Moderators and mediators of antipsychotic response in delusional disorder: Further steps are needed

Table 1 Potential moderators and mediators of antipsychotic response in delusional disorder

Moderators	Mediators
Gender	Antipsychotic plasma concentrations
Reproductive status	Blood flow to brain
Age	Brain glucose metabolism
Comorbidity	Dopamine receptor occupancy
Brain lesions	Estrogen levels
Genetic factors
D2 receptor genes
Metabolizing enzyme genes

Table 2 Therapeutic implications of brain lesions in delusional disorder

Ref.	Study design	Imaging method	Age	Contrast group	DD type	Main findings
Moderators of treatment response (structural brain findings)
Miller et al[45], 1989	Prospect	CT, MRI	Case 1: 86	Schizophr (n = 1)	Persecutory	Structural brain disease in all 3 cases contributed to treatment resistance
			Case 2: 72	Bipolar disorder (n = 1)
			Case 3: 62
Mediators of treatment response (changes in functional brain findings)
Wada et al[69], 1999	Case report	SPECT	Age = 78	-	Somatic	Reduced regional cerebral blood flow in the left temporal and parietal lobes improved at remission
Ota et al[70], 2003	Case report	SPECT	Age = 72	-	Somatic	Decreased perfusion in the left temporal and parietal lobes improved after treatment
Hayashi et al[71], 2004	Case report	SPECT	Age = 77	-	Somatic	Reduced regional cerebral blood flow in the left temporal and parietal lobes improved after treatment
Narumoto et al[74], 2006	Case report	SPECT	Age = 82	-	Somatic	Global decrease in rCBF
						Reversed in all non-stroke areas after remission
Hayashi et al[72], 2010	Case report	SPECT	Age = 42	-	Somatic	Reduced regional cerebral blood flow in the left temporal and parietal lobes normalized after treatment
Freudenmann et al[48], 2010	Prospect.	PET	Age = 27	Organic DD (n = 1)	Somatic	SPECT: D2R occupancy predicted remission
		SPECT				PET: Glucose metabolism in putamen and thalamus did not normalize with remission
Uezato et al[73], 2012	Case report	SPECT	Age = 53	-	Somatic	Hyperperfusion in the right temporal lobe normalized after electroconvulsive therapy

DD: Delusional disorder; CT: Computerized tomography; MRI: Magnetic resonance imaging; SPECT: Single photon emission computed tomography; rCBF: Regional cerebral blood flow; PET: Positron emission tomography. DaT: Striatal dopamine transporter; D2R: D2 receptor.