Essential Trace Elements in Psychiatric Disorders: Mechanistic Pathways and Therapeutic Implications

Abstract

Essential trace elements—including zinc (Zn), iron (Fe), copper (Cu), selenium (Se), manganese (Mn), molybdenum (Mo), and cobalt (Co)—participate in neurotransmission, redox regulation, mitochondrial function, immune signaling, and neuroendocrine processes. Increasing evidence suggests that disturbances in trace-element homeostasis may be associated with several psychiatric disorders; however, the strength and consistency of the evidence remain heterogeneous. This narrative review integrates recent human clinical studies with relevant biochemical, mechanistic, and selected preclinical evidence concerning trace-element dysregulation and psychiatric outcomes. Among the elements examined, Zn and Se have the strongest interventional support. Meta-analyses of randomized controlled trials suggest that adjunctive Zn supplementation may reduce depressive symptom severity in some populations, whereas individual trials indicate possible symptomatic benefit in attention-deficit/hyperactivity disorder (ADHD). Findings for Se also suggest potential benefit, particularly in postpartum depression, although generalizability across populations remains uncertain. Observational studies have associated lower Fe indices with greater ADHD symptom burden, cognitive difficulties, and atypical neurodevelopment, while higher circulating Cu concentrations have been reported in major depressive disorder and autism spectrum disorder. Evidence concerning Mn, Mo, and Co remains limited and inconsistent and is derived mainly from small observational studies. Mechanisms involving oxidative stress, mitochondrial dysfunction, excitatory–inhibitory imbalance and altered monoaminergic signaling are biologically plausible but do not independently establish clinical causality. Overall, disturbances in essential trace-element homeostasis have been associated with mood disorders, neurodevelopmental conditions, and cognitive dysfunction. Nevertheless, substantial heterogeneity in study design, biomarker matrices and assays, sample characteristics, and control of confounding limits causal interpretation. Longitudinal and interventional studies using standardized methods are therefore needed to clarify temporal and causal relationships and to determine whether targeted micronutrient assessment or supplementation provides clinically meaningful benefit in psychiatric practice.

Keywords

• Essential trace elements
• mental health
• psychiatry
• review

Supporting Institution

No financial support was received from any individual, institution, or organization for the conduct or publication of this study.

Ethical Statement

Since public data and related literature were analysed in our study, there was no ethical violation.

Thanks

The authors express their sincere appreciation to all researchers whose scholarly contributions formed the basis of this review.

Psikiyatrik Bozukluklarda Esansiyel iz Elementler: Mekanistik Yolaklar ve Terapötik Çıkarımlar

Abstract

Çinko (Zn), demir (Fe), bakır (Cu), selenyum (Se), manganez (Mn), molibden (Mo) ve kobalt (Co) gibi esansiyel iz elementler; nörotransmisyon, oksidatif denge, mitokondriyal işlev, bağışıklık sistemi düzenlenmesi ve nöroendokrin sinyal iletiminde önemli roller üstlenmektedir. Giderek artan kanıtlar, bu elementlerin homeostazındaki bozulmaların çeşitli psikiyatrik bozukluklarla ilişkili olabileceğini düşündürmektedir; ancak mevcut bulguların gücü ve tutarlılığı heterojendir. Bu anlatısal derleme, iz element düzensizliği ile psikiyatrik sonuçlar arasındaki ilişkileri değerlendiren güncel insan klinik çalışmalarını, ilgili biyokimyasal, mekanistik ve seçilmiş klinik öncesi kanıtlarla birlikte bütünleştirmektedir. İncelenen elementler arasında en güçlü müdahale kanıtları çinko ve selenyum için bildirilmiştir. Randomize kontrollü çalışmaların meta-analizleri, özellikle ek tedavi olarak uygulanan çinko desteğinin bazı depresyon örneklemlerinde belirti şiddetini azaltabileceğini; tekil çalışmalar ise dikkat eksikliği/hiperaktivite bozukluğunda (DEHB) klinik belirtilerde iyileşme sağlayabileceğini düşündürmektedir. Selenyum desteğine ilişkin bulgular da özellikle doğum sonrası depresyon bağlamında olası bir yarara işaret etmekle birlikte, farklı popülasyonlara genellenebilirliği sınırlıdır. Gözlemsel çalışmalar düşük demir göstergeleri ile DEHB belirti şiddeti, bilişsel güçlükler ve atipik nörogelişim arasında; yüksek bakır konsantrasyonları ile majör depresif bozukluk ve otizm spektrum bozukluğu arasında ilişkiler bildirmiştir. Manganez, molibden ve kobalta ilişkin kanıtlar ise çoğunlukla küçük örneklemli gözlemsel çalışmalara dayanmakta, sınırlı ve tutarsız bir görünüm sergilemektedir. Oksidatif stres, mitokondriyal işlev bozukluğu, eksitatör-inhibitör dengesizlik ve monoaminerjik sinyal değişiklikleri biyolojik açıdan olası açıklamalar sunsa da bu mekanizmalar klinik nedenselliği tek başına kanıtlamamaktadır. Genel olarak, esansiyel iz element homeostazındaki bozulmalar duygudurum bozuklukları, nörogelişimsel durumlar ve bilişsel işlev bozukluğu ile ilişkilendirilmiştir. Bununla birlikte, çalışma tasarımları, biyobelirteç değerlendirme yöntemleri, örneklem özellikleri ve karıştırıcı değişkenlerdeki belirgin heterojenlik kesin nedensel yorumları sınırlandırmaktadır. Bu nedenle, nedensel ve zamansal ilişkileri açıklığa kavuşturmak ve hedefe yönelik mikrobesin değerlendirmesi veya desteğinin psikiyatri pratiğinde klinik yarar sağlayıp sağlamadığını belirlemek için standardize yöntemlere dayanan uzunlamasına ve girişimsel çalışmalara ihtiyaç vardır.

Keywords

• Esansiyel iz elementler
• ruh sağlığı
• psikiyatri
• derleme

Supporting Institution

Bu çalışmanın yürütülmesi veya yayınlanması için herhangi bir birey, kurum veya kuruluştan finansal destek alınmamıştır.

Ethical Statement

Çalışmamızda kamuya açık veriler ve ilgili literatür analiz edildiğinden, etik ihlal söz konusu değildir.

Thanks

Yazarlar, bu incelemenin temelini oluşturan bilimsel katkılarından dolayı tüm araştırmacılara içten teşekkürlerini sunarlar.

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