Mini-Review on the Possible Interconnections between the Gut-Brain Axis and the Infertility-Related Neuropsychiatric Comorbidities
Abstract
:1. The Current Understanding of the “Second Brain”
2. Disruptive Factors in Enteric Eubiosis and the Influence on Colonisation in Neonates
3. Enteric Microbial Variations in Childhood: The Heritable and Social Components
4. How Is the HPA Axis Influenced?
5. How Infertility and Associated Drugs Disrupt the HPA Axis?
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Number of Patients | Main Observations | Reference |
---|---|---|
33 autistic children | After the administration of a probiotic for 21 days which contained three species of Lactobacillus (acidophilus, casei and delbruecki), two of Bifidobacterium (longum, bifidum), 88% of individuals reported a significant reduction in ATEC, 52% for constipation and 48% for diarrhoea | [72] |
10 autistic children and controls and 9 siblings | After the administration of a probiotic three times a day for four months which comprised of three strains, including: Lactobacillus, Bifidobacterium and Streptococcus, increased levels of Bacteroidetes and Firmicutes were reported, concomitant with the normalisation of Lactobacillus and Bifidobacterium spp. ratio | [73] |
75 infants | After the administration in the first months of life of a probiotic which contained one species of Lactobacillus (rhamnosus) for half a year, at the age of 13, approximately 17.1% of the children from the placebo group have been diagnosed with ASD or ADHD and none from the probiotic group | [74] |
11 autistic children | Compared the administration of a probiotic, containing three species of Lactobacillus (acidophilus, bulgaricus and bifidum), to a cohort receiving 500 mg of Vancomycin four times per day for two months. There was a significant improvement in the general health as assessed by a clinical psychologist | [75] |
30 autistic children ranging from 5 to 9 years | Following the administration of a probiotic containing two species of Lactobacillus (acidophilus and rhamnosus) and one of Bifidobacterium (longum) for three months, PCR-based methods revealed increased levels of Bifidobacterium and Lactobacillus. This was subsequently associated with a reduction in the body weight, autistic symptomatology and of gastrointestinal symptoms based on the ATEC and 6-GSI questionnaires, respectively | [76] |
62 autistic children | Following the administration of a probiotic which contained one species of Lactobacillus (plantarum WCSF1) for three months, the placebo group was found to have a higher prevalence for antisocial behaviours, anxiety and communication deficits than the probiotic group | [77] |
12-year-old autistic boy with severe cognitive disability | Following the administration of a probiotic (VSL#3) for one month—containing three species of Bifidobacterium (breve, longum and infantis), five of Lactobacillus (acidophilus, plantarum, casei, bulgaricus, delbrueckii subsp) and two of Streptococcus (thermophilus, salivarius subsp.), with an additional month of follow-up—the severity of the abdominal symptoms had significantly reduced. This was followed by an overall improvement of the core symptomatic panel | [78] |
65 schizophrenic patients | After the administration of one species of Lactobacillus (rhamnosus strain GG) and one of Bifidobacterium (animalis subsp. lactis strain Bb12) for three and a half months, the patients no longer manifested any specific symptom | [79] |
31 chronic schizophrenic patients and 27 placebo | After the administration for three and a half months of one species of Lactobacillus (rhamnosus strain GG) and one of Bifidobacterium (animalis subsp. lactis strain Bb12), a bowel movement improvement was observed, which has been positively correlated with the reduction of a series of specific biomarkers | [80] |
56 schizophrenic patients | After the administration of an adjuvant probiotic which contained one species of Candida (albicans) and one of Saccharomyces (cerevisiae) over a four-month period, it was found that there was a reduction in Candida IgG only in men, associated with a better functioning of the GM, and with no significant differences for Saccharomyces in both groups | [81] |
Type of Drug | Number of Patients | Main Observations | Reference |
---|---|---|---|
CC | 50 patients (25 couples) | CC have exacerbated symptoms of PMS in 9 out of 14 women only (e.g., irritability and mood swings) | [83] |
CC | 1 male patient | The patient in this study was diagnosed with oligoteratospermia and had received CC. The treatment culminated in depressive symptoms for five consecutive days. After the treatment was discontinued, it took an additional seven days until he made a full recovery | [84] |
CC and hMG | 454 (139 women who had not previously taken any drug and 315 who had previously received medication) | This cross-sectional, self-reported study concluded that both CC (n = 162) and hMG (n = 153) act as agonists and could trigger disorders such as depression according to the STAI through a disturbance of the HPA axis. Significant differences were noted between the groups, with those women taking either CC or hMG reporting a higher incidence of psychological effects | [85] |
OC | 34 women (17 COC and 17 placebo) | During the seven-day study period, the COC users displayed more depressive symptoms when compared to the placebo cohort according to the CD scale. This was highlighted by a specific reactivity at the level of the insular cortex, respectively, the first one-third and the lowest portion of the frontal lobe through fMRI both before as well as during the treatment | [86] |
OC | 76 women (38 OC and 38 placebo) | A significant percentage (77%) of the total adolescent cohort had one side effect manifested. Interestingly, the number and type of side effects were identical in both the OC and placebo groups after the completion of CES-D | [87] |
HC | 1,061,997 Danish women | Compared with the relative low risk once with aging, adolescents have been more predisposed to the subsequent usage of antidepressants following the administration of HC | [88] |
HC | 2532 women (232 oestrogen–progestin, 58 progestin only and 948 with no treatment) | The use of combined hormone contraception has been higher in Caucasians with MDD, while those on progesterone monotherapy displayed more hypersomnia, weight gain and a relatively worse physical functioning. Those with the COC were singnificantly less depressed than those in the other two groups according to the QIDS score | [89] |
HC | 75,528 postpartum women | From the total, 7.8% were prescribed antidepressants, while 5% have been diagnosed with depression, percentages which differ depending on the type of the hormonal contraception. It should be noted that the women had previously served in the US army | [90] |
HC | 815,662 Swedish women | The high CI (95%) OR indicate a strong correlation between psychotropic drug usage among adolescents compared with the older women | [91] |
CC versus AIs for PCOS as well as gonadotropins versus CC versus AIs in patients with an unknown cause of infertility | 3258 patients (1650 women and 1608 men) | In women who were not previously taking any antidepressants, MD did not negatively influence the fertility chances, but instead slightly increased the likelihood of pregnancy. However, in 90 of the women who had taken antidepressants previously, there was an increased risk of miscarriage, while in men, active MD reduced the likelihood for conception | [92] |
GnRHa | 29 women (agonist) | GnRHa has been positively correlated with a pronounced depression-like symptomatology, analogue with anxiety, but this have been considered an overlap of the pre-existing condition in euthymic participants according to the HAM-A, HAM-D and VAS-A and VAS-D | [93] |
Number of Patients | Main Observations | Reference |
---|---|---|
1000 patients (couples) | After the completion of the FPI-derived questionnaire prior to the beginning of the procedure, CFA has been partially validated. A post hoc EFA has explained two associated factors and the invariance between genders regarding stress-related states | [107] |
1146 infertile patients | Using GAD-7 in parallel with a simple and multiple logistic method of classification has revealed that generalised anxiety is common among infertile women, which was positively correlated with four specific indices | [108] |
1506 infertile patients | In accordance with PHQ-9 scores and through a simple and multiple logistic method of classification, it has been concluded that depression is predominant in women, a series of variables being positively correlated with its triggering | [109] |
511 infertile women and 1017 controls | Based on a personalised version of SF-36, it has been concluded that the relatives have a significant impact upon the decision making, more precisely towards divorce, remarriage or adoption, independently of the social degree | [110] |
1620 infertile women | While women recorded low scores in FertiQol in three specific subscales and high scores in SCREENIVF, this indicates that women present a high risk for developing emotional problems in contrast with their partners, both during and after the procedure | [111] |
2180 patients from which 1049 are men and 1131 women | After the measurement of the severity of depression-like symptoms and infertility distress with MHI-5 and COMPI Fertility Problem Stress Scales, the predisposition for neuropsychiatric disorders have been almost three times higher, which was directly correlated with infertility-related distress in both groups | [112] |
338 infertile patients and 1953 controls | Based on CIDI, BDI and GHQ-12, approximately 29% of the patients who had experienced infertility, especially women had increased risks for PDD and anxiety compared with controls. Those who have a child were more prone to panic disorder, while in men there was a reduction in the QOL | [113] |
1468 infertile men and 942 controls | IIEF-5, PEDT and IELT, concomitant with SAS and SDS have revealed that compared with controls, the incidence of PE and ED has been significantly higher for the infertile patients, similar for anxiety and depression. Negative associations have been noted in IELT and IIEF-5 for anxiety and depression | [114] |
2783 men | In total, 1750 men completed the Androgen Deficiency in the Aging Male (ADAM) and the Sexual Health Inventory for Men (SHIM) questionnaires. Through a multivariable logistic model, positive correlations between the prevalence for ED and the results obtained in ADAM have been noted. After the serum measurements of a series of biomarkers, no associations between T values with the symptoms of ED or TDS have been reported | [115] |
5936 infertile women | 1031 women who had never sought specialised advice for their infertility problem showed higher odds for depression, ovulation and metabolic disorders. Even though 728 of them pursued a treatment, 303 displayed increased chances to develop depression, tumours, menstrual disorders or infections at the level of urinary tract | [116] |
6567 women with or without a history of IVF | With a median of seventeen years follow-up and by using a multivariate predictor, 411 women from the cohort have been admitted with mental diagnostics within the hospital, from which 93 had previously pursued IVF and 318 did not | [117] |
9175 infertile women and 9175 controls | Women who had previously received treatment were less likely to be hospitalised for mental disorders or substance abuse/intoxication compared to controls. This risk was statistically significant, similar for hospitalisation during a decade post-treatment follow-up, but with exceptions in two indices. Furthermore, those who had given birth were less likely predisposed for anxiety, depression and substance abuse/intoxication in contrast with those who did not, the percentages regarding hospitalisations being identical between women who did not have a baby and controls | [118] |
13,027 infertile men and 23,860 controls | It has been established that infertile men are predisposed to metabolic and cardiovascular disorders and substance abuse in contrast with those who underwent testing only or were vasectomised | [119] |
98,320 women | When a pregnancy failed, women were at increased risk for psychiatric disorders and substance abuse compared with the women who gave birth after the infertility evaluation. No significant differences have been noted regarding the prevalence of anxiety, eating disorders or OCD | [120] |
HUNT 2006–2008 n = 9200 womenHUNT 1 and HUNT 2 n = 5873 sub-fertile women and HUNT 2 n = 12,987 women | North-Trøndelag Health Study has been one of the biggest cross-sectional population-based studies designed to determine the predisposition of CNS disorders. Nevertheless, the results obtained are antithetical. No conclusive evidence has been found in two of them to link the incidence of infertility with the common mental health disorders, but the third confirms the causality | [121,122,123] |
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Simionescu, G.; Ilie, O.-D.; Ciobica, A.; Doroftei, B.; Maftei, R.; Grab, D.; McKenna, J.; Dhunna, N.; Mavroudis, I.; Anton, E. Mini-Review on the Possible Interconnections between the Gut-Brain Axis and the Infertility-Related Neuropsychiatric Comorbidities. Brain Sci. 2020, 10, 384. https://doi.org/10.3390/brainsci10060384
Simionescu G, Ilie O-D, Ciobica A, Doroftei B, Maftei R, Grab D, McKenna J, Dhunna N, Mavroudis I, Anton E. Mini-Review on the Possible Interconnections between the Gut-Brain Axis and the Infertility-Related Neuropsychiatric Comorbidities. Brain Sciences. 2020; 10(6):384. https://doi.org/10.3390/brainsci10060384
Chicago/Turabian StyleSimionescu, Gabriela, Ovidiu-Dumitru Ilie, Alin Ciobica, Bogdan Doroftei, Radu Maftei, Delia Grab, Jack McKenna, Nitasha Dhunna, Ioannis Mavroudis, and Emil Anton. 2020. "Mini-Review on the Possible Interconnections between the Gut-Brain Axis and the Infertility-Related Neuropsychiatric Comorbidities" Brain Sciences 10, no. 6: 384. https://doi.org/10.3390/brainsci10060384