Although there are substantial numbers of exceptions, defective poly-ZNFs (e.g., BLI3, ZEBs, and ZICs) tend to be associated with the NDDs with gross abnormality in brain morphology and/or structure, whereas dysfunction of the C2H2-ZNFs harboring additional domains, such as KRAB and SCAN (e.g., ZNF18, ZNF34, ZNF81, ZNF427, ZNF673, ZNF804A, and ZBTB20) are linked to the development of NDDs with abnormality in higher-order brain functions, such as cognitive deficit, memory loss, and emotional changes, represented by ID, ASDs, schizophrenia, MDD, and/or BAD. This evidence concerns the gene ZNF81 and major depressive disorder.