Many neurotransmitters
Neurotransmitter
Neurotransmitters are endogenous chemicals that enable neurotransmission. It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron to another "target" neuron, muscle cell, or gland cell. Neurotransmitt…
gamma-Aminobutyric acid
gamma-Aminobutyric acid, or γ-aminobutyric acid, or GABA, is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly respon…
What neurotransmitters are involved in generalized anxiety disorder?
Amino acid neurotransmitters. Dysregulation of GABA inhibitory neurotransmission has been documented in several anxiety disorders (reviewed in 124 ). GABA A receptor downregulation is observed in patients who have GAD and has been hypothesized to play a role in the etiology of this illness (reviewed in 68 ).
Is dysregulation of neurotransmitters unique to mood and anxiety disorders?
Disruption in neurotransmitter, neuropeptide, and neuroendocrine signaling is not unique to mood and anxiety disorders; a great deal of overlap between diagnostic syndromes should be expected. For example, dysregulation of the generalized stress response is common to numerous medical and psychiatric diagnoses.
Which neurotransmitters are involved in the pathophysiology of depression?
a. Norepinephrine b. Serotonin d. Acetylcholine Postmortem and/or brain imaging studies of individuals with depression reveal a widespread decrease in serotonin 5-HT1A-receptor subtype binding in frontal, temporal, and limbic cortex, as well as serotonin-transporter binding in cerebral cortex and hippocampus.
Is GABA inhibitory neurotransmitter downregulated in anxiety disorders?
Dysregulation of GABA inhibitory neurotransmission has been documented in several anxiety disorders (reviewed in124). GABAAreceptor downregulation is observed in patients who have GAD and has been hypothesized to play a role in the etiology of this illness (reviewed in68).
What is glutamate in PTSD?
Glutamate plays a critical role in hippocampal-dependent associative learning and in amygdala-dependent emotional processing in stressful conditions or following stress exposure. Inappropriate glutamate signaling therefore could contribute to the processing distortion experienced by many patients who have PTSD.
What is the role of the amygdala in the development of fear?
The amygdala is responsible for the expression of fear and aggression as well as species-specific defensive behavior, and it plays a role in the formation and retrieval of emotional and fear-related memories. (Fig. 2depicts the amygdala’s involvement in fear circuitry).
What genes are associated with high behavioral inhibition?
Genes associated with high behavioral inhibition include CRFand SERT. Internalizing neuroticism is associated with the gene encoding glutamic acid decarboxylase, the rate-limiting enzyme in the synthesis of GABA from glutamate (reviewed in107). GENERALIZED ANXIETY DISORDER.
What is mood disorder?
Mood and anxiety disorders are characterized by a variety of neuroendocrine, neurotransmitter, and neuroanatomical disruptions. Identifying the most functionally relevant differences is complicated by the high degree of interconnectivity between neurotransmitter- and neuropeptide-containing circuits in limbic, brain stem, ...
Which brain regions are responsible for interpreting social behavior?
The brain regions responsible for interpreting social behavior include the superior temporal gyrus, thalamus, and PFC. Amygdala hyperactivity may mediate the inaccurate interpretations of social behavior in patients who have GAD.120. Neurotransmitter and Neuroendocrine Signaling in Generalized Anxiety Disorder.
Which brain regions are activated by emotional stimuli?
In healthy subjects and in recently deployed veterans of war who have PTSD, presentation of emotional stimuli, as compared with neutral stimuli, elicits activation in ventral frontolimbic brain regions, including the ventromedial PFC, inferior frontal gyrus , and ventral anterior cingulate gyrus.
Which steroid is the main stress steroid?
In humans, the main stress steroid is cortisol; in rats it is corticosterone. HPA axis activity is regulated by numerous other limbic system structures, including the amygdala, which enhances HPA axis activity, and the hippocampus, which suppresses HPA axis activation (Fig. 3). Open in a separate window.
How does behavioral therapy help with anxiety?
Thus, behavioral therapy enables an individual to re-learn conditioned responses (behaviors) and to thereby challenge behaviors that have become conditioned responses to fear and anxiety , and which have previously given rise to further maladaptive behaviors.
What is the pathophysiology of GAD?
The pathophysiology of GAD is an active and ongoing area of research often involving the intersection of genetics and neurological structures. Generalized anxiety disorder has been linked to changes in functional connectivity of the amygdala and its processing of fear and anxiety. Sensory information enters the amygdala through the nuclei of the basolateral complex (consisting of lateral, basal and accessory basal nuclei). The basolateral complex processes the sensory-related fear memories and communicates information regarding threat importance to memory and sensory processing elsewhere in the brain, such as the medial prefrontal cortex and sensory cortices. Neurological structures traditionally appreciated for their roles in anxiety include the amygdala, insula and orbitofrontal cortex (OFC). It is broadly postulated that changes in one or more of these neurological structures are believed to allow greater amygdala response to emotional stimuli in individuals who have GAD as compared to individuals who do not have GAD.
What is the diagnosis of GAD?
The diagnostic criteria for GAD as defined by the Diagnostic and Statistical Manual of Mental Disorders DSM-5 (2013) , published by the American Psychiatric Association, are paraphrased as follows: "Excessive anxiety or worry" experienced most days over at least six month and which involve a plurality of concerns.
Can benzodiazepines cause anxiety?
While there are no substances that are known to cause generalized anxiety disorder (GAD), certain substances or the withdrawal from certain substances have been implicated in promoting the experience of anxiety. For example, even while benzodiazepines may afford individuals with GAD relief from anxiety, withdrawal from benzodiazepines is associated with the experience of anxiety among other adverse events like sweating and tremor.
Is there a genetic basis for anxiety?
The relationship between genetics and anxiety disorders is an ongoing area of research. It is broadly understood that there exists an hereditary basis for GAD, but the exact nature of this hereditary basis is not fully appreciated. While investigators have identified several genetic loci that are regions of interest for further study, there is no singular gene or set of genes that have been identified as causing GAD. Nevertheless, genetic factors may play a role in determining whether an individual is at greater risk for developing GAD, structural changes in the brain related to GAD, or whether an individual is more or less likely to respond to a particular treatment modality. Genetic factors that may play a role in development of GAD are usually discussed in view of environmental factors (e.g., life experience or ongoing stress) that might also play a role in development of GAD. The traditional methods of investigating the possible hereditary basis of GAD include using family studies and twin studies (there are no known adoption studies of individuals who suffer anxiety disorders, including GAD ). Meta-analysis of family and twin studies suggests that there is strong evidence of a hereditary basis for GAD in that GAD is more likely to occur in first-degree relatives of individuals who have GAD than in non-related individuals in the same population. Twin studies also suggest that there may be a genetic linkage between GAD and major depressive disorder (MDD), which may explain the common occurrence of MDD in individuals who suffer GAD (e.g., comorbidity of MDD in individuals with GAD has been estimated at approximately 60% ). When GAD is considered among all anxiety disorders (e.g., panic disorder, social anxiety disorder), genetic studies suggest that hereditary contribution to the development of anxiety disorders amounts to only approximately 30-40%, which suggests that environmental factors are likely more important to determining whether an individual may develop GAD. In regard to environmental influences in the development of GAD, it has been suggested that parenting behaviour may be an important influence since parents potentially model anxiety-related behaviours. It has also been suggested that individuals who suffer GAD have experienced a greater number of minor stress-related events in life and that the number of stress-related events may be important in development of GAD (irrespective of other individual characteristics).
Is there a genetic linkage between GAD and MDD?
Twin studies also suggest that there may be a genetic linkage between GAD and major depressive disorder (MDD), which may explain the common occurrence of MDD in individuals who suffer GAD (e.g., comorbidity of MDD in individuals with GAD has been estimated at approximately 60% ).
What is the diagnosis of anxiety disorder?
Anxiety, experienced as excessive, uncontrollable worry about a variety of topics In the absence of respective stimuli or In a manner disproportionate to their potentially posed risk, is the key diagnostic criterion of generalized anxiety disorder (GAD). 1 GAD poses an epidemiological challenge, and with a comparably late age at which sufferers receive a correct diagnosis and a considerable comorbidity with other anxiety disorders, depressive disorders, as well as trauma- and stressor-related disorders. 2 Its etiological interrelatedness with dimensional measures of trait anxiety, such as pathological worry, fear of uncertainty, or neuroticism, and Its high rate of treatment resistance have attracted the attention of psychiatric geneticists aiming at identifying biomarkers of disease risk and treatment response.
What is the first line of pharmacotherapy for GAD?
The drug classes of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors ( SNRIs) have generally been considered part of the first-line pharmacotherapies for GAD, whereupon the SSRI escitalopram and the SNRIs venlafaxine and duloxetine (both approved by the US Food and Drug Administration for the treatment of GAD) have received the most attention in studies exploring the potential of genetic markers to predict treatment response or side effects.
What is GAD genetics?
This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism. We inspect clinical genetic evidence for the familialityl heritability of GAD and cross-disorder phenotypes based on family and twin studies. Recent advances of linkage studies, genome-wide association studies, and candidate gene studies (eg, 5-HTT, 5-HT1A, MAOA, BDNF) are outlined. Functional and structural neuroimaging and neurophysiological readouts relating to peripheral stress markers and psychophysiology are further integrated, building a multilevel disease framework. We explore etiologic factors in gene-environment interaction approaches investigating childhood trauma, environmental adversity, and stressful life events in relation to selected candidate genes ( 5-HTT, NPSR1, COMT, MAOA, CRHR1, RGS2 ), Additionally, the pharmacogenetics of selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor treatment are summarized ( 5-HTT, 5-HT2A, COMT, CRHR1 ). Finally, GAD and trait anxiety research challenges and perspectives in the field of genetics, including epigenetics, are discussed.
What are the factors that influence the incidence of GAD?
Besides childhood traumata, gene-environment approaches have explored a variety of external factors potentially influencing GAD incidence rate or intermediate phenotype intensity, ranging from daily stressors and family environment to natural disasters.
Is there a linkage study for GAD?
To the best of our knowledge, there is no linkage study available focusing on GAD proper. However, genome-wide linkage analysis of extreme neuroticism personality traits (highest scoring 10th percentile on the Neuroticism-Extraversion-Openness Personality Inventory [NEO]) in 2657 individuals revealed suggestive evidence for loci on chromosomes 19q13, 21q22, and 22q11. 16 Additionally, a meta-analytical combination of eight independent neuroticism (EPQ) genome -wide linkage studies in 14 811 individuals found nominally significant risk loci on chromosomes 9, 11, 12, and 14. 17
Is anxiety related to separation anxiety?
Within the anxiety spectrum, it is closely related to childhood separation anxiety, social phobia, and panic, whereas during later developmental stages, a shared genetic origin with other internalizing disorders, especially MDD, becomes apparent.
Is GAD a genetic disorder?
GAD is a heritable condition with a moderate genetic risk (heritability of approximately 30%). Within the anxiety spectrum, it is closely related to childhood separation anxiety, social phobia, and panic, whereas during later developmental stages, a shared genetic origin with other internalizing disorders, especially MDD, becomes apparent. This overlap with PD and MDD can partially be explained by genetic contributions toward neuroticism. The most promising GWAS on trait anxiety severity or latent anxiety disorder factor scores detected encouraging hits in THBS2 and CAMKMT, in addition to studies centered around neuroticism, pointing repeatedly toward SNPs in an inversion polymorphism on chromosome 8, which showed extended genetic correlation with an anxiety disorder phenotype, Moreover, in candidate gene studies—partly combined with imaging and physiological readouts—converging evidence has been gathered for GAD susceptibility genes within the serotonergic and calecholaminergic systems ( 5-HTT, 5-HT1A, MAOA) as well as for the BDNF gene. Furthermore, gene-environment studies have highlighted the importance of early developmental trauma and recent stressful life events in interaction with molecular plasticity markers and their combined relevance to GAD, trait anxiety, and anxiety sensitivity ( 5-HTT, NPSR1, COMT, MAOA, CRHR1, RGS2 ). Finally, pharmacogenetic approaches applied to SSRI and SNRI treatment of GAD point to a potentially predictive role of serotonergic candidate genes ( 5-HTT, 5-HT2A ), as well as the COMT and CRHR1 genes. Broader predictive investigations of the GAD disease course development and trait anxiety therapy response might benefit from the growing impact of epigenetics in neuropsychiatry, defining a compelling cross-link between genomic load and personal history. In summary, this line of research is expected to aid in the identification of neurobiological disease risk and treatment response markers for indicated preventive and individualized therapeutic approaches in the overall effort to more effectively lower the individual and socioeconomic burden of GAD.