The monoamine hypothesis has been accepted as the most common hypothesis of major depressive disorder (MDD) for a long period because of its simplicity and understandability. Actually, most currently ...used antidepressants have been considered to act based on the monoamine hypothesis. However, an important problem of the monoamine hypothesis has been pointed out as follows: it fails to explain the latency of response to antidepressants. In addition, many patients with MDD have remained refractory to currently used antidepressants. Therefore, monoamine‐alternate hypotheses are required to explain the latency of response to antidepressants. Such hypotheses have been expected to contribute to identifying hopeful new therapeutic targets for MDD. Past studies have revealed that the volume of the hippocampus is decreased in patients with MDD, which is likely caused by the failure of the hypothalamic–pituitary–adrenal axis and following elevation of glucocorticoids. Two hypotheses have been proposed to explain the volume of the hippocampus: (i) the neuroplasticity hypothesis; and (ii) the neurogenesis hypothesis. The neuroplasticity hypothesis explains how the hippocampal volume is decreased by the morphological changes of hippocampal neurons, such as the shortening length of dendrites and the decreased number and density of spines. The neurogenesis hypothesis explains how the hippocampal volume is decreased by the decrease of neurogenesis in the hippocampal dentate gyrus. These hypotheses are able to explain the latency of response to antidepressants. In this review, we first overview how the neuroplasticity and neurogenesis hypotheses have been developed. We then describe the details of these hypotheses.
Physical activity is one of the modifiable factors of cognitive decline and dementia with the strongest evidence. Although many influential reviews have illustrated the neurobiological mechanisms of ...the cognitive benefits of physical activity, none of them have linked the neurobiological mechanisms to normal exercise physiology to help the readers gain a more advanced, comprehensive understanding of the phenomenon. In this review, we address this issue and provide a synthesis of the literature by focusing on five most studied neurobiological mechanisms. We show that the body’s adaptations to enhance exercise performance also benefit the brain and contribute to improved cognition. Specifically, these adaptations include, 1), the release of growth factors that are essential for the development and growth of neurons and for neurogenesis and angiogenesis, 2), the production of lactate that provides energy to the brain and is involved in the synthesis of glutamate and the maintenance of long-term potentiation, 3), the release of anti-inflammatory cytokines that reduce neuroinflammation, 4), the increase in mitochondrial biogenesis and antioxidant enzyme activity that reduce oxidative stress, and 5), the release of neurotransmitters such as dopamine and 5-HT that regulate neurogenesis and modulate cognition. We also discussed several issues relevant for prescribing physical activity, including what intensity and mode of physical activity brings the most cognitive benefits, based on their influence on the above five neurobiological mechanisms. We hope this review helps readers gain a general understanding of the state-of-the-art knowledge on the neurobiological mechanisms of the cognitive benefits of physical activity and guide them in designing new studies to further advance the field.
•The body’s adaptations to exercise benefit the brain.•A comprehensive overview of the neurobiological mechanisms.•Aerobic and resistance exercise promote the release of growth factors.•Aerobic exercise, Tai Chi and yoga reduce inflammation.•Tai Chi and yoga decrease oxidative stress.
Despite being considered primarily a mood disorder, major depressive disorder (MDD) is characterized by cognitive and decision making deficits. Recent research has employed computational models of ...reinforcement learning (RL) to address these deficits. The computational approach has the advantage in making explicit predictions about learning and behavior, specifying the process parameters of RL, differentiating between model-free and model-based RL, and the computational model-based functional magnetic resonance imaging and electroencephalography. With these merits there has been an emerging field of computational psychiatry and here we review specific studies that focused on MDD. Considerable evidence suggests that MDD is associated with impaired brain signals of reward prediction error and expected value ('wanting'), decreased reward sensitivity ('liking') and/or learning (be it model-free or model-based), etc., although the causality remains unclear. These parameters may serve as valuable intermediate phenotypes of MDD, linking general clinical symptoms to underlying molecular dysfunctions. We believe future computational research at clinical, systems, and cellular/molecular/genetic levels will propel us toward a better understanding of the disease.
Highlights • We propose the ‘exercise-glucocorticoid paradox’. • Similar to chronic stress, exercise increases glucocorticoid. • Chronic stress or glucocorticoid exposure is detrimental to cognition, ...mood and the brain. • Chronic exercise is beneficial to cognition, mood and the brain. • CORT functions to elevate dopamine in the mPFC under exercise but not stress.
Low back pain (LBP) is the most common cause of chronic pain. Numerous clinical scales are available for evaluating pain, but their objective criteria in the management of LBP patients remain ...unclear. This study aimed to determine an objective cutoff value for a change in the Pain Intensity Numerical Rating Scale (ΔPI-NRS) three months after LBP treatment. Its utility was compared with changes in six commonly used clinical scales in LBP patients: Pain Disability Assessment Scale (PDAS), Pain Self-Efficacy Questionnaire (PSEC), Pain Catastrophizing Scale (PCS), Athens Insomnia Scale (AIS), EuroQoL 5 Dimension (EQ5D), and Locomo 25. We included 161 LBP patients treated in two representative pain management centers. Patients were partitioned into two groups based on patient's global impression of change (PGIC) three months after treatment: satisfied (PGIC = 1, 2) and unsatisfied (3-7). Multivariate logistic regression analysis was performed to explore relevant scales in distinguishing the two groups. We found ΔPI-NRS to be most closely associated with PGIC status regardless of pre-treatment pain intensity, followed by ΔEQ5D, ΔPDAS, ΔPSEC, and ΔPCS. The ΔPI-NRS cutoff value for distinguishing the PGIC status was determined by ROC analysis to be 1.3-1.8 depending on pre-treatment PI-NRS, which was rounded up to ΔPI-NRS = 2 for general use. Spearman's correlation coefficient revealed close relationships between ΔPI-NRS and the six other clinical scales. Therefore, we determined cutoff values of these scales in distinguishing the status of ΔPI-NRS≥2 vs. ΔPI-NRS<2 to be as follows: ΔPDAS, 6.71; ΔPSEC, 6.48; ΔPCS, 6.48; ΔAIS, 1.91; ΔEQ5D, 0.08; and ΔLocomo 25, 9.31. These can be used as definitive indicator of therapeutic outcome in the management of chronic LBP patients.
•Suicide is a common cause of death among university students•Students who do not undergo health examinations are at greater risk of suicide•Men and those seeking mental health consultations are also ...at greater risk of suicide•We would like to propose that the annual health examination, in which most of students participate, should be used as a place for creating awareness for mental health problems at university.
To clarify the risk factors for suicide among university students, we collected the data of students who died of any cause from 1992 to 2017 from the accident records of the Yamaguchi University. Sociodemographic and clinical data from the health examination and medical records of the university were examined. Chi-squared analysis was used. Of the 93 students who died, 48 were suicide cases over 26 years. Overall suicide rate was 17.4/100,000 persons. No longitudinally significant difference in suicide rate was seen between the same-age population (1998–2017; 20.0) and the university students. Higher risk of suicide in students was seen among males (odds ratio OR =3.5, 95% confidence interval CI=1.49-8.22; 1992–2017), those who did not undertake a health examination in the year when they died by suicide (OR =5.82, 95% CI =2.41-14.04), and those who had usage history in the center for mental health consultations (OR =23.29, 95% CI =9.03-60.07) from 2006 to 2017. Characteristic risk factor was that they had undergone no health examination, representing unfavorable attitudes towards seeking help. We propose that the annual health examination should be used as a place for creating awareness for mental health problems.
Recent studies have indicated potential links between short bouts of physical activity like stair-climbing and enhanced creative thinking. However, previous research featured limitations, such as ...using an uncommon 3 flights round-trip design and lacking baseline creative thinking evaluations. To rectify these limitations and build a more comprehensive understanding, the present study adopts a between-subjects pretest posttest comparison design to scrutinize the effects of ascending stair-climbing on both divergent and convergent thinking. 52 subjects underwent a pretest, followed by random assignment to one of four interventions: ascending stair-climbing for 2, 5, or 8 flights, or taking an elevator for 8 flights, before progressing to a posttest. The results revealed a notable improvement in convergent thinking, measured by the increased number of solved matchstick arithmetic problems (d = 1.165), for participants who climbed 2 flights of stairs compared to those who took the elevator. However, climbing 5 or 8 flights showed no such impact on convergent thinking, and stair-climbing, regardless of the number of flights, did not influence divergent thinking. These findings underscore the utility of brief stair-climbing as an accessible means to enhance convergent thinking in everyday settings, providing a nuanced insight into the relationship between physical activity and creative thinking processes.
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