Roluperidone, a novel drug currently in Phase 3 trials, is showing promise in addressing the negative symptoms of schizophrenia, which have historically been difficult to treat. Unlike traditional antipsychotics that primarily target dopamine pathways to alleviate positive symptoms like hallucinations and delusions, Roluperidone blocks serotonin at sigma and α-adrenergic receptors.
Gregory P. Strauss, PhD, a schizophrenia researcher and founder of the Clinical Affective Neuroscience (CAN) lab at the University of Georgia, is optimistic about Roluperidone's potential. According to Strauss, data indicates that Roluperidone improves overall functioning in schizophrenia by specifically targeting avolition, a significant negative symptom characterized by a reduced desire for goal-directed activities.
Strauss stated, "I believe that because the drug improved motivation, an improvement in all other domains was possible. Low motivation might underlie why individuals have reductions in social activity, goal-directed activity, recreational activity, speaking, and expressing emotion." This suggests that avolition may be a central negative symptom in schizophrenia, and its effective treatment could lead to broader improvements in patients' lives.
The Challenge of Anosognosia
Another critical aspect of schizophrenia is anosognosia, a lack of awareness of one's illness. Xavier Amador, PhD, author of I Am Not Sick, I Don't Need Help, considers anosognosia a hallmark feature of schizophrenia, affecting approximately half of diagnosed individuals. Anosognosia is associated with dysfunction in the pre-frontal and frontal brain regions and is the strongest predictor of medication refusal and discontinuation, leading to increased involuntary hospitalizations and poorer psychosocial functioning.
Amador developed the LEAP (Listen, Empathize, Agree, and Partner) system to address anosognosia, emphasizing relationship-building rather than direct confrontation. This approach aims to redirect the patient's energy, similar to martial arts techniques that redirect an opponent's force.
Schizophrenia as a Syndrome
William T. Carpenter, MD, co-founder of the Brain and Behavior Research Foundation, proposed in 1974 that schizophrenia is better understood as a syndrome rather than a specific disease. This perspective gained traction with the publication of DSM-5 in 2013. Carpenter argues that schizophrenia encompasses at least six separable aspects of psychopathology, none of which are unique to the condition, sharing transdiagnostic similarities with disorders like depression. However, Carpenter notes that many aspects of this conceptualization were relegated to Section 3 of the DSM-5, rather than included in the main diagnostic criteria.
Neuroscientific Perspectives
Karl Friston, FMedSci FRSB, FRS, a British neuroscientist, uses neuroimaging and advanced statistical methods to model brain function in both typical and pathological states. Friston suggests that the positive symptoms of schizophrenia may be a "functional compensation" for underlying neurological anomalies, such as difficulties with eye movements. These anomalies may impair the brain's ability to efficiently process sensory data, leading to compensatory "work-arounds" that result in miscalculations about the world, ultimately manifesting as hallucinations and delusions.
