Association between early risk factors and level of functioning at age seven in children at familial risk for schizophrenia or bipolar disorder - The Danish High Risk and Resilience Study VIA 7

Variable	Definition	Rating
Risk factors during pregnancy
Unwanted pregnancy	The pregnancy was not wanted	Yes
No
Unplanned pregnancy	The pregnancy was not planned	Yes
No
Medication intake by biological mother during pregnancy	Biological mother took regular medicine during the pregnancy	Yes
No
Cigarette smoking by biological mother during pregnancy	Biological mother smoked cigarettes during pregnancy	Yes
No
Alcohol consumption by biological mother during pregnancy	Biological mother drank alcohol during pregnancy	Yes, once weekly
Alcohol consumption by biological mother during pregnancy	Biological mother drank alcohol during pregnancy	Yes, sometimes
No
Drug use by biological mother during pregnancy	Biological mother took drugs during pregnancy	Yes
No
Stressful life events for biological mother during pregnancy	Stressful life events for biological mother during pregnancy (for instance critical illness or death in the family, financial problems, unstable housing conditions)^*	0–3 stressful life events
Risk factors during the child’s first years of life
Spent the most time with the child during the first years of life (0–3 years old)	Person that the child spent the most time with during the first three years of life	Biological parent
Other
Stressful life events for primary caregiver during the child’s first years of life (0–3 years old)	Stressful life events for the primary caregiver during the child’s first years of life (0–3 years) (for instance psychosocially, death in the family, disease)^*	0–3 stressful life events
Stressful life events for the child during the child’s first years of life (0–3 years old)	Stressful life events for the child during the child’s first years of life (0–3 years) (for instance psychosocially, death in the family, disease)^*	0–3 stressful life events
Comforting (0–12 months old)	Scale from 1 to 7, with 1 indicating that the child was happy, easy to comfort and pleased most of the time, and 7 indicating that the child was difficult to comfort and displeased most of the time	1–7
Eating (0–12 months old)	Scale from 1 to 7, with 1 indicating no problems with eating, and 7 indicating a lot of trouble with eating and keeping weight	1–7
Sleeping (0–12 months old)	Scale from 1 to 7, with 1 indicating no problems with sleeping, and being rested and happy after sleep, and 7 indicating sleeping unrestful and interruptedly most of the time, often being tired and not well rested	1–7
Hypersensitivity (0–48 months old)	The child responds very strongly to stimuli, is particularly sensitive and overreact to what he/she experiences, and displays avoidant behaviour. The child easily becomes anxious, starts to cry or freezes at certain stimuli. The child responds with discomfort to e.g. touching, loud noises, strong light or an unknown smell or taste	Yes
No
Hyposensitivity (0–48 months old)	The child doesn’t respond to stimuli (i.e. what is happening around them), even though he/she doesn’t seem sad or anxious. The child clearly doesn’t respond as much as other children to e.g. noises, smell, taste, touch	Yes
No
Stimulation seeking (0–48 months old)	The child displays stimulus-seeking behaviour to a degree where he/she accidentally destroys things or does something, that is potentially self-harming	Yes
No
Attachment behaviour (9–24 months old)	The child displays poor attachment behaviour meaning that the child doesn’t seek a parent or another familiar adult if he/she gets upset, scared or frightened	Yes
No

Note.

* Parental severe mental illness were excluded as a stressful life event

Linear regression model of the association between number of early risk factors and CGAS-score in children with familial high risk for schizophrenia, children with familial high risk for bipolar disorder and children of parents without these disorders

TABLE 2

Demographic and clinical characteristics of children, index parents and non-index parents from families with parental schizophrenia, parental bipolar disorder and families without schizophrenia or bipolar disorder

	FHR-SZ	FHR-BP	PBC	*P-value*	*P-value*
	FHR-SZ	FHR-BP	PBC	*P-value*	Pairwise comparisons
FHR-SZ vs. PBC	FHR-BP vs. PBC	FHR-BP vs. FHR-SZ
Children, N	202	120	200	-	-	-	-
Female, N (%)	93 (46.04)	56 (46.67)	93 (46.50)	0.993^b	-	-	-
Age at inclusion, mean (SD)	7.84 (0.22)	7.86 (0.20)	7.81 (0.20)	0.097^c	-	-	-
CGAS^a, N, mean (SD)	199, 68.07 (15.40)	118, 73.55 (14.91)	197, 77.71 (13.47)	<0.001^c	<0.001^c	0.015^c	0.001^c
Index parents, N	200	116	204	-	-	-	-
Female, N (%)	111 (55.50)	64 (55.17)	115 (56.37)	0.974^b	-	-	-
Age at child’s birth, mean (SD)	30.20 (6.14)	33.12 (7.03)	32.83 (4.78)	<0.001^c	<0.001^c	0.670^c	<0.001^c
Employed or studying, N (%)	93 (49.73)	61 (55.96)	185 (92.04)	<0.001^b	<0.001^b	<0.001^b	0.301^b
Education, N	178	109	197
Primary/lower secondary, N (%)	54 (30.34)	10 (9.17)	8 (4.06)
Upper secondary, vocational short cycle tertiary, N (%)	76 (42.70)	45 (41.28)	95 (48.22)	<0.001^b	<0.001^b	0.142^b	<0.001^b
Bachelor degree, equivalent or higher, N (%)	48 (26.97)	54 (49.54)	94 (47.72)
Non-index parents, N	186	114	192	-	-	-	-
Female, N (%)	82 (44.09)	51 (44.74)	83 (43.23)	0.966^b	-	-	-
Age at child’s birth, mean (SD)	30.92 (6.37)	33.10 (5.39)	32.97 (4.28)	<0.001^c	<0.001^c	0.814^c	0.001^c
Employed or studying, N (%)	133 (75.14)	93 (85.32)	179 (95.21)	<0.001^b	<0.001^b	0.003^b	0.040^b
Education, N	176	106	187
Primary/lower secondary, N (%)	31 (17.61)	5 (4.72)	10 (5.35)
Upper secondary, vocational short cycle tertiary, N (%)	86 (48.86)	44 (41.51)	89 (47.59)	<0.001^b	<0.001^b	0.543^b	<0.001^b
Bachelor degree, equivalent or higher, N (%)	59 (33.52)	57 (53.77)	88 (47.06)

Notes. FHR-SZ = familial high risk for schizophrenia; FHR-BP = familial high risk for bipolar disorder; PBC = population based controls; Index parent = the affected biological parent or the matched control; Non-index parent = the other biological parent;

a CGAS = Children’s Global Assessment Scale. Ranges from 1–100, with higher scores indicating better functioning;

b Chi-square test of independency in contingency table;

c One-way ANOVA

TABLE 3

Pairwise comparisons of early risk factors during pregnancy and the child’s first years of life in children with familial high risk for schizophrenia, children at familial high risk for bipolar disorder and children of parents without these disorders

Early risk factor		FHR-SZ	FHR-BP	PBC	*P-value*	*P-value*
		FHR-SZ	FHR-BP	PBC	*P-value*	Pairwise comparisons
		FHR-SZ vs. PBC	FHR-BP vs. PBC	FHR-SZ vs. FHR-BP
N (%)	N (%)	N (%)	-	-	-	-
Risk factors during pregnancy
Unwanted pregnancy
-	Yes	21 (10.77)	7 (5.93)	2 (1.02)	<0.001^a	<0.001^a	0.011^a	0.146 ^a
-	No	174 (89.23)	111 (94.07)	195 (98.98)
Unplanned pregnancy
-	Yes	81 (41.12)	27 (22.88)	28 (14.14)	<0.001^a	<0.001^a	0.047^a	0.001^a
-	No	116 (58.88)	91 (77.12)	170 (85.86)
Medication intake by biological mother during pregnancy
-	Yes	51 (26.02)	24 (20.51)	19 (9.64)	<0.001^a	<0.001^a	0.007^a	0.269^a
-	No	145 (73.98)	93 (79.49)	178 (90.36)
Cigarette smoking by biological mother during pregnancy
-	Yes	79 (40.93)	27 (23.48)	21 (10.71)	<0.001^a	<0.001^a	0.003^a	0.002^a
-	No	114 (59.07)	88 (76.52)	175 (89.29)
Alcohol consumption by biological mother during pregnancy
-	Yes, once weekly	9(4.66)	4 (3.39)	4 (2.05)	0.377^b	-	-	-
-	Yes, sometimes	46 (23.83)	37 (31.36)	57 (29.23)	0.377^b	-	-	-
-	No	138 (71.50)	77 (65.25)	134 (68.72)
Drug use by biological mother during pregnancy
-	Yes	8 (3.98)	1 (0.85)	0 (0.00)	0.004^b	0.007^b	0.372^b	0.162^b
-	No	193 (96.02)	117 (99.15)	199 (100.00)
Stressful life events for biological mother during pregnancy^e
-	None	55 (31.25)	34 (31.19)	87 (47.54)	<0.001^a	<0.001^a	<0.001^a	0.968^a
-	One	56 (31.82)	37 (33.94)	66 (36.07)	<0.001^a	<0.001^a	<0.001^a	0.968^a
-	Two	34 (19.32)	21 (19.27)	23(12.57)
-	Three	31(17.61)	17 (15.60)	7 (3.83)
Risk markers during the child’s first years of life
Spent the most time with the child during the first years of life (0–3 years old)
-	Biological parent	190 (95.96)	117 (100.00)	195 (100.00)	0.001^b	0.007^b	NA	0.028^b
-	Other	8 (4.04)	0 (0.00)	0 (0.00)
Stressful life events for primary caregiver during the child’s first years of life (0–3 years old)^e
-	None	34 (16.83)	22 (18.33)	87 (43.50)	<0.001^a	<0.001^a	<0.001^a	0.438^a
-	One	52 (25.74)	22 (18.33)	58 (29.00)	<0.001^a	<0.001^a	<0.001^a	0.438^a
-	Two	54 (26.73)	32 (26.67)	38 (19.00)
-	Three	62 (30.69)	44 (36.67)	17 (8.50)
Stressful life events for the child during the child’s first years of life (0–3 years old)^e
-	None	57 (28.22)	43 (35.83)	117 (58.50)	<0.001^a	<0.001^a	<0.001^a	0.159^a
-	One	60 (29.70)	28 (23.33)	58 (29.00)	<0.001^a	<0.001^a	<0.001^a	0.159^a
-	Two	45 (22.28)	33 (27.50)	16 (8.00)
-	Three	40 (19.80)	16 (13.33)	9 (4.50)
Comforting (0–12 months old)^f
-	Median (IQI)	2 (1;3)^c	2 (1;2)^c	1 (1;2)^c	0.180^d	-	-	-
Eating (0–12 months old)^f
-	Median (IQI)	1 (1;3)^c	1 (1;2)^c	1 (1;2)²	0.139^d	-	-	-
Sleeping (0–12 months old)^f
-	Median (IQI)	2 (1;3)^c	2 (1;3)^c	1 (1;3)^c	0.388^d	-	-	-
Hypersensitivity (0–48 months old)
-	Yes	41 (20.60)	25 (21.19)	29 (14.65)	0.212^a	-	-	-
-	No	158 (79.40)	93(78.81)	169 (85.35)
Hyposensitivity (0–48 months old)
-	Yes	12 (6.06)	2 (1.69)	4 (2.02)	0.062^b	-	-	-
-	No	186 (93.94)	116 (98.31)	194 (97.98)
Stimulation seeking (0–48 months old)
-	Yes	45 (22.73)	20 (17.09)	24 (12.18)	0.022^a	0.006^a	0.225^a	0.233^a
-	No	153 (77.27)	97 (82.91)	173 (87.82)
Attachment behavior (9–24 months old)
-	Yes	49 (25.00)	19 (16.38)	32 (16.24)	0.055^a	-	-	-
-	No	147 (75.00)	97 (83.62)	165 (83.76)
Mean cumulative risk
-	Number of risk factors	4.78 (2.34)^g	4.03 (2.15)^g	2.83 (1.74)^g	<0.001^h	<0.001^h	<0.001^h	0.006^h

Notes. FHR-SZ = familial high risk for schizophrenia; FHR-BP = familial high risk for bipolar disorder; PBC = population based controls; NA = not available.

a Pearson chi2;

b Fisher’s exact;

c IQI = Interquartile Interval;

d Wilcoxon (Mann-Whitney) rank-sum, Kruskal-Wallis;

e Possible to mention up to three stressful life events;

f Variable rated on a scale from 1 to 7, with 1 indicating no problems in the area, and 7 indicating substantial problems in the area;

g Standard deviation;

h Oneway anova

Articles in this issue

DOI: https://doi.org/10.2478/sjcapp-2022-0001 | Journal eISSN: 2245-8875

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Language: English

Page range: 12 - 23

Published on: Mar 30, 2022

Published by: Center for Evidence-based Psychiatry

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© 2022 Anette Faurskov Bundgaard, Nicoline Hemager, Ditte Lou Gantriis, Nanna Lawaetz Steffensen, Birgitte Klee Burton, Ditte Ellersgaard, Camilla Jerlang Christiani, Katrine S. Spang, Anders Helles Carlsen, Vibeke Bliksted, Kerstin J. Plessen, Jens Richardt Møllegaard Jepsen, Merete Nordentoft, Ole Mors, Anne A. E. Thorup, Aja Neergaard Greve, published by Center for Evidence-based Psychiatry
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Volume 10 (2022): Issue 1 (January 2022)

Association between early risk factors and level of functioning at age seven in children at familial risk for schizophrenia or bipolar disorder - The Danish High Risk and Resilience Study VIA 7

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