Progress in Neuro-psychopharmacology & Biological Psychiatry

BACKGROUND: DNA methylation as a biomarker is well suited to investigate dynamic processes, such as symptom improvement. For this study we focus on epigenomic state or trait markers as early signatures of cognitive improvement in individuals receiving a cognitive intervention. We performed a first epigenome-wide association study (EWAS) on patients with cognitive dysfunction in depression comparing those with vs without cognitive dysfunction and those cognitively improving vs non-improving following a cognitive intervention...

BACKGROUND: Negative symptoms (NS) are a core symptom domain in schizophrenia spectrum disorders and are associated with poorer social and vocational functioning, and with increased likelihood and durations of hospital admission. NS are not well understood, limiting available interventions. However, numerous studies have reported associations between neurocognitive domains and NS severity. Thus, one promising area in understanding NS is in relation to neurocognition. Currently, the specificity of the relationship between NS and neurocognition is unknown, meaning that there is no consensus regarding which neurocognitive domain is most strongly associated with NS...

BACKGROUND: Previous studies have reported a variety of gut microbiota alterations in patients with schizophrenia. However, none of these studies has investigated gut microbiota in patients with the deficit subtype of schizophrenia (D-SCZ) that can be characterized by primary and enduring negative symptoms. Therefore, in this study we aimed to profile gut microbiota of individuals with D-SCZ, compared to those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). METHODS: A total of 115 outpatients (44 individuals with D-SCZ and 71 individuals with ND-SCZ) during remission of positive and disorganization symptoms as well as 120 HCs were enrolled...

Alterations of functional network connectivity have been implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). Recent studies also suggest that the temporal dynamics of functional connectivity (dFC) can be altered in these disorders. Here, we summarized the existing literature on dFC in SCZ and BD, and their association with psychopathological and cognitive features. We systematically searched PubMed, Web of Science, and Scopus for studies investigating dFC in SCZ and BD and identified 77 studies...

Aversive memory extinction comprises a novel learning that blocks retrieving a previously formed traumatic memory. In this sense, aversive memory extinction is an excellent tool for decreasing fear responses. However, this tool it's not effective in the long term because of original memory spontaneous recovery. Thus, searching for alternative strategies that strengthen extinction learning is essential. In the current study, we evaluated the effects of a novel context (i.e., novelty) exposure on aversive memory extinction enhancement over days and the dopaminergic system requirement...

Alzheimer's disease (AD) is often not recognized or is diagnosed very late, which significantly reduces the effectiveness of available pharmacological treatments. Metabolomic analyzes have great potential for improving existing knowledge about the pathogenesis and etiology of AD and represent a novel approach towards discovering biomarkers that could be used for diagnosis, prognosis, and therapy monitoring. In this study, we applied the untargeted metabolomic approach to investigate the changes in biochemical pathways related to AD pathology...

The gut microbiome plays a significant role in methamphetamine addiction. Previous studies using short-read amplicon sequencing have described alterations in microbiota at the genus level and predicted function, in which taxonomic resolution is insufficient for accurate functional measurements. To address this limitation, we employed metagenome sequencing to intuitively associate species to functions of gut microbiota in methamphetamine-induced conditioned place preference. We observed differential perturbations of species-level functional profiling of the gut microbiota across phases of METH-induced CPP, with alterations in SCFA metabolism and bacterial motility at the acquisition phase and substance dependence-alcoholism pathway and amino acid metabolism at the extinction phase...

Schizophrenia is a complex multi-factor neurological disorder that caused an array of severe indelible consequences to the individuals and society. Additionally, anti-schizophrenic drugs are unsuitable for treating negative symptoms and have more significant side effects and drug resistance. For better treatment and prevention, we consider exploring the pathogenesis of schizophrenia from other perspectives. A growing body of evidence of 22q11.2 deletion syndrome (22q11DS) suggested that the occurrence and progression of schizophrenia are related to mitochondrial dysfunction...

Cognitive dysfunction contributes significantly to the burden caused by Major Depressive Disorder (MDD). Yet, while compelling evidence suggests that different biological processes play a part in both MDD aetiology and the development of cognitive decline more generally, we only begin to understand the molecular underpinnings of depression-related cognitive impairment. Developments in psychometric assessments, molecular high-throughput methods and systems biology derived analysis strategies advance this endeavour...

Various psychiatric diseases are characterized by aberrant cognition and emotional regulation. This includes inappropriately attributing affective salience to innocuous cues, which can be investigated using translationally relevant preclinical models of fear discrimination. Activity in the underpinning corticolimbic circuitry is governed by parvalbumin-expressing GABAergic interneurons, which also regulate fear discrimination. Kv3 voltage-gated potassium channels are highly expressed in these neurons and are important for controlling their activity, suggesting that pharmacological Kv3 modulation may regulate fear discrimination...

In humans, cocaine abuse during adolescence poses a significant risk for developing cognitive deficits later in life. Among the regions responsible for cognitive processes, the medial prefrontal cortex (mPFC) modulates temporal order information via mechanisms involving the mammalian-target of rapamycin (mTOR)-mediated pathway and protein synthesis regulation. Accordingly, our goal was to study the effect of repeated cocaine exposure during both adolescence and adulthood on temporal memory by studying the mTOR pathway in the mPFC...

Co-use of marijuana and tobacco products is the second most common drug combination among adolescents. Nicotine (NIC) and cannabinoid use during adolescence induce similar detrimental changes, raising the hypothesis that simultaneous exposure could result in even more severe outcomes. Thus, we investigated whether the co-exposure to NIC and the synthetic cannabinoid WIN 55,212-2 (WIN) in adolescent mice causes behavioral outcomes different from those observed after exposure to a single drug. Male Swiss mice were exposed twice daily to NIC, WIN, or NIC + WIN during adolescence (PND28-47) or adulthood (PND70-89)...

Various aspects of folate and tetrahydrobiopterin (BH4) metabolism disturbances have been detected in patients with schizophrenia.Data were obtained that disturbances in the pterins (folates and BH4) metabolism can be associated with oxidative stress and inflammation, but has not yet been confirmed in clinical studies in schizophrenia. Within the framework of this study, a correlation and factor analysis of biochemical markersof pterin metabolism, inflammation and redox imbalance in patients with schizophrenia was performed in order to test the hypothesis of the single etiopathogenetic node, including the studied biochemical processes...

The interplay of social, psychological, and biological stresses can trigger mental health conditions such as major depressive disorder (MDD), adjustment disorder, and posttraumatic stress disorder (PTSD). The endocannabinoid system (ECS), comprising endocannabinoids and cannabinoid receptors, is the critical pathway that mediates responses to stress stimuli. This study aimed to investigate the ECS's impact on responding to chronic social instability stress (SIS). Wistar (WIS) rats and an endogenously depressed rat model, Wistar-Kyoto (WKY), were used to evaluate depression- and anxiety-like behavioral responses, cognitive function, hormone levels, and ECS function...

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a level 1a evidence-based treatment for major depression, but high cost of care and limited effectiveness in naturalistic cohorts have been lingering criticisms. This naturalistic, retrospective cohort analysis compares the effect of once and twice daily treatment protocols of rTMS using quality assurance data collected at an Australian private psychiatric hospital. METHODS: A total of 210 inpatients self-selected into two groups receiving up to 30 sessions of either daily (n = 101) or twice daily (n = 109) 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC)...

Dopamine type 2 receptors (D2 Rs) constitute the main molecular target in the pharmacotherapy of schizophrenia. However, the second and third generation of antipsychotics comprises multi-target ligands, also binding serotonin type 3 receptors (5-HT3 Rs) and other receptor classes as well. Here, we examined two experimental compounds (marked compound K1697 and K1700) from the group of 1,4-di-substituted aromatic piperazines, previously described in the study of Juza et al., 2021, and compared them with the chosen reference antipsychotic, aripiprazole...

No abstract text is available yet for this article.

Repeated exposure to substances of abuse results in an increase in some behavioral responses. This phenomenon, called behavioral sensitization (BS), is well described in preclinical models. However, its existence in humans is still a matter of debate. After a review of preclinical evidence of BS and its mechanisms in animal models, we reviewed the evidence supporting the existence of BS in humans, despite the limited research available in this regard. We focused our review on opioids and psychostimulants, since they share the ability to promote addictive behaviors...

Identifying and integrating the neural correlates of suicidal ideation and behaviors is crucial to expand the knowledge and develop targeted strategies to prevent suicide. This review aimed to describe the neural correlates of suicidal ideation, behavior and the transition between them, using different magnetic resonance imaging (MRI) modalities, providing an up-to-date overview of the literature. To be included, the observational, experimental, or quasi-experimental studies must include adult patients currently diagnosed with major depressive disorder and investigate the neural correlates of suicidal ideation, behavior and/or the transition using MRI...

Tardive dyskinesia (TD) is a persistent involuntary complex movement disorder that is known to occur with long-term antipsychotic treatment. Despite being a well-recognized complication of this treatment, its symptoms are often masked by the antipsychotic agents, only to become apparent upon reducing or terminating the treatment. In an effort to advance our understanding of TD pathophysiology and to identify potential therapies, the current study aimed to establish an animal model of TD by administering haloperidol to rats and to evaluate the efficacy of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), in ameliorating TD symptoms...