Table 1.
The present table reports, in alphabetical order, the most relevant information of each eligible selected publication (NA = not available).
| Author(s) and (Year) | Groups (N) | Diagnostic Criteria of BD/SUD | Gene(s) | Main Findings | NOS Scale |
|---|---|---|---|---|---|
| Banach et al. (2018) [58] | 436 BD (76 AAD) M = 199 (47 ± 14), F = 237 (44 ± 15) 417 CTRs M = 202 (45 ± 8), F = 215 (46 ± 6) |
DSM-IV |
CLOCK (Clock Circadian Regulator) ARNTL (Aryl Hydrocarbon Receptor Nuclear Translocator Like) TIMELESS (Timeless Circadian Regulator) PER3 (Period Circadian Regulator 3) |
ARNTL gene (rs11600996) and PER3 gene (rs228642) polymorphisms were associated with an increased risk of BD/AAD in a group of male patients; moreover, two other polymorphisms of the PER3 gene, rs228682 and rs2640909, were associated with both AAD and family history of affective disorders. | 8 |
| Bortolasci et al. (2014) [59] | 45 BD (Smoking 31) M = 12. F = 33 (44.5 ± 8.9) 91 MD (Smoking 36) M = 22, F = 69 (47.0 ± 8.2) 199 CTRs (Smoking 77) M = 82, F = 117 (46.4 ± 8.3) |
DSM-IV | PON1 (Paraoxonase 1) | Lowered plasma PON1 activity was a trait marker of major depression and that PONQ192R gene–environment (such as smoking) interactions differentially predict the odds of depression and bipolar disorder. | 7 |
| Bortolasci et al. (2014a) [60] | 45 BD 91 MD 197 CTRs 143 TUD (between all groups) M = 115, F = 218 |
DSM-IV | PON1 (Paraoxonase 1) | TRAP levels were significantly associated with higher plasma PON1 activity, the RR functional genotype, non-smoking by RR carriers, male gender and a higher BMI. TRAP levels were significantly lower in patients with mood disorders than in controls, but this association was no longer significant after considering the effects of the above predictors. The risk in the subgroup with low TRAP levels is increased by a smoking X RRenotype interaction and decreased by male gender, the RR genotype, and higher BMI and PON1 activity. Plasma PON1 activity, the PON1 Q192R functional genotypes and specific interactions between this genotype and smoking contribute significantly to TRAP levels. Gender and BMI also appear to influence TRAP levels. | 7 |
| Chang et al. (2015) [61] | 530 BP-I (59 AD) M = 277, F = 253 (34.32 ± 12.35) 788 BP-II (135 AD) M = 413, F = 375 (32.37 ± 11.53) 672 CTRs M = 442, F = 230 35.65 ± 10.68 |
DSM-IV-TR SADS-L |
ALDH2 (Aldehyde Dehydrogenase 2 Family Member) ADH1B (Alcohol Dehydrogenase 1B (Class I), Beta Polypeptide) |
BP-II + AD associated to ALDH2 and ADH1B, but BP-I + AD associated only to ALDH2. | 7 |
| Cui et al. (2011) [62] | 182 PAFDs M = 73, F = 109 (NA) 214 CAFDs M = 101, F = 113 (39.67 ± 10.98) 472 CTRs M = 197, F = 275 (30.21 ± 11.04) |
DSM-III-R and DSM-IV |
NGFB (Nerve Growth Factor BETA subunit) |
In women, NGFB gene was associated with primary affective disorders (PAFDs) but not with substance disorder comorbid with AFDs (CAFDs). | 8 |
| Gorwood et al. (2000) [63] | 21 BD + AD M = 14, F = 7 (45.8 ± 9.45) 31 BD M = 15, F = 16 (53.4 ± 10.7) 35 AD M = 25 (46.2 ± 9.8) 35 CTRs M = 25 (43.5 ± 6.5) |
DSM-III-R |
DRD2 (Dopamine Receptor D2) |
In this sample, there is no evidence for a significant influence of the A1 allele of the D2 dopamine receptor gene in the specific association between bipolar disorder and alcohol dependence. | 8 |
| Gratacòs et al. (2008) [64] | 165 substance abuse disorders M = 72.6% (39.0) 341 anxiety disorders, consisting of 173 panic disorder patients and 168 obsessive-compulsive patients M = 24.1% (36.02) M = 34.0% (35.9) M = 7.4% (24.4) 229 eating disorders M = 65.4% (45.6) 917 SCZ M = 44.3% (44.9) 625 affective disorders consisting of 203 bipolar disorders and 422 major depressions M = 32.7% (49.5) M = 51.7% (46.8) 2 CTRs groups: 607 CTRs 330 CTRs M = 56.1% (56.1) |
DSM-IV | The comprehensive search set rendered 10 physiological pathways and a total of 338 candidate genes. |
GHRH (growth hormone releasing hormone) was associated with anxiety disorders, PREB (prolactin regulatory element) was linked with eating disorders, and GRIK5 (ionotropic kainate glutamate receptor 5) was correlated to bipolar disorder. Moreover, rs945032, a functional SNP of the bradykinin receptor B2 gene (BDKRB2) was associated to three disorders (panic disorder, substance abuse, and bipolar disorder). |
8 |
| Hartz et al. (2011) [65] | 916 BD (367 Nicotine dependent) M = 359, F = 557 (43.5 ± 13.2) 1028 CRTs (269 Nicotine dependent) M = 599, F = 429 (52.9 ± 17.7) |
DSM-IV |
CHRNB3 (Cholinergic Receptor Nicotinic Beta 3 Subunit) CHRNA5 CHRNA3 (Cholinergic Receptor Nicotinic ALFA 3 E 5 Subunit) |
Bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes. Besides, variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder. | 7 |
| Huang et al. (2003) [66] | 52 BD 208 MD 83 SCZ 96 CTRs M = 51, F = 45 (40.97 ± 15.9) |
DSM-III-R |
HTR1B (5-Hydroxytryptamine Receptor 1B) |
There was an association between substance abuse disorder and major depression with the h5-HTR1B G861C locus in the patient population. This association was not found in bipolar disorder, schizophrenia, alcoholism, and suicide. | 7 |
| Lydall et al. (2011 [67] | 506 BD NA 510 CTRs NA |
ICD-10 RDC DSM-III-R |
GWAS genome-wide association study | The authors conducted a genome-wide association study (GWAS) in which they genotyped 372 193 SNPs. The authors found 3799 SNPs nominally associated with alcoholic bipolar patients. | 8 |
| Mazza et al. (2010) [68] | 131 BD (65 SUD) 65 CTRs F (n = 100), M (n = 96) |
DSM-IV |
5HTR2C (serotonin 2C receptor) |
Evidence of the association between the functional rs6318 polymorphism of 5HTR2C in bipolar disorder. | 7 |
| Mandelli et al. (2011) [69] | 131 BD (66 SUD) 64 CTRs F = 49.7% |
DSM-IV |
IL1b (Interleukin 1 Beta) NOS1AP (Nitric Oxide Synthase 1 Adaptor Protein) TRPM2 (Transient Receptor Potential Cation Channel Subfamily M Member 2) |
This study does not support a role of IL1b, NOS1AP, and TRPM2 in BD. IL1b may have a role in SUD. | 7 |
| Novak et al. (2010) [70] | 319 BD (152 Smokers) M = 121. F = 198 (46.6) 204 Schizophrenia (126 Smokers) M = 139, F = 65 (43) 500 CTRs Matched for age, gender and ethnicity |
DSM-IV ICD 10 |
NR4A1 NR4A2 NR4A3 (Nuclear Receptor Subfamily 4 Group A Member 1, 2 E 3) |
NR4A3 marker rs1131339 is significantly associated with the risk of smoking, as well as with the degree of smoking, in a population of individuals with bipolar disorder. | 8 |
| Prossin et al. (2018) [71] | 107 BD-I M = 32, F = 56 (41.9 ± 12.1) (50 AUD) M = 8, F = 18 (40.6 ± 16.6) 28 CTRs |
DSM-IV | TSPO (Translocator Protein) | Interactions were confirmed both for TSPO with BD and TSPO with AUD | 7 |
| Reginsson et al. (2017) [72] | F: SCZ = 600 (35.7) BPD = 772 (63.3) |
NA | NA | There are evidences of common genetic roots of the observed comorbidity between addiction and psychotic disorders SCZ and BPD. | 7 |
| Sharp et al. (2014) [73] | 1099 BP (143 AD) NA 997 AD NA 1056 CTRs NA |
RDC SADS-L OPCRIT DSM-IV ICD-10 |
TACR1 (Tachykinin Receptor 1) | Authors report a replicated significant association with intron 1 TACR1 mutations in BD in the BD + ADS subgroup and ADS cases in comparison with a population of healthy controls. | 6 |
| Szczepankiewicz et al. (2006) [74] | 317 BD (42 AA) M = 131 (30 ± 11), F = 186 (33 ± 12) 350 CTRs M = 139 (41 ± 12), F = 211 (40 ± 11) |
DSM-IV |
DRD1 DRD2 DRD3 DRD4 (dopamine receptor D1, D2, D3, D4) |
The analyzed polymorphisms of the dopamine genes may not be associated in the shared genetic vulnerability to bipolar disorder and alcohol abuse. | 8 |