PMC:6218602 / 2725-4569 JSONTXT

{"project":"2_test","denotations":[{"id":"30425662-1373598-41865323","span":{"begin":553,"end":554},"obj":"1373598"},{"id":"30425662-7968076-41865323","span":{"begin":553,"end":554},"obj":"7968076"},{"id":"30425662-11982449-41865323","span":{"begin":553,"end":554},"obj":"11982449"},{"id":"30425662-7526446-41865323","span":{"begin":553,"end":554},"obj":"7526446"},{"id":"30425662-427544-41865324","span":{"begin":928,"end":929},"obj":"427544"},{"id":"30425662-7187776-41865324","span":{"begin":928,"end":929},"obj":"7187776"},{"id":"30425662-3952506-41865324","span":{"begin":928,"end":929},"obj":"3952506"},{"id":"30425662-8782289-41865324","span":{"begin":928,"end":929},"obj":"8782289"},{"id":"30425662-11743943-41865325","span":{"begin":1472,"end":1473},"obj":"11743943"},{"id":"30425662-3046553-41865326","span":{"begin":1836,"end":1838},"obj":"3046553"},{"id":"30425662-16518132-41865327","span":{"begin":1840,"end":1842},"obj":"16518132"}],"text":"Treatment-resistant schizophrenia (TRS) remains one of the greatest therapeutic challenges in psychiatry. Schizophrenia is a complex neurodevelopmental syndrome; with disease processes occurring in utero that may disrupt the formation of critical neural circuits and result in widespread brain dysconnectivity. Hints of altered neural circuitry, for example delays in gross and fine motor skill development, often evolve during childhood and may precede the first subtle signs of psychosis during late adolescence in those who will develop the illness (1–4). Adolescents with disrupted neural circuit development and circuit dysconnectivity related to the progression of the disease often begin to exhibit sub-threshold psychotic symptoms during developmental periods associated with increasing gray matter (GM) volume and refinement of cortical circuits including synaptic pruning, reinforcement, and neuronal synchronization (5–8). The gradual alterations in brain connectivity and subsequent symptoms can persist for years before psychosis emerges and diagnosis and antipsychotic medications are initiated. In most cases, individuals with schizophrenia progress with an illness that is characterized by periods of exacerbation and remission of psychosis. Recovery is dependent on compliance with and response to optimized antipsychotic medication, the development of a strong therapeutic alliance to treatment team members, and intensive social and vocational support (9). Even with the best antipsychotic treatments that are available today and access to full functional supports, a sub-population of patients with schizophrenia will never attain an optimal response to treatment and remain very ill. These are the patients who have treatment-refractory illness or in the case of non-response to clozapine, ultra-resistant disease (10, 11)."}