Depression in adults with epilepsy: Relationship to psychobiological variables

Table 1 Demographic and clinical features of the patients with epilepsy, patients with comorbid depression and patients without comorbid behavioral disorders

Demographic and clinical features	Patients (total) (n = 105)	Patients with epilepsy and comorbid depression (n = 51)	Patients with epilepsy and without comorbidpsychiatric disorders(n = 54)	P-value
Male/female	52/53	20/31	32/22	-
Age; yr	20-48 (30.87 ± 7.88)	20-48 (30.37 ± 7.68)	20-45 (31.40 ± 8.14)	0.511
Age at onset of disease; yr	1-40 (16.70 ± 8.68)	1-35 (14.69 ± 7.90)	3-40 (18.78 ± 9.05)	0.02
Duration of illness; yr	3-35 (13.89 ± 7.64)	4-31 (15.31 ± 7.20)	3-35 (12.42 ± 7.88)	0.57
Family history of epilepsy (positive)	17 (16.19%)	10 (19.61%)	7 (12.96%)	-
Type of epilepsy:
GTC	39 (37.14%)	21 (41.18%)	18 (33.33%)	-
Complex partial/partial epilepsy with secondary generalization:	66 (62.86%)	30 (58.52%)	36 (66.67%)	-
Frontal	26 (24.76%)	11 (21.57%)	15 (27.78%)
Temporal	36 (34.29%)	16 (31.37%)	20 (37.04%)	-
Parietal	4 (3.81%)	3 (5.88%)	1 (1.85%)	-
Side of epileptic foci:
Right	29 (27.62%)	15 (29.41%)	14 (25.93%)	-
Left	37 (35.24%)	15 (29.41%)	22 (40.74%)	-
AED(s) utilized
CBZ	55 (52.38%)	25 (49.02%)	30 (54.7%)	-
VPA	28 (22.87%)	11 (21.57%)	17 (31.48%)	-
Polytherapy	22 (20.95%)	15 (29.41%)	7 (12.96%)	-
Dose of AED(s) utilized; mg/d
CBZ	400-1200 (764.62 ± 342.6)	400-1200 (735.34 ± 358.5)	400-1200 (722.34 ± 377.9)	0.437
VPA	200-1400 (783.27 ±425.5)	200-1400 (777.27 ±400.2)	200-1400 (750.28 ± 452.7)	0.436
Duration of treatment; yr	2-30 (9.08 ± 4.13)	2-30 (9.12 ± 4.48)	3-20 (9.04 ± 3.80)	0.212
Serum drug level; µg/mL
CBZ	3.50-12.80 (9.05 ± 3.3)	3.50-12.80 (9.12 ± 4.5)	3.50-11.9 (8.14 ± 3.6)	0.924
VPA	30.04-115.40 (85.88 ± 35.0)	60.54-115.40 (80.64 ± 45.0)	30.04-102.60 (70.74 ± 35.0)	0.875
Degree of control on AED(s)
Controlled	28 (26.67%)	12 (23.53%)	16 (29.63%)	-
Partially controlled	23 (21.90%)	10 (19.61%)	13 (24.07%)	-
Uncontrolled	54 (51.43%)	29 (56.86%)	25 (46.30%)	-

Values are expressed as mean ± SD and number (%). Controlled: Seizure free for ≥ 1 year; partially controlled: occasional or rare in frequency; uncontrolled: very frequent or frequent in frequency. GTC: Generalized tonic-clonic; AEDs: Antiepileptic drugs; CBZ: Carbamazepine; VPA: Valproate; PHT: Phenytoin.

Table 2 Significance between patients and control subjects in scores of depression, hormones and neurotransmitters in relation to epilepsy related and treatment related variables

Epilepsy-related variables	BDI-II	HAM-A	Free testosterone	SHBG	Serotoni (n)	Noradrenaline	Adrenaline
Type of epilepsy
Generalized (n = 39)
P1	0.016	0.538	0.347	0.476	0.001	0.169	0.008
Focal ( n = 66)
P1	0.102	0.458	0.816	0.125	0.01	0.049	0.004
P2	0.364	0.861	0.212	0.65	0.093	0.563	0.505
Focal epilepsies
Frontal ( n = 26)
P1	0.076	0.8	0.567	0.255	0.019	0.253	0.065
Temporal ( n = 36)
P1	0.33	0.494	0.75	0.231	0.008	0.039	0.014
P3	0.387	0.77	0.053	1	0.884	0.683	0.456
Parietal ( n = 4)
P1	0.065	0.658	0.325	0.467	0.822	0.385	0.184
P3	0.483	0.668	0.095	0.564	0.567	0.655	1
P4	0.168	0.635	0.538	0.229	0.112	1	0.596
Side of epileptic activity
Right ( n = 29)
P1	0.011	0.896	0.631	0.202	0.027	0.127	0.023
Left ( n = 37)
P1	0.474	0.388	0.95	0.282	0.012	0.047	0.017
P5	0.149	0.518	0.197	0.248	0.754	0.685	0.779
CBZ ( n = 55)
P1	0.07	0.069	0.512	0.61	0.011	0.085	0.028
P6	0.725	0.224	0.457	0.205	0.196	0.713	0.304
P7	0.03	0.006	0.334	1	0.293	0.465	0.237
VPA ( n = 28)
P1	0.443	0.784	0.451	0.129	0.001	0.044	0.007
P7	0.032	0.069	0.432	0.813	0.859	0.391	0.609
Polytherapy ( n = 22)
P1	0.001	0.084	0.936	1	0.017	0.349	0.02
Controlled ( n = 28)
P1	0.11	0.001	0.873	0.873	0.013	0.805	0.042
P8	0.01	0.026	0.024	0.462	0.658	0.047	0.094
P9	0.0001	0.0001	0.067	0.564	0.534	0.086	0.659
Partially uncontrolled ( n = 23)
P1	0.06	0.6	0.352	0.265	0.014	0.068	0.005
P9	0.3	0.173	0.873	0.624	0.567	0.951	0.164
Uncontrolled ( n = 54)
P1	0.000	0.253	0.254	0.79	0.004	0.017	0.012

CBZ: Carbamazepine; VPA: Valproate; BDI-II: Beck depression inventory – 2nd Edition; HAM-A: Hamilton anxiety rating scale; SHBG: Sex hormone binding globulin; P1: Patients vs controls; P2: Generalized vs focal; P3: Versus frontal; P4: Versus temporal; P5: Right vs left; P6: CBZ vs VPA; P7: Versus polytherapy; P8: Versus partially controlled; P9: Versus uncontrolled.

Table 3 Comparative statistics between patients with epilepsy and comorbid depression, patients without comorbid psychiatric disorders and control subjects in psychosocial-, hormonal- and neurotransmitter-related variables

	BDI-II	HAM-A	Free testosterone (pg/mL)	SHBG (nmol/L)	Serotonin (ng/mL)	Noradrenaline (ng/mL)	Adrenaline (ng/mL)
Patients with epilepsy (n = 105)
Range	3.0-47.0	4.0-44.0	9.0-24.0	118.0-200.0	0.0-74.9	1.1-100.5	0.1-521.4
Mean	28.08	20.63	18.75	159.75	43.39	27.93	65.4
Skewness	0.13	0.2	-1.65	-0.04	-0.36	1.32	2.83
Std. error of skewness	0.33	0.33	1.01	1.01	0.51	0.72	0.75
25th percentiles	22	13	11.75	121.25	24.38	2.45	0.1
50th percentiles	26	22	21	160.5	42.8	4.7	0.1
75th percentiles	33	27	23.5	197.5	64.2	58.45	0.93
Patients with epilepsy and comorbid depression (n = 51)
Range	3.0-47.0	4.0-44.0	9.0-24.0	118.0-200.0	0.0-64.2	1.1-100.5	0.1-521.4
Mean	28.08	20.65	18.75	159.75	23.67	27.93	65.4
Skewness	0.13	0.2	-1.65	-0.04	0.97	1.32	2.83
Std. error of skewness	0.3	0.3	1.01	1.01	0.58	0.72	0.75
25th percentiles	22	13	11	121.25	6.4	2.45	0.1
50th percentiles	26	22	21	160.5	21.4	4.7	0.1
75th percentiles	33	27	23	197.5	42.8	58.45	0.93
Patients with epilepsy and without comorbid psychiatric disorders (n = 54)
Range	1.0-19.0	1.0-15.0	5.0-100.0	17.3-185.0	0.0-74.9	4.5-213.4	0.1-1.2
Mean	7.62	6.15	44.73	110.44	43.39	58.13	0.39
Skewness	0.76	0.64	0.66	0.15	-0.36	1.51	1.12
Std. error of skewness	0.33	0.33	0.66	0.64	0.51	0.66	0.69
25th Percentiles	5	3.5	24	76.25	24.38	5	0.1
50th Percentiles	8	7	24	105.50	42.8	31.4	0.1
75th Percentiles	9	8	80	162.50	64.2	98.3	0.95
Control subjects (n = 68)
Range	1.0-51.0	2.0-48.0	5.0-100.0	80.0-185.0	42.8-107.0	1.5-493.2	0.1-1897.0
Mean	12.59	14	57.14	103.07	74.9	135.42	269.84
Skewness	1.93	1.47	-0.14	2.04	0.18	1.71	2.59
Std. Error of skewness	0.29	0.29	0.6	0.60	0.79	0.62	0.51
25th percentiles	6	6.25	19	83.00	62.2	23.15	3.08
50th percentiles	10.5	10	68	91.00	74.9	128	51.5
75th percentiles	15.75	15.75	95	116.50	96.3	186.8	383.88
Significance
P1	0.031	0.519	0.717	0.219	0.001	0.028	0.000
P2	0.001	0.000	0.741	0.817	0.007	0.173	0.001
P3	0.000	0.825	0.182	0.008	0.001	0.016	0.014
P4	0.000	0.000	0.054	0.029	0.012	0.128	0.965

BDI-II: Beck depression inventory-2nd edition; HAM-A: Hamilton anxiety rating scale; SHBG: Sex hormone binding globulin; P1: Patients versus control subjects; P2: Patients with comorbid depression versus control subjects; P3: Patients without comorbid psychiatric disorders versus control subjects; P4: Patients with comorbid depression versus patients without comorbid psychiatric disorders.

Table 4 Correlations between scores of depression, anxiety, hormonal- and neurotransmitters related variables

Variables	BDI-II	HAM-A	Free testosterone	SHBG	Serotonin	Noradrenaline	Adrenaline
BDII	-
HAM-A	0.69 0.000	-
Free testosterone	0.2 0.8	0.4 0.6	-
SHBG	0.6 0.4	0.8 0.2	-0.2 0.8	-
Serotonin	-0.447 0.048	-0.569 0.009	-1 1	-0.274 0.389	-
Noradrenaline	-0.028 0.458	-0.576 0.032	-0.113 0.677	0.006 0.981	-0.632 0.038	-
Adrenaline	-0.094 0.825	0.016 0.971	-0.123 0.628	-0.196 0.422	0 1	0.733 0.039	-
Age	0.077 0.59	0 0.997	0.106 0.597	-0.2 0.8	-0.118 0.621	-0.143 0.714	0.133 0.753
Age at onset	0.04 0.778	0.04 0.778	0.3 0.2	-0.4 0.6	-0.352 0.128	0.25 0.516	-0.312 0.452
Duration of illness	-0.007 0.96	-0.007 0.96	0.238 0.262	0.316 0.684	0.176 0.458	-0.305 0.425	-0.078 0.854
Dose	-0.141 0.552	-0.141 0.552	0.266 0.333	-0.258 0.742	0.229 0.289	-0.775 0.225	-0.084 0.844
Drug level	-0.073 0.54	-0.019 0.476	0.23 0.523	-0.273 0.417	0.008 0.97	-0.291 0.335	-0.284 0.397

BDI-II: Beck depression inventory – 2nd edition; HAM-A: Hamilton anxiety rating scale; SHBG: Sex hormone binding globulin.