Ketamine, an NMDA receptor antagonist, disrupted electric signaling and navigation in the weakly electric fish Gnathonemus petersii, a candidate model for schizophrenia. Lower doses increased locomotion and erratic movement, while higher doses reduced electric organ discharges, indicating positive schizophrenia-like symptoms. A low dose of haloperidol did not normalize these symptoms, suggesting further testing with more antipsychotic doses is needed to confirm the model's predictive validity.
A proposed framework, the Perceptual Theory of Schizophrenia (PerTh), contends that instability in retinal dopamine signaling may initiate a subset of schizophrenia cases. Retinal dopamine normally controls visual gain and spatial frequency processing; genetic liabilities for schizophrenia are argued to converge on retinal dopamine homeostasis, producing corrupted sensory input. This noisy signal is proposed to cascade through thalamocortical pathways, disrupting salience formation and driving compensatory synaptic changes that leave weak connections vulnerable to pruning. The theory aims to explain symptom timing, the predominance of auditory over visual hallucinations, and heterogeneity, without replacing existing models, and generates testable predictions about retinal function in psychosis.
The spatial organization of the cingulate cortex, rather than the thickness of a single region, predicts the intensity of psychedelic experiences under psilocybin. In a double-blind, placebo-controlled crossover study with 25 healthy participants, an anterior–posterior gradient in cingulate thickness significantly predicted psychedelic experience intensity. The previously reported finding that rostral anterior cingulate cortex thickness alone predicts emotional responses showed a comparable effect size but did not reach statistical significance, likely due to the smaller sample size. These results suggest that the pattern of cortical thickness across the cingulate cortex, not focal measures, serves as a neuroanatomical marker of variability in psychedelic response.
Individual differences in how people respond to psilocybin are linked to the structural organization of the cingulate cortex. A previous finding that thickness of a specific cingulate region predicted emotional responses was not replicated. Instead, a broader anterior-to-posterior gradient of cingulate thickness predicted the overall intensity of the psychedelic experience, and general cingulate thickness was associated with the balance between anxiety and visionary states. These results suggest that patterns of cortical thickness across the cingulate, rather than a single region, may serve as a neuroanatomical marker for predicting psychedelic response, with potential implications for personalized dosing in therapy.