The Breathomics Profile of Volatile Sulfur Compounds in the Bipolar Spectrum, Does It Represent a Potential Tool for Early Diagnosis?

<b>Background/Objectives:</b> Emerging laboratory technologies, such as breathomics, may enhance the early diagnosis of psychiatric disorders, including Bipolar Disorder (BD). This study investigates the detection of volatile sulfur compounds (VSCs) in exhaled breath as potential biomarkers for BD, comparing VSC levels between individuals with BD, healthy controls, and individuals with non-pathological hyperactivity. <b>Methods:</b> A matched case-control study was conducted involving 24 patients with BD and 95 healthy controls recruited at the University Hospital of Cagliari. Controls were selected using a matched-pair design based on age (±5 years) and sex through a block-matching technique to ensure comparability with cases. Participants underwent psychiatric interviews, completed the Mood Disorder Questionnaire (MDQ), and had their exhaled breaths analyzed for VSCs using a gas chromatograph (OralChroma™). Controls were selected and randomized for age and sex. <b>Results:</b> Patients with BD exhibited significantly higher levels of methyl mercaptan (CH₃SH) compared to healthy controls (18.62 ± 5.04 vs. 9.45 ± 18.64 ppb, <i>p</i> = 0.022). Among individuals without BD, those with positive MDQ scores showed lower levels of CH₃SH than those with negative scores (9.17 ± 5.42 vs. 15.05 ± 18.03); however, this difference did not reach statistical significance (<i>p</i> = 0.254), highlighting how the deep connection between some clinical and laboratory aspects needs to be investigated more thoroughly. <b>Conclusions:</b> The results suggest a correlation between oral dysbiosis and metabolic alterations in patients with BD, with CH₃SH levels being higher in cases compared to controls. Further studies are needed to validate the use of VSCs as potential biomarkers for BD and to investigate their role in individuals with non-pathological hyperactivity.