Different presence of Chlamydia pneumoniae, herpes simplex virus type 1, human herpes virus 6, and Toxoplasma gondii in schizophrenia: meta-analysis and analytical study

Figures & data

Table 1 Nested-PCR conditions for characterization of Chlamydia pneumoniae, HSV-1, HHV-6, and Toxoplasma gondii

Step	Chlamydia pneumoniae		HSV-1		HHV-6	Toxoplasma gondii
	PCR (external)	PCR (internal)	PCR (external)	PCR (internal)	PCR (external and internal)	PCR (external)	PCR (internal)
Initial denaturalization	94°C 4 min	94°C 4 min	94°C 1 min	94°C 1 min	94°C 2 min	94°C 1 min	94°C 1 min
Denaturalization	94°C 1 min	94°C 1 min	94°C 10 sec	94°C 10 sec	94°C 15 sec	94°C 10 sec	94°C 10 sec
Hybridization	52°C 1 min	54°C 1 min	58°C 20 sec	67°C 20 sec	54°C 20 sec	57°C 10 sec	63°C 10 sec
Extension	72°C 1 min	72°C 1 min	72°C 20 sec	72°C 20 sec	72°C 20 sec	72°C 30 sec	72°C 15 sec
Final extension	72°C 10 min	72°C 10 min	72°C 2 min	72°C 2 min	72°C 2 min	72°C 2 min	72°C 2 min
Number of cycles	40	40	35	30	40	40	40

Abbreviations: HHV, human herpes virus; HSV, herpes simplex virus; PCR, polymerase chain reaction; min, minutes; sec, seconds.

Table 2 Analysis and evaluation of studies included in the meta-analysis

Microorganism	Reference	Sample	Technique	Determination	Descriptive statistics				Inferential statistics			Quality			Global OR (95% CI; P-value)
					Cases		Controls		OR	95% CI	Weight (%)	S	C	E
					Pos	Neg	Pos	Neg
Chlamydia pneumoniae	^Citation15	BL	N-PCR	DNA	4	6	6	109	12.11	2.68–54.75	14.91	**	**	**	5.96 (3.42–10.39; P<0.001)
	^Citation16	BL	PCR	DNA	14	58	9	216	5.79	2.43–13.79	41.01	**	**	**
	^Citation16	BR	PCR	DNA	4	30	1	34	4.53	0.67–30.64	8.45	**	**	**
	^Citation17	BL	PCR	DNA	11	61	8	217	4.89	1.88–12.70	35.64	**	**	**
HSV-1	^Citation18	BR	PCR	DNA	0	8	0	16	1.94	0.03–106.66	0.50	***		*	1.17 (0.88–1.54; P=0.273)
	^Citation19	SE	ELISA	IgG	26	21	297	227	0.95	0.52–1.71	15.30	***	**	*
	^Citation20	SE	ELISA	IgG	41	19	70	40	1.23	0.63–2.41	13.00	****	**	*
	^Citation21	BR	HIB	DNA	0	20	0	21	1.05	0.02–55.36	0.50	****		*
	^Citation22	BR	N-PCR	DNA	0	14	0	26	1.83	0.03–97.01	0.50	***		*
	^Citation23	SE	IFA	IgG	18	20	27	14	0.47	0.19–1.16	8.00	****		*
	^Citation24	SE	ELISA	IgG	7	4	3	6	3.50	0.55–22.30	2.40	***	**	*
	^Citation25	SE	IFA	Ab	41	0	25	0	1.63	0.03–84.59	0.50	**		*
	^Citation26	SE	ELISA	IgG	15	15	8	36	4.50	1.58–12.84	6.30	***	**	*
	^Citation27	BR	IPA	Ag	0	25	0	16	0.65	0.01–34.23	0.50	***
	^Citation28	BR	N-PCR	DNA	0	30	0	23	0.77	0.01–40.28	0.50	***	**	*
	^Citation29	BR	HIB	DNA	0	25	0	31	1.24	0.02–64.45	0.50	***		*
	^Citation30	SE	ELISA	IgG	105	87	54	38	0.85	0.51–1.40	19.30	***	**	*
	^Citation31	SE	ELISA	IgG	503	177	192	91	1.35	1.00–1.82	32.30	***	**	*
HHV-6	^Citation22	BR	N-PCR	DNA	0	14	1	25	0.59	0.02–15.34	38.16	***		*	0.34 (0.49–2.42; P=0.283)
	^Citation24	SE	ELISA	IgG	8	3	9	0	0.13	0.01–2.85	42.21	***	**	**
	^Citation28	BR	N-PCR	DNA	0	30	0	23	0.77	0.01–40.28	19.63	***	**	**
Toxoplasma gondii	^Citation19	SE	ELISA	IgG	16	31	123	401	1.68	0.90–3.16	14.10	***	**	*	2.50 (1.40–4.47; P=0.002)
	^Citation22	BR	N-PCR	DNA	0	14	0	26	1.83	0.03–97.01	1.90	***		*
	^Citation32	SE	ELISA	Ab	5	13	16	164	3.94	1.25–12.48	10.40	***	**	*
	^Citation32	SE	ELISA	Ab	5	15	16	164	3.42	1.10–10.63	10.60	***	**	*
	^Citation33	SE	ELISA	Ab	66	34	11	39	6.88	3.13–15.11	13.00	**	*	**
	^Citation34	SE	ELISA	Ab	60	197	171	511	0.91	0.65–1.27	16.00	****	**	**
	^Citation35	SE	ELISA	Ab	15	165	37	495	1.22	0.65–2.27	14.20	****	**	***
	^Citation36	SE	ELISA	Ab	16	24	5	32	4.27	1.37–13.28	10.50	**	**	*
	^Citation37	SE	ELISA	Ab	14	24	3	24	4.67	1.19–18.35	9.20	****	**	**

Notes: Asterisks indicate the level of study quality: from low quality (*) to (****) high quality.

Abbreviations: Ab, antibody; Ag, antigen; BL, blood; BR, biopsy of brain tissue; C, Comparability; CI, confidence interval; E, Exposure; ELISA, enzyme-linked immunosorbent assay; HHV, human herpes virus; HIB, hybridization; HSV, herpes simplex virus; IFA, immunofluorescence assay; IgG, immunoglobulin G; IPA, immunoperoxidase assay; N-PCR, nested-polymerase chain reaction; Neg, negative; OR, odds ratio; PCR, polymerase chain reaction; Pos, positive; S, Selection; SE, serum.

Table 3 Positive samples for IgG, IgA, and DNA in patients with schizophrenia and in controls

		IgG			IgA			DNA*
		Cases (n=142)	Controls (n=142)	P-value	Cases (n=142)	Controls (n=142)	P-value	Cases (n=128)	Controls (n=143)
Chlamydia pneumoniae	Samples (%)	41 (28.9)	47 (33.1)	0.521	29 (20.4)	31 (21.8)	0.885	2 (1.6)	0 (0)
HSV-1	Samples (%)	125 (88.0)	124 (87.3)	1.000	12 (8.5)	27 (19.0)	0.015	1 (0.8)	2 (1.4)
HHV-6	Samples (%)	112 (78.9)	100 (70.4)	0.133	3 (2.1)	4 (2.8)	1.000	1 (0.8)	2 (1.4)
Toxoplasma gondii	Samples (%)	56 (39.4)	29 (20.4)	0.001	1 (0.7)	2 (1.4)	0.624	1 (0.8)	0 (0)

Note:

* DNA was scarcely present in samples, so the P-values were not calculated.

Abbreviations: IgA, immunoglobulin A; IgG, immunoglobulin G; HHV, human herpes virus; HSV, herpes simplex virus.

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