Brata Et Al. 2025
Brata Et Al. 2025
https://doi.org/10.1057/s41599-025-04484-w OPEN
                  Academic stress, which is a frequent experience for university students, has been demon-
                  strated to have a considerable effect on their academic performance. However, the con-
                  ceptual basis linking the biological mechanism of stress with educational outcomes remains
                  fragmented. This systematic literature review seeks to synthesize current knowledge on the
                  biological and educational perspectives of academic stress and its impact on student per-
                  formance. Using the PRISMA framework, a comprehensive search was conducted in the
                  Scopus database, yielding an initial pool of 4054 articles. After applying predefined inclusion
                  and exclusion criteria focused on academic stress in university students, 31 articles were
                  selected for detailed analysis. The review identifies four key theoretical foundations: the
                  neurocognitive aspects of stress and performance, the neurophysiology of stress, epigenetic
                  regulation of stress, and stress and genetic variations. Based on these insights, the study
                  proposes three main directions for subsequent studies: enhancing the understanding of stress
                  mechanisms, developing effective educational interventions, and employing interdisciplinary
                  approaches in subsequent studies. These findings aim to provide a comprehensive framework
                  for optimizing academic performance by deepening our understanding of the biological and
                  educational dimensions of stress.
                  A
                  Introduction
                          cademic stress is a physiological, emotional, cognitive, and behavioral response to stimuli
                          that can influence students’ capacity to adjust to the educational setting (Pozos‐Radillo et
                          al. 2016). This multifaceted nature of academic stress aligns with the bio-psycho-social
                  paradigm (WHO, 2001), which highlights the integration of biological, psychological, and social
                  components in understanding stress. Stress is also defined as an adaptive systemic process that
                  consists of three stages: perceiving a stressor, experiencing systemic imbalance manifested as
                  symptoms, and responding to restore equilibrium. Three components identified in this systemic
                  process are the stimuli that trigger stress, the symptoms indicating imbalance, and coping
                  strategies (Castillo-Navarrete et al. 2024). Academic stress among university students can be
                  caused by factors such as academic workload, poor peer relationships, inadequate facilities, and
1 Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, Malang, Indonesia. 2 Department of Biology, Faculty of
Mathematics and Natural Sciences, Universitas Negeri Medan, Medan, Indonesia. ✉email: hendrabio@um.ac.id
academic demands that exceed students’ adaptive capacities                 Research has investigated the interaction between BDNF and
(Bedewy and Gabriel, 2015; Reddy et al. 2018). This phenomenon             cortisol during acute stress, revealing that serum BDNF levels are
is particularly common among students, especially those studying           responsive to stress and that there is an antagonistic relationship
in fields with extensive content, and can significantly impact their         between BDNF dynamics and cortisol (Linz et al. 2019).
overall development during their education (Briones et al. 2024).             A variety of biological parameters have been extensively used
   Various studies have measured the levels of academic stress             to detect psychological stress; however, the current literature lacks
experienced by students and identified its triggers through sur-            a thorough examination of the relationship between these bio-
veys and rating scales (Mayya et al. 2022; Špiljak et al. 2022). A         logical markers and academic performance. For instance, studies
survey of university students found an academic stress prevalence          indicate that levels of BDNF and cortisol are crucial for under-
of 51.1%, with workload, time constraints, and academic diffi-              standing stress (Ballestar-Tarín et al. 2024), but their direct
culties being the main stressors (Zamroni et al. 2018). Several            impact on academic achievement is underexplored. Similarly,
studies confirm a significant correlation between academic stress            heart rate variability and sAA have been identified as significant
and students’ mental well-being (Córdova Olivera et al. 2023;              indicators of stress (Armario et al. 2020; Brodersen and Lorenz,
Barbayannis et al. 2022; Ojewale, 2020). High-stress levels among          2020), yet knowledge of how these physiological responses cor-
university students are associated with persistent mental health           relate with students’ academic outcomes is limited. Existing stu-
issues and can affect their academic performance (Stirparo et al.          dies primarily focus on the acute and chronic effects of
2024).                                                                     psychosocial stress on these biological parameters (Hermann
   Academic-related stress can lead to decreased academic                  et al. 2021; Castillo-Navarrete et al. 2023), but the specific bio-
achievement, reduced motivation, and an increased risk of mental           logical mechanisms explaining how academic stress affects aca-
health problems, such as depression, anxiety, sleep disorders, and         demic performance remain poorly understood. This gap indicates
substance abuse (Córdova Olivera et al. 2023; Pascoe et al. 2020;          the need for further research to elucidate the biological basis of
Wyatt and Oswalt, 2013). Stress levels are found to be a sig-              academic stress and its direct consequences on academic
nificant predictor of academic performance, with perceived stress           achievement.
negatively impacting both mental health and academic perfor-                  Several systematic reviews have explored stress in academic
mance (Amhare et al. 2021; Javaid et al. 2024). In another study           settings with various focuses and approaches. Jiménez-Mijangos
(Almarzouki, 2024), stress negatively affects cognitive functions          et al. (2023) examined stress and anxiety detection methods in
such as working memory, which is crucial for academic skills,              universities using psychological instruments and biological sig-
potentially reducing academic performance.                                 nals. They analyzed advancements, limitations, challenges, and
   Understanding the biological response to stress is crucial for          potential research pathways for detecting stress in classrooms.
comprehending the mechanisms and impacts of stress and mental              This study provided valuable insights, although it focused more
health (Nadal et al. 2021). Analysis at the micro level provides           on psychological and biological aspects without directly linking
precise information about the biochemical, psychophysiological,            them to academic performance. Conversely, Shanbhog and
and neurological processes underlying behavior. This level of              Medikonda (2023) emphasized the detrimental effects of stress on
analysis is critical for developing models and insights related to         students’ sleep quality, which can, in turn, influence their aca-
neuropsychological and neurophysiological disorders (de la                 demic performance. Nevertheless, the connection between stress
Fuente et al. 2019). Physiological parameters, such as heart rate          and academic performance, especially within a biological frame-
variability and hormone levels, can be used as biological markers          work, is still not well comprehended.
to objectively measure stress and its intensity (Armario et al.               Although these two systematic reviews have made significant
2020). Studies reveal that academic stress has a significant impact         contributions to the understanding of stress detection and its
on the cardiovascular system, leading to increased heart rate,             effects on mental health and sleep quality, there is still a paucity
blood pressure, and reduced heart rate variability, indicating             of research in this area that requires further investigation. One
sympathetic autonomic stress dominance (La Rovere et al. 2022;             such gap is the lack of studies that directly link the biological
Seipäjärvi et al. 2022).                                                   parameters of stress in research with academic performance. The
   A number of studies have shown that salivary alpha-amylase              existing studies tend to focus more on stress detection meth-
(sAA) levels increase in response to psychological stress, such as         odologies and their impact on specific health aspects, rather than
during exams or high-risk situations (Brodersen and Lorenz,                comprehensively integrating biological and psychological per-
2020). sAA has been used to assess autonomic nervous system                spectives. Secondly, a review of the literature on the use of various
function in clinical populations and shows secretion patterns that         methodologies to detect stress reveals a lack of emphasis on the
could be valuable indicators of autonomic nervous system dys-              theoretical framework that bridges the biological and psycholo-
function typically occurring in chronic stress-related pathologies         gical parameters used to specifically influence academic perfor-
(Ali and Nater, 2020). These studies found a positive relationship         mance. This highlights the necessity for a literature review that
between sAA and sympathetic nervous system activity during                 integrates biological and psychological perspectives to gain a
stress, indicating its sensitivity to psychosocial stress and potential    deeper understanding of the mechanisms of academic stress and
use as a non-invasive measure of stress in clinical and research           its impact on academic performance. To this end, this systematic
settings (Rashkova et al. 2012).                                           literature review study was guided by several research questions
   In addition to salivary alpha-amylase (sAA), other biological           (RQs), namely:
markers, such as brain-derived neurotrophic factor (BDNF) and                 RQ1: What are the principal elements of research on the
cortisol, are essential for understanding the body’s stress                relationship between stress and academic performance?
response. Levels of BDNF and cortisol are key indicators in stress            RQ2: What are the theoretical or conceptual foundations
research (Jiang et al. 2017; Hermann et al. 2021; Castillo-                employed in the stress and academic performance literature?
Navarrete et al. 2023). Harb et al. (2017) found that BDNF                    RQ3: What are some prospective avenues of inquiry in the field
protein levels were negatively correlated with hair cortisol and           of academic stress and academic performance?
somatic complaints, while hair cortisol showed a positive corre-              By identifying and analyzing limitations in previous studies,
lation with mental disorders. Acute and chronic psychosocial               this study seeks to provide evidence-based recommendations for
stress, such as academic stress, can affect peripheral BDNF and            future subsequent studies. These include new approaches to
cortisol levels (Myint et al. 2021; Castillo-Navarrete et al. 2023).       measuring and analyzing academic stress, as well as interventions
that can help college students manage stress and improve their               related to academic performance, (2) The study population
academic performance.                                                        consists of university students, (3) The article is an original
                                                                             research article, not a review, (4) Only open access articles, and
Methods                                                                      (5) Articles are published in English.
The study employs a systematic literature review (SLR) approach,                A comprehensive search of electronic databases was conducted
a desk-based research method characterized by its rigorous,                  using Scopus, resulting in a total of 4054 articles related to
standardized, and verifiable methodology. This ensures the review             academic stress, depression, and anxiety. The articles were then
is replicable, transparent, objective, unbiased, and thorough                filtered to focus on those emphasizing academic stress, depres-
(Višić, 2022; Boell and Cecez-Kecmanovic, 2015). The SLR                     sion, and anxiety, narrowing the selection to 1116 articles. At this
approach helps researchers systematically map the current state              stage, 293 articles were excluded because their primary focus was
of the literature, providing a structured exploration of topics and          not on stress, depression, or anxiety within the academic context
findings, and serves as a foundation for further investigations               of university students.
(Pati and Lorusso, 2018).                                                       The subsequent criterion applied was the study population,
                                                                             which had to be comprised of university students. This resulted in
                                                                             the exclusion of 501 articles. Consequently, 615 articles were
Search strategy. The search for relevant literature was conducted            excluded on the grounds that the population under consideration
using the Scopus database. Scopus is a prominent citation and                included school students, university staff, professionals, or
indexing database that provides access to global peer-reviewed               patients at a university hospital. Subsequently, the articles were
literature across a wide range of subject areas (Renjith and                 further screened to include only those published in English,
Pradeepkumar, 2021). Automated screening with user-friendly                  resulting in a total of 456 articles. This step excluded 45 articles
operations can save time and costs while enhancing search                    that were reviews, conference papers, letters, books, or articles not
accuracy with specific keywords (Van Dinter et al. 2021).                     in the English language. In the subsequent phase, the focus was
Leveraging advanced features in Scopus enables researchers to                narrowed to include only open-access articles, reducing the
narrow their search to the most pertinent and current articles               number to 222 articles. At this point, 234 articles were excluded
within their field of study.                                                  because they were not open access.
    In order to obtain relevant data, this study utilized specific               A manual screening process was conducted to ensure
keywords within the “search” menu of the Scopus database,                    eligibility, resulting in the final inclusion of 31 articles. During
employing Boolean conjunction operators to achieve a more                    this step, 190 articles were excluded for reasons such as being
focused result set. The key search comprised (TITLE (“academic               related to pandemic-related stress, lacking biological measure-
stress” OR “academic-related stress” OR “exam stress” OR                     ments, not being related to academic performance, involving
“examination stress” OR “task stress” OR “work-load stress”                  unhealthy samples, not focusing on university students, or being
OR “perceived stress” OR “psychological stress” OR anxiety OR                review articles. This process concluded with a total of 31 studies
depression) AND TITLE-ABS-KEY (biomarker OR molecular                        included in the review, following the stringent criteria outlined in
OR physiology OR physiological OR biology OR biological OR                   the PRISMA guidelines.
salivary OR saliva OR cortisol OR hormone OR genetic OR
epigenetic OR methylation OR bdnf OR neuron OR bmi OR
“body mass index”) AND TITLE-ABS-KEY (“academic perfor-                      Data extraction and analysis. The data and information from the
mance” OR “academic achievement” OR “academic success” OR                    collected 31 articles were tabulated using Microsoft Excel. The
grade* OR gpa OR cgpa OR score OR “academic attainment” OR                   extraction table contains information on the authors, year of
“academic outcome*“) AND TITLE-ABS-KEY (student* OR                          publication, research methodology, sample size, theoretical or
university OR college OR undergraduate OR graduate OR                        conceptual framework, biological parameters, psychological
postgraduate OR pre-service) AND NOT TITLE-ABS-KEY                           instruments, main results, and limitations of the study. The table
(school OR pupil* OR staff OR professionals OR patients))                    proved invaluable in the recording of pertinent information
AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (LAN-                           during the content analysis and synthesis phases. The data
GUAGE, “English”)) AND (LIMIT-TO (OA, “all”)).                               obtained from the reviewed articles were organized and subjected
    A comprehensive selection technique was employed to identify             to analysis. Subsequently, a textual narrative synthesis was con-
relevant articles, following the Preferred Reporting Items for               ducted. Narrative synthesis is a method for combining and
Systematic Reviews and Meta-Analyses (PRISMA) guidelines, as                 summarizing data from multiple studies, relying on the use of
illustrated in Fig. 1. Using these search terms and patterns, we             words and literature to describe the synthesis findings (Jahan
conducted the search on June 6, 2024, identifying 4054 articles              et al. 2022).
related to academic stress, depression, and anxiety mentioned in
titles, abstracts, and keywords. To focus the analysis on this               Results
theme, the first search was refined to include only articles where             A systematic review was conducted using the Scopus database,
the keywords appeared in the title.                                          which identified a large pool of studies related to academic stress,
                                                                             depression, and anxiety. Through a rigorous multi-step screening
Inclusion and exclusion criteria. We applied the Preferred                   process, articles were filtered based on specific inclusion criteria
Reporting Items for Systematic Reviews and Meta-Analyses                     such as relevance to academic stress among university students,
(PRISMA) model to guide the inclusion and exclusion processes,               availability in English, and open-access status. Additional manual
aiming to identify articles that strictly met the criteria. The              screening ensured that only studies aligning with the review’s
PRISMA guidelines were developed to facilitate transparent and               focus on academic stress, biological measurements, and academic
comprehensive reporting of systematic reviews, ensuring that the             performance were included. This thorough process resulted in the
methods and results are detailed enough for users to assess the              final selection of 31 articles. The detailed decision-making process
reliability and applicability of the review’s findings (Page et al.           is presented in Fig. 1.
2021). The following key points formed the basis of the inclusion
criteria used in this systematic literature review (SLR): (1) The            Key aspects of research. The analysis identified 31 relevant stu-
primary focus of the article is on stress, depression, or anxiety            dies within the scope of research conducted across 19 countries.
Fig. 1 PRISMA flowchart for the search strategy and selection procedure. The selection process resulted in 31 articles that met the criteria for further
analysis.
Two studies were conducted in African countries, namely Uganda                  We identified 12 studies that used 10 specific markers to
and South Africa. Eight studies were conducted in Europe, cov-               discuss how academic stress biologically affects academic
ering Finland, the UK, Croatia, Germany, and Italy. Six studies              performance. Some of these parameters utilized neurophysiolo-
were carried out in the US and Canada. Nine studies were con-                gical, genetic, and epigenetic frameworks, linked to cognitive
ducted in Asian countries, including Hong Kong, Pakistan,                    psychology and educational concepts. Table 2 presents the types
Lebanon, Saudi Arabia, Iran, Japan, and India. Finally, six articles         of parameters, the sample sizes used, and a discussion based on
were from South America, covering Chile, Brazil, and Mexico. All             their findings, which contribute to understanding the relationship
articles reported research examining stress, anxiety, and depres-            between stress and academic performance.
sion among university students. Each study used biological and
psychological approaches to identify stress and develop discus-              Psychological instruments of stress measurement. All the studies
sions on the impact of stress on academic performance (Table 1).             analyzed employed psychological instruments to detect psychoso-
                                                                             cial stress related to academics. These tools allowed researchers to
Biological parameters. Thirty-four biological parameters were                gather data on various aspects of mental health and behavior. The
used across the 31 studies analyzed. Some of these studies uti-              most frequently used instrument was the State-Trait Anxiety
lized biological parameters to identify stress, depression, or               Inventory (STAI), which appeared in 12 articles. The Abbreviated
anxiety status without necessarily explaining their interactions             Mathematics Anxiety Scale (AMAS) was utilized in two articles to
with academic performance. For example, several studies                      assess mathematics anxiety. Other anxiety instruments, such as the
employed salivary proteins to detect the body’s response to                  Test Anxiety Inventory (TAI), Hamilton Anxiety Rating Scale
academic stress (Zallocco et al. 2021; Cai et al. 2018; Špiljak              (HAM-A), and Generalized Anxiety Disorder Scale (GAD-7), were
et al. 2024). Cardiovascular parameters were also widely used                also used, demonstrating validity and reliability across different
for detecting stress, depression, and anxiety across various                 populations. The Perceived Stress Scale (PSS) appeared in three
studies (Nakamura et al. 2010; Abromavičius et al. 2023; Cronje              articles to measure perceived stress levels. The SISCO Inventory of
et al. 2024). A portion of these studies used biological para-               Academic Stress (SISCO) was employed in two articles to evaluate
meters to evaluate the impact of interventions aimed at reducing             academic stress among university students, focusing on stressors,
stress, anxiety, and depression (Harris et al. 2019; Mäkelä et al.           symptoms, and coping strategies. The Visual Analog Scale (VAS)
2023; Usichenko et al. 2020). Cortisol, one of the most fre-                 was used in four articles to gauge the intensity of various subjective
quently used parameters, was found to be associated with stu-                experiences, including academic stress, depression, and anxiety.
dents’ academic stress levels (Anjum et al. 2021; Jamieson et al.            Additionally, the Depression Anxiety Stress Scale (DASS-21) was
2021). However, not all researchers explored how these biolo-                employed in three articles to simultaneously measure depression,
gical parameters are related to and can explain their implica-               anxiety, and stress. Lastly, the Beck Depression Inventory (BDI),
tions for academic achievement.                                              used in three articles, assessed the severity of depression (Table 3).
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                                                                                                            Table 1 (continued)
                                                                                                            Authors (Year)        Country   Journal                   Biological parameters                    Psychological              Research focus
                                                                                                                                                                                                               instruments
                                                                                                            Cardozo et al.        Brazil    Advance in Psy Edu        Cortisol dan alpha-amylase saliva        State-Trait Anxiety        Active Learning and Academic
                                                                                                            (2020)                                                                                             Inventory (STAI)           Stress
                                                                                                            Ferreira et al.       Brazil    BMC Medical Edu           Salivary cortisol                        State-Trait Anxiety        Relationship between physiological
                                                                                                            (2020)                                                                                             Inventory (STAI)           stress, test anxiety, self-efficacy,
                                                                                                                                                                                                                                          and meaning that students
                                                                                                                                                                                                                                          attribute to the experience
                                                                                                            Malanchini et al.     U.K.      Translational             Genetic similarity                       Abbreviated Math           Relationship between math anxiety
                                                                                                            (2020)                          Psychiatry                                                         Anxiety                    and low math self-confidence,
                                                                                                                                                                                                                                                                                REVIEW ARTICLE
Table 2 Biological parameters of stress and their association with academic performance.
 Biological parameters          Authors (Year)                Sample (n)      Contribution to the concept of academic performance and stress
 Brain wave (qEEG)              Cronje et al. (2024)          158             Stress and anxiety are associated with decreased alpha waves and
                                                                              increased delta waves in the left temporal lobe, which are associated
                                                                              with learning and memory. This condition is thought to affect academic
                                                                              performance.
 Cortisol                       Cardozo et al. (2023)         139             High cortisol can impair memory, attention, and executive function, all of
                                                                              which are important for academic performance. Stress hormones
                                                                              indirectly affect learning circuits by impacting intermediate brain regions
                                                                              like the hippocampus, amygdala, and tegmental nucleus of the striatum.
                                                                              This leads to interference with the creation of strong memories.
                                Brodersen and Lorenz          43              It is possible that chronic stress due to frequent exams promotes HPAA
                                (2020)                                        adaptation and reduces cortisol responses despite sympathetic nervous
                                                                              system (SNS) responses and perceived stress.
                                Ferreira et al (2020) &       32              Self-efficacy might shield students from the adverse impacts of stress
                                Ringeisen et al. (2019)       92              and anxiety on their performance. The findings support the transactional
                                                                              model of test anxiety, where self-efficacy is crucial in mitigating the
                                                                              stress response (cortisol) and enhancing test performance.
                                Cipra and Muller-Hilke        98              There was a positive correlation between test anxiety and cortisol levels.
                                (2019)                                        Additionally, surface learning approaches were associated with lower
                                                                              test anxiety and improved learning outcomes, while strategic
                                                                              approaches were linked to the least anxiety and the highest academic
                                                                              success.
 BDNF                           Castillo-Navarrete et al.     91              There may be a relationship between academic stress and BDNF levels.
                                (2024)                                        BDNF is vital for dendritic branching, synaptic plasticity, and long-term
                                                                              potentiation (LTP), influencing memory, learning, and, consequently,
                                                                              learning outcomes.
 Global DNA Methylation         Castillo-Navarrete et al.     91              At the final assessment, the global DNA methylation percentage
 (5-mC)                         (2024)                                        increased from the baseline as stress levels rose. Psychosocial stress
                                                                              can alter global DNA methylation patterns, impacting how individuals
                                                                              perceive and physiologically respond to stressors. The rise in DNA
                                                                              methylation may potentially lead to a reduction in BDNF levels. Further
                                                                              research is needed to examine the methylation of specific BDNF genes
                                                                              and related genes to clarify this relationship.
 Heart Rate Variability (HRV)   Wong et al. 2023              90              Students who experience higher stress and have lower HRV levels tend
                                                                              to perform better academically. This could be because elevated stress,
                                                                              up to an optimal point, may enhance their focus and improve their
                                                                              performance. However, the precise optimal level of stress for peak
                                                                              performance remains unclear. Additionally, high-achieving students with
                                                                              lower HRV do not necessarily experience greater stress, as indicated by
                                                                              non-significant STAI results. This might be due to their effective coping
                                                                              strategies or other factors that require further investigation.
 Visual and Auditory Reaction   Pradhan et al. (2014)         100             The results of this study support the Execution Focus Model: Anxiety
 Time (VRT, ART)                                                              affects performance by changing how a person focuses and uses
                                                                              attentional resources, not simply because of resource limitations. Stress
                                                                              affects how a person makes decisions and focuses attention via the
                                                                              sympathetic nervous system and the HPAA.
 Vitamin D                      Ibrahim and Audi (2021)       157             College students with anxiety symptoms had significantly lower levels of
                                                                              Vitamin D. Vitamin D plays a key role in proliferation, differentiation,
                                                                              neurotropism, neuroprotection, neurotransmission, and neuroplasticity.
                                                                              It is not yet known how vitamin D plays a role in mental pathology.
                                                                              However, Vitamin D deficiency may have an impact on academic
                                                                              performance.
 Genetic similarity             Malanchini et al. (2020)      3410 twin       Research suggests that genetic variants associated with math anxiety,
                                                              couples         attitudes toward math, and math achievement are likely unrelated to
                                                                              variations in general anxiety. This suggests that genetic factors
                                                                              influencing specific aspects of math may be different from genetic
                                                                              factors influencing general academic performance.
 Brain activity (fMRI)          Pizzie et al. (2020)          74              Academic performance in math may be influenced by certain genetic
                                                                              variants that are specific to math and different from genes that regulate
                                                                              general academic performance.
 SNP Val66Met BDNF              Bedard et al. (2017)          252             Individuals with high self-efficacy are better able to cope with the
                                                                              negative effects of loneliness, regardless of their genotype.
 Table 3 Psychological instruments used together with                         employed in different studies. Wong et al. (2023) conducted a
 biological parameters.                                                       correlational study to identify associations between several stress
                                                                              and anxiety indicators and exam competence. Peter et al. (2023)
                                                                              used Ambulatory Assessment, Anjum et al. (2021) utilized a
 Psychological instruments                                Acronym      n
                                                                              comparative study, Malanchini et al. (2020) conducted a twin
 State-Trait Anxiety Inventory                            STAI         12     study, Jamieson et al. (2021) employed a multilevel design, and
 Perceived Stress Scale                                   PSS          3      Bedard et al. (2017) used a case-control study.
 Visual Analog Scale                                      VAS          4
 Beck Depression Inventory                                BDI          3
 SISCO Inventory of Academic Stress                       SISCO        2
 Depression Anxiety Stress Scale                          DASS-21      3      Conceptual framework of stress and performance. A variety of
 Pittsburgh Sleep Quality Index                           PSQI         2      theoretical frameworks from different research areas, such as
 Abbreviated Mathematics Anxiety Scale                    AMAS         2      learning methods, neurophysiology, psychology, genetics, and
 Center for Epidemiological Studies Depression Scale      CES-D        2      epigenetics in studies of stress and academic performance, are
 Generalized Anxiety Disorder Scale                       GAD          1      illustrated in Table 5. We classified these theories based on the
 Stressor Appraisal Scale                                 SAS          1      identified research clusters and categorized them according to the
 Test Anxiety Inventory                                   TAI          1      foundational theories or concepts associated with each cluster. In
 Math Anxiety Rating Scale                                MARS         1      this way, we demonstrate that the association between stress and
 Ambulatory Assessment Stress Scale                       AASS         1      academic performance can be depicted from various theoretical
 Hamilton Anxiety Rating Scale                            HAM-A        1      perspectives. Furthermore, Fig. 2 illustrates a conceptual frame-
 Student Stress Scale                                                  1
                                                                              work of stress and academic performance developed based on the
                                                                              analysis of scientific articles, providing a clear visualization of
                                                                              how different theories and concepts interact within the context of
Approaches to data gathering. In analyzing the data collection                this research.
methods used across the 31 articles reviewed, it is evident that                 Of the 31 articles, only 74.18% (n = 23) discussed the theories
various study designs were employed, reflecting diverse approa-                they employed. The remaining 25.81% (n = 8) did not specifically
ches to investigating academic stress and performance in biolo-               mention the underlying theories of their research, possibly
gical contexts. The methods can be broadly categorized into                   because the focus was not on forming a hypothesis-driven
experimental, observational, and mixed-method research. Table 4               argument based on the relationship between stress, anxiety,
summarizes the research designs, authors, and years of                        depression and academic performance. The focus of these articles
publication.                                                                  was on the detection or intervention to reduce academic-related
   The crossover study design emerged as one of the most                      stress, depression, or anxiety (Abromavičius et al. 2023; Anjum
common approaches in experimental methods, accounting for                     et al. 2021; Ibrahim and Audi, 2021; Kabrita and Hajjar-Muça,
9.7% of all studies. This type of study, as conducted by Cardozo              2016; Nakamura et al. 2010; Tripathi et al. 2022; Usichenko et al.
et al. (2023), Nakamura et al. (2010), and Usichenko et al. (2020),           2020; Zallocco et al. 2021).
involves administering multiple interventions sequentially to
participants. Blinded trial designs also accounted for 9.7% of all            Neurocognitive stress and performance. Wong et al. (2023) found
studies and were included in the research by Mäkelä et al. (2023),            that students who experienced higher stress levels with lower
Márquez-Morales et al. (2021), and Kato-Kataoka et al. (2016).                heart rate variability (HRV) actually had better academic per-
Within-subject and between-subject designs were used in studies               formance. This finding suggests that when stress increases to an
by Zallocco et al. (2021), Brodersen and Lorenz (2020), and Pizzie            optimal level, students may become more focused on their tasks,
et al. (2020), also comprising 9.7%. Quasi-experimental designs,              thereby enhancing their performance. However, the anxiety
as seen in Harris et al. (2019) and Cardozo et al. (2020),                    assessment results in this study were not significant, indicating
accounted for 6.4% of all studies. Špiljak et al. (2024) employed a           that students with high academic scores and lower HRV did not
prospective and interventional method, which was the only study               necessarily experience higher levels of stress. These students
of this type reviewed. Cai et al. (2018) was also the only study              might possess effective coping strategies that help them manage
using randomized controlled trials (RCTs), considered the gold                stress despite having low HRV.
standard in experimental research due to their ability to minimize               The study by Brodersen and Lorenz (2020) showed that
bias through randomization. Lastly, Abromavičius et al. (2023)                perceived stress and salivary alpha-amylase were higher during
applied measurement and modeling techniques, accounting for                   exams compared to homework conditions, but there was no
3.2% of all studies. All articles employing interventions with this           significant increase in cortisol levels. This indicates that exams
method are classified under the 1st level of prevention, focusing              trigger a high-stress response and activation of the sympathetic
on programs aimed at mitigating academic stress before it                     nervous system but do not activate the hypothalamic-pituitary-
escalates into a significant issue.                                            adrenal axis (HPAA) response. Ringeisen et al. (2019) found that
   Observational study designs are a significant component of the              anxiety and cortisol levels increased on exam days compared to
reviewed articles, highlighting the importance of non-                        control days. Self-efficacy was found to be negatively correlated
interventional approaches in understanding symptoms and the                   with anxiety and positively correlated with exam scores,
relationships between variables in natural conditions. Cross-                 suggesting that students with high self-efficacy perceive exams
sectional studies, including those by Cronje et al. (2024), Mujinya           as challenges that can be overcome rather than threats.
(2022), Tripathi et al. (2022), Ibrahim and Audi (2021), Tavakoli                Cai et al. (2018) found that the group receiving attention bias
et al. (2017), and Kabrita and Hajjar-Muça (2016), are the most               modification intervention showed a significant change in
common observational design in the reviewed articles. Long-                   attention bias scores after training, but there was no significant
itudinal studies, such as those conducted by Castillo-Navarrete               change in salivary alpha-amylase levels. These findings suggest a
et al. (2023), Cipra and Muller-Hilke (2019), Ringeisen et al.                reduction in attention towards stressors following training,
(2019), and Pradhan et al. (2014), involve repeated observations              although the lack of a well-validated psychosocial stressor may
of the same variables over a period of time. Various observational            have contributed to the absence of significant changes in
designs, besides cross-sectional and longitudinal, were also                  biological responses. Pradhan et al. (2014) reported that stress,
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REVIEW ARTICLE                         HUMANITIES AND SOCIAL SCIENCES COMMUNICATIONS | https://doi.org/10.1057/s41599-025-04484-w
measured through increased pulse rate, blood pressure, and                 processes. Studies also found a correlation between concentration,
reaction time, significantly affected students’ cognitive function          brain waves, and exam results, indicating that students who focus
before exams. Students with higher stress levels showed longer             longer tend to achieve better grades or show significant
touch and audio reaction times, as well as faster visual reaction          improvement between exams (Kokubo and Shoji, 2017). Addi-
times, indicating that stress impacts the somatosensory cortex             tionally, brain activity scans using fMRI evaluated activity in the
areas that process touch and visual stimuli.                               prefrontal cortex (PFC). The cognitive reappraisal process
                                                                           involves the PFC, a brain area responsible for executive functions
Neurophysiology stress and performance. EEG analysis shows that            like planning, decision-making, and cognitive control. Increased
stress and anxiety are associated with decreased alpha waves and           activity in the PFC can enhance the ability to focus, solve pro-
increased delta waves in the left temporal lobe, which plays a             blems, and think critically, which are all essential for solving
crucial role in learning and memory processes (Cronje et al.               mathematical tasks (Pizzie et al. 2020).
2024). This condition could potentially affect academic perfor-               The hypothalamic-pituitary-adrenal axis (HPAA) is involved
mance, where a decrease in alpha waves might indicate a reduced            in the systemic effects of stress, depression, and anxiety, which
capacity for relaxation and focus, while an increase in delta waves        also play a role in the neurophysiology of cognition. Cortisol, as
may suggest disruption or inhibition in learning and memory                the primary stress hormone in the HPA axis, is one of the most
                                                                           widely used biomarkers in research related to academic stress
                                                                           (Anjum et al. 2021; Cardozo et al. 2020; Ringeisen et al. 2019;
 Table 5 Mapping of articles on theory clusters and                        Kato-kataoka et al. 2016; Špiljak et al. 2024; Cardozo et al. 2023;
 keywords.                                                                 Mäkelä et al. 2023; Peter et al. 2023; Jamieson et al. 2021;
                                                                           Brodersen and Lorenz, 2020; Ferreira et al. 2020; Cipra and
                                                                           Muller-Hilke, 2019). In stressful situations such as exam stress,
 Cluster of theory        Keywords            Article (n)   Percentage
                                                                           serotonin, acetylcholine, and inflammatory cytokines are
 Neurocognitive stress    Transactional       8             25.80          released as stress signals that activate the HPA axis (Hall et al.
 and performance          theory
                                                                           2012). Stress signals also activate the sympathetic nervous
                          Attention bias
                          theory
                                                                           system response, causing a positive feedback loop and a
                          Execution focus                                  continuous cycle between the HPAA and the sympathetic
                          model                                            nervous system (Hong et al. 2022). When the HPA axis is
                          Self-efficacy                                     activated, stress hormones are released, including corticotropic
 Neurophysiology stress   Brain activity      8             25.80          releasing hormone (CRH) from the hypothalamus (Contoreggi,
 and performance          HPAA                                             2015), which then stimulates the anterior pituitary to release
 Stress and epigenetic    DNA methylation     2             6.45           adrenocorticotropic hormone (ACTH) (Fukuoka et al. 2020).
 regulations              BDNF                                             ACTH, in turn, regulates the production of glucocorticoids,
 Genetic variations and   SNP Val66Met of     3             9.68           such as cortisol, from the adrenal glands (Lightman et al. 2020).
 stress                   BDNF gene                                        Elevated cortisol levels can negatively impact memory, atten-
                          Math-related gene                                tion, and executive functions, all of which are essential for
                          Polygenic gene
                                                                           academic performance (Ouanes and Popp, 2019). Stress
                          NPS and NPSR1
 Total                                        21            67.74
                                                                           hormones affect learning circuits through intermediary brain
                                                                           regions like the hippocampus, amygdala, and striatum
Fig. 2 Conceptual framework of academic stress and performance based on the analyzed studies (Source: Author's own elaboration). The framework
illustrates the theoretical scope and keywords representing the current research developments.
tegmental nuclei, causing disruptions in the formation of strong             targeted approach to assessing academic stress among university
memories (Cardozo et al. 2023).                                              students (Castillo-Navarrete et al. 2024). This instrument, along
                                                                             with others, contributes to a nuanced understanding of academic
Stress and epigenetic regulations. Stress can trigger epigenetic             stress and supports the development of targeted interventions to
changes that affect gene expression and modulate the psycho-                 improve student well-being and academic performance.
biological response to stress (Stoffel et al. 2022). These changes              The findings of this review underscore the multidimensional
involve DNA methylation of genes involved in the stress response             nature of academic stress, as evidenced by the significant inter-
and development (Unternaehrer and Meinlschmidt, 2016). Aca-                  actions between biological markers, psychological coping strate-
demic stress is believed to cause epigenetic changes that affect             gies, and social influences identified across the studies analyzed.
gene expression related to learning and memory, such as the                  This aligns with the Bio-Psycho-Social paradigm (WHO, 2001),
BDNF gene (Castillo-Navarrete et al. 2023). Some studies use                 which emphasizes the integration of biological, psychological, and
brain-derived neurotrophic factor (BDNF) as a biomarker of                   social factors in understanding stress and wellbeing. Key results
neuronal plasticity, linking explanations between academic per-              reveal that markers such as BDNF and cortisol are highly sensi-
formance and epigenetic regulation influenced by stress. BDNF                 tive to stress but show variability depending on psychological
plays a significant role in memory formation and processing                   states and social contexts, such as peer support and institutional
through the regulation of synaptic plasticity, including synapto-            environment. These findings resonate with recent theoretical
genesis and long-term potentiation (LTP), the primary cellular               advancements, such as the conceptual model for managing stress
mechanisms underlying learning and memory (Soliman et al.                    and promoting wellbeing (de la Fuente et al. 2024), which inte-
2010; Karpova, 2014). Castillo-Navarrete et al. (2023) observed              grates these dimensions into a cohesive framework.
that academic stress could increase global DNA methylation                      The analysis of research designs employed across the reviewed
percentage and decrease BDNF levels in blood plasma. Tavakoli                studies provides significant insights into the methodologies used
et al. (2017) reported that male students with higher depression             to explore academic stress and performance within biological
scores had lower BDNF levels.                                                contexts. Each design offers unique advantages and limitations,
                                                                             contributing to the overall understanding of the field. Despite the
Genetic variations and stress. Genetic variation, particularly the           richness of insights provided by these designs, there remains a
Val66Met polymorphism in the BDNF gene, can affect individual                notable scarcity of mixed-method approaches in the literature.
cognition and emotions (Al-Hatamleh et al. 2019; He et al. 2018).            Mixed-methods research, which combines qualitative and quan-
Bedard et al. (2017) found that individuals with low self-efficacy            titative techniques, has the potential to offer a more compre-
were more likely to have high depression compared to those with              hensive perspective by integrating detailed numerical data with
high self-efficacy, regardless of their BDNF genotype. The study              contextual understanding. Its underrepresentation suggests a
also showed that individuals with the Val/Val genotype might                 missed opportunity to explore academic stress from both statis-
have poor neurocognitive vulnerability to experiences of lone-               tical and narrative perspectives, which could enrich our under-
liness. Malanchini et al. (2020) observed 3410 pairs of identical            standing of complex phenomena and lead to more nuanced
and fraternal twins to separate the influence of genetic and                  interventions. Addressing this gap could enhance future research
environmental factors on traits related to attitudes and mathe-              and provide a more holistic view of the interplay between aca-
matical abilities. The study’s findings suggest that academic per-            demic stress and performance.
formance in mathematics is influenced by specific genetic variants
for mathematics and is different from the genes regulating general
academic performance.                                                        Theoretical underpinnings. The findings provide insights into
                                                                             how academic stress, measured through various biological para-
                                                                             meters, can affect students’ academic performance and cognitive
Discussion                                                                   function. The findings by Wong et al. (2023) support the concept
Certain parameters in the context of genetics and epigenetics can            that stress at an optimal level can enhance academic performance
serve as potential biomarkers for understanding the complexity of            by increasing focus, although the exact optimal level remains
academic performance. A polygenic analysis study of the NPS                  unclear. However, this also highlights that effective coping stra-
and NPSR1 genes found that neuroticism genetics can predict                  tegies play a crucial role in mitigating the negative impacts of
stress in high-pressure situations, such as academic exams (Peter            stress, as seen in students with low HRV but high academic
et al. 2023). Tavakoli et al. (2017) utilized brain-derived neuro-           performance. These findings can be explained by the transac-
trophic factor (BDNF), a crucial neurotrophic factor involved in             tional theory of stress and coping by Lazarus and Folkman
the growth and maintenance of nerve cells in the brain. However,             (1984).
this study did not explain the implications of stress on learning               The transactional theory of stress focuses on how individuals
and memory, which could affect academic performance. Simi-                   appraise and manage stress (Zhao et al. 2020; Spătaru et al. 2024).
larly, studies examining gut microbiota diversity (Marquez-                  According to this theory, stress is not merely the result of external
Morales et al. 2021; Kato-Kataoka et al. 2016) did not provide               situations or stimuli, but also arises from an individual’s
detailed explanations of how the gut–brain axis connection under             perception of the situation and their ability to cope with it.
stress conditions could influence academic performance.                       Several studies (Brodersen and Lorenz, 2020; Ringeisen et al.
   The use of psychological instruments in these studies allowed             2019) within the scope of this review have utilized this theoretical
researchers to collect comprehensive data on various aspects of              framework to explain the relationship between stress and
mental health and behavior, facilitating the development of more             academic performance, supported by evidence from biological
effective interventions to address academic-related psychosocial             parameters.
stress. By assessing different dimensions of stress, anxiety, and               Brodersen and Lorenz (2020) underscore the role of HPAA
depression, research has provided deeper insights into how these             adaptation in response to chronic stress, such as frequent exams,
factors interact and impact individuals in both biological and               which may reduce cortisol response despite the activation of the
academic contexts. Although the SISCO Inventory of Academic                  sympathetic nervous system. This finding aligns with the concept
Stress is not the most widely used scale, its focus on stressors,            of appraisal in transactional theory, where an individual’s
symptoms, and coping strategies offers a comprehensive and                   perception of a situation influences their stress response. The
findings from Ringeisen et al. (2019) emphasize the importance of          academic potential. It is suggested that different academic
self-efficacy in managing stress and improving academic                    potentials in individuals may be influenced by different genes
performance. High self-efficacy can change the perception of               (Rimfeld et al. 2015). Understanding how genetic variability can
exams from threats to manageable challenges, thereby reducing             affect stress responses could lead to the development of more
anxiety and enhancing performance.                                        tailored and personalized interventions to help individuals
   Within the context of attention bias theory, the results from          manage stress more effectively, particularly in high-pressure
Cai et al. (2018) indicate that attention bias modification                environments like exams (Peter et al. 2023).
interventions can reduce attention toward stressors, although                Overall, the findings from these studies support the importance
effects on biological parameters like alpha-amylase may require           of biological parameters in measuring stress responses and
clearer and more validated stress conditions to demonstrate               suggest that academic stress can affect performance in complex,
significant changes. This suggests that the effectiveness of               context-dependent ways. This emphasizes the need for a multi-
interventions depends on the validity and intensity of the                dimensional approach to understanding the impact of academic
stressors used.                                                           stress on student performance. To provide a comprehensive
   The execution focus model employed by Pradhan et al. (2014)            understanding of the intricate relationships among various factors
also confirms that stress affects how the brain processes                  influencing academic stress and performance, a conceptual
information, reflected in changes in reaction times. While there           framework is illustrated in Fig. 2. This framework synthesizes
is general support for the role of reaction time in academic              findings from the analyzed studies, highlighting the intercon-
performance, the differing results in this study may reflect               nected roles of neurophysiological mechanisms, epigenetic
variations in coping strategies or optimal stress levels that have        regulations, genetic variations, and other psychological factors
not been fully explained, indicating a need for further research to       in shaping academic outcomes.
understand these complex relationships.
   The results from EEG and fMRI analyses indicate the
importance of brain regions like the left temporal lobe and               Future research directions. Research on the association between
prefrontal cortex in academic performance under stress. The               stress, anxiety, and depression with academic performance has
decrease in alpha waves and increase in delta waves observed in           evolved rapidly and has been examined from various perspectives.
the EEG studies (Cronje et al. 2024) suggest that stress can              From our review, however, we argue that several areas require
interfere with brain functions associated with learning and               further exploration to enhance our understanding of the com-
memory, potentially reducing students’ ability to perform                 plexity of academic performance as an outcome of various
academically. Furthermore, the increased activity in the pre-             interrelated factors and study contexts. To provide recommen-
frontal cortex during cognitive reappraisal (Pizzie et al. 2020)          dations for forthcoming research, we evaluated the limitations
highlights the role of executive functions in managing stress and         and explored the potential and gaps from studies over the past
performing complex cognitive tasks, such as mathematics. This             three years included in our analysis. This procedure resulted in
suggests that training students in cognitive strategies that enhance      three major potential research agendas, as discussed below.
PFC activity could potentially improve their academic outcomes.
   The findings on HPAA’s role in stress response highlight its            Academic performance and stress mechanism. Efforts to uncover
significance in academic settings where stress levels are often            the influence of stress on academic performance have been the
high. Although there is strong evidence of cortisol’s negative            focus of many studies. Various biomarkers have been used to
impact on cognitive function (Ouanes and Popp, 2019), the                 identify changes in the body’s biological functions when an
inconsistencies in findings regarding cortisol’s relationship with         individual experiences stress. Nonetheless, our understanding of
exam performance (Ferreira et al. 2020; Ringeisen et al. 2019)            the biological mechanisms linking stress to academic perfor-
suggest that cortisol alone may not be a definitive predictor of           mance remains incomplete. Future studies need to investigate the
academic outcomes. Factors such as different cortisol measure-            biological processes influencing academic performance and use
ment methods, individual differences in stress responses, and             biomarkers that can more closely explain the relationship
variations in exam environments could contribute to these                 between stress mechanisms and academic performance (Cronje
inconsistencies. Understanding how the HPAA and sympathetic               et al. 2024; Castillo-Navarrete et al. 2023; Peter et al. 2023).
nervous system influence academic performance has important                   The use of cardiovascular parameters as markers of stress
implications for education. Providing adequate resources for              presence is widespread in research (Anjum et al. 2021; Usichenko
counseling units and training students on stress management               et al. 2020; Zallocco et al. 2021). However, cardiovascular
strategies have been recommended to address high levels of                parameters cannot directly explain how stress, whether acute or
academic stress among students (Munyaradzi and Addae, 2018).              chronic, affects academic performance. While stress can trigger
Implementing strategies to foster a more conducive academic               cardiovascular responses, its effects on memory, concentration,
environment has been suggested based on the predictive                    and cognitive abilities are more influenced by how stress interacts
relationship between stress coping, self-efficacy, and academic            with the central nervous system and involves various hormones
satisfaction (Estrada-Araoz et al. 2024).                                 (Lindau et al. 2016; Vogel and Schwabe, 2016). Cardiovascular
   The discussion on epigenetic changes driven by stress under-           parameters are part of a series of processes initiated in the brain,
scores the complexity of how academic stress impacts cognitive            impacting the body’s readiness for a ‘fight or flight’ response to
functions at the molecular level. Epigenetic regulation, such as          pressure (Shah et al. 2019).
BDNF gene methylation, suggests that the effects of stress on                The detection of neurophysiological signals, such as electro-
students are not only evident in their psychological and                  dermal activity (Abromavičius et al. 2023), electroencephalogram
physiological responses but also at a deeper molecular level,             (EEG) (Cronje et al. 2024), and functional magnetic resonance
ultimately influencing academic performance and cognitive                  imaging (fMRI) (Pizzie et al. 2020), has also been used in several
abilities. Understanding these epigenetic mechanisms is crucial           studies analyzed and contributes to the understanding of the
for explaining how stress can impact learning and memory                  relationship between stress and central and autonomic nervous
abilities in students.                                                    system activities. Measurement techniques using such parameters
   The research on genetic variations and academic performance            have drawbacks; they are time-consuming and can introduce bias
extends the scope of studies on the genetic factors influencing            due to the potential stress caused by sensor placement or
participation in experiments (Jiménez-Mijangos et al. 2023). To              educational interventions that not only focus on cognitive aspects
obtain accurate and comprehensive results, we suggest using non-             but also consider individual biological aspects in supporting
invasive biomarkers in more natural settings.                                optimal academic performance.
   Cortisol, the primary stress hormone involved in mechanisms
in the central nervous system, is the most widely used parameter             Research on educational interventions. Cardozo et al. (2023)
in the analyzed studies. Cortisol levels are known to be                     found that implementing active learning methods combined with
associated with student stress (Anjum et al. 2021; Cardozo                   formative assessments can reduce exam stress and anxiety and
et al. 2020; Ringeisen et al. 2019). The advantage of this                   improve students’ academic performance compared to traditional
parameter is its ability to be measured non-invasively from                  lecture methods. These results indicate that more interactive and
urine (Borghi et al. 2021), saliva (Kato-Kataoka et al. 2016), and           student-centered approaches have the potential to create a more
hair (van den Heuvel et al. 2022; Heming et al. 2023; Romero-                conducive learning environment and support better academic
Romero et al. 2023). However, inconsistencies in study results               achievement (Angraini, et al. 2023). For instance, learning that
regarding the effects of stress on cortisol levels and academic              uses the joyful-inquiry interactive demonstration model assisted
performance necessitate further research (Brodersen and                      by Android games has been shown to improve students’ cognitive
Lorenz, 2020; Ferreira et al. 2020; Ringeisen et al. 2019; Cipra             learning outcomes by engaging them more actively in the learning
and Muller-Hilke, 2019). Recognizing the complexity of                       process (Mustikasari et al. 2020). Additionally, Dou et al. (2018)
academic performance as a result of interactions among various               and Muntholib et al. (2024) argue that students’ self-efficacy is
factors, not just physiological but also psychological and social,           influenced by the learning strategies or models implemented.
we suggest that upcoming studies consider an interdisciplinary               Specifically, learning models that accommodate active student
approach.                                                                    participation in investigating topics can enhance self-efficacy.
   Based on the analysis of existing studies, brain-derived                  This investigative process allows students to build confidence
neurotrophic factor (BDNF) emerges as a promising biomarker                  through active class discussions and presenting their findings to
in elucidating the influences of psychological factors and                    peers, fostering strong problem-solving skills (Fitriani et al. 2020).
educational strategies on academic performance. BDNF is a                       Furthermore, self-efficacy has become a trending variable in
neurotrophin abundantly expressed in the brain and plays a                   the application of collaborative science learning over the past
critical role in the survival, growth, and cognitive function of             decade. It is frequently associated with motivation, learning
neurons under normal and neuropathological conditions                        systems, and e-learning. These findings indicate that integrating
(Ismail et al. 2020). This marker can also be measured non-                  self-efficacy into various learning models, especially in STEM
invasively through urine (Olivas-Martinez et al. 2023) and                   fields, holds significant promise for enhancing students’ engage-
saliva (Ballestar-Tarín et al. 2024), making it more comfortable             ment and performance in the classroom (Marlina et al. 2024).
for participants and reducing the risk of stress bias due to                    However, further research is needed, especially longitudinal
plasma sampling procedures. Additionally, it facilitates                     studies, to observe the long-term impact of these active
repeated sampling in longitudinal study designs or ambulatory                methods. Additionally, it is essential to explore various
assessment.                                                                  variations of active learning methods and evaluate their
   In the context of academic stress, peripheral BDNF levels may             effectiveness, including integration with technology, to identify
fluctuate, with the potential for significant decreases in students            the most effective approaches for application in different
facing chronic academic pressure (Castillo-Navarrete et al. 2023;            educational contexts. Developing and evaluating these methods
Tavakoli et al. 2017). In other studies, acute stress induced by             is crucial to help students manage stress and improve their
academic exams increased BDNF production (Myint et al. 2021).                academic performance (Cardozo et al. 2023; Wong et al. 2023).
These varied findings present opportunities to explore BDNF as a              The crucial role of self-efficacy in student success and its
potential biomarker in understanding how effective management                connections to psychological, physiological, and educational
strategies and assessments can mitigate the negative impacts of              aspects, highlights the need for further interdisciplinary
academic stress on academic performance.                                     research into this area.
   Given the potential of BDNF as a biomarker for academic                      Several studies suggest that the impact of stress on academic
performance, it is essential to conduct in-depth studies on the              achievement may vary and may be influenced by various factors
genetic and epigenetic regulation that influences BDNF synthesis.             (Brodersen and Lorenz, 2020; Ferreira et al. 2020; Wong et al.
Polymorphisms in the BDNF gene have been associated with                     2023). The influence of stress on academic performance is not
variations in cognitive performance, particularly in tasks invol-            linear and can be affected by other factors such as self-efficacy,
ving psychomotor speed, working memory, and executive                        motivation, individual learning approaches, and emotional
function (Dowlati et al. 2020; Wiłkość et al. 2016). The BDNF                intelligence (Ferreira et al. 2020; Ringeisen et al. 2019; Wong
Val66Met gene polymorphism is also linked to mental health,                  et al. 2023; Cipra and Muller-Hilke, 2019; MacCann et al. 2022).
which can affect academic performance (Bedard et al. 2017).                  These findings suggest that subsequent studies should consider
These genetic factors can provide insights into how individuals              these variables to obtain a more comprehensive understanding of
respond differently to academic stress, which in turn can                    the relationship between stress and academic performance. Thus,
influence optimal learning strategies and curriculum adjustments              a holistic approach to examining the interaction between stress
to enhance academic outcomes.                                                and other psychological factors can provide deeper insights into
   Beyond genetic regulation, epigenetic aspects also play a crucial         efforts to improve student academic achievement.
role in BDNF expression and could be an area for further                        Another approach to reducing the negative impact of stress
exploration in educational research. Epigenetic regulation, such as          and enhancing students’ well-being is through the development of
global DNA methylation, MeCP2, and various non-coding RNAs,                  educational programs that encourage students’ connection to
has been shown to influence BDNF expression (Castillo-                        nature and their knowledge of environmental issues (Sulfa et al.
Navarrete et al. 2023; Lee et al. 2019; Lipovich et al. 2012;                2024). These programs have the potential to benefit not only
Modarresi et al. 2021). Research in this area could provide new              students’ mental health but also increase their awareness and
insights into how educational environments and social experi-                responsibility toward the environment. Continued inquiry could
ences interact with biological factors to shape students’ academic           explore the potential of this intervention in learning practices,
performance. This has implications for developing more effective             particularly in the natural sciences, to assess its impact on
reducing academic stress and improving students’ well-being and           approaches are needed to address the complexities of academic
academic performance.                                                     performance (Rodríguez-Torres et al. 2024; Vajaradul et al. 2021).
   Prospective research should develop predictive models based            Anticipated studies should focus not only on identifying stress
on individuals’ biological responses to stress, as suggested by           within academic environments (Acevedo et al. 2021; Jiménez-
Abromavičius et al. (2023). Predictive models can help identify           Mijangos et al. 2023; Shanbhog and Medikonda, 2023), but also
individuals more susceptible to stress and potentially experien-          on evaluating the impact of interventions from a broader
cing declines in academic performance. Additionally, it is                perspective (Špiljak et al. 2024; Mäkelä et al. 2023). This will
essential to develop interventions tailored to individual needs,          pave the way for developing more effective and relevant
as proposed by Peter et al. (2023). A more personalized approach          interventions tailored to the needs of students.
to intervention strategies is likely to yield more optimal results
because it can accommodate individual variations in response to
stress and their psychological needs. This approach requires a            Limitations of the study
deep understanding of the biological and psychological factors            Although this study successfully identified several significant
contributing to stress so that interventions are truly effective in       findings regarding the relationship between stress, depression,
reducing the negative impact of stress on academic performance            and anxiety with academic performance among university stu-
(Lee et al. 2019).                                                        dents, there are some limitations that should be noted. The
                                                                          limitation of using only the Scopus database restricts the scope of
Interdisciplinary approach. From the eligibility analysis of              the study. The diversity of articles on the Web of Science could
222 studies included in the topic analysis, only 31 studies com-          offer different perspectives. It is recommended to incorporate
bined biological and psychological approaches in examining the            additional databases in future directions to enhance the breadth
topic of stress and academic performance (Fig. 1). Further con-           and accuracy of the findings. The restriction of the search to
tent analysis showed that only 12 of these studies genuinely              English-language and open-access articles could potentially
integrated interdisciplinary approaches in the analysis and dis-          overlook relevant studies published in other languages or hidden
cussion of their research findings (Table 2). This indicates a gap         behind paywalls of subscription-based journals. Additionally, the
in more holistic approaches, considering that academic achieve-           strict inclusion criteria, such as focusing solely on university
ment is highly likely influenced by interactions among various             students, may limit the generalizability of the findings. Pro-
factors, including genetics, epigenetic regulation, and environ-          spective research should explore academic stress across different
ment (Lee et al. 2019). Indeed, some reviewed studies focused             educational levels to provide a more comprehensive under-
more on biological studies without comprehensively linking them           standing. Nevertheless, the results of this analysis provide a strong
to psychological and social aspects (Abromavičius et al. 2023;            foundation for further research on this topic.
Kabrita and Hajjar-Muça, 2016; Špiljak et al. 2024).
   Most of the analyzed studies predominantly employed
quantitative methods, including both experimental and observa-
tional approaches (Table 4). Only one study adopted a mixed-              Conclusion
method approach in its methodology (Ferreira et al. 2020). This           This study reviewed literature exploring the relationship between
limitation may hinder the generation of findings that are more             academic stress and academic performance through a structured
generalizable and relevant across various contexts. While                 literature review, employing content analysis techniques. From
quantitative approaches promise standardization, control, relia-          this analysis, we identified three key aspects in the literature,
bility, and a stronger basis for making causal claims, qualitative        encompassing biological parameters, psychological instruments,
approaches offer a broader context, phenomenological under-               and research methodologies used. Commonly utilized biological
standing, and insights into behavioral complexities (Sockolow             parameters include cardiovascular measures, cortisol hormone
et al. 2016). Therefore, the use of mixed methods is highly               levels, and salivary α-amylase. We also found several psycholo-
recommended for ongoing explorations to achieve a broader                 gical instruments frequently used to measure stress, anxiety, and
perspective, a more in-depth analysis, and a better understanding         depression among university students. In terms of methodology,
of the complexities of education and cognition (Poortinga and             the research generally employed quantitative approaches and
Fontaine, 2022). For example, a comprehensive mixed-method                rarely applied mixed-method approaches.
study that combined electrodermal activity (EDA) measurements                As key findings, this study identifies two important points.
with qualitative analysis of video recordings of the learning             First, there are four main theoretical foundations that can be used
process revealed that hands-on learning, which is generally               to understand the interaction between stress and academic per-
assumed to foster higher student engagement, could actually               formance in the context of biology and education: the neuro-
trigger more stress rather than productive involvement (Sung              physiology of cognition and emotion, stress and the
et al. 2023). This serves as a concrete example of how mixed-             hypothalamic-pituitary-adrenal axis, stress and epigenetic reg-
method research can enhance the understanding of academic                 ulation, and genetic variation and stress. Second, we recommend
stress.                                                                   three future directions emphasizing the development of students’
   A more comprehensive methodology can also minimize bias                academic performance. Further studies should focus on under-
associated with self-report measurements in psychological                 standing the mechanisms of stress and academic performance,
instruments. Next step in the research should consider incorpor-          educational interventions, and interdisciplinary research
ating more objective measures to complement self-reported data.           approaches. These findings are expected to guide future studies in
In addition to objective measures such as physically or                   the fields of education and psychology to optimize students’
physiologically measured data, direct observations by researchers,        academic performance through a deeper understanding of the
which are less influenced by respondents’ personal perceptions,            impact of stress.
are also recommended.
   Additionally, current interventions tend to be limited and are
not yet integrated with strategies aimed at holistically enhancing        Data availability
academic performance. Hence, interdisciplinary studies that not           All data is available in the published literature of the primary
only rely on quantitative data but also involve qualitative               source.
Received: 11 September 2024; Accepted: 23 January 2025;                                        assessment, improved cardiac physiology knowledge and decreased pre-test
                                                                                               stress and anxiety. Front Physiol 14:1261199. https://doi.org/10.3389/fphys.
                                                                                               2023.1261199
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