Volume reduction and shape abnormality of the hippocampus have been associated with mood disorders. However, the hippocampus is not a uniform structure and consists of several subfields, such as the cornu ammonis (CA) subfields CA1–4, the dentate gyrus (DG) including a granule cell layer (GCL) and a molecular layer (ML) that continuously crosses adjacent subiculum and CA fields. It is known that cellular and molecular mechanisms associated with mood disorders may be localized to specific hippocampal subfields. Thus, it is necessary to investigate the link between the in vivo hippocampal subfield volumes and specific mood disorders, such as bipolar disorder (BD) and major depressive disorder (MDD). In the present study, we used a state-of-the-art hippocampal segmentation approach, and we found that patients with BD had reduced volumes of hippocampal subfields, specifically in the left CA4, GCL, ML, and both sides of the hippocampal tail, compared to healthy subjects and patients with MDD. The volume reduction was especially severe in patients with bipolar I disorder (BD-I). We also demonstrated that hippocampal subfield volume reduction was associated with the progression of the illness. For patients with BD-I, the volumes of the right CA1, ML and Sub decreased as the illness duration increased, and the volumes of both sides of the CA2/3, CA4, and hippocampal tail had negative correlations with the number of manic episodes. These results indicated that among the mood disorders the hippocampal subfields were more affected in BD-I compared to BD-II and MDD, and manic episodes had focused progressive effect on the CA2/3 and CA4 and hippocampal tail.

Chloroquine and hydroxychloroquine are commonly used drugs in the treatment of malaria as well as chronic diseases, such as rheumatoid arthritis, and systemic lupus erythematosus. Although various reports on possible psychiatric side effects of these drugs exist, the nature and extent of these effects remain poorly understood. Moreover, the relevance of these drugs in the treatment of early stages of COVID-19 necessitates a careful estimation of their side effects. Here, we provide a systematic review of the psychiatric side effects associated with chloroquine and hydroxychloroquine. We used PubMed, Scopus, and Web of Science platforms to identify relevant literature published between 1962 and 2020. Search terms included chloroquine, hydroxychloroquine, psychiatry, psychosis, depression, anxiety, bipolar disorder, delirium, and psychotic disorders. Only case reports and clinical trials were included. All studies included records of psychiatric side effects induced by either chloroquine or hydroxychloroquine or both. Both retrospective and prospective, randomized as well as non-randomized population studies were included. Overall, the psychiatric side effects are dose- and sex-independent. The most common psychiatric side effects reported are increased speech output/ excessive talking, increased psychomotor activity, irritable mood, auditory hallucinations, delusion of grandiosity, and suicide attempts, likely due to brain intoxicationbe of chloroquine or hydroxychloroquine. The symptoms can develop in a few hours to 11 weeks after drug intake and are normally reversed within a week after the drug withdrawal. We conclude that CQ and HCQ have the potential to induce psychiatric side effects. This study calls for further investigation of psychiatric symptoms induced by these drugs in the short and long term.