Exploring neuropsychiatric manifestations of vitamin B complex deficiencies

Abstract

B complex vitamins, a group of eight water-soluble vitamins, play interconnected roles in maintaining nervous system health. Thiamine (B1), riboflavin (B2), and niacin (B3) are essential as co-enzymes in numerous metabolic reactions related to energy production. Thiamine is involved in the Krebs cycle, riboflavin in the electron transport chain, and niacin plays a key role in both glycolysis and the Krebs cycle. These metabolic processes are vital for sustaining the integrity of the nervous system, as the energy produced is critical for the functioning of nerve cells. Deficiencies in these vitamins can lead to significant neurological and psychiatric conditions, including Wernicke Korsakoff syndrome, Parkinson's disease, and various mental illnesses. Additionally, pyridoxine (B6), folate (B9), and cobalamin (B12) are indispensable coenzymes for the methylation of homocysteine to methionine, a process critical to nervous system function. Elevated homocysteine levels, resulting from deficiencies of these vitamins, are associated with higher risks of depression and dementia. Thus, imbalances in these vitamins can disrupt key biochemical pathways, leading to neuropsychiatric disorders. The literature reviewed underscores the importance of daily intake of B complex vitamins to maintain normal serum levels and optimal neuronal function. This review aims to elucidate the neuropsychiatric manifestations associated with deficiencies in these vitamins.

Keywords: cobalamin; complex B vitamins; folate; neuropsychiatric manifestations; niacin; pyridoxine; riboflavin; thiamine.

Figure 1

Age-related neuropsychiatric manifestations associated with B-vitamins deficiency. In the embryogenesis, B1 deficiency may cause defects in neural tube formation (5). In children, deficiency of B-vitamins may cause intellectual disability, polyneuropathy or seizures and epilepsy, depending on which vitamin is deficient (–7). In adults, the deficiency may present in form of behavioral disorders, mood disorders, encephalopathy and polyneuropathy (–8). Then, 5 of 29 on the elderly, B-vitamins deficiency may manifest as mood disorders, behavioral disorders, autonomic dysfunction, polyneuropathy and encephalopathy (, –12).

Figure 2

Age-related distribution of vitamin B deficiencies and their associated nervous system disorders. During embryogenesis, deficiencies in vitamins B9 and B12 are linked to the development of neural tube defects (, , –16). In childhood, deficiencies in vitamins B6, B9, and B12 can lead to neurological conditions such as polyneuropathy, seizures, epilepsy, and encephalopathy (4, 5, 8, 10, 17, 18). Additionally, vitamin B9 and B12 deficiencies may contribute to language development impairments (4, 5, 8, 10, 17, 18). In adulthood, vitamin B9 and B12 deficiencies are associated with encephalopathy, myelopathy, and various behavioral and mood disorders, while deficiencies in B6, B9 and B12 can also cause polyneuropathy (, , –24).

Figure 3

(a) Pentose Phosphate Pathway, highlighting the role of niacin (B3) in the synthesis of 6-phosphogluconolactone and ribulose-5-phosphate, as well as thiamine’s (B1) involvement in the production of 9 of 29 transketolase (TK) (8, 30, 31, 34, 35); (b) Glycolysis pathway, demonstrating niacin’s (B3) role in the conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate, and its links to both the Pentose Phosphate Pathway and the Krebs Cycle (34, 35); (c) Krebs Cycle, illustrating its connection to glycolysis, Electron Transport Chain, and Fatty Acid Beta-Oxidation pathway. It highlights thiamine’s (B1) role in catalyzing enzymes such as Pyruvate Dehydrogenase and α-Ketoglutarate Dehydrogenase, (e) riboflavin’s (B2) contribution to fumarate production, and niacin’s (B3) importance in the synthesis of α-Ketoglutarate and succinate (, , , , –35); (d) Electron Transport Chain, emphasizing niacin’s (B3) role in redox reactions and riboflavin’s (B2) function as an electron-shuttling cofactor (, –36).

Figure 4

Folate-dependent remethylation process, highlighting riboflavin´s (B2) importance in the production of N-5,10-Methyltetrahydrofolate, a crucial step to S-adenosylmethionine (SAMe) production (43).

Figure 5

Transmethylation Pathway illustrating the folate-dependent remethylation process. This figure emphasizes the role of riboflavin (B2) in producing N-5,10-methyltetrahydrofolate, pyridoxine (B6) in synthesizing N-5,10-methylenetetrahydrofolate, and folate (B9) in forming tetrahydrofolate (8, 10, 26, 27, 32, 33). Additionally, it highlights the combined function of folate (B9) and cobalamin (B12) in the synthesis of methionine synthase (9, 13, 20, 22, 44, 61).