Thyroid hormone signaling: Contribution to neural function, cognition, and relationship to nicotine

Abstract

Cigarette smoking is common despite its adverse effects on health, such as cardiovascular disease and stroke. Understanding the mechanisms that contribute to the addictive properties of nicotine makes it possible to target them to prevent the initiation of smoking behavior and/or increase the chance of successful quit attempts. While highly addictive, nicotine is not generally considered to be as reinforcing as other drugs of abuse. There are likely other mechanisms at work that contribute to the addictive liability of nicotine. Nicotine modulates aspects of the endocrine system, including the thyroid, which is critical for normal cognitive functioning. It is possible that nicotine’s effects on thyroid function may alter learning and memory, and this may underlie some of its addictive potential. Here, we review the literature on thyroid function and cognition, with a focus on how nicotine alters thyroid hormone signaling and the potential impact on cognition. Changes in cognition are a major symptom of nicotine addiction. Current anti-smoking therapies have modest success at best. If some of the cognitive effects of nicotine are mediated through the thyroid hormone system, then thyroid hormone agonists may be novel treatments for smoking cessation therapies. The content of this review is important because it clarifies the relationship between smoking and thyroid function, which has been ill-defined in the past. This review is timely because the reduction in smoking rates we have seen in recent decades, due to public awareness campaigns and public smoking bans, has leveled off in recent years. Therefore, novel treatment approaches are needed to help reduce smoking rates further.

MorbiNet Study: Hypothyroidism Comorbidity Networks in the Adult General Population

“…Several studies found higher T3 levels in smokers (54). Smoking is associated with hyperthyroidism and negatively associated with hypothyroidism (55) and the prevalence of subclinical hypothyroidism was markedly reduced among smokers (56).…”

Vulnerability of the Hippocampus to Insults: Links to Blood–Brain Barrier Dysfunction

“…Experimental induction of hypothyroidism produces a rapid reduction in hippocampal neurogenesis [372,373]. This is accompanied by selective impairments on tests of HDLM-effects that are well established and replicable [374]. In sum, for humans, there is good evidence for hippocampal impairment in clinical hypothyroidism, but it is unclear if this is first or foremost.…”

Anxiety Disorders in Evolutionary Perspective

“…Hippocampal neurogenesis is thought to play a role in memory, and this may be the mechanism by which thyroid hormone levels influence cognition (21). It has been suggested that thyroid hormone may control the expression of ChAT, the gene responsible for acetylcholine synthesis (22). Hashimoto's encephalopathy is a controversial and poorly understood condition characterised by cognitive dysfunction (in addition to seizures, movement disorders and neuropsychiatric symptoms) associated with thyroid peroxidase antibodies in patients who are euthyroid (23).…”