Table 1.

Summary of current clinical evidence for the relationship between brain iron (Fe) and mental disorders.

Mental Disorders	Participants/Samples	Brain Iron Levels	Methods/Strategies	Key Findings	References
Depression	Depressed patients	Elevated (putamen, thalamus)	quantitative susceptibility mapping (QSM)	The study indicates the role of excess brain iron in deep gray matter in depression. It also suggests iron may be a potential biomarker for further understanding the pathophysiological mechanism of depression.	[96]
Depression	Late-life depressive patients (on antidepressant medication)	Elevated with the progression of depression: medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (dACC), occipital areas, habenula, brainstem, and cerebellum.	magnetic resonance imaging (MRI)-based QSM	It strengthens the understanding of the progression of brain iron deposition in late-life depression in patients on antidepressant medication and highlight the close relationship between magnetic susceptibility in the medial frontal areas and depression.	[97]
Depression	Patients With Recurrent Depression	Elevated (frontal lobes, temporal lobe structures, occipital lobes hippocampal regions, putamen, thalamus, cingulum, and cerebellum)	QSM	Brain iron deposition has been found to be associated with the overall duration of disease onset, rather than the severity of depression.	[98]
Depression	Depressive population	Decreased (hypotransferrinemia)	Blood iron detection	The hypotransferrinemia observed in the depressive population could correspond to a new form of brain functional iron deficiency.	[24]
Anxiety disorders	PD patients with anxiety	Elevated (ventral mPFC, ventral ACC, precuneus, angular gyrus, middle occipital gyrus, and supplementary motor area (SMA), hippocampus, and substantia nigra)	QSM	Increased iron accumulation in the fear circuit in PD patients with anxiety might contribute to the development of anxiety in PD.	[103]
ADHD	ADHD children aged 8–14 years	Decreased estimated brain iron levels in both the right and left thalamus	MRI	Low iron in the thalamus may contribute to ADHD pathophysiology	[142,143]
ADHD	ADHD children aged 6–14 years	Deficient iron in bilateral striatums, anterior cingulum, olfactory gyrus, and right lingual gyri	QSM	Brain iron deficiency in these brain regions might be related with ADHD, which might be valuable for further studies.	[140]
ASD	children with autism aged 2–3, 3–4, 4–5, and 5–6 years	Decreased iron contents (in caudate nucleus, dentate nucleus, and splenium of the corpus callosum for the 2–3 years group; in the frontal white matter, caudate nucleus, red nucleus, substantia nigra, dentate nucleus, and splenium of the corpus callosum for the 3–4, 4–5, and 5–6 years groups)	MRI enhanced T2*-weighted angiography (ESWAN) sequence scans	The brain iron content of children with autism is lower than that of normal children	[154]
Schizophrenia	Patients with first-episode schizophrenia	Decreased iron levels in the bilateral substantia nigra, left red nucleus and left thalamus	QSM effective transverse relaxation rate (R2*) maps	Decreased iron concentration is found in grey matter nuclei of patients with first-episode schizophrenia	[116]
Schizophrenia	an adult cohort of individuals with chronic schizophrenia aged 18–65 years	Elevated brain iron (thalamus)	inverse-normalized T2*-weighted contrast (1/nT2*)	Thalamic iron accumulation may act as a potential marker of schizophrenia	[118]
Schizophrenia	Post-mortem human brain samples	Elevated brain iron (the prefrontal cortex)	inductively coupled plasma-mass spectrometry (ICP-MS) Western Blots	It provides a pathophysiologic link between perturbed cortical iron biology and schizophrenia and indicates that achievement of optimal cortical iron homeostasis could offer a new therapeutic target	[60]
Schizophrenia	individuals with chronic schizophrenia	Increased iron in the putamen	ultra-high field 7 T QSM magnetic resonance spectroscopy (MRS)	Elevated iron levels in the dorsal striatum may be associated with a network-wide impact on iron distribution within other brain regions.	[119]