Neurological Soft Signs in Schizophrenia Spectrum Disorders

Neurological soft signs (NSS) encompass subtle impairments in motor coordination, sensory integration and sequencing of complex movements that do not localise to a discrete brain lesion. These signs appear in the majority of individuals with schizophrenia spectrum disorders, from first-episode psychosis to chronic stages, and in some unaffected relatives, suggesting a neurodevelopmental origin. NSS exhibit both trait components—remaining stable across episodes—and state components—fluctuating with symptom severity, particularly negative and cognitive dimensions. Their presence correlates with poorer functional outcomes, reflecting aberrant cortical inhibition, altered connectivity in motor and association networks, and increased neural noise. As quantitative, non-invasive markers, NSS hold promise for early identification, monitoring disease progression and tailoring interventions aimed at motor and cognitive remediation.

Research from Nature Portfolio

A seminal prospective study tracked first-episode patients over one year, assessing NSS alongside neuropsychological performance and negative symptom profiles. Patients with prominent negative symptoms displayed persistently higher NSS—particularly motor coordination deficits—and poorer working memory compared with those without such symptoms. Although general improvements occurred across both groups, the negative-symptom subgroup retained elevated NSS levels, delineating two distinct clinical trajectories. This work underscores NSS as stable markers linked to negative symptomatology and cognitive dysfunction in early psychosis.

Neurological Soft Signs in Schizophrenia Spectrum Disorders publication trend

The graph below shows the total number of articles in neurological soft signs in schizophrenia spectrum disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Neurological soft signs: Minor sensorimotor irregularities—such as subtle coordination or integration deficits—not attributable to focal neurological lesions.

Motor coordination: The ability to execute smooth, accurate, and controlled movements.

Sensory integration: The process by which the brain organises and interprets sensory inputs to produce coherent perception and action.

Psychomotor slowing: A reduction in the speed and spontaneity of thought and movement, often reflected in slowed gait and speech.

Cortical inhibition: Neurophysiological mechanisms that suppress excitatory activity in the cortex, maintaining balanced network function.

Resting-state functional connectivity: Patterns of synchronous brain activity measured during rest, reflecting the integrity of large-scale neural networks.

References

1. Psychomotor Slowing in Psychosis and Inhibitory Repetitive Transcranial Magnetic Stimulation. JAMA Psychiatry (2024).
2. The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity. Brain (2023).
3. Neurodevelopmental predictors of treatment response in schizophrenia and bipolar disorder. Psychological Medicine (2024).
4. A systematic review and meta-analysis of neurological soft signs in relatives of people with schizophrenia. BMC Psychiatry (2011).
5. Neurological Soft Signs in Schizophrenia: An Update on the State- versus Trait-Perspective. Frontiers in Psychiatry (2018).
6. Course of neurological soft signs in first-episode schizophrenia: Relationship with negative symptoms and cognitive performances. Scientific Reports (2015).
7. Motor abnormalities are associated with poor social and functional outcomes in schizophrenia. Comprehensive Psychiatry (2022).
8. Neurological Soft Signs and Psychopathology in Chronic Schizophrenia: A Cross-Sectional Study in Three Age Groups. Frontiers in Psychiatry (2018).