Talk:Anxiety

From PsychonautWiki
Jump to navigation Jump to search

Neurological Analysis

An overview of the cognitive models for anxiety

A wealth of research demonstrates that anxious individuals display an attentional bias towards threatening sources of information, and this effect is less consistent and typically not observed in non-anxious individuals.

There exists 7 cognitive models with a general lack of agreement, which makes it difficult to understand why attention is biased towards threat in anxious individuals.

The mechanism of attentional biases can best be understood by examining three interrelated aspects of attentional bias:

1) The observed components of attentional bias

  • speed at which attention is drawn to threat stimuli
  • difficulty disengaging attention from threat stimuli (ruled by higher-order cortical structures, such as the prefrontal cortex and its subunits and functionally related structures (e.g., anterior cingulate cortex, orbitofrontal cortex may be neural mechanisms)
  • attentional avoidance of the threat cue

2) The mechanisms that may mediate the expression of these components

  • the amygdala, a brain structure located in the temporal lobes, is critically involved in the processing of fear-related information and expression of fear-related behavior
  • attentional control, the cognitive ability to regulate attentional allocation

3) The stage of information processing during which the mediating mechanisms operate.

  • automatic preconscious processing towards threat
  • strategic processing, processing that is intentional, controllable, capacity-limited, and dependent on awareness such as emotional regulation[1]

Anxious individuals had difficulty in engaging the medial PFC[prefrontal cortex] during the threat condition.

"Behaviorally, monitoring for a mild shock increased the amount of subsequent response interference, consistent with findings that emotion interferes with cognitive performance, especially when the task is more effortful — as when conflict needs to be resolved during incongruent trials. The pattern of behavioral results is also consistent with the idea that threat processing consumes processing resources required for executive control, much like other more phasic emotional manipulations (Pessoa, 2009); but see Hu et al. (in press). Notably, RT interaction effects were positively associated with state anxiety. Thus, participants with higher state anxiety levels showed greater interference during threat (relative to safe). The effect of individual differences in anxiety on cognitive performance has been extensively documented in non-emotional tasks (Bishop, 2009; Eysenck and Calvo, 1992; Eysenck et al., 2007). Effects in tasks involving emotional stimuli have also been reported, such as the emotional Stroop task in which high-anxious participants showed slower responses to stimuli containing threat relative to neutral words (Koven et al., 2003; Williams et al., 1996)."

"In particular, the medial PFC and thalamus are involved in the regulation of anxiety-related behaviors in non-human primates (Kalin et al., 2005). Human neuroimaging studies have described the engagement of the medial PFC (Banks et al., 2007; for review Ochsner and Gross, 2005) and thalamus (Herwig et al., 2007; Goldin et al., 2008) in emotion regulation, too. In the present study, during the cue phase, we observed a negative linear relationship between state anxiety scores and differential responses (threat vs. safe) in both medial PFC and right thalamus. Given the role of the medial PFC and thalamus (Herwig et al., 2007; Goldin et al., 2008; Kalin et al., 2005) in emotion regulation, it is conceivable that the negative relationship reflected the relatively poorer ability of high-anxious individuals to regulate affective responses during shock anticipation. It is noteworthy that the negative relationship was present in the threat condition but not in the safe condition (when the conditions were probed individually), suggesting that the pattern was specific to threat."[2]

Anxious individuals experience time dilation under short intervals

"The main finding from the present study is that the modulation of subjective time perception by stimulus valence in anxious relative to nonanxious individuals is strongly dependent on the duration of the stimulus. With short exposure durations (2 seconds), anxious individuals perceived threat stimuli to last longer than neutral stimuli, whereas non-anxious individuals did not. There were no anxiety-related differences in time perception with stimulus exposures exceeding 2 seconds (i.e., 4- and 8-second durations). We interpret these findings as reflecting enhanced arousal in anxious individuals in response to mild threat stimuli at early stages of stimulus evaluation."[3]

Diet and exercise independently impact the different behavioral domains of anxiety and cognition

Relative abundances of differing gut bacteria are correlated with anxiety and cognition.

"In this study we found that a HFD[High Fat Diet] was able to cause significant anxiety with no rescue by exercise while exercise, but not HFD, was able to enhance cognition. We also found that exercise alone robustly altered the gut microbial community and did not rescue the changes induced by a HFD but, in fact, the changes caused by exercise were completely orthogonal to those induced by a HFD. Additionally, we found numerous, independent associations of specific OTUs and taxa with body weight, anxiety, and cognition that will need to be empirically tested to determine their importance. These data have important public health implications not only in terms of obesity but also determining how the gut microbial community relates to behavioral domains and how it may be used as a biomarker or reshaped to effect changes in anxiety and cognition."[4]

NMDA receptors play a key role

"We recently studied the behaviour of genetically modified mice in which the NR1 subunit of the NMDA receptor was deleted specifically from the granule cells of the dentate gyrus and found evidence for a role for hippocampal NMDA receptors in both learning and anxiety (Niewoehner et al., 2007)."

"So what does the ventral hippocampus do? The nature of the anatomical connections to and from the ventral hippocampus may provide a clue to its function. The ventral sub-region differs markedly from the dorsal sub-region in its anatomical connections (for reviews see Dolorfo and Amaral, 1998, Krettek and Price, 1977, Moser and Moser, 1998). It projects to the prefrontal cortex and is closely connected to the bed nucleus of the stria terminalis (BNST) and the amygdala, as well as other sub-cortical structures which are associated with the hypothalamic-pituitary-adrenal (HPA) axis. This strong connectivity between ventral hippocampus and both the hypothalamus and the amygdala, made it tempting to propose a role for the ventral sub-region in aspects of emotionality."

"There is considerable additional evidence from lesion studies in rodents that the hippocampus is important for anxiety. Hippocampal lesions and, specifically ventral hippocampal lesions, have robust effects on ethologically based, unconditioned laboratory tests of anxiety which generate an approach/avoidance conflict."

"Therefore, studies with transgenic animals with hippocampal-specific NMDA receptor subunit deletions support a key role for hippocampal NMDA receptors in anxiety. However, at present these genetically modified mice are unable to differentiate between contributions from dorsal and ventral sub-regions of the hippocampus. To resolve along these lines a pharmacological approach is required. In a recent study, the NMDA receptor antagonist AP5 has been infused locally into either the dorsal or ventral hippocampus of rats prior to testing on the elevated plus maze (Nascimento Hackl and Carobrez, 2007). This study revealed an anxiolytic effect of 6 and 24 nmol AP5, but only when infused into the ventral hippocampus. There was no effect of the drug on measures of anxiety on the elevated plus maze when infused into dorsal hippocampus, using either AP5 (Nascimento Hackl and Carobrez, 2007) or the related compound AP7 (Padovan et al., 2000). This study thus provides evidence for a role for ventral hippocampal NMDA receptors in anxiety."[5]

Histamine receptors are involved

"The effects of acute H3R blockade on anxiety and cognition (Bongers et al, 2004) differ remarkably from those of constitutive H3R deficiency. Wheras measures of anxiety in anxiety tests involving exploratory behaviour and avoidable anxiety-provoking stimuli such as measured in the elevated plus maze are increased after acute H3R blockade (Bongers et al., 2004), they are decreased under conditions of constitutive H3R deficiency."

"How could H3R deficiency increase AVP[arginine vasopressin] levels in the amygdala? As H3R stimulation inhibits neuronal histamine release and reduces stimulation of H1 receptors, H3R deficiency in the amygdala might increase histamine release, which could increase stimulation of H1 receptors and subsequently increase AVP levels. Such effects might be region-specific. H1 receptor densities were similar in cortex (Toyota et al., 2002) and lower in the hypothalamus (Takahashi et al., 2002) of H3R^-/- than in wild-type mice. In H3R^-/- mice, changes in histamine levels and turnover (Takahashi et al., 2002; Toyota et al., 2002) could have contributed to altered AVP levels. The change in AVP levels could be the result of a compensatory change due to H3R deficiency in utero and/or adulthood. As there were several weeks between behavioural testing and perfusion of the mice, it is unlikely that the changes in AVP levels do not reflect baseline differences and are the result of behavioural stimulation. H3R^-/- mice have normal brain levels of dopamine, norepinephrine and serotonin or any of their metabolites (Toyota et al., 2002)."[6]

Neurobiology

"Anxiety and fear symptoms (e.g., panic, phobias) are regulated by an amygdala-centered circuit. Worry, on the other hand, is regulated by a cortico-striato-thalamocortical (CSTC) loop. These circuits may be involved in all anxiety disorders, with the different phenotypes reflecting not unique circuitry but rather divergent malfunctioning within those circuits."[7]

References

  1. Cisler, J. M., & Koster, E. H. (2010). Mechanisms of attentional biases towards threat in anxiety disorders: An integrative review. Clinical psychology review, 30(2), 203-216. https://doi.org/10.1016/j.cpr.2009.11.003
  2. Choi, J. M., Padmala, S., & Pessoa, L. (2012). Impact of state anxiety on the interaction between threat monitoring and cognition. Neuroimage, 59(2), 1912-1923. https://doi.org/10.1016/j.neuroimage.2011.08.102
  3. Bar-Haim, Y., Kerem, A., Lamy, D., & Zakay, D. (2010). When time slows down: The influence of threat on time perception in anxiety. Cognition and Emotion, 24(2), 255-263. https://doi.org/10.1080/02699930903387603
  4. Kang, S. S., Jeraldo, P. R., Kurti, A., Miller, M. E. B., Cook, M. D., Whitlock, K., ... & Fryer, J. D. (2014). Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Molecular neurodegeneration, 9(1), 36. https://doi.org/10.1186/1750-1326-9-36
  5. Barkus, C., McHugh, S. B., Sprengel, R., Seeburg, P. H., Rawlins, J. N. P., & Bannerman, D. M. (2010). Hippocampal NMDA receptors and anxiety: at the interface between cognition and emotion. European journal of pharmacology, 626(1), 49-56. https://doi.org/10.1016/j.ejphar.2009.10.014
  6. Rizk, A., Curley, J., Robertson, J., & Raber, J. (2004). Anxiety and cognition in histamine H3 receptor−/− mice. European Journal of Neuroscience, 19(7), 1992-1996. https://doi.org/10.1111/j.1460-9568.2004.03251.x
  7. Stahl, S. M., & Stahl, S. M. (2013). Stahl's essential psychopharmacology: neuroscientific basis and practical applications. Cambridge university press. 393.