Understanding the genetics and neurobiological pathways behind addiction (Review).

The hypothesis issued by modern medicine states that many diseases known to humans are genetically determined, influenced or not by environmental factors, which is applicable to most psychiatric disorders as well. This article focuses on two pending questions regarding addiction: Why do some individuals become addicted while others do not? along with Is it a learned behavior or is it genetically predefined? Recent data suggest that addiction is more than repeated exposure, it is the synchronicity between intrinsic factors (genotype, sex, age, preexisting addictive disorder, or other mental illness), extrinsic factors (childhood, level of education, socioeconomic status, social support, entourage, drug availability) and the nature of the addictive agent (pharmacokinetics, path of administration, psychoactive properties). The dopamine-mesolimbic motivation-reward-reinforcement cycle remains the most coherent physiological theory in addiction. While the common property of addictive substances is that they are dopamine-agonists, each class has individual mechanisms, pharmacokinetics and psychoactive potentials.

Neuroplasticity and depression: Rewiring the brain's networks through pharmacological therapy (Review).

In modern society, depression is one of the most common mental illness; however, its pathophysiology is not yet fully understood. A great body of evidence suggests that depression causes changes in neuroplasticity in specific regions of the brain which are correlated to symptom severity, negative emotional rumination as well as fear learning. Depression is correlated with atrophy of neurons in the cortical and limbic brain regions that control mood and emotion. Antidepressant therapy can exhibit effects on neuroplasticity and reverse the neuroanatomical changes found in depressed patients. The investigation of fast-acting agents that reverse behavioral and neuronal deficiencies of chronic depression, especially the glutamate receptor antagonist NMDA ketamine, and the cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are of real interest in current research. Actual medication such as serotonin (5-HT) selective reuptake inhibitor (SSRI) antidepressants, require weeks to months of administration before a clear therapeutic response. The current review aimed to underline the negative effects of depression on neuroplasticity and present the current findings on the effects of antidepressant medication.

Long-term histological results of ossicular chain reconstruction using bioceramic implants.

Middle ear problems are addressed using tympanoplasty, which requires a mobile tympanic membrane and secure sound-conducting mechanism. The present is a long-term, retrospective, non-controlled study on the results of ossiculoplasty using bioceramic implants of autochthonous origin and which defined the statistical relevant factors that could influence the rate of implant rejection. In a cohort of 108 patients ossiculoplasties with bioceramic implants were performed and patients were followed up clinically for a period of minimum 7 years. Several factors were identified that could influence the results of the implantation and the statistical correlations were studied. The rejection rate after 9.12 years was 21% (23 patients). Histological integration rate was 79% (85 patients), similar to results reported in literature for both bioceramic and titanium implants. Hydroxyapatite has many of the ideal characteristics required to be a good prosthesis with a high degree of biocompatibility, very low extrusion rate, low risk of disease transmission and good functional results. Although perhaps considered of historical interest, bioceramic implants are cheaper and can be produced locally, which is a great advantage for struggling economies.

Efficacy of electroconvulsive therapy as a potential first-choice treatment in treatment-resistant depression (Review).

Electroconvulsive therapy (ECT) is a technique that has been used since 1938 to treat several psychiatric disorders as a replacement for chemically induced seizures. Despite its history of stigma, controversy and low accessibility, ECT is found to be beneficial and efficient in severe cases of depression where medication fails to bring results. Titration tables developed over time, based on evidenced-based medicine, have made this treatment technique safe and, in some cases, the first choice of treatment. The aim of the review was to summarize the research conducted on the efficacy of ECT on major depressive disorder and variables studied such as technique, comorbidities and medication as well as the effects and outcomes of this procedure. At the same time, the application and correlations with other psychiatric and neurological disorders, including catatonia, agitation and aggression in individuals with dementia, schizophrenia, and epilepsy were assessed. There are no statistically demonstrated effects due to the fact that a small number of moderate-quality studies have been published; however, the combination of ECT technique with standard medication and care, can improve patient outcome. Furthermore, with regard to ECT, widespread and robust volume changes in both cortical and subcortical regions have been shown. Antidepressant response and volumetric increases appear to be limited by the specific neuroplasticity threshold of each patient.

Korsakoff syndrome: An overlook (Review).

This review aimed to analyze the latest neurobiological findings regarding Korsakoff syndrome, since alcoholism is the most prevalent addiction worldwide. In addition, we analyzed the optimal treatment that can be administered in order to minimize the symptoms and improve the outcome of these patients. The disruption of memory circuits within the brain of alcoholic patients results in the amnestic syndrome known as Korsakoff syndrome. It is generally characterized by a chronic neuropsychiatric syndrome caused by vitamin B1 (thiamine) deficiency. Other categories of patients can develop Korsakoff syndrome without consuming alcohol such as AIDS patients, terminally ill cancer patients, or patients with chronic infections and malnutrition. Vitamin B1 is required in the Krebs cycle for production of adenosine triphosphate (ATP). It is also a cofactor in the production of acetylcholine and certain neurotransmitters. Alcohol consumption can decrease the intake, gastrointestinal absorption and cellular utilization of vitamin B1. Treatment of alcohol withdrawal along with high doses of vitamin B1 can improve the general outcome of patients. A small percentage of patients can recover from Wernicke's encephalopathy with no permanent brain damage. The onset of Korsakoff syndrome darkens the prognosis. Alcohol abstinence is an absolute recommendation and prevents the extension of neural damage.

Immunological and hormonal mechanisms in Alzheimer's disease.

Alzheimer's disease (AD) is a disorder which is today treated and approached at the crossroad of two medical specialties - psychiatry and neurology. The insidious onset which can often mimic depressive disorders or other type of psychiatric disorders, the behavioral changes, the paranoid thoughts usually send people to the psychiatrist, while the brain changes observed on magnetic resonance imaging (MRI) scans and other imaging techniques may indicate the need for neurological monitoring also. The complex symptomatology and progression of this dementia requires a multidisciplinary approach and recent studies focused on adding a third perspective: a metabolic one. The common findings regarding type 2 diabetes and AD made some researchers to informally name it "the third type diabetes". This mini review aims to highlight the mechanisms through which brain insulin resistance can lead to cognitive impairment and to make a short overview of the current findings which demonstrate why insulin may be a promising adjunctive treatment of Alzheimer's dementia, for certain patients.

Morphopathological changes in obsessive-compulsive disorder.

The pathophysiology of the obsessive-compulsive disorder (OCD) has been studied for many years using several structural magnetic resonance imaging, discovering that the anomalies of function and structure of the brain are widespread, they involve different areas, structures and circuits with a complex interconnectivity. More than that, these anomalies cover all the life of a patient, from early childhood, due to variations of developmental stages until adult life. The research is highly important also because OCD has a major hereditary factor, with the phenotype variance between 27-47% due to hereditary factors. Under this paper, that follows last 10 years studies in this area, we will find some relevant findings consisting on neuroanatomic changes, the morphology findings of striatum, globus pallidus and thalamus, the blood flow circuit changes in various regions of the brain, brain connectivity and various correlations of them. Not to forget that OCD must be understand as an emotional disorder but in the same time as a cognitive disorder too. This approach highlights the abnormalities that have been found in brain regions involved in the cognitive and emotional behavior, as for example: extended temporal, parietal, and occipital regions, anterior cingulate, frontal gyrus, amygdala.

Morphopathological approaches in alcoholism.

Alcohol morphopathology has been studied over time, being a central interest of specialists, due to the negative consequences it has on the brain and the entire central nervous system (CNS). This paper is a review of the literature that emphasizes one of the problems of the modern world, that of the compulsive consume of alcohol, having a great global spread. The studies analyzed are topical, being carried out in recent years and consider the harmful effects of alcohol on brain formations, such as corpus callosum, gray and white matter, hippocampus, and hypothalamus. At the same time, alcohol is a risk factor for cardiovascular diseases, and in combination with other harmful substances, increases the risk of various diseases, such as neurodegeneration. Abusive alcohol consumption can bring epigenetic changes and alter the typical functioning of cognitive functions. This paper focuses on alcohol consumption on adolescents and young people, which is a serious problem nowadays. Alcohol also influences the way of behavioral expression, becoming a risk for the development of mental disorders. However, alcohol withdrawal is another problem with different effects and must be in the attention of specialists.

Clozapine: An Updated Overview of Pharmacogenetic Biomarkers, Risks, and Safety-Particularities in the Context of COVID-19.

BACKGROUND: clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. OBJECTIVE: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. DATA SOURCES: a search was performed in two databases (PubMed and Web of Science) using the specific keywords "clozapine" and "schizophrenia", "side effects", "agranulocytosis", "TRS", or "bipolar affective disorder (BAF)" for the last ten years. STUDY ELIGIBILITY CRITERIA: clinical trials on adults with acute symptoms of schizophrenia or related disorders. RESULTS: we selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. LIMITATIONS: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions' severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.