Neuroimaging studies of vulnerability to Alcohol Use Disorder (AUD) have identified structural and functional variations which might reflect inheritable features in alcohol-naïve relatives of AUD individuals (FH+) compared to controls having no such family history (FH-). However, prior research did not simultaneously account for childhood maltreatment, any clinically significant disorder and maternal AUD. Therefore, we mainly aimed to investigate the brain structure and reward-related neural activations (fMRI), using whole-brain analysis in FH+ young adults with no prevalent confounders.

46 FH+ and 45 FH- male and female participants had no severe childhood maltreatment exposure, neither any psychiatric disorder or AUD, nor a prenatal exposure to maternal AUD. We used a 3 T MRI coupled with a whole brain voxel-based method to compare between groups the grey matter volumes and activations in response to big versus small wins during a Monetary Incentive Delay task. The Childhood Trauma Questionnaire score was used as confounding variable in the analyses to account for the remaining variance between groups.

Compared to FH- controls, FH+ participants had smaller grey matter volumes in the frontal and cingulate regions as well as in the bilateral nucleus accumbens and right insula. The FH+ participants’ fMRI datasets denoted a blunted activation in the middle cingulum with respect to FH- controls’ during the processing of reward magnitude, and a greater activation in the anterior cingulum in response to anticipation of a small win.

Family history of alcohol use disorder is linked to structural and functional variations including brain regions involved in reward processes.

Metabolic syndrome and impaired insulin sensitivity may occur as side effects of atypical antipsychotic drugs. However, studies of peripheral insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR) or oral glucose tolerance tests (OGTT) suggest that abnormal glucose metabolism is already present in drug-naive first-episode schizophrenia (DNFES). We hypothesized impairments of neuronal insulin signaling in DNFES.

To gain insight into neuronal insulin-signaling in vivo, we analyzed peripheral blood extracellular vesicles enriched for neuronal origin (nEVs). Phosphorylated insulin signal transduction serine-threonine kinases pS312-IRS-1, pY-IRS-1, pS473-AKT, pS9-GSK3β, pS2448-mTOR, pT389-p70S6K and respective total protein levels were determined in plasma nEVs from 48 DNFES patients and healthy matched controls after overnight fasting.

Upstream pS312-IRS-1 was reduced at trend level (p = 0.071; this condition may amplify IRS-1 signaling). Exploratory omnibus analysis of downstream serine-threonine kinases (AKT, GSK3β, mTOR, p70S6K) revealed lower phosphorylated/total protein ratios in DNFES vs. controls (p = 0.013), confirming decreased pathway activation. Post-hoc-tests indicated in particular a reduced phosphorylation ratio of mTOR (p = 0.027). Phosphorylation ratios of p70S6K (p = 0.029), GSK3β (p = 0.039), and at trend level AKT (p = 0.061), showed diagnosis-dependent statistical interactions with insulin blood levels. The phosphorylation ratio of AKT correlated inversely with PANSS-G and PANSS-total scores, and other ratios showed similar trends.

These findings support the hypothesis of neuronal insulin resistance in DNFES, small sample sizes notwithstanding. The counterintuitive trend towards reduced pS312-IRS-1 in DNFES may result from adaptive feedback mechanisms. The observed changes in insulin signaling could be clinically meaningful as suggested by their association with higher PANSS scores.

Little is known about changes in brain functioning after first-episode psychosis (FEP). Such knowledge is important for predicting the course of disease and adapting interventions. Functional magnetic resonance imaging has become a promising tool for exploring brain function at the time of symptom onset and at follow-up.

A systematic review of longitudinal fMRI studies with FEP patients according to PRISMA guidelines. Resting-state and task-activated studies were considered together.

Eleven studies were included. These reported on a total of 236 FEP patients were evaluated by two fMRI scans and clinical assessments. Five studies found hypoactivation at baseline in prefrontal cortex areas, two studies found hypoactivation in the amygdala and hippocampus, and three others found hypoactivation in the basal ganglia. Other hypoactivated areas were the anterior cingulate cortex, thalamus and posterior cingulate cortex. Ten out of eleven studies reported (partial) normalization by increased activation after antipsychotic treatment. A minority of studies observed hyperactivation at baseline.

This review of longitudinal FEP samples studies reveals a pattern of predominantly hypoactivation in several brain areas at baseline that may normalize to a certain extent after treatment. The results should be interpreted with caution given the small number of studies and their methodological and clinical heterogeneity.

Impaired illness awareness or insight into illness (IIA) is a common feature of schizophrenia that contributes to medication nonadherence and poor clinical outcomes. Neuroimaging studies suggest IIA may arise from interhemispheric imbalance in frontoparietal regions, particularly in the posterior parietal area (PPA) and the dorsolateral prefrontal cortex (dlPFC). In this pilot study, we examined the effects of transcranial direct current stimulation (tDCS) on brain regions implicated in IIA.

Eleven patients with schizophrenia with IIA (≥3 PANSS G12) and 10 healthy controls were included. A crossover design was employed where all participants received single-session bi-frontal, bi-parietal, and sham stimulation in random order. For each condition, we measured (i) blood oxygen level-dependent (BOLD) response to an illness awareness task pre- and post-stimulation, (ii) regional cerebral blood-flow (rCBF) prior to and during stimulation, and (iii) changes in illness awareness.

At baseline, patients with schizophrenia showed higher BOLD-response to an illness awareness task in the left-PPA compared to healthy controls. Bi-parietal stimulation reduced the interhemispheric imbalance in the PPA compared to sham stimulation. Relatedly, bi-parietal stimulation increased rCBF beneath the anode (21% increase in the right-PPA), but not beneath the cathode (5.6% increase in the left-PPA). Bi-frontal stimulation did not induce changes in rCBF. We found no changes in illness awareness.

Although single-session tDCS did not improve illness awareness, this pilot study provides mechanistic justification for future investigations to determine if multi-session bi-parietal tDCS can induce sustained changes in brain activity in the PPA in association with improved illness awareness.

Despite the great number of resting state functional connectivity studies on Eating Disorders (ED), no biomarkers could be detected yet. Therefore, we here focus on a different measure of resting state activity that is neuronal variability. The objective of this study was to investigate neuronal variability in the resting state of women with ED and to correlate possible differences with clinical and psychopathological indices.

58 women respectively 25 with Anorexia Nervosa (AN), 16 with Bulimia Nervosa (BN) and 17 matched healthy controls (CN) were enrolled for the study. All participants were tested with a battery of psychometric tests and underwent a functional Magnetic Resonance Imaging (fMRI) resting state scanning. We investigated topographical patterns of variability measured by the Standard Deviation (SD) of the Blood-Oxygen-Level-Dependent (BOLD) signal (as a measure of neuronal variability) in the resting-state and their relationship to clinical and psychopathological indices.

Neuronal variability was increased in both anorectic and bulimic subjects specifically in the Ventral Attention Network (VAN) compared to healthy controls. No significant differences were found in the other networks. Significant correlations were found between neuronal variability of VAN and various clinical and psychopathological indices.

We here show increased neuronal variability of VAN in ED patients. As the VAN is relevant for switching between endogenous and exogenous stimuli, our results showing increased neuronal variability suggest unstable balance between body attention and attention to external world. These results offer new perspective on the neurobiological basis of ED. Clinical and therapeutic implication will be discussed.

Few studies have investigated alterations of olfactory neuroepithelium (ONE) as a biomarker of schizophrenia, and none its association with cognitive functioning.

Fresh ONE cells from twelve patients with schizophrenia and thirteen healthy controls were collected by nasal brushing, cultured in proper media and passed twelve times. Markers of cell proliferation (BrdU incorporation, Cyclin-D1 and p21 protein level) were quantified.Cognitive function was measured using Brief Neuropsychological Examination-2. Primary outcome: proliferation of ONE cells from schizophrenic patients at passage 3. Secondary outcome: association between alteration of cell proliferation and cognitive function.

Fresh ONE cells from patients showed a faster cell proliferation than those from healthy controls at passage 3. An opposite trend was observed at passage 9, ONE cells of patients with schizophrenia showing slower cell proliferation as compared to healthy controls. In schizophrenia, overall cognitive function (Spearman’s rho -0.657, p < 0.01), verbal memory – immediate recall, with interference at 10 s and 30 s (Spearman’s rho from -0.676 to 0.697, all p < 0.01) were inversely associated with cell proliferation at passage 3.

Fresh ONE cells collected by nasal brushing might eventually represent a tool for diagnosing schizophrenia based upon markers of cell proliferation, which can be easily implemented as single-layer culture. Cell proliferation at passage 3 can be regarded as a promising proxy of cognitive functioning in schizophrenia. Future studies should replicate these findings, and may assess whether ONE alterations are there before onset of psychosis, serving as an early sign in patients with at risk mental state.

Genomic sequencing plays an increasing role in genetic research, also in psychiatry. This raises challenges concerning the validity and type of the informed consent and the return of incidental findings. However, no solution currently exists on the best way to obtain the informed consent and deliver findings to research subjects.

This study aims to explore the attitudes among potential stakeholders in psychiatric genomic research toward the consenting procedure and the delivery of incidental findings.

We developed a cross-sectional web-based survey among five groups of stakeholders. A total of 2637 stakeholders responded: 241 persons with a mental disorder, 671 relatives, 1623 blood donors, 74 psychiatrists, and 28 clinical geneticists.

The stakeholders wanted active involvement as 92.7% preferred a specific consent and 85.1% wanted to receive information through a dynamic consent procedure. The majority of stakeholders preferred to receive genomic information related to serious or life-threatening health conditions through direct contact (69.5%) with a health professional, i.e. face-to-face consultation or telephone consultation (82.4%). Persons with mental disorders and relatives did not differ in their attitudes from the other stakeholder groups.

The findings illustrate that the stakeholders want to be more actively involved and consider consent as a reciprocal transaction between the involved subjects and the researchers in the project. The results highlight the importance of collaboration between researchers and clinical geneticists as the latter are trained, through their education and clinical experience, to return and explain genomic data to patients, relatives, and research subjects.

Brain structural connectome comprise of a minority of efficiently interconnected rich club nodes that are regarded as ‘high-order regions’. The remission of major depressive disorder (MDD) in response to selective serotonin reuptake inhibitor (SSRI) treatment could be investigated by the hierarchical structural connectomes’ alterations of subnetworks.

Fifty-five MDD patients who achieved remission underwent diffusion tensors imaging (DTI) scanning from 3 cohorts before and after 8-weeks antidepressant treatment. Five hierarchical subnetworks namely, rich, local, feeder, rich-feeder and feeder-local, were constructed according to the different combinations of connections and nodes as defined by rich club architecture. The critical treatment-related subnetwork pattern was explored by multivariate pattern analysis with support vector machine to differ the pre-/post-treatment patients. Then, relationships between graph metrics of discriminative subnetworks/ nodes and clinical variables were further explored.

The feeder-local subnetwork presented the most discriminative power in differing pre-/post- treatment patients, while the rich-feeder subnetwork had the highest discriminative power when comparing pre-treatment patients and controls. Furthermore, based on the feeder connection, which indicates the information transmission between the core and non-core architectures of brain networks, its topological measures were found to be significantly correlated with the reduction rate of 17-item Hamilton Rating Scale for Depression.

Although pathological lesion on MDD relied on abnormal core organization, disease remission was association with the compensation from non-core organization. These results suggested that the dysfunctions arising from hierarchical subnetworks are compensated by increased information interactions between core brain regions and functionally diverse regions.

The hippocampus is not a uniform structure, but rather consists of multiple, functionally specialized subfields. Few studies have explored hippocampal subfield volume difference in the same sample of major depressive disorder (MDD) and bipolar disorder (BD) cases. We aimed to investigate the difference of hippocampal subfield volume between patents with MDD and BD and healthy controls (HCs).

A total of 102 MDD and 55 BD patients and 135 HCs were recruited and underwent T1-weighted image. Hippocampal subfield volume was calculated by automated segmentation and volumetric procedures developed by Iglesias et al. and implemented in FreeSurfer. Volume differences between the groups were analyzed using the analysis of covariance and controlling for age, sex, and total intracranial cavity volume.

Patients with MDD had significantly reduced volumes in the bilateral cornu ammonis 1 (CA1), CA4, the granule cell layer (GCL), molecular layer (ML), whole hippocampus, the left CA2/3, and right presubiclum and subiculum. Patients with BD had significantly reduced volumes in the right CA1, GCL, and the whole hippocampus as compared to HCs. No significant volume differences were observed between the MDD and BD groups. Illness duration was negatively correlated with volumes of the left CA1, CA4, ML, presubiculum, subiculum, and the whole hippocampus in patients with BD.

We observed hippocampal subfield volume reductions in both MDD and BD, a finding which more prominent in MDD. The inverse correlation between BD illness duration and hippocampal subfield volume may evidence the neuroprogressive nature of BD.