alters 5-HT2C signalling. This feedback loop with 5-HT2A/5-HT2C is how the outer cortex layers can exert some control over our neuropeptides, specifically opioid peptides, oxytocin and vasopressin. This alteration in this limbic-layer V axis may create the profound change in social cognition (and sometimes cognition as a whole) that is observed in schizophrenia. However, genesis of the actual alterations is a much more complex phenomena. The role of inhibitory transmission The cortico-basal ganglia-thalamo-cortical loop is the source of the ordered input necessary for a higher level upper cortical loop. Feedback is controlled by the inhibitory potential of the cortices via the striatum. Through 5-HT2A efferents from layer V of the cortex transmission proceeds through the striatum into the globulus pallidus internal and substantia nigra pars compacta. This core input to the basal ganglia is combined with input from the subthalamic nucleus. The only primarily dopaminergic pathway in this loop is a reciprocal connection from the substantia nigra pars reticulata to the striatum. Dopaminergic drugs such as dopamine releasing agents and direct dopamine receptor agonists create alterations in this primarily GABAergic pathway via increased dopaminergic feedback from the substantia nigra pars compacta to the striatum. However, dopamine also modulates other cortical areas, namely the VTA; with efferents to the amygdala and locus coeruleus, likely modulating anxiety and paranoid aspects of psychotic experience. As such, the glutamate hypothesis is probably not an explanation of primary causative factors in positive psychosis, but rather might possibly be an explanation for negative symptoms. Dopamine hypothesis of schizophrenia elaborates upon the nature of abnormal lateral structures found in someone with a high risk for psychosis. Altered signalling cascades Again, thalamic input from layer V is a crucial factor in the functionality of the human brain. It allows the two sides to receive similar inputs, thus be able to perceive the same world. In psychosis, thalamic input loses much of its integrated character: hyperactive core feedback loops overwhelm the ordered output. This is due to excessive D2 and 5-HT2A activity. This alteration in input to the top and bottom of the cortex. The altered 5-HT signal cascade enhances the strength of excitatory thalamic input from layer V. This abnormality, enhancing the thalamic-cortical transmission cascade versus the corticostriatal control, creates a feedback loop, resulting in abnormally strong basal ganglia output. The root of psychosis (experiences that cannot be explained, even within their own mind) is when basal ganglia