Pica — Comprehensive Research Report

1. Disease Information

Overview. Pica is a feeding and eating disorder defined by the persistent eating of nonnutritive, nonfood substances that is developmentally inappropriate, not part of a culturally sanctioned practice, and — when it co-occurs with another mental or medical condition — severe enough to independently warrant clinical attention. Commonly ingested substances include earth/clay (geophagia), ice (pagophagia), starch (amylophagia), paper (xylophagia), hair (trichophagia), feces (coprophagia), chalk, soap, ash, paint chips, and metal objects.

Key identifiers: - MONDO: MONDO:0001441 (per Mondo Disease Ontology; cross-referenced across OMIM, Orphanet, MeSH, NCIt) (Mondo Disease Ontology) - DSM-5-TR: Feeding and Eating Disorders chapter; criteria require persistent nonnutritive/nonfood ingestion for ≥1 month, developmentally inappropriate, not culturally sanctioned, and clinically significant if comorbid with another condition — some clinical sources suggest requiring a minimum duration of 2 years for definitive diagnosis in some settings (DSM-5-TR Update) - ICD-11: A single unified code (no longer split by age, unlike ICD-10) - ICD-10-CM: F98.3 (children/adolescents), F50.8 (previously) / effective Oct 1, 2024, F50.83 for adults (StatPearls) - MeSH: D010842 "Pica"

Synonyms/subtypes: geophagia/geophagy (clay/soil), pagophagia (ice), amylophagia (starch), xylophagia (wood/paper), trichophagia (hair), coprophagia (feces), lithophagia (stones), plumbophagia (paint/lead objects).

Evidence base: Information is derived from a mix of case reports/series, cross-sectional surveys (largely in pregnant women and children with developmental disabilities), a small number of population-based cohort studies, and disease/behavioral registries — there is comparatively little large-scale EHR-based epidemiology, and no dedicated national disease registry.

2. Etiology

Disease causal factors: Pica does not have a single unifying cause; it is best modeled as a convergent behavioral endpoint reached via several overlapping causal routes: 1. Nutritional deficiency-driven (iron, and to a lesser extent zinc) — the best-supported mechanistic route 2. Neurodevelopmental — high co-occurrence with autism spectrum disorder (ASD) and intellectual disability (ID), often as a form of self-stimulatory/automatically-reinforced behavior 3. Physiological/gravid state — pregnancy-associated pica, possibly linked to nausea and cultural practice 4. Psychiatric — reported in obsessive-compulsive spectrum conditions, schizophrenia, and in the context of severe psychosocial deprivation 5. Culturally sanctioned geophagia that becomes classified as pathological only when it causes harm or exceeds a normative threshold

Genetic risk factors: There is no known single causal gene or Mendelian etiology for pica as an isolated disorder. Pica is, however, a recognized behavioral feature of several genetic neurodevelopmental syndromes: - Smith-Magenis syndrome (RAI1 gene, 17p11.2 deletion/mutation) — food-related problem behaviors, including pica, are reported at levels comparable to or exceeding Prader-Willi syndrome ("For food preoccupation, Smith-Magenis syndrome adults scored higher (8.6 ± 3.4) compared to Prader-Willi syndrome adults (8.1 ± 2.0)") - Prader-Willi syndrome (15q11-q13 paternal deletion/UPD; MAGEL2) — pica reported, notably exacerbated during comorbid Kleine-Levin-type hypersomnia episodes: "During hypersomnia episodes... the patient exhibited exacerbated hyperphagia, pica, poor emotional control, stereotyped speech and agitated behavior upon awakening" (PMID:8650457) - Broader ASD/ID genetic etiologies (fragile X, Rett syndrome, etc.) confer elevated pica risk indirectly through the ID/ASD phenotype rather than a pica-specific mechanism

Environmental/demographic risk factors: - Iron deficiency anemia (strongest and most reversible risk factor) - Zinc deficiency - Pregnancy, particularly third trimester, and pregnancy-associated nausea (aOR 3.60 for third trimester; aOR 2.11 for nausea; PMID:34252052) - Lower socioeconomic status, food insecurity, malnutrition - Childhood age (peak prevalence in toddlers/preschoolers) - Female sex (some adolescent studies) and lower paternal education - End-stage chronic kidney disease / hemodialysis - Sickle cell disease - Psychosocial deprivation, institutionalization, limited parental supervision - Cultural transmission (geophagia is normative in parts of sub-Saharan Africa; prevalence estimates in pregnancy range "from 0.007% in Denmark to 92.5% in Nigeria")

Protective factors: - Adequate iron/zinc nutritional status - Iron repletion is both a protective and therapeutic intervention — a scoping review of 20 studies found "identification of pica symptoms allowed treatment for iron deficiency and led to resolution of all symptoms in all 20 articles" (PMID:37220446) - Structured behavioral supports in individuals with ASD/ID (differential reinforcement, environmental enrichment)

Gene-environment interaction: The clearest interaction model is genetic vulnerability to neurodevelopmental disability (ASD/ID) combined with an environmental/behavioral reinforcement pathway (automatic sensory reinforcement from oral exploration), compounded in some cases by superimposed micronutrient deficiency. No formal GWAS or CTD gene-environment interaction datasets specific to pica were identified.

3. Phenotypes

Suggested HPO terms and characteristics:

Table (click to expand)

Phenotype	HPO term (suggested)	Notes
Pica (core behavioral phenotype)	HP:0011856 Pica (behavioral abnormality)	Core diagnostic feature
Iron deficiency anemia	HP:0001891 (Iron deficiency anemia)	Frequent comorbid lab finding
Zinc deficiency	HP:0008875 (or general "abnormal trace element level")	Less well quantified
Failure to thrive / malnutrition	HP:0001508	In children with severe/chronic pica
Intellectual disability	HP:0001249	Strong comorbidity, not causal per se
Autistic behavior	HP:0000729	Strong comorbidity
Constipation / abdominal pain	HP:0002019 / HP:0002027	From bezoar/obstruction complications
Elevated blood lead level	HP:0500058 (or general toxic exposure phenotype)	From paint-chip/soil pica
Intestinal obstruction	HP:0005214	Bezoar-related complication
Dental injury/wear	HP:0000679 (Abnormal dentition)	From ingesting hard/abrasive substances
Parasitic infection (helminthiasis)	— (infectious, not core HPO)	From geophagia

Onset: Typically emerges in early childhood (18 months–6 years is developmentally normal mouthing; pathological pica is diagnosed only beyond the developmentally appropriate window, generally after age 2). Also arises de novo in pregnancy (often 2nd–3rd trimester) and can appear at any age in the context of ID/ASD, psychiatric illness, or acquired nutritional deficiency (e.g., post-bariatric surgery, dialysis).

Severity/progression: Highly variable — from mild, self-limited toddler pica that resolves spontaneously, to severe, chronic, treatment-refractory pica in individuals with profound ID/ASD requiring lifelong behavioral management. Course can be episodic (pregnancy-limited) or persistent/progressive (in ASD/ID populations, where recurrence across developmental waves is common — "19.55% reported pica at least at two waves" in the ALSPAC cohort).

Frequency in general population: General-population prevalence estimates range from about 3.5%–5% in children (DSM-5 cites ~5% in school-age children), with a peak around 36 months (~2.29% in one large birth cohort) declining thereafter.

Quality of life impact: Direct QoL instruments specific to pica are lacking; impact is inferred from complication burden (GI obstruction, lead neurotoxicity, parasitic disease, social stigma, caregiver burden in ASD/ID populations, and interference with renal replacement therapy adherence in CKD).

4. Genetic/Molecular Information

Pica as an isolated entity is not a monogenic disease — there are no OMIM-cataloged "Pica" causal genes, no ClinVar pathogenic-variant entries specific to pica, and no dedicated GWAS Catalog hits. Genetic contribution is indirect, mediated through: - Syndromic ID/ASD genes (e.g., RAI1 [HGNC:9857] in Smith-Magenis syndrome; MAGEL2 [HGNC:6814] and the 15q11-q13 imprinted locus in Prader-Willi syndrome) - Possible heritable contribution to iron-handling/anemia susceptibility (e.g., variants affecting iron absorption), though no pica-specific variant has been established

Epigenetics: No pica-specific epigenetic studies identified; Prader-Willi syndrome's imprinting mechanism is relevant only insofar as it explains the syndromic food-related behavior phenotype, not pica specifically.

Chromosomal abnormalities: None specific to pica; relevant only via the syndromic ID conditions above (15q11-q13 deletion/UPD for PWS; 17p11.2 deletion for Smith-Magenis).

5. Environmental Information

Toxin exposure: Lead-based paint and contaminated soil are the dominant environmental hazards — "Children eating paint chips from pre-1978 homes can accumulate lead levels that damage the developing nervous system, impair cognition, and cause behavioral problems that persist for years."
Geophagic clay contamination: Toxic metals (arsenic, cadmium, lead) have been documented in clay consumed as pica by pregnant women in Ghana (PMC7071753), raising heavy-metal exposure risk.
Infectious agents: Geophagia is a recognized route for soil-transmitted helminth infection (Ascaris, Trichuris, hookworm) and exposure to bacteria/fungi/parasite ova in ingested soil.
Lifestyle factors: Low socioeconomic status, food insecurity, and limited maternal education correlate with higher pica prevalence in several African antenatal cohorts.

6. Mechanism / Pathophysiology

Pathophysiology is incompletely understood and represents parallel, only partially overlapping causal chains rather than one pathway. The best-characterized causal chain:

Iron-deficiency route: Chronic iron deficiency (dietary insufficiency, GI blood loss, pregnancy-related iron demand, malabsorption) → reduced CNS iron availability (iron is a cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis) → disrupted central dopaminergic neurotransmission → aberrant craving/reward-seeking behavior directed at nonnutritive substances → pica. Supporting review language: "The strong association of pica with iron deficiency anemia (IDA) lends credence to the hypothesis that dopamine transmission may be disrupted in this disorder... a common central pathway such as mediation by decreased CNS dopamine neurotransmission has been reported to be a specific result of iron deficiency" (PMID:35674869, The Neurology and Psychopathology of Pica).

A secondary, self-reinforcing loop exists for clay/kaolin-type pica: ingested clay binds free iron in the gut lumen ("adsorption of Fe2+ and Fe3+ to the negatively charged and large active surface area of kaolinite may lead to a reduction of available iron in the duodenum"), worsening the underlying deficiency — i.e., the coping behavior paradoxically deepens the causal deficiency.

Zinc-dopamine route: Zinc is a cofactor/modulator of the dopamine transporter (DAT), acting as "a potent non-competitive blocker of substrate translocation," and zinc deficiency is separately implicated in monoaminergic dysregulation (parallel literature in depression, PMC5337390), offering a second nutrient-neurotransmitter mechanistic arm converging on the same dopaminergic endpoint.

Neurodevelopmental/behavioral route (ASD/ID): In this population, pica is generally conceptualized not as a deficiency-driven craving but as a behavior maintained by automatic (sensory) reinforcement — oral/tactile sensory-seeking, similar to other stereotyped/self-stimulatory behavior, occurring independent of nutritional status. This is the dominant model in the applied-behavior-analysis literature: "Pica is a life-threatening form of challenging behavior displayed by individuals with intellectual and developmental disabilities and is typically maintained by automatic reinforcement."

Emesis/nausea-adaptive route (model-organism-derived hypothesis, translational to pregnancy-pica): In rats (a species incapable of vomiting), toxin/chemotherapy exposure induces kaolin consumption as a compensatory, adaptive behavior substituting for emesis: cisplatin/copper sulfate → activation of dopamine D2 receptors in the chemoreceptor trigger zone and 5-HT3 receptors on gastric vagal afferents → induction of pica/kaolin intake, blocked by ondansetron (5-HT3 antagonist) and other standard antiemetics. This has been proposed as informing the human pregnancy-nausea association (pica correlating with nausea, aOR 2.11), though direct human confirmation of this specific mechanism is lacking (a HUMAN_MODEL_MISMATCH-type gap).

Cell types/processes involved: Nigrostriatal and mesolimbic dopaminergic neurons (GO:0007212 dopamine receptor signaling pathway), area postrema/chemoreceptor trigger zone chemosensory neurons, vagal visceral afferents, enterocytes (iron/zinc absorption, duodenal mucosa).

GO term suggestions: GO:0007212 (dopamine receptor signaling pathway), GO:0006826 (iron ion transport), GO:0006829 (zinc ion transport), GO:0042493 (response to drug — antiemetic pharmacology context).

Tissue damage / biochemical abnormalities: Iron-deficiency erythropoiesis; possible lead-induced neurotoxicity from paint/soil pica; mucosal/GI mechanical injury from bezoar formation.

7. Anatomical Structures Affected

Primary "organ" involved (behavioral origin): CNS — basal ganglia/striatal dopaminergic circuits, area postrema (UBERON:0002298 basal ganglia; UBERON:0002162 area postrema)
Secondary/complication organs:
GI tract (UBERON:0005409 stomach; UBERON:0002108 small intestine): bezoar formation (trichobezoar, lithobezoar/phytobezoar), obstruction, perforation, intussusception (Rapunzel syndrome)
Hematologic system: iron-deficiency anemia
Renal system: implicated bidirectionally in CKD/dialysis patients
Dentition: abrasive wear/injury from hard substances
Nervous system: lead neurotoxicity from paint/soil ingestion
Cell types (Cell Ontology): enterocyte (CL:0000584), erythroid precursor cells, dopaminergic neuron (CL:0000700)
Subcellular: mitochondrial/cytosolic tyrosine hydroxylase-dependent dopamine synthesis machinery; DAT (dopamine transporter) at presynaptic plasma membrane
Laterality: Not applicable (systemic/behavioral).

8. Temporal Development

Onset: Most commonly childhood (peak toddler/preschool, ~2–4 years), also common in the 2nd–3rd trimester of pregnancy, and can present at any age secondary to ID/ASD, psychiatric illness, or acquired systemic disease (CKD/dialysis, post-bariatric surgery).
Progression: Variable — in typically developing children, largely self-limited and resolves with development; in ASD/ID and syndromic populations, tends to be chronic/persistent and can recur across developmental stages (ALSPAC cohort: recurrence at multiple assessment waves in ~20% of affected children).
Course pattern: Episodic in pregnancy-associated cases (resolves post-partum in most); can be chronic/relapsing-remitting in ASD/ID and CKD-associated cases.
Remission: Frequently spontaneous with age/development in young children; treatment-induced remission is well documented for iron-deficiency-associated pica (rapid resolution with iron repletion).
Critical periods: Toddlerhood is a period where pica must be distinguished from normative developmental mouthing (hence DSM-5's developmental-inappropriateness criterion); third trimester of pregnancy is a recognized vulnerability window.

9. Inheritance and Population

Prevalence: General pediatric population ~3.5%–5%; pregnancy/postpartum populations show an aggregated meta-analytic prevalence of 27.8% with substantial heterogeneity (0.007%–92.5% across countries) (Fawcett et al., Int J Gynaecol Obstet 2016;133(3):277-83, PMID:26892693); ASD populations 23.2% overall (28.1% with comorbid ID, 14.0% without ID) versus 8.4% in general developmental-delay populations and 3.5% in typically developing controls (Fields et al., Pediatrics 2021;147(2):e20200462, PMID:33408069).
Inheritance pattern: Not a Mendelian trait; multifactorial/behavioral. Syndromic pica (Smith-Magenis, Prader-Willi) follows the inheritance pattern of the underlying syndrome (imprinting disorder / autosomal, typically de novo deletion).
Sex ratio: Some adolescent-population studies show female predominance; pregnancy-associated pica is obviously female-specific by definition.
Geographic distribution: Marked geographic variation, with geophagia most normalized/prevalent in sub-Saharan Africa (Nigeria up to 92.5% in some antenatal cohorts; Uganda 57% in one Kampala antenatal cohort, PMID:34252052) versus <1% in some Western cohorts (Denmark ~0.007%).
Age distribution: Bimodal-ish clustering — early childhood peak and reproductive-age (pregnancy) peak, plus elevated rates in institutionalized/ID populations across the lifespan.

10. Diagnostics

Laboratory tests: CBC, serum ferritin, serum iron/TIBC/transferrin saturation, zinc level, lead level (especially with paint/soil pica), stool ova and parasites (with geophagia), electrolytes (particularly relevant in CKD-associated pica).
Biomarkers: Serum ferritin is the most sensitive/specific marker of iron deficiency in the absence of inflammation; must be interpreted alongside CRP given ferritin's acute-phase reactant behavior.
Imaging: Abdominal X-ray/CT for suspected bezoar or radiopaque foreign material (especially with lithophagia/soil ingestion); used in complication workup rather than primary diagnosis.
Endoscopy: For suspected gastric bezoar (trichobezoar, phytobezoar).
Clinical criteria: DSM-5-TR (above); ICD-11 single code; differential diagnosis includes ARFID (Avoidant/Restrictive Food Intake Disorder — distinguished by lack of interest in food vs. specific craving for nonfood items), OCD, and culturally normative geophagia (excluded from diagnosis unless clinically harmful/excessive).
Structured assessment instrument: PARDI (Pica, ARFID, and Rumination Disorder Interview) — a semi-structured, multi-informant clinical interview developed by Bryant-Waugh, Micali, Cooke, Lawson, Eddy, and Thomas (2018) to diagnose Pica, ARFID, and Rumination Disorder per DSM-5 criteria, with separate child and adult/young-person versions.
Screening in special populations: No dedicated newborn/genetic screening exists; screening is opportunistic — iron studies in patients presenting with pica, and behavioral screening for pica in ASD/ID clinical intake protocols (e.g., Food-Related Problem Questionnaire, originally developed for Prader-Willi syndrome, also applied to Smith-Magenis syndrome).

11. Outcome/Prognosis

Mortality: Direct mortality from pica itself is rare but can occur via severe complications (bowel perforation/peritonitis from bezoar, lead encephalopathy, severe parasitic disease, choking/airway obstruction from foreign objects).
Morbidity: Primary morbidity burden comes from complications — iron-deficiency anemia, GI obstruction/bezoar (including Rapunzel syndrome causing "multiple sites of simultaneous intussusception"), dental injury, lead neurotoxicity with lasting cognitive/behavioral effects in children, and helminthic/parasitic infection from geophagia.
Recovery potential: Excellent when driven by a reversible nutritional deficiency (iron/zinc repletion resolves symptoms in the large majority of reported cases) or when pregnancy-limited (typically resolves postpartum). Prognosis is more guarded/chronic in ASD/ID-associated and CKD-associated pica, where the underlying driver (neurodevelopmental disability, chronic renal failure) is not reversible.
Prognostic factors: Presence/absence of reversible nutrient deficiency; presence of comorbid ASD/ID (associated with chronicity); severity/type of ingested material (hard/sharp/toxic objects carry higher complication risk); access to behavioral intervention.

12. Treatment

Pharmacotherapy / nutritional: - Iron supplementation — first-line when iron deficiency is identified; strongly supported ("treatment for iron deficiency... led to resolution of all symptoms in all 20 articles," PMID:37220446) - Zinc supplementation when zinc deficiency is documented - N-acetylcysteine (NAC) — a glutamatergic modulator with evidence in body-focused repetitive behaviors (trichotillomania, excoriation, onychophagia); mechanistically plausible but not directly evidence-based for pica/trichophagia specifically — an extrapolation from the related BFRB literature (PMID:35681955), representing a knowledge gap - Treatment of underlying psychiatric or renal disease as applicable

Behavioral interventions (primary treatment modality in ASD/ID populations): - Differential reinforcement of alternative behavior (DRA) - Response interruption and redirection (RIRD) - Response blocking / noncontingent reinforcement with competing stimuli - Preliminary evidence supports combined RIRD + DRA as effective; systematic reviews note the evidence base, while promising, remains limited in rigor and sample size (Moline et al., Clin Psychol Psychother 2021, PMID unlisted in search; McAdam et al. 2004)

Surgical/procedural: Endoscopic or surgical removal of bezoars; management of intestinal obstruction/perforation/intussusception (Rapunzel syndrome cases).

Supportive care: Environmental modification (removing access to hazardous nonfood items, especially lead paint remediation), nutritional counseling, caregiver education and supervision strategies.

Suggested MAXO terms: - MAXO:0000088 (dietary intervention) — for iron/zinc repletion - MAXO:0000011 (physical therapy) — not typically applicable - MAXO:0000079 (genetic counseling) — for syndromic cases (Smith-Magenis, Prader-Willi) - MAXO:0000950 (supportive care) - A specific "applied behavior analysis" / DRA MAXO term should be verified via OAK search (uv run runoak -i sqlite:obo:maxo search "behavioral intervention") — not confirmed in this research pass

Experimental treatments: No dedicated registered clinical trials targeting pica as a primary endpoint were identified in this search; most trial-registry data intersects only tangentially (e.g., iron-deficiency treatment trials that report pica as a secondary outcome).

13. Prevention

Primary prevention: Adequate maternal/childhood iron and zinc nutrition; lead-paint abatement in housing (especially pre-1978 housing stock) to reduce a major complication pathway.
Secondary prevention: Screening for iron deficiency in at-risk groups (pregnant women, children with developmental disabilities, CKD/dialysis patients) to catch and treat the reversible driver before pica-related complications occur.
Behavioral/environmental interventions: Structured environmental modification and caregiver supervision in ASD/ID populations; parasite-prevention education (handwashing, safe water) in geophagia-endemic regions.
Counseling: Genetic counseling relevant for syndromic causes (Smith-Magenis, Prader-Willi); antenatal counseling on pica risks (helminth exposure, heavy-metal contamination in some geophagic clays) is explicitly recommended by several African antenatal-care studies.
Public health: Water/soil sanitation and deworming programs in geophagia-endemic regions; lead-abatement housing policy.

14. Other Species / Natural Disease

Taxonomy: Reported informally in companion animals (dogs, cats — behavioral pica, e.g., ingestion of non-food objects, sometimes linked to nutritional deficiency or gastrointestinal disease) though this is a distinct veterinary literature not deeply cross-validated here; NCBITaxon:9615 (Canis lupus familiaris), NCBITaxon:9685 (Felis catus).
Comparative biology / model relevance: The rodent "pica" model (below) is mechanistically analogous but serves a different biological function (emesis surrogate) than human pica, which is an important translational caveat — this is a candidate HUMAN_MODEL_MISMATCH note for curation, since rat kaolin-intake pica is a compensatory antiemetic behavior (a normal physiological substitute in a non-vomiting species) rather than a disease state, whereas human pica is itself the pathological entity.

15. Model Organisms

Rodent pica-as-emesis-proxy model (the dominant model-organism literature under the term "pica"): - Species: Rat (Rattus norvegicus), mouse (Mus musculus) — species that cannot vomit - Model type: Induced/pharmacological — kaolin (clay) consumption induced by emetogenic agents (cisplatin, copper sulfate, radiation, motion) serves as a quantifiable surrogate for emesis/nausea, not a direct model of human pica pathology: "Since rats lack a vomiting response... kaolin consumption (pica behavior) can indirectly reflect the degree of vomiting in rats" and "pica in rats is analogous to emesis... mediated by the same mechanisms as vomiting in humans." - Mechanism reproduced: Dose-dependent kaolin intake following cisplatin/copper sulfate, mediated via dopamine D2 receptors in the chemoreceptor trigger zone and 5-HT3 receptors on gastric vagal afferents; blocked by ondansetron and other clinical antiemetics (5-HT3/NK1 antagonists, corticosteroids) — validating the model's translational relevance to human chemotherapy-induced nausea/vomiting (CINV), not to human pica per se. - Adaptive-response framing: One line of research frames kaolin consumption as adaptive/protective — "kaolin consumption helps rats recover from chemotherapy-induced illness" — reinforcing that this rodent behavior, while phenotypically named "pica," is a physiologically distinct, arguably beneficial behavior rather than a disease model. - Limitations: This model does not recapitulate the core human disease features (chronic craving behavior, nutrient-deficiency linkage, ASD/ID-associated automatic reinforcement); it is best used for CINV/antiemetic pharmacology research, not for modeling human pica pathophysiology directly. No dedicated genetic mouse model (knockout/transgenic) of nutrient-deficiency-driven or ASD-associated pica behavior was identified in this search — a clear model-system gap. - Resources: No MGI/RGD-curated "pica" phenotype term beyond general behavioral/ingestive-behavior annotations was found in this pass; would require a dedicated MGI phenotype-ontology query to confirm.

Key Knowledge Gaps (for curation flagging)

No confirmed human neuroimaging (DAT-PET/SPECT) data directly testing the dopamine-deficiency hypothesis in pica patients — the mechanism is inferred from the iron-deficiency/dopamine literature generally, not measured directly in pica cohorts (candidate KNOWLEDGE_GAP).
The rodent kaolin/emesis pica model's translational relevance to human craving-driven pica is uncertain — candidate HUMAN_MODEL_MISMATCH (the rodent model captures an antiemetic behavior, not the human disease's core phenomenology).
No RCT-level pharmacotherapy evidence for pica itself (iron-repletion evidence is observational/case-series-based; NAC evidence is extrapolated from related BFRB conditions).
No dedicated GWAS, ClinVar, or OMIM entries for pica as an isolated trait.