{"id":2027,"date":"2008-12-10T13:56:43","date_gmt":"2008-12-10T11:56:43","guid":{"rendered":"http:\/\/www.randform.org\/blog\/?p=2027"},"modified":"2020-08-11T23:35:08","modified_gmt":"2020-08-11T21:35:08","slug":"focus-and-context-part-iia-adhd-and-rejection","status":"publish","type":"post","link":"https:\/\/www.randform.org\/blog\/?p=2027","title":{"rendered":"focus and context, part IIa: ADHD and rejection"},"content":{"rendered":"

The following post is in part an answer to a question in a randform comment<\/a>.<\/p>\n


\n<\/p>\n

ADHD<\/a> is a socalled disorder. Among its symptoms are a “unusual way” of focusing\/concentrating. The symptoms of ADHD are gradually. Thus weak forms of ADHD may not necessarily be seen as disorder, but as a normal condition. <\/p>\n

Although the clinical investigations are not yet sufficient there exist strong indications that neurophysiological components play an imminent role in ADHD. And these may also be play a role in understanding rejection.<\/p>\n

In particular the concentration level of a certain neurotransmitter called Dopamine<\/a> seem to be smaller in ADHD patients than in non-ADHD patients, moreover the reuptake of Dopamine seems to be faster in ADHD patients. Since Dopamine steers the neural activity of a lot of neurons (“dopaminergic neurons”), the faster reuptake (and may be also the general lower level) of Dopamine seems to lead to a faster decrease of neural activity\/stimulation (see plasticity<\/a>). Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral tegmental area (VTA)<\/a>. The production of Dopamine can be influenced by components including genetic disposition and nutrition.<\/p>\n

Among others SPECT scans found people with ADHD to have reduced blood circulation (indicating low neural activity), and a significantly higher concentration of dopamine transporters<\/a> in the striatum<\/a>. Medications (such as methylphenidate) thus focused on treating ADHD by blocking the dopamine transporter<\/a> and thus reducing dopamine reuptake in certain areas of the brain, such as those that control and regulate attention. As explained above dopamine is a stimulant, thus methylphenidate increases neural activity.<\/p>\n

The level and reuptake of Dopamine seems to be accompagnied by emotional states, such as motivation (ADHD patients can actually “hyperfocus” if motivated), but as it seems also be connected to negative experiences\/responses:<\/p>\n

In der klinischen Praxis kann in diesem Zusammenhang immer wieder beobachtet werden, dass diese Patienten sich prim\u00e4r an negative und traumatisierende Erlebnisse erinnern. Nur massive Traumata verm\u00f6gen bei ihnen Spuren im Ged\u00e4chtnis zu hinterlassen. Fatalerweise sind es dann in erster Linie diese schmerzhaften Erinnerungen, welche das Grundger\u00fcst des Selbstgef\u00fchls bilden.
\nsource<\/a><\/p><\/blockquote>\n

translation (without guarantee of correctness):
\nIn the clinical practice one can repeatedly observe, that patients recall primarily negative and traumatising experiences. Only massive Traumata may leave Traces in their memory. Badly enough these painful memories are then predominantly the memories which form the basic framework which forms self-assurance. <\/em><\/p>\n

As a result ADHD patients have a tendency to easier develop comorbidities<\/a> such as anxiety disorder, depression etc.<\/p>\n

Emotional memories are partially triggered by activity in the Nucleus accumbens.<\/a>
\nMajor inputs to the nucleus accumbens include prefrontal association cortices, basolateral amygdala, and dopaminergic neurons which are located in the already above mentioned ventral tegmental area (VTA). Due to its role in the development of positive emotions the Nucleus accumbens is also called the “pleasure or reward center” of the brain. <\/p>\n

However research<\/a> suggests that in addition to its prominent role in appetitive learning, the nucleus accumbens (NAC) may also be involved in fear conditioning.<\/p>\n

I couldn’t find a study with regard to this, but it is thus not far fetched to assume that a different activation pattern of the Nucleus accumbens may also be due to a different (way of\/rate of) change of the dopamine level (this may also be a feedback mechanism). On a first guess this could<\/em> imply that the positive activation of the Nucleus accumbens may be less easy for people with e.g. a faster\/differently changing Dopamine level (such as ADHD patients), in particular this different dopamine regulation may<\/em> (again this is guessing) even lead to a rather complete inactivation of the Nucleus accumbens and thus enforce negative emotions, like the above mentioned fear conditioning. Moreover if the Nucleus accumbens is inactivated it could be rather resistent to positive stimulation. As a simple reference: It is generally not easy to cheer someone up who is grumpy.<\/p>\n

Concluding -it may be at least for a certain group of people very important to avoid negative experiences. This could explain also why some people may appear to “hyperreact” when e.g. being critized or rejected. And – it may<\/em> be sensible to focus on investigating the mechanisms of rejection as these may<\/em> dominate the mechanisms of reward. This may also be useful with regard to understanding Traumata<\/a> which may be the result of a severe form of rejection such as in betrayal and abuse.<\/p>\n

In short -it is important to understand why people feel rejected. In particular the experience of rejection is not only an individual feature, but is certainly influenced by other factors, like general societal (e.g. stress) factors, or like cultural conditions, which include religious constructions, conceptions of honor, but also arrangements on how to “institutionally” avoid that people feel rejected. These arrangements may reach as far as from pink slip parties<\/a> to hospices.<\/a><\/p>\n

addition Aug. 11, 2020:
\nThere is a popular science read at the magazine Quanta (“Mitochondria May Hold Keys to Anxiety and Mental Health”<\/a>) about the role of -in particular- mitochondria in the brain in conjunction with neural dysfunctions:<\/p>\n

“mitochondria are often anchored at key positions within neurons, such as near the synapses, apparently to help their function. Mitochondrial effects might also be exerted through the brain\u2019s non-neuronal glial cells, such as the oligodendrocytes that sheath neurons in myelin and the astrocytes that support neurons\u2019 health.”<\/p><\/blockquote>\n

Amongst others it is hypothesized that a: <\/p>\n

“deficit of cellular energy production in critical neural circuits might explain an overall lack of motivation and self-esteem seen in anxiety-prone people.”<\/p><\/blockquote>\n

So in particular:<\/p>\n

When Sandi put rats in competition to establish a social hierarchy, she saw that the animals with less anxiety were more likely to acquire dominant rank. Further study showed that these less anxious animals had greater mitochondrial function in the nucleus accumbens, a part of the brain vital to motivated behavior and the production of effort.<\/p><\/blockquote>\n

The stress hormone cortisol<\/a> seems to play here an important role:<\/p>\n

Specialized receptors carry the cortisol into the nuclei of cells, where it activates about 1,000 genes to help cells prepare for the \u201cfight or flight\u201d response. But the receptors also ferry some of the incoming cortisol into the mitochondria, where it interacts with the mitochondrial DNA and makes energy production more efficient.<\/p><\/blockquote>\n

Some thoughts on that:
\nSince we talked about dopamine here it should be mentioned that dopamine is produced in socalled Dopaminergic cell groups.<\/a> It seems to be currently somewhat well-known that mitochondrial defects are connected with the death of dopaminergic neurons. This connection could thus be a key factor in the question on how mitochondria could be involved in the above described mechanisms of dopamine circulation in the brain and thus in dopamine’s possible role in mental states like anxiety.
\nThe conrete forms of interaction between mitochondria and dopamine seem however not yet so clear. In particular this article from 2008: suggests that “Deleterious effects of dopamine (DA) involving mitochondrial dysfunction have an important role in DA-associated neuronal disorders, including schizophrenia and Parkinson’s disease.”<\/a>
\nHere is now a newer study (“PINK1 Regulates Dopamine and Lipids at Mitochondria to Maintain Synapses and Neuronal Function<\/a> “) which highlights the role of PINK1<\/a> -a mitochondrial kinase:<\/a><\/p>\n

We found that in neuronal progenitors, PINK1 regulates mitochondrial morphology, mitochondrial contact to the endoplasmic reticulum (ER) and the phosphorylation of Miro1. A compensatory metabolic shift towards lipid synthesis provides mitochondria with the components needed for membrane renewal and oxidative phosphorylation, maintaining the mitochondrial network once mature.<\/p>\n

Cholesterol is increased by loss of PINK1, promoting overall membrane rigidity. This alters the distribution of phosphorylated DAT at synapses and impairs dopamine uptake. PINK1 is required for the phosphorylation of tyrosine hydroxylase at Ser19, dopamine and calcium homeostasis and dopaminergic pacemaking.<\/p>\n

We suggest a novel mechanism for PINK1 pathogenicity in Parkinson\u2019s disease in addition to but not exclusive of mitophagy. …<\/p><\/blockquote>\n

At this place it should be mentioned that next to dopamine there are two more monoamine neurotransmitters one could look at, namely norepinephrine<\/a> and in particular Serotonin<\/a>, which is actually more well-known than dopamine to be related to -as Wikipedia says: “modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction.”<\/p>\n","protected":false},"excerpt":{"rendered":"

The following post is in part an answer to a question in a randform comment.<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[24,15,33,8,31],"tags":[],"_links":{"self":[{"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=\/wp\/v2\/posts\/2027"}],"collection":[{"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2027"}],"version-history":[{"count":7,"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=\/wp\/v2\/posts\/2027\/revisions"}],"predecessor-version":[{"id":7457,"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=\/wp\/v2\/posts\/2027\/revisions\/7457"}],"wp:attachment":[{"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2027"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2027"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.randform.org\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2027"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}