In individuals with autism, schizophrenia, and certain physical disorders (such as Kleine-Levin syndrome), nonnutritive substances may be eaten. In such instances, pica should not be noted as an additional diagnosis.

According to the DSM 5, mineral deficiencies are occasionally associated with pica; however, biological abnormalities are rarely found in individuals with pica. People practicing forms of pica, such as geophagy, pagophagy and amylophagy, are more likely anemic, have low hemoglobin concentration in their blood, lower levels of red blood cells (hematocrit), or have lower plasma zinc levels. Specifically, practicing geophagy is more likely to associated with anemia or low hemoglobin. Practicing pagophagy and amylophagy were more highly associated with anemia. Additionally, being a child or pregnant woman practicing pica was associated with higher chance of being anemic or having low hemoglobin relative to the general population. More recently, cases of pica have been tied to the obsessive–compulsive spectrum, and there is a move to consider OCD in the cause of pica. However, pica is currently recognized as a mental disorder by the widely used "Diagnostic and Statistical Manual of Mental Disorders" (DSM-IV). Sensory, physiological, cultural and psychosocial perspectives have also been used by some to explain the causation of pica. It has been proposed that mental-health conditions, such as obsessive-compulsive disorder (OCD) and schizophrenia, can sometimes cause pica.

However, pica can also be a cultural practice not associated with a deficiency or disorder. Ingestion of kaolin (white clay) among African-American women in the US state of Georgia shows the practice there to be a DSM-IV "culture-bound syndrome" and "not selectively associated with other psychopathology". Similar kaolin ingestion is also widespread in parts of Africa. Such practices may stem from health benefits such as the ability of clay to absorb plant toxins and protect against toxic alkaloids and tannic acids.