scholarly journals Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Neuron ◽  
2015 ◽  
Vol 86 (5) ◽  
pp. 1189-1202 ◽  
Author(s):  
Janine Arloth ◽  
Ryan Bogdan ◽  
Peter Weber ◽  
Goar Frishman ◽  
Andreas Menke ◽  
...  
2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Sevag Kaladchibachi ◽  
Fabian Fernandez

Circadian timekeeping can be reset by brief flashes of light using stimulation protocols thousands of times shorter than those previously assumed to be necessary for traditional phototherapy. These observations point to a future where flexible architectures of nanosecond-, microsecond-, and millisecond-scale light pulses are compiled to reprogram the brain’s internal clock when it has been altered by psychiatric illness or advanced age. In the current review, we present a chronology of seminal experiments that established the synchronizing influence of light on the human circadian system and the efficacy of prolonged bright-light exposure for reducing symptoms associated with seasonal affective disorder. We conclude with a discussion of the different ways that precision flashes could be parlayed during sleep to effect neuroadaptive changes in brain function. This article is a contribution to a special issue onCircadian Rhythms in Regulation of Brain Processes and Role in Psychiatric Disorderscurated by editors Shimon Amir, Karen Gamble, Oliver Stork, and Harry Pantazopoulos.


Author(s):  
Rebecca McKnight ◽  
Jonathan Price ◽  
John Geddes

Organic psychiatric disorders result from brain dys­function caused by organic pathology inside or outside the brain. Dementia is the most common condition, with Alzheimer’s disease alone affecting 1 per cent of the population at 60 years, rising to 40 per cent over 80 years. Many of the rarer organic psychiatric dis­orders tend to affect a wider age range, but present in similar ways. Given the changing demographics of most developed countries, disorders producing cognitive im­pairment in older adults are becoming increasingly important for provision of healthcare services and in daily clinical practice. This chapter will cover the more common causes of cognitive impairment, and there is additional information in Chapters 18 and 20 on psych­iatry of older adults in psychiatry and medicine. There are three common clinical presentations of or­ganic psychiatric disorders: … 1 Delirium— an acute generalized impairment of brain function, in which the most important feature is impairment of consciousness. The disturbance of brain function is generalized, and the primary cause is often outside the brain; for example, sepsis due to a urinary tract infection. 2 Dementia— chronic generalized impairment, in which the main clinical feature is global intellectual impairment. There are also changes in mood and behaviour. The brain dysfunction is generalized, and the primary cause is within the brain; for example, a degenerative condition such as Alzheimer’s disease. 3 Specific syndromes— which include disorders with a predominant impairment of isolated areas; for example, memory (amnesic syndrome), thought, mood, or personality change. These include neurological disorders that frequently result in organic psychological complications; for example, epilepsy…. Table 26.1 lists the main categories of psychiatric disorder associated with organic brain disease. The following sections describe these syndromes and the psychiatric consequences of a number of neurological conditions. Organic causes of other core psychiatric conditions (e.g. anxiety and psychosis) are covered in the relevant specific chapters. Delirium is characterized by an acute impairment of consciousness producing a generalized cognitive impairment. The word delirium is derived from the Latin, ‘lira’, which means to wander from the furrow. Delirium is a common condition, affecting up to 30 per cent of patients in general medical or surgical wards, with the primary cause often being a sys­temic illness. The term ‘acute confusional state’ is a synonym for delirium.


2005 ◽  
Vol 36 (2) ◽  
pp. 108-115 ◽  
Author(s):  
Bernd Saletu ◽  
Peter Anderer ◽  
Gerda M. Saletu-Zyhlarz ◽  
Roberto D. Pascual-Marqui

Different psychiatric disorders, such as schizophrenia with predominantly positive and negative symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function, which in many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a keylock principle, since the drug should normalize the deviant brain function. This is supported by 3–dimensional low-resolution brain electromagnetic tomography (LORETA), which identifies regions within the brain that are affected by psychiatric disorders and psychopharmacological substances.


2020 ◽  
Author(s):  
Wouter J. Peyrot ◽  
Alkes L. Price

AbstractPsychiatric disorders are highly genetically correlated, and many studies have focused on their shared genetic components. However, little research has been conducted on the genetic differences between psychiatric disorders, because case-case comparisons of allele frequencies among cases currently require individual-level data from cases of both disorders. We developed a new method (CC-GWAS) to test for differences in allele frequency among cases of two different disorders using summary statistics from the respective case-control GWAS; CC-GWAS relies on analytical assessments of the genetic distance between cases and controls of each disorder. Simulations and analytical computations confirm that CC-GWAS is well-powered and attains effective control of type I error. In particular, CC-GWAS identifies and discards false positive associations that can arise due to differential tagging of a shared causal SNP (with the same allele frequency in cases of both disorders), e.g. due to subtle differences in ancestry between the input case-control studies. We applied CC-GWAS to publicly available summary statistics for schizophrenia, bipolar disorder and major depressive disorder, and identified 116 independent genome-wide significant loci distinguishing these three disorders, including 21 CC-GWAS-specific loci that were not genome-wide significant in the input case-control summary statistics. Two of the CC-GWAS-specific loci implicate the genes KLF6 and KLF16 from the Kruppel-like family of transcription factors; these genes have been linked to neurite outgrowth and axon regeneration. We performed a broader set of case-case comparisons by additionally analyzing ADHD, anorexia nervosa, autism, obsessive-compulsive disorder and Tourette’s Syndrome, yielding a total of 196 independent loci distinguishing eight psychiatric disorders, including 72 CC-GWAS-specific loci. We confirmed that loci identified by CC-GWAS replicated convincingly in applications to data sets for which independent replication data were available. In conclusion, CC-GWAS robustly identifies loci with different allele frequencies among cases of different disorders using results from the respective case-control GWAS, providing new insights into the genetic differences between eight psychiatric disorders.


2019 ◽  
Vol 20 (13) ◽  
pp. 3207 ◽  
Author(s):  
Hidetoshi Komatsu ◽  
Mamoru Fukuchi ◽  
Yugo Habata

Tremendous advances have been made recently in the identification of genes and signaling pathways associated with the risks for psychiatric disorders such as schizophrenia and bipolar disorder. However, there has been a marked reduction in the pipeline for the development of new psychiatric drugs worldwide, mainly due to the complex causes that underlie these disorders. G-protein coupled receptors (GPCRs) are the most common targets of antipsychotics such as quetiapine and aripiprazole, and play pivotal roles in controlling brain function by regulating multiple downstream signaling pathways. Progress in our understanding of GPCR signaling has opened new possibilities for selective drug development. A key finding has been provided by the concept of biased ligands, which modulate some, but not all, of a given receptor’s downstream signaling pathways. Application of this concept raises the possibility that the biased ligands can provide therapeutically desirable outcomes with fewer side effects. Instead, this application will require a detailed understanding of the mode of action of antipsychotics that drive distinct pharmacologies. We review our current understanding of the mechanistic bases for multiple signaling modes by antipsychotics and the potential of the biased modulators to treat mental disorders.


2015 ◽  
Vol 282 (1805) ◽  
pp. 20142516 ◽  
Author(s):  
Pauline Belujon ◽  
Anthony A. Grace

Although, historically, the norepinephrine system has attracted the majority of attention in the study of the stress response, the dopamine system has also been consistently implicated. It has long been established that stress plays a crucial role in the pathogenesis of psychiatric disorders. However, the neurobiological mechanisms that mediate the stress response and its effect in psychiatric diseases are not well understood. The dopamine system can play distinct roles in stress and psychiatric disorders. It is hypothesized that, even though the dopamine (DA) system forms the basis for a number of psychiatric disorders, the pathology is likely to originate in the afferent structures that are inducing dysregulation of the DA system. This review explores the current knowledge of afferent modulation of the stress/DA circuitry, and presents recent data focusing on the effect of stress on the DA system and its relevance to psychiatric disorders.


2019 ◽  
Vol 26 (1) ◽  
pp. 21-42 ◽  
Author(s):  
Sophie Laguesse ◽  
Dorit Ron

Although historically research has focused on transcription as the central governor of protein expression, protein translation is now increasingly being recognized as a major factor for determining protein levels within cells. The central nervous system relies on efficient updating of the protein landscape. Thus, coordinated regulation of mRNA localization, initiation, or termination of translation is essential for proper brain function. In particular, dendritic protein synthesis plays a key role in synaptic plasticity underlying learning and memory as well as cognitive processes. Increasing evidence suggests that impaired mRNA translation is a common feature found in numerous psychiatric disorders. In this review, we describe how malfunction of translation contributes to development of psychiatric diseases, including schizophrenia, major depression, bipolar disorder, and addiction.


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