Breakthrough Clinical Results
Alto Neuroscience announced positive results from an independent, prospective replication study validating theta-band inter-trial coherence (ITC) as a robust EEG biomarker for schizophrenia. The study, involving 155 schizophrenia patients and 272 healthy controls, showed theta ITC strongly differentiates patients from healthy individuals and correlates with cognitive performance. This validates Alto's use of theta ITC as a primary outcome measure in its ongoing Phase 2 trial of ALTO-101, a novel PDE4 inhibitor for cognitive impairment associated with schizophrenia (CIAS). The findings highlight a more objective approach to identifying patients and measuring treatment effects in schizophrenia, an area previously hampered by subjective measures and biological heterogeneity. Alto plans to publish full details in upcoming medical conferences or peer-reviewed publications.
Key Highlights
- Independent replication study validates theta-band ITC as a robust biomarker for schizophrenia.
- Theta ITC strongly differentiates schizophrenia patients from healthy controls and correlates with cognitive performance.
- Theta ITC outperforms traditional EEG markers in distinguishing patients from controls.
- Findings support Alto's use of theta ITC as a primary outcome measure in its Phase 2 trial of ALTO-101 for CIAS.
Incidence and Prevalence
Global Incidence and Prevalence of Schizophrenia: Latest Estimates
Prevalence Estimates
Schizophrenia affects approximately 24 million people worldwide, making it less common than other mental disorders. The point prevalence averages approximately 4.5 per 1,000 population. More recent studies indicate that the prevalence of schizophrenia is 0.5-1% globally, with high heritability (80-85%) and complex transmission patterns.
From 1990 to 2019, schizophrenia raw prevalence increased from 14.2 to 23.6 million (a 65% increase). However, age-standardized estimates remained stable globally during this period. In countries with high socio-demographic index (SDI), both prevalence and DALYs increased, while in countries with low SDI, the age-standardized incidence decreased and DALYs remained stable.
In a 2021 study across six US states, annual prevalence of schizophrenia among Medicaid beneficiaries ranged between 2.30% and 2.71%. In 2017, states with the highest rates (KS, MS, MO) showed higher prevalence (4.01%).
Incidence Rates
The annual incidence of schizophrenia averages 15 per 100,000 population. The risk of developing schizophrenia over one's lifetime averages 0.7%.
In a 2025 study examining young people aged 15-24, the incidence rates of first contact diagnosis of schizophrenia ranged from 17.6 to 28.2 per 100,000, while the cumulative incidence rate ranged from 28.2 to 42.3 per 100,000. This study found that the incidence of schizophrenia was 57% higher when using the cumulative method compared to first contact diagnosis (IRR = 1.57, 95% CI: 1.30-1.90, p < .001). Research suggests that first contact cases under-estimate the true incidence because of later transitions to schizophrenia.
From 1990 to 2019, schizophrenia incidence increased from 941,000 to 1.3 million (a 37% increase). In the 2021 US study, annual incidence among Medicaid beneficiaries ranged between 0.31% and 0.39% during 2012-2016, with states with the highest rates showing an incidence of 0.52% in 2017.
Demographic and Risk Factors
Significant variations in incidence exist, with urbanicity, male gender, and history of migration being associated with a higher risk for developing the illness. The male/female ratio of schizophrenia burden has remained stable at 1.1 over the past 30 years. This ratio decreases from younger to older age groups, with raw prevalence in females higher than males after age 65. Males have earlier age of onset, while females have longer life expectancy.
Genetic factors and gene-environment interactions together contribute to over 80% of the liability for developing schizophrenia. Having a first-degree relative diagnosed with schizophrenia increases the risk significantly, with a rate ratio of 9.31.
Environmental factors linked to higher likelihood of developing schizophrenia include cannabis use, prenatal infection or malnutrition, perinatal complications, and history of winter birth.
Importantly, prevalence and burden estimates for schizophrenia are probably underestimated as the Global Burden of Diseases study does not account for mortality from schizophrenia.
Key Unmet Needs and Target Populations for Schizophrenia
Treatment-Resistant Populations
Treatment-resistant schizophrenia (TRS) affects approximately 30%-50% of people with schizophrenia in the European Union, representing a significant unmet need. Despite clozapine being the gold standard for TRS, it remains alarmingly underutilized in industrialized countries. Delaying clozapine treatment has a negative impact on long-term outcome, highlighting the need for earlier intervention. The m-RESIST intervention (smartwatch, mobile app, web-based platform) showed moderate to high acceptance among TRS patients, suggesting digital health solutions may help address this gap.
Metabolic and Physical Health Concerns
Patients with schizophrenia face significant metabolic syndrome (MS) challenges, contributing to increased cardiovascular burden and reduced life expectancy. Antipsychotics increase the risk of developing diabetes with a hazard ratio of 2.04 compared to periods without antipsychotic use, with a dose-response association particularly for second-generation antipsychotics. This population requires personalized therapeutic approaches addressing both psychological and metabolic aspects.
Cancer Screening Gaps
Adults with severe mental illness (including schizophrenia) are at greater risk of cancer than those without SMI but are less likely to take up available cancer screening. Currently, there is no RCT evidence for any method of encouraging cancer screening uptake in people with SMI.
Specific Subgroups Requiring Targeted Approaches
Several subgroups have been identified as requiring specialized interventions: - Patients with autistic features (34.1% of studied population) showed greater severity in psychopathology and social decline with lower incidence rates of symptomatic remission - Sexual and gender minority (SGM) populations experience minority stress with sizable gaps in knowledge about schizophrenia rates and severity - Non-obese patients may represent a subgroup where dietary glutamic acid consumption is associated with greater depression symptomatology - Patients with specific genetic variants (G allele and GG genotype of rs3757 in DGCR8, carriers of NGFR SNPs rs2072446 and rs11466162) - Male patients, those with young age at diagnosis, and those with in-patient diagnosis have significantly increased risk of progression from schizophrenia spectrum disorder to schizophrenia - Patients with sex-specific differential AKT activity showing divergent roles in males and females - Patients with low concentrations of nitric oxide who might benefit from nitric oxide donors - Patients with altered cellular composition and dysregulated immune-related genes
Healthcare System and Stigma Challenges
Stigma towards people diagnosed with severe mental disorders remains one of the main obstacles for receiving timely and relevant healthcare. Both service users and healthcare professionals manifest stereotypes, prejudices, and discriminatory behavior, with structural aspects of the health system contributing to stigmatization. There is a clear need for healthcare professionals to have more education, specialization, and skill development related to mental health issues.
Drug used in other indications
ALTO-101 Clinical Trials for Non-Schizophrenia Indications
After a thorough review of available information, there is no data available regarding ALTO-101 clinical trials for indications other than schizophrenia. The pharmaceutical compound ALTO-101 does not appear in the current research literature accessible for this query.
The absence of information extends to:
- No documented clinical trials for ALTO-101 in any therapeutic areas
- No intervention models or treatment protocols established for this compound
- No data on potential applications for conditions beyond schizophrenia
- No research findings related to ALTO-101's mechanism of action or efficacy
While other atypical antipsychotics such as aripiprazole and brexpiprazole have established clinical profiles and approved indications, ALTO-101 does not appear to have publicly available clinical trial information at this time.
For patients and clinicians interested in novel treatments for psychiatric or neurological conditions, it would be advisable to consult clinical trial registries such as ClinicalTrials.gov or contact pharmaceutical manufacturers directly for the most current information on investigational compounds like ALTO-101.
The development of new pharmaceutical interventions typically involves a rigorous clinical trial process with multiple phases testing safety and efficacy across various patient populations. When such information becomes available for ALTO-101, it would provide valuable insights into potential therapeutic applications beyond schizophrenia.