Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice

Schizophrenia (SCZ) is a chronic and severe mental disease that affects around 1% of the population. The precise etiology of SCZ still remains largely unknown, and no conclusive mechanisms are firmly established. Recent advances in epidemiological and clinical investigation support an overwhelmingly strong neurodevelopmental origin for SCZ. Here, we demonstrated that Unc-51-like kinase 4 (Ulk4), a novel risk factor for major mental disorders including schizophrenia, is involved in the corticogenesis. Deletion of Ulk4 in mice led to significantly thinner layers of II–III, and V in the cerebral cortex, which was confirmed in conditional Ulk4 deletion mice achieved by Cre-loxp strategy. This abnormality might be caused by decreased intermediate neural progenitors and increased apoptosis. Thus, our data suggest that Ulk4 manipulates the behaviors of neural progenitors during brain development and, when functionally defective, leads to the reduction of specific cortical layers. This anomaly may increase predisposition to a range of neurodevelopmental disorders, including SCZ.

Mental Challenges Facing in India Following the Pandemic-Covid 19

Currently all folks experiencing emotions, thought and situations we've never experienced before. The cholera pandemics followed by the flu pandemic were highlights of the 19th centuary. As Covid 19 initially creps in and subsequently spreads at a galloping pace, it's been ravaging from country after country. The pandemic has significant and variable psychological impact in each country counting on the stage of pandemic foremost response to the pandemic has been fear and sense of clear and imminent danger. Fears have ranged from those supported facts unfounded fears supported information or misinformation circulating within the media. The fears of contracting the illness also are frequent and ranges from misinterpreting every fear or cough as a Covid infection, wanting a test finished reassurance albeit there are strict guidelines for testing. Psychological state issues following Covid19 pandemic include emotional difficulties like depression, anxiety, biological effects like sleep, appetite disturbance also as severe mental disease and substance misuse.

Understanding Schizophrenia: Genetic Causes and Treatment

Schizophrenia is a severe mental disease. The word schizophrenia literally means split mind. There are three major categories of symptoms which include positive, negative and cognitive symptoms. The disease is characterized by symptoms of hallucination, delusions, disorganized thinking and speech. Schizophrenia is related to many other mental and psychological problems like suicide, depression, hallucinations. Including these, it is also a problem for the patient’s family and the caregiver. There is no clear reason for the disease, but with the advances in molecular genetics; certain epigenetic mechanisms are involved in the pathophysiology of the disease. Epigenetic mechanisms that are mainly involved are the DNA methylation, copy number variants. With the advent of GWAS, a wide range of SNPs is found linked with the etiology of schizophrenia. These SNPs serve as ‘hubs’; because these all are integrating with each other in causing of schizophrenia risk. Until recently, there is no treatment available to cure the disease; but anti-psychotics can reduce the disease risk by minimizing its symptoms. Dopamine, serotonin, gamma-aminobutyric acid, are the neurotransmitters which serve as drug targets in the treatment of schizophrenia. Due to the involvement of genetic and epigenetic mechanisms, drugs available are already targeting certain genes involved in the etiology of the disease.

Functional connectomics of affective and psychotic pathology

ABSTRACTConverging evidence indicates that groups of patients with nominally distinct psychiatric diagnoses are not separated by sharp or discontinuous neurobiological boundaries. In healthy populations, individual differences in behavior are reflected in variability across the collective set of functional brain connections (functional connectome). These data suggest that the spectra of transdiagnostic symptom profiles observed in psychiatric patients may map onto detectable patterns of network function. To examine the manner through which neurobiological variation might underlie clinical presentation we obtained functional magnetic resonance imaging (fMRI) data from over 1,000 individuals, including 210 diagnosed with a primary psychotic disorder or affective psychosis (bipolar disorder with psychosis and schizophrenia or schizoaffective disorder), 192 presenting with a primary affective disorder without psychosis (unipolar depression, bipolar disorder without psychosis), and 608 demographically and data-quality matched healthy comparison participants recruited through a large-scale study of brain imaging and genetics. Here, we examine variation in functional connectomes across psychiatric diagnoses, finding striking evidence for disease connectomic “fingerprints” that are commonly disrupted across distinct forms of pathology and appear to scale as a function of illness severity. Conversely, other properties of network connectivity were preferentially disrupted in patients with psychotic illness, but not patients without psychotic symptoms. This work allows us to establish key biological and clinical features of the functional connectomes of severe mental disease.SIGNIFICANCE STATEMENTHistorically, most research on the biological origins of psychiatric illness has focused on individual diagnostic categories, studied in isolation. Mounting evidence suggests nominally distinct psychiatric diagnoses are not separated by clear neurobiological boundaries. Here, we derive functional connectomic signatures in over 1,000 individuals including patients presenting with specific categories of impairment (psychosis), clinical diagnoses, or severity of illness as reflected in treatment seeking. Our analyses revealed features of connectome functioning that are commonly disrupted across distinct forms of pathology, scaling with clinical severity. Conversely, other aspects of network connectivity were preferentially disrupted in patients with psychotic illness, but not patients without psychotic symptoms. These data have important implications for the establishment of functional connectome fingerprints of severe mental disease.

The Portuguese Mental Health Law –the Criteria for Compulsory Internment

The Portuguese Mental Health Law is complex, aiming to ensure patients liberties and basic civil rights are respected. A specific part of this law regards the compulsory internment and its criteria, being as protective as possible, in order to prevent wrongful internments for people against their will.The aim of this study is to analyze the mechanisms available to ensure liberty, in a law apparently about coercion.The methods used consisted in analyzing the law and interpreting its most important details, mentioning them so they can be read and used as examples.It can be concluded that the Portuguese law has a very strict list of mandatory criteria for the possibility of the compulsory internment, as a way of ensuring no people suffer it wrongfully. The most important being that no person can be interned compulsory if not considered to suffer from a severe mental disease, not being that enough and having to at least present risk for themselves or others, or to juridical goods of high value. Thus, revaluation of the patient is mandatory only five days after the internment by two different doctors, being the same process assured from then on every two months. Only possible flaw lays on the fact that there is no maximum amount of time predicted for internment, being that always dependent of the revaluations made. Although, the law is considered to be good and prevent abusive use of the compulsory internments.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The evolution of genomic stability to a mechanism in reproduction and psychiatry

There are two forms of immune defense, the specific or adaptive immune defense and the unspecific innate immune defense. Vaccination is utilized against specific bacteria via the adaptive immune system. The innate immunity DNA stress defense is a non-toxic mechanism developed in yeasts and conserved in mammals and in plants. Although the steroidal hormone cascade has overtaken the stress response and allows superfast response via non-genomic receptors, the old innate immunity response is still mediated via the steroidal hormones cascade. The classical drug/receptor model has provided for many solutions, however, in antibiotics, cancer, and in severe mental diseases this model reaches to certain limits. The NIH/Department of Mental Health has developed a new model that shows severe mental diseases may be immune diseases that can be treated by replacing old diseased nerve cells by new healthy nerve cells, where the old innate immunity may be exploited. This means that severe mental diseases are physical diseases. A newly developed model, where modifications of the steroidal hormone cascade help to understand bipolarity, schizophrenia, and PTSD in men and women can be transferred to gynecological hormone modifications in women, where innate immunity is mediated via the same steroidal hormone cascade. Treatment via immune response via the DNA cascade should be developed in cancer, infections and severe mental disease, because foreign cells or diseased cells may be removed by the unspecific innate immunity.