(1) Background: Neurological Soft Signs (NSS) are subtle neurological abnormalities that are more common in schizophrenia patients than in healthy individuals and have been regularly observed in neuroleptic-naive first-episode patients, supporting the hypothesis that they are an intrinsic component of schizophrenia. (2) Methods: a review of articles published in the last ten years (from January 2013 to January 2023) was carried out on articles published in ScienceDirect and PubMed, by following the PRISMA Statement extension for scoping reviews (PRISMA-ScR), which evaluated the impact of NSS in correlation with the symptomatology, neuroleptic treatment, and the cerebral structural changes of patients with schizophrenia. (3) Results: thirty articles were included, among them twelve included MRI structural evaluation and four studies with a longitudinal design. (4) Conclusions: interest in researching NSS has increased in recent years, but questions remain about their origin and relationship to schizophrenia symptoms, thus this study aims to fill in information gaps in the hope that future research will help provide individualized treatment. It is suggested that NSS in schizophrenia might have an inherited genetic relationship pattern, thus being in line with a trait viewpoint. Most of the research revealed that schizophrenia patients had higher NSS scores than healthy controls, however, they were rather similar to their first-degree relatives, thus, also arguing in favor of a trait perspective. The greatest improvement in scores is seen in those with a remitting course, as shown by declining NSS ratings concurrent with symptomatology.

Schizophrenia is a complex and incompletely elucidated pathology that affects sensorimotor function and also produces numerous therapeutic challenges. The aims of this cross-sectional study were to identify the profile of neurological soft signs (NSS) in patients with predominantly negative symptoms of schizophrenia (PNS) compared with patients with schizophrenia who do not present a predominance of negative symptoms (NPNS) and also to objectify the impact of treatment on the neurological function of these patients. Ninety-nine (n = 99; 56 females and 43 males) patients diagnosed with schizophrenia according to DSM-V were included; these patients were undergoing antipsychotic (4 typical antipsychotics, 86 atypical antipsychotics, and 9 combinations of two atypical antipsychotics) or anticholinergic treatment (24 out of 99) at the time of evaluation, and the PANSS was used to identify the patients with predominantly negative symptoms (n = 39), the Neurological Evaluation Scale (NES) was used for the evaluation of neurological soft signs (NSS), and the SAS was used for the objectification of the extrapyramidal side effects induced by the neuroleptic treatment, which was converted to chlorpromazine equivalents (CPZE). The study’s main finding was that, although the daily dose of CPZE did not represent a statistically significant variable, in terms of neurological soft signs, patients with PNS had higher rates of NSS.

Extensive epidemiological evidence links psychosis (PZ)—particularly schizophrenia (SCZ)—with disproportionate periodontal destruction, suggesting shared biological vulnerability. Beyond local tissue damage, periodontitis provides a clinically accessible translational paradigm for systemic redox dysregulation, where sustained inflammatory activation coincides with measurable oxidative injury and exhaustion of antioxidant (AO) defenses across cardiometabolic and neuropsychiatric domains. In this critical narrative review, we argue that the excess periodontal burden in PZ reflects a “pathological confluence” shaped by antipsychotic-associated iatrogenic factors, rapid metabolic deterioration, and chronic oxidative distress. We appraise the thioredoxin-interacting protein (TXNIP)–NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) axis as a metabolic–redox sensor linking dysglycemia to periodontal inflammasome activation and downstream cytokine signaling, and address the advanced glycation end-products (AGEs)–receptor for advanced glycation end-products (RAGE) axis as a key immunometabolic redox pathway. We further discuss mitochondrial dysfunction, impaired mitophagy, and mitochondrial deoxyribonucleic acid (mtDNA) leakage as damage-associated molecular patterns (DAMPs) that can amplify systemic “silent inflammation”. Integrating evidence on periodontal pathogen–host interactions and redox-sensitive neuroimmune pathways (including NADPH oxidase 4 (NOX4)-linked microglial activation), we propose periodontitis as a plausible upstream amplifier that may exacerbate vascular dysfunction and compromise blood–brain barrier (BBB) integrity. Finally, we outline clinically measurable biomarker readouts to operationalize redox-informed integrated care and highlight the need for pragmatic trials targeting clinically meaningful endpoints to improve somatic longevity in PZ-spectrum populations. We acknowledge that current human evidence is largely associative and that the proposed mechanistic links remain hypothesis generating.