Drug addiction, schizophrenia

Women with schizophrenia have specific health needs that differ from those of men and that change through successive life stages. We aimed to review the biopsychosocial literature on schizophrenia that addresses clinically important questions related to the treatment of women, including somatic morbi-mortality, hyperprolactinemia, comorbid substance use disorders, social risk factors, and medication effectiveness/safety. Data search terms were as follows: (Morbidity AND mortality) OR hyperprolactinemia OR ("substance use disorders" OR addictions) OR ("social risk factors") OR ("drug safety" OR prescription) AND women AND schizophrenia...

The M4 muscarinic acetylcholine receptor (M4 mAChR) has emerged as a drug target of high therapeutic interest due to its expression in regions of the brain involved in the regulation of psychosis, cognition, and addiction. The mAChR agonist, xanomeline, has provided significant improvement in the Positive and Negative Symptom Scale (PANSS) scores in a Phase II clinical trial for the treatment of patients suffering from schizophrenia. Here we report the active state cryo-EM structure of xanomeline bound to the human M4 mAChR in complex with the heterotrimeric Gi1 transducer protein...

Alcohol consumption has been linked to numerous negative health outcomes although it has some beneficial effects on moderate dosages, the most severe of which being alcohol-induced hepatitis. The number of people dying from this liver illness has been shown to climb steadily over time, and its prevalence has been increasing. Researchers have found that alcohol consumption primarily affects the brain, leading to a wide range of neurological and psychological diseases. High-alcohol-consumption addicts not only experienced seizures, but also ataxia, aggression, social anxiety, and variceal hemorrhage that ultimately resulted in death, ascites, and schizophrenia...

N-Methyl-D-aspartate receptors (NMDARs) composed of different splice variants display distinct pH sensitivities and are crucial for learning and memory, as well as for inflammatory or injury processes. Dysregulation of the NMDAR has been linked to diseases like Parkinson's, Alzheimer's, schizophrenia, and drug addiction. The development of selective receptor modulators, therefore, constitutes a promising approach for numerous therapeutical applications. Here, we identified (R)-OF-NB1 as a promising splice variant selective NMDAR antagonist...

(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as 'K2', 'K9' or 'Spice'. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances...

Neurodegenerative diseases (NDDs) and neuropsychiatric disorders (NPDs) are two common causes of death in elderly people, which includes progressive neuronal cell death and behavioral changes. NDDs include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and motor neuron disease, characterized by cognitive defects and memory impairment, whereas NPDs include depression, seizures, migraine headaches, eating disorders, addictions, palsies, major depressive disorders, anxiety, and schizophrenia, characterized by behavioral changes...

The polygenic nature of neurological and psychiatric syndromes and the significant impact of environmental factors on the underlying developmental, homeostatic, and neuroplastic mechanisms suggest that an efficient therapy for these disorders should be a complex one. Pharmacological interventions with drugs selectively influencing the epigenetic landscape (epidrugs) allow one to hit multiple targets, therefore, assumably addressing a wide spectrum of genetic and environmental mechanisms of central nervous system (CNS) disorders...

The neurotensin receptor 1 (NTS1 ) is a G protein-coupled receptor (GPCR) with promise as a drug target for the treatment of pain, schizophrenia, obesity, addiction, and various cancers. A detailed picture of the NTS1 structural landscape has been established by X-ray crystallography and cryo-EM and yet, the molecular determinants for why a receptor couples to G protein versus arrestin transducers remain poorly defined. We used 13 Cε H3 -methionine NMR spectroscopy to show that binding of phosphatidylinositol-4,5-bisphosphate (PIP2) to the receptor's intracellular surface allosterically tunes the timescale of motions at the orthosteric pocket and conserved activation motifs - without dramatically altering the structural ensemble...

OBJECTIVE: The purpose of this study was to assess HIV risk, perceptions of risk, and potential adherence to preexposure prophylaxis (PrEP) for the prevention of HIV infection among people who inject drugs (PWID), who self-report HIV negative status and access mobile outreach intravenous drug use (IVDU) services. METHODS/SAMPLE: Participants (N = 93) were non-Hispanic White (59.1%) and Hispanic (36.6%), between the ages of 18 and 63 years, primarily male (58.1%), who reported a length of IVDU between 1 and >20 years and accessed mobile outreach IVDU services in a metropolitan area of the Southwestern United States; all self-reported HIV-negative status...

Synaptic modification in postnatal development is essential for the maturation of neural networks. Developmental maturation of excitatory synapses occurs at the loci of dendritic spines that are dynamically regulated by growth and pruning. Striatal spiny projection neurons (SPNs) receive excitatory input from the cerebral cortex and thalamus. SPNs of the striatonigral direct pathway (dSPNs) and SPNs of the striatopallidal indirect pathway (iSPNs) have different developmental roots and functions. The spatial and temporal dynamics of dendritic spine maturation of these two types of SPNs remain elusive...

BACKGROUND: Research on child sexual abuse increasingly focuses on sexually offending females; however, there is a lack of research that focuses on the individuals being affected. Studies have suggested that the consequences for those affected by sexually offending males and females are comparable. OBJECTIVE: The aim is to compare mental health consequences of sexual abuse perpetrated by women versus men in quantity and type. PARTICIPANTS AND SETTING: Data was anonymously retrieved from the German-wide contact point "help line sexual abuse" from 2016 to 2021...

Transcranial magnetic stimulation (TMS) is a method of noninvasive brain stimulation developed since the 1980s. Repetitive transcranial magnetic stimulation (rTMS) is one of the methods of noninvasive brain stimulation, which is increasingly used to treat psychiatric disorders. Recent years witnessed a dynamic growth in the number of sites offering therapy with rTMS and of the interest of patients in this method in Poland. This article presents the position statement of the working group of the Section of Biological Psychiatry of the Polish Psychiatric Association concerning the proper patients selection and safety of use of rTMS in the therapy of psychiatric conditions...

Trace amines are endogenous molecules distributed in the central nervous system and peripheral tissues that resemble common biogenic amines in terms of subcellular localization, chemical structure, and metabolism. Trace amine-associated receptor (TAAR) is a kind of evolutionarily conserved G-protein-coupled receptors in vertebrates, in which TAAR1 is a functional regulator of monoamine transmitters such as dopamine and serotonin. TAAR1 is widely considered as a potential therapeutic target for schizophrenia, depression and drug addiction...

Endocannabinoids (eCBs) and the expanded endocannabinoid system (ECS)-"endocannabinoidome", consists of the endogenous ligands, eCBs, their canonical and non-canonical receptor subtypes, and their synthesizing and metabolizing enzymes. This system modulates a wide range of body functions and acts as a retrograde signaling system within the central nervous system (CNS) by inhibition of classical transmitters, and plays a vital modulatory function on dopamine, a major neurotransmitter in the CNS. Dopamine is involved in different behavioral processes and contributes to different brain disorders-including Parkinson's disease, schizophrenia, and drug addiction...

Schizophrenia patients demonstrate variations in response to different therapies that are currently being used for the treatment of disorders, such as augmentation therapy (ECT or mood stabilizer) and combination therapy (with antipsychotics). These therapies are also used to treat schizophrenia patients in Pakistan; however, patients show poor overall response. Therefore, this study was conducted to investigate the association between the patients' response to treatment and the use of antipsychotic agents, with variability in overall response, within different groups of patients...

OBJECTIVE: Prolonged social withdrawal (PSW) or hikikomori and problematic internet use (PIU) have attracted the attention of mental health experts worldwide. The scientific literature suggests a complex relationship between these conditions and psychotic-like experiences (PLEs) or disorders. In the present cross-sectional study, we tested the role of PIU symptoms as a moderator of the relationship between symptoms of PSW and PLEs in a sample of 238 Italian emerging adults. METHOD: Data was collected using the 25-item Hikikomori Questionnaire, the Internet Disorder Scale, the Brief Prodromal Questionnaire, and the Brief Symptom Inventory...

The aim of the study was to evaluate factors that may contribute to the persistence of positive, negative and other psychopathological symptoms of schizophrenia. All patients were treated in general psychiatric wards between January 2006 and December 2017. The initial study sample comprised of the medical reports of 600 patients. The main, specified inclusion criterion for the study was schizophrenia as a discharge diagnosis. Medical reports of 262 patients were excluded from the study due to no neuroimaging scans being available...

Substance use disorders are more prevalent in schizophrenia, but the causal links between both conditions remain unclear. Maternal immune activation (MIA) is associated with schizophrenia which may be triggered by stressful experiences during adolescence. Therefore, we used a double-hit rat model, combining MIA and peripubertal stress (PUS), to study cocaine addiction and the underlying neurobehavioural alterations. We injected lipopolysaccharide or saline on gestational days 15 and 16 to Sprague-Dawley dams...

We recently reported an economic choice task in which squirrel monkeys chose between differing amounts of remifentanil, a fast-acting opioid, or a food reward to develop a preclinical screen for evaluating potential pharmacotherapies for opioid dependence. Herein, two known opioid addiction treatments are evaluated using this task, as well as a potential new agent, cariprazine, a dopamine D2/D3 receptor partial agonist currently used to treat bipolar disorder and schizophrenia. Preclinical rodent studies suggest this class of compounds may reduce opiate self-administration...

Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the association between opioid addiction, withdrawal, and schizophrenia. Thus, we exposed zebrafish larvae at 2 days post-fertilization (dpf) to domperidone (DPM) and morphine, followed by morphine withdrawal. Drug-induced locomotion and social preference were assessed, while the level of dopamine and the number of dopaminergic neurons were quantified...