Severe behavioural issues such as impulsive action and suicide have since long been associated with low levels of cholesterol. While it is known that cholesterol plays a role in neural development and hence low levels of serum lipids could have long-term effects on behaviour, no longitudinal studies showed the association of serum lipids levels with impulsivity. We aimed to examine the prognostic properties of serum lipid levels during childhood and adolescence on measures of impulsivity during early adulthood in a representative birth cohort sample.

We have investigated whether serum lipid levels measured at 9, 15, 18 and 25 years of age have an association with impulsivity in 25 years old young adults. This analysis was based on data of the birth cohort representative samples of the Estonian Children Personality Behaviour and Health Study (original n = 1238). Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale.

Total and low-density lipoprotein (LDL) cholesterol measured in boys aged 9, 15 and 18 years predicted disinhibition and thoughtlessness in 25-year-old young adults. High scores of disinhibition were associated with low total and LDL cholesterol levels in males but, while less consistently, with high total and LDL cholesterol levels in females. Cross-sectional analysis did not result in systematic outcomes.

Serum lipid levels could have an impact on the development of Maladaptive Impulsivity starting from an early age. This effect of cholesterol continues throughout adolescence into young adulthood.

Findings from animal studies indicate that the early gut bacteriome is a potential mechanism linking maternal prenatal stress with health trajectories in offspring. However, clinical studies are scarce and the associations of maternal psychological profiles with the early infant faecal bacteriome are unknown. This study aimed to investigate the associations of prenatal stressors and distress with early infant faecal bacterial profiles in a South African birth cohort study.

Associations between prenatal symptoms of depression, distress, intimate partner violence (IPV) and posttraumatic stress disorder (PTSD) and faecal bacterial profiles were evaluated in meconium and subsequent stool specimens from 84 mothers and 101 infants at birth, and longitudinally from a subset of 69 and 36 infants at 4–12 and 20–28 weeks of age, respectively, in a South African birth cohort study.

Infants born to mothers that were exposed to high levels of IPV had significantly higher proportions of Citrobacter and three unclassified genera, all of which belonging to the family Enterobacteriaceae detected at birth. Proportions of these Enterobacteriaceae remained significantly increased over time (birth to 20–28 weeks of life) in infants born to mothers with high levels of IPV exposure compared to infants from mothers with no/low IPV exposure. Infants born to mothers exposed to IPV also had higher proportions of the genus Weissella at 4–12 weeks compared to infants from mothers with no/low IPV exposure. Faecal specimens from mothers exposed to IPV had higher proportions of the family Lactobacillaceae and lower proportions of Peptostreptococcaceae at birth. Maternal psychological distress was associated with decreased proportions of the family Veillonellaceae in infants at 20–28 weeks and a slower decline in Gammaproteobacteria over time. No changes in beta diversity were apparent for maternal or infant faecal bacterial profiles in relation to any of the prenatal measures for psychological adversities.

Maternal lifetime IPV and antenatal psychological distress are associated with altered bacterial profiles in infant and maternal faecal bacteria. These findings may provide insights in the involvement of the gut bacteria linking maternal psychological adversity and the maturing infant brain.

The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS).

This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers.

In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023).

Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.

Peripheral gene expression of several molecular pathways has been studied in major depressive disorder (MDD) with promising results. We sought to investigate some of these genes in a treatment-free Latino sample of Mexican descent.

The sample consisted of 50 MDD treatment-free cases and 50 sex and age-matched controls. Gene expression of candidate genes of neuroplasticity (BDNF, p11, and VGF), inflammation (IL1A, IL1B, IL4, IL6, IL7, IL8, IL10, MIF, and TNFA), the canonical Wnt signaling pathway (TCF7L2, APC, and GSK3B), and mTOR, was compared in cases and controls. RNA was obtained from blood samples. We used bivariate analyses to compare subjects versus control mean mRNA quantification of target genes and lineal regression modelling to test for effects of age and body mass index on gene expression.

Most subjects were female (66%) with a mean age of 26.7 (SD 7.9) years. Only GSK3B was differentially expressed between cases and controls at a statistically significant level (p = 0.048). TCF7L-2 showed the highest number of correlations with MDD-related traits, yet these were modest in size.

GSK3B encodes a moderator of the canonical Wnt signaling pathway. It has a role in neuroplasticity, neuroprotection, depression, and other psychiatric phenotypes. We found that adding population diversity has the potential to elicit distinct peripheral gene expression markers in MDD and MDD-related traits. However, our results should only be considered as hypothesis-generating research that merits further replication in larger cohorts of similar ancestry.

To evaluate the involvement of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in schizophrenia-like behaviour in young animals exposed to maternal immune activation (MIA).

To this aim, on the 15th gestational day, the females received an injection of lipopolysaccharides. When the animals completed 7, 14 and 45 postnatal days, they were killed and the whole brain was dissected for biochemical analysis. Animals with 45 postnatal days were submitted to behavioural tests of locomotor activity, social interaction and stereotyped movements.

It was observed that the animals presented schizophrenia-like behaviour at 45 postnatal days associated with the increase of NLRP3 inflammasome expression and IL-1β levels on 7, 14 and 45 postnatal days.

This study shows that MIA may be associated with a schizophrenia-like behaviour. This behaviour can be induced to a neuroinflammatory profile in the brain. These evidences may base future studies on the relationship between neuroinflammation and psychiatric disorders.

Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms.

To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE.

This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale.

24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259).

Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.

It has been hypothesised that neuropsychiatric symptoms, including psychosis, can be the result of a milder brain bioenergetic defect produced by mitochondrial dysfunction; however, mitochondrial dysfunction can be present in other organs or systems. The aim of the study was to investigate whether clinical conditions associated with mitochondrial disorders (CAMDs) were frequently present in schizophrenia.

A previously used questionnaire regarding the CAMDs was administered to patients and controls in a direct interview with a trained psychiatrist. The frequencies of CAMDs in 164 patients with schizophrenia were compared to those in 156 age- and sex-matched controls.

Severe fatigue, seizures, constipation and diabetes were significantly more frequent in patients with schizophrenia than in control subjects and apparently not related to pharmacological treatment.

The results of the present study suggest that multi-systemic mitochondrial dysfunction may be an underlying mechanism involved in schizophrenia.

Sustained immune activation leads to cognitive dysfunctions, depression-, and anxiety-like behaviours in humans and rodents. It is modelled by administration of lipopolysaccharides (LPS) to induce expression of pro-inflammatory cytokines that then activate indoleamine 2,3 dioxygenase (IDO1), the rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism. Here, we ask whether chronic IDO1 inhibition by 1-methyl-tryptophan (1-MT, added at 2 g/l in the drinking water) or chronic inhibition of tryptophan 2,3 dioxygenase (TDO2), another enzyme capable of converting tryptophan to kynurenine, by 680C91 (15 mg/kg per os), can rescue LPS-induced (0.83-mg/kg intraperitoneally) anxiety and cognitive deficits. We also investigate the acute effects of 680C91 on serotonergic, dopaminergic, and kynurenine pathway metabolites.

We examined LPS-induced deficits in trace fear conditioning and anxiety in the light–dark box and elevated plus maze (EPM) in group-housed C57Bl6/N mice. Kynurenine pathway metabolites and monoamine levels were measured via high-performance liquid chromatography.

Chronic blockade of IDO1 with 1-MT did not rescue cognitive deficits or abrogate the anxiogenic behaviour caused by LPS despite a decrease in the brain kynurenine:tryptophan ratio. However, 1-MT by itself demonstrated anxiolytic properties in the EPM. Acute and chronic inhibition of TDO2 elevated brain levels of tryptophan, while chronic inhibition of TDO2 was unsuccessful in rescuing cognitive deficits and abrogating the anxiety caused by LPS.

In line with previous studies, we show that LPS administration induces anxiety and cognitive dysfunctions in mice that however were not reversed by chronic blockade of IDO1 or TDO2 at the doses used.

To investigate the association of prenatal alcohol exposure (PAE) and early neurodevelopment in the first 2 years of life, adjusting for maternal socio-demographic and psychosocial factors, in the Drakenstein Child Health Study (DCHS), a South African birth cohort study.

The DCHS comprises a population-based birth cohort of 1143 children, of which a subsample completed the Bayley Scales of Infant Development-III (BSID-III) at 6 (n = 260) and 24 months of age (n = 734). A subset of alcohol-exposed and -unexposed children was included in this analysis at age 6 (n = 52 exposed; n = 104 unexposed) and 24 months (n = 92 exposed; n = 184 unexposed). Multiple hierarchical regression was used to explore the associations of PAE with motor and language development.

PAE was significantly associated with decreased gross motor [odds ratio (OR) = 0.16, 95% confidence interval (CI) = 0.06–0.44, p = 0.001] or fine motor (OR = 0.16, 95% CI = 0.06–0.46, p = 0.001) functioning after adjusting for maternal socio-demographic and psychosocial factors at 6 months of age only. No significant effects were found in either receptive or expressive communication and cognitive outcomes at either time points.

PAE has potentially important consequences for motor development in the first 2 years of life, a period during which the most rapid growth and maturation occur. These findings highlight the importance of identifying high-risk families in order to provide preventive interventions, particularly in antenatal clinics and early intervention services.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has been shown to have a statistically and clinically significant anti-depressant effect. The present pilot study was carried out to investigate if right prefrontal low-frequency rTMS as an add-on to electroconvulsive therapy (ECT) accelerates the anti-depressant effect and reduces cognitive side effects.

In this randomised, controlled, double-blind study, thirty-five patients with major depression were allocated to ECT+placebo or ECT+low-frequency right prefrontal rTMS. The severity of depression was evaluated during the course using the Hamilton scale for depression (the 17-item as well as the 6-item scale) and the major depression inventory (MDI). Furthermore, neuropsychological assessment of cognitive function was carried out.

The study revealed no significant difference between the two groups for any of the outcomes, but with a visible trend to lower scores for MDI after treatment in the placebo group. The negative impact of ECT on neurocognitive functions was short-lived, and scores on logical memory were significantly improved compared to baseline 4 weeks after last treatment. The ECT-rTMS group revealed generally less impairment of cognitive functions than the ECT-placebo group.

The addition of low-frequency rTMS as an add-on to ECT treatment did not result in an accelerated response. On the contrary, the results suggest that low-frequency rTMS could inhibit the anti-depressant effect of ECT.

The aim of the study was to assess whether the auditory brainstem response (ABR) profiling test for schizophrenia (SZ) would recognise schizoaffective disorder (SZA) patients as SZ or not.

Male and female SZA patients (n = 16) from the psychosis unit at Uppsala University Hospital were investigated. Coded sets of randomised ABR recordings intermingled with patients with SZ, adult attention-deficit hyperactivity disorder (ADHD) and healthy controls were analysed by an independent party blinded to clinical diagnoses.

The ABR profiling test for SZ was positive in 5/16 patients (31%) and negative in 11/16 patients (69%) with SZA. A surprising finding was that 4/16 (25%) SZA patients were positive for the ABR profiling test for ADHD.

With the ABR profiling test, a minority of patients with SZA tested positive for SZ. In contrast, a majority (85%) of patients with SZ in a previous study tested positive. These preliminary results leave us ignorant whether SZA should be regarded as a SZ-like disorder or a psychotic mood disorder and add to the questions regarding the validity of this diagnostic entity. However, the ABR profiling method is still in its infancy and its exploration in a range of psychiatric disorders is warranted.

We provide a closer look at the result of a randomised, placebo-controlled, active-reference (quetiapine XR), flexible-dose, 6-week study of brexpiprazole in schizophrenia, which did not meet its primary endpoint – change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. We also investigate potential expectancy bias from the well-known side-effect profile of the active reference that could have affected the study outcome.

Pre-specified sensitivity analyses of the primary end point were performed using analysis of covariance (ANCOVA) last observation carried forward (LOCF) and observed cases (OC). Post hoc analyses of change from baseline in PANSS total score were performed using the mixed model for repeated measures approach with treatment groups split by having typical adverse events with potential for functional unblinding, for example, somnolence, increase in weight, dizziness, dry mouth and sedation.

Pre-specified sensitivity analyses showed separation from placebo for brexpiprazole at week 6: LOCF, ANCOVA: −4.3 [95% CI (−8.0, −0.5), p = 0.0254]. OC, ANCOVA: −3.9 [95% CI (−7.3, −0.5), p = 0.0260]. Patients treated with brexpiprazole experiencing typical adverse events with potential for functional unblinding before or at Week 2 had a least square (LS) mean PANSS change of −29.5 (improvement), with a difference in change from baseline to Week 6 in PANSS total score between brexpiprazole and placebo of −13.5 [95% CI (−23.1, −4.0), p = 0.0057], and those who did not had an LS mean change of −18.9 and a difference between brexpiprazole and placebo of −2.9 [95% CI (−7.2, 1.4), p = 0.1809].

Pre-specified sensitivity analyses showed separation from placebo for brexpiprazole at Week 6. A post hoc analysis suggested a potential confounding of efficacy rating towards symptom improvement in patients who experience known side effects of quetiapine XR.

This study was carried out to delineate differences between major depressive disorder (MDD) and healthy controls in dynorphin and kappa opioid receptor (KOR) levels in association with changes in the β-endorphin – mu opioid receptor (MOR) and immune-inflammatory system.

The present study examines dynorphin, KOR, β-endorphin, MOR, interleukin (IL)-6 and IL-10 in 60 drug-free male participants with MDD and 30 age-matched healthy males.

Serum dynorphin, KOR, β-endorphin and MOR are significantly higher in MDD as compared to controls. The increases in the dynorphin/KOR system and β-endorphin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls with a bootstrapped (n = 2000) area under the receiver operating curve of 0.972. The dynorphin/KOR system is significantly decreased in depression with comorbid nicotine dependence.

Our findings suggest that, in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorphin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by (a) exerting immune-regulatory activities attenuating the primary immune response and (b) modulating reward responses and mood as well as emotional and behavioural responses to stress.

Glucagon-like peptide-1 receptors (GLP-1Rs) are widely expressed in the brain. Evidence suggests that they may play a role in reward responses and neuroprotection. However, the association of GLP-1R with anhedonia and depression diagnosis has not been studied. Here, we examined the association of GLP-1R polymorphisms with objective and subjective measures of anhedonia, as well as depression diagnosis.

Objective [response bias assessed by the probabilistic reward task (PRT)] and subjective [Snaith-Hamilton Pleasure Scale (SHAPS)] measures of anhedonia, clinical variables and DNA samples were collected from 100 controls and 164 patients at McLean Hospital. An independent sample genotyped as part of the Psychiatric Genomics Consortium (PGC) was used to study the effect of putative GLP-1R polymorphisms linked to response bias in PRT on depression diagnosis.

The C allele in rs1042044 was significantly associated with increased PRT response bias, when controlling for age, sex, case-control status and PRT discriminability. AA genotype of rs1042044 showed higher anhedonia phenotype based on SHAPS scores. However, analysis of PGC major depressive disorder data showed no association between rs1042044 and depression diagnosis.

Findings suggest a possible association of rs1042044 with anhedonia but no association with depression diagnosis.

Although the assessment of expression of serotonin-related genes in experimental animals has become a common strategy to shed light on variations in brain serotonergic function, it remains largely unknown to what extent the manipulation of serotonin levels causes detectable changes in gene expression. We therefore chose to investigate how sub-acute depletion or elevation of brain serotonin influences the expression of a number of serotonin-related genes in six brain areas.

Male Wistar rats were administered a serotonin synthesis inhibitor, para-chlorophenylalanine (p-CPA), or a serotonin reuptake inhibitor, paroxetine, for 3 days and then sacrificed. The expression of a number of serotonin-related genes in the raphe nuclei, hypothalamus, amygdala, striatum, hippocampus and prefrontal cortex was investigated using real-time quantitative PCR (rt-qPCR).

While most of the studied genes were uninfluenced by paroxetine treatment, we could observe a robust downregulation of tryptophan hydroxylase-2 in the brain region where the serotonergic cell bodies reside, that is, the raphe nuclei. p-CPA induced a significant increase in the expression of Htr1b and Htr2a in amygdala and of Htr2c in the striatum and a marked reduction in the expression of Htr6 in prefrontal cortex; it also enhanced the expression of the brain-derived neurotrophic factor (Bdnf) in raphe and hippocampus.

With some notable exceptions, the expression of most of the studied genes is left unchanged by short-term modulation of extracellular levels of serotonin.