation and suppression impair plasticity [197], need judicious use of anti-inflammatory agents, especially in early phases [198] |
Increase pro-plasticity factors | Likely most relevant for individuals who are in ongoing phases of illness and/or for biotypes with longstanding premorbid cognitive impairment, prefrontal dysfunction, cortical hypoexcitability, and hypotheized hypoplasticity | Offer cognitive and social cognitive training, psycho-social therapies Use neuromodulation and/or pharmacotherapy to enhance cognitive training effects Encourage regular aerobic exercise Consider prescribing pro-plasticity agents: e.g. metformin, valproic acid or other HDAC inhibitors, D-serine, cholinergic M4 allosteric modulators [198,199,200,201] Early music training may serve as a long-term protective intervention [186] |
Modulate the trajectory of prefrontal critical period plasticity/dysregulated plasticity | Likely most relevant for a subgroup of individuals who are late in the clinical high-risk period or who are in their first episode of psychosis without evidence of long premorbid decline May include biotypes without marked premorbid cognitive impairment who show cortical hyperexcitability and hypothesized hyperplasticity Might be important in early-phase individuals who have marked neuroinflammation? | Judicious use of GABA-ergic medications that reduce cortical excitability and reverse dysregulated plasticity responses (e.g., benzodiazepines, possibly gabapentin) Prescribe antioxidants to mitigate dysplasticity effects of oxidative stress [202] Develop an in-depth understanding of psychosocial and biological protective factors in clinical high-risk individuals who manifest brain changes but do not transition into psychosis |
