Advantageous developmental outcomes of advancing paternal age.

Advanced paternal age (APA) at conception has been associated with negative outcomes in offspring, raising concerns about increasing age at fatherhood. Evidence from evolutionary and psychological research, however, suggests possible link between APA and a phenotypic advantage. We defined such advantage as educational success, which is positively associated with future socioeconomic status. We hypothesised that high IQ, strong focus on the subject of interest and little concern about 'fitting in' will be associated with such success. Although these traits are continuously distributed in the population, they cluster together in so-called 'geeks'. We used these measures to compute a 'geek index' (GI), and showed it to be strongly predictive of future academic attainment, beyond the independent contribution of the individual traits. GI was associated with paternal age in male offspring only, and mediated the positive effects of APA on education outcomes, in a similar sexually dimorphic manner. The association between paternal age and GI was partly mediated by genetic factors not correlated with age at fatherhood, suggesting contribution of de novo factors to the 'geeky' phenotype. Our study sheds new light on the multifaceted nature of the APA effects and explores the intricate links between APA, autism and talent.

Promoting medication adherence among patients with bipolar disorder: a multicenter randomized controlled trial of a multifaceted intervention.

BACKGROUND: The present research aimed to investigate the efficacy of a multifaceted intervention that included motivational interviewing (MI) and psychoeducation in improving medication adherence (MA) among patients with bipolar disorder (BD). METHOD: A multicenter, cluster randomized, observer-blind, controlled, parallel-group trial was conducted in ten academic centers in Iran. Patients with BD were randomly assigned to the experimental group (EXP; n = 136) or the usual care group (UC; n = 134). The EXP group received five sessions of MI and psychoeducation together with their family members. The primary outcome measure was changes in scores on the Medication Adherence Rating Scale from baseline to 6 months post-intervention. Other outcome measures included serum levels of mood stabilizers, clinical symptoms, quality of life, as well as measures of intention, beliefs about medicine, perceived behavioral control, automaticity, action and coping planning, and adverse reactions. RESULTS: Medication adherence improved over time in both groups, but patients in the EXP group improved more (baseline score: 6.03; score at the sixth month: 9.55) than patients in the UC group (baseline score: 6.17; score at the sixth month: 6.67). In addition, patients in the EXP group showed greater improvement than patients in the UC group in almost all secondary outcomes 6 months following the intervention. CONCLUSIONS: Multifaceted interventions that include motivational-interviewing and psychoeducation can significantly improve MA and clinical and functional outcomes in patients with BD. TRIAL REGISTRATION NUMBER: The trial was registered with theClinicalTrials.gov database (NCT02241863) https://clinicaltrials.gov/ct2/show/NCT02241863.

Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers.

BACKGROUND: Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia. METHODS: We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb(2+)), manganese (Mn(2+)), cadmium (Cd(2+)), copper (Cu(2+)), magnesium (Mg(2+)), and zinc (Zn(2+)), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry. RESULTS: We found higher early-life Pb(2+) exposure among patients with schizophrenia than controls. The differences in log Mn(2+) and log Cu(2+) changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb(2+) levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb(2+) levels and adult IQ. CONCLUSIONS: In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis.

Alexithymia and its relationships with acute phase proteins and cytokine release: an updated review.

The alexithymia construct is multidimensional and comprises several features: (a) difficulty in identifying and describing feelings, (b) difficulty in distinguishing feelings from the bodily sensations, (c) diminution of fantasy, and (d) concrete and poorly introspective thinking. Altered immune responses have been seen in some psychiatric disorders and several data suggest that analogous changes could also be observable in alexithymia. Hence, the aim of this review is to investigate the relationships between alexithymia and acute phase proteins and cytokines in psychiatric, psychosomatic and medical diseases. Several studies have reported an association between alexithymia and higher circulating levels of acute phase proteins, especially C-Reactive Protein. Moreover, in alexithymic subjects the pro-inflammatory and anti-inflammatory cytokine balance may be tuned toward a pro-inflammatory imbalance with a concomitant altered cell-mediated immunity. These findings may be consistent with the "“stress-alexithymia hypothesis"”. Therefore, the screening of alexithymic traits and the administration of appropriate psychological and psychotherapeutical interventions should be integral parts of disease management programs. Supplying such interventions will probably help with prevention of the development of the disease and/or its exacerbation by improving the quality of life of alexithymic individuals.

Serum and CSF PDGF-AA and FGF-2 in relapsing-remitting multiple sclerosis: a case-control study.

BACKGROUND AND PURPOSE: Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-A (PDGF-AA) are potent modulators of oligodendrocytes, the main responsible cells for myelin regeneration. We measured FGF-2 and PDGF-AA in the sera and cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RR-MS) and compared these values with control subjects. METHODS: Twenty-three patients with RR-MS and 23 subjects without inflammatory and demyelinating diseases were included. Serum samples of the patients were collected in both relapse and remission phases and were analyzed with ELISA method. CSF was drawn during the relapse period. Blood and CSF were drawn from control subjects for comparison. Wilcoxon and Mann-Whitney U-test and Spearman's rank correlation were used for analysis. P values of <0.05 were considered significant. RESULTS: Age and sex distribution were similar in both groups. Serum values of FGF-2 were higher in relapse phase compared with remission phase, with a trend toward significance (P=0.052). CSF PDGF-AA showed significant negative correlation with disease duration (correlation coefficient=-0.58, P=0.004). Serum levels of PDGF did not differ between two phases significantly. There was no difference in serum and CSF values of these factors between patients and controls. When we compared patients with prolonged disease with controls, a significant difference between the CSF levels of PDGF-AA was observed (mean±SEM 2.78±0.8 in controls vs. 0.55±0.29 in patients with MS≥2 years, P<0.05). CONCLUSION: Our study was the first to show that CSF PDGF-AA is related to disease duration. Supporting previous findings we showed that serum and CSF levels of these factors are weak indicators of disease severity.

Sympathetic skin response (SSR) in multiple sclerosis and clinically isolated syndrome: a case-control study.

OBJECTIVE: To compare the sympathetic skin responses (SSRs) in patients with multiple sclerosis (MS), clinically isolated syndrome (CIS), and healthy controls. METHODS: SSR was recorded on both hands and feet in 30 patients and 20 healthy controls. SSR results (latency measurements) were compared in patients with normal or abnormal brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs). RESULTS: Twenty-three (76.6%) and sixteen patients (53.3%) with MS had abnormal SSR recordings based on 2-standard deviation (SD) or 3-SD (from the mean of the control group) abnormality criteria, respectively. Sixty-six percent and 40 percent of patients had abnormal (>2SD) SSR in at least one hand and one foot, respectively. Patients with absent SSR had more severe disease and higher Expanded Disability Status Scale (EDSS) scores. Fourteen patients had an EDSS of zero, of whom nine had abnormal SSR and others had at least one abnormal EP study. Patients with abnormal SSR had significantly more abnormal BAEPs and SEPs than patients with normal SSR. SSR latencies were significantly correlated with EDSS and disease duration (P<0.01). All patients had at least one abnormal electrophysiological study. ROC-curve analysis showed that a cut-off score of 7008 ms as the sum of all-4-limb SSR latencies had a 80% sensitivity and 95% specificity for differentiating MS patients from healthy controls. CONCLUSIONS: This study suggests that SSR is a useful tool for assessment of autonomic function and can be complementary to EDSS and other electrophysiological studies in patients with MS and CIS.

Meningoencephalitis associated with hepatitis A infection: a case report and review of literature.

Hepatitis A virus uncommonly causes neurological problems. Among these manifestations meningoencephalitis is very rare. We describe the clinical and laboratory features of a young boy with hepatitis A associated meningoencephalitis and compare it with other cases which had the same diagnoses.