Investigating Early Adolescent Sex Differences in Hippocampal and Amygdala Volumes,Sleep Quality and Psychological Distress

Abstract

Adolescence is a period of significant brain development and decreased sleep quality, making it an ideal period to investigate early indicators of anxiety disorders such as psychological distress. The amygdala and hippocampus have been implicated in the neurobiology of anxiety symptoms. Sex-based differences in anxiety symptoms and sleep quality suggest sex-specific indicators may be preferable to a “one size fits all” approach. N = 70 early adolescents (12 years) completed the Pittsburgh Sleep Quality Index (PSQI), Kessler psychological distress scale (K10) and MRI scanning. Female participants were found to be poorer sleepers and to have higher psychological distress levels. Females also had larger right amygdala and hippocampal volumes than males controlling for total brain volume. Findings of sex-based differences in amygdala and hippocampal volumes as well as sleep and psychological distress at age 12 may represent an important step in elucidating sex specific early indicators of future mental health disorders.

Keywords

early adolescence sleep psychological distress amygdala hippocampus

Introduction

Typically, in youth, symptom profiles of mental health disorders such as anxiety are amorphous and sub-syndromal, prior to the development of a discrete disorder that often persists into adulthood. The ability to predict the increased likelihood of future anxiety disorders based on behavioural or neuroanatomical measures has the potential to greatly reduce the burden on the individual and society through early interventions which are typically more effective (Membride, 2016). Indeed, previous studies have demonstrated the effectiveness of psychological interventions in reducing anxiety symptoms with lasting effects in child and early adolescent participants (Dadds et al., 1997). However, the early detection of sub-syndromal symptoms of anxiety such as psychological distress in general population samples of young people remains a challenge. Furthermore, in addition to the heightened potential for psychological distress, changes in sleep quality and ongoing brain development makes early adolescence an important, albeit complex, developmental period to investigate.

Sex-based differences in the effectiveness of treatment options suggests that further investigation according to the neural and behavioural correlates for females and males with anxiety related symptoms is needed (Grubbs et al., 2015). Anatomically, male brains have been shown to be, on average approximately 10% larger and this difference has been shown to persist even after controlling for differences in body size (Giedd et al., 2012). Without adjusting for total brain volume (TBV), the volume of subcortical structures also tend to be larger in males (Giedd et al., 2012). However, studies that report TBV adjusted subcortical structures tend to show that females have larger hippocampal volumes while males have larger amygdala volumes, with these differences suggested to result from the influence of steroid hormones and thus may largely develop during adolescence (after pubertal onset) (Neufang et al., 2009).

Sleep patterns also change in the transition from childhood into adolescence, and it is now well established that sleep quality diminishes with development (Carskadon, 2011). During adolescence, bedtimes tend to get later due to a biologically driven circadian rhythm phase delay while wake times for formal activities such as school remain fixed (Carskadon, 2011). This is of increased concern given the well-established association between sleep quality and mental health and wellbeing (Goldstein & Walker, 2014; Jamieson et al., 2020; Wulff et al., 2010). Furthermore, sex differences in bedtime, sleep quality and the neurophysiology of sleep have been widely reported (Markovic et al., 2020; Zhang et al., 2016). The circadian rhythm phase delay, which often results in difficulty getting to sleep early enough to achieve the recommended sleep time, has been shown to commence around 1 year earlier in females than males (Hagenauer et al., 2009). Zhang et al. (2016) reported that while insomnia symptoms increased for both males and females during adolescence, the increase was significantly larger for females.

Hippocampus, Sleep and Anxiety Symptoms

The size, function and development of the hippocampus has been shown to be closely associated with symptoms associated with anxiety (Geuze et al., 2005). Neural connections between the hippocampus and the medial prefrontal cortex (mPFC) are believed to play a crucial role in the “anxiety circuit” (Parfitt et al., 2017). In rodents, hippocampal lesions and smaller hippocampal volumes have been linked to a reduced ability to unlearn anxiety provoking associations suggesting a possible link between the hippocampus and anxiety symptoms (Cominski et al., 2014). The hippocampus is also considered to be a highly stress-susceptible brain structure with exposure to prolonged stress shown to result in a reduction in neurons (Bennett & Lagopoulos, 2014). Anxiety is often inter-related with the concept of stress, and therefore, research on stress or exposure to stressful events also informs our understanding of anxiety. The Kessler 10 (K10) is a 10 item measure of psychological distress which has demonstrated a linear relationship with the diagnostic criteria for Anxiety and Affective disorders (Andrews & Slade, 2001). Our previous study of hippocampal GMV in early adolescents (N = 32, 15 female) found a significant negative relationship between the volume of the left CA1 region of the hippocampus and K10 scores (controlling for gender), with smaller GMV being associated with higher levels of psychological distress (Broadhouse et al., 2019).

Sex-based differences have also been reported in relation to early life stress exposure and hippocampal volume. In a retrospective study of participants aged 22 years who had experienced early life abuse and neglect, hippocampal volume (in males) was best predicted by neglect prior to 8 years of age while female hippocampal volume was best predicted by abuse between the ages of 10 and 16 years, but not neglect (Teicher et al., 2018). In rodent studies, during the reproductive cycle, females have been shown to have increased density of dendritic spines in the CA1 region of the hippocampus compared to males, and when exposed to a stressful event, male rats CA1 dendritic spine density increased while females decreased (Shors et al., 2001).

The majority of research looking at the association between sleep and the hippocampus has focused on memory consolidation. It is now well established that transference of the days’ memories from the hippocampus to the cortex occurs during sleep through activation of a hippocampal – cortical circuit (Rasch & Born, 2013). Additionally, hippocampal volume has been shown to be positively associated with sleep duration in a study of participants aged 5–18 years (Taki et al., 2012). Perhaps most pertinent though is the role of the hippocampus in the encoding of emotionally memories. Several studies have now demonstrated increased hippocampal (and amygdala) activation during the encoding of emotional memories with increased activation positively associated with retention of emotional memories (Walker & van der Helm, 2009). Sex-based differences have been reported in hippocampal and amygdala activation during memory retrieval and content generalization tasks with male participants demonstrating increased activation of the dorsal hippocampus while female participants show increased activation of the amygdala (Keiser et al., 2017). Keiser et al. (2017) suggested that this difference may play a part in the retrieval and generalization of fear memories and partially explain the observed differences in anxiety symptoms and PTSD rates which are two to three times higher in females (Kessler et al., 2012).

Amygdala, Sleep and Anxiety Symptoms

The amygdala is widely acknowledged to be implicated in fear and emotional processing (Phelps & LeDoux, 2005). Projections originating from the amygdala and running to the hypothalamus have been shown to mediate autonomic nervous system activation in response to fear and anxiety provoking stimuli (Phelps & LeDoux, 2005). As with the above-mentioned hippocampal findings, we found a significant negative relationship between amygdala volume and psychological distress in early adolescents; more specifically, smaller left basal and accessory amygdala substructures are associated with increased distress (Broadhouse et al., 2019). In a study comparing female and male adults, participants were asked to use cognitive reappraisal techniques to down-regulate emotional responses to negatively valenced images. Researchers found that while males and females achieved a similar level of reduction in emotional response, females showed greater activation in the prefrontal cortex (PFC) while males showed a greater decrease in amygdala activity (McRae et al., 2008). Of note, sleep has been shown to have a significant influence on amygdala activation (Walker & van der Helm, 2009). Studies have shown that adult participants who are allowed normal sleep demonstrate decreased activation of the amygdala to emotional stimuli while those who are deprived of sleep demonstrate increased activation to the same stimuli (Walker & van der Helm, 2009).

The Current Study

A causal model is proposed whereby the onset of puberty (typically commencing earlier for females than males) leads to changes in sleep-wake patterns which, when combined with societal pressures, negatively impacts sleep quality. The resultant reduction in sleep quality then impacts brain development, particularly in the hippocampus and amygdala. These brain structures have been shown to be related to affective disorders, whereby alterations in their development may increase the likelihood of the future development of anxiety and other mental health problems. Due to the earlier onset of puberty in females, we would expect to see evidence of this causal model commencing at an earlier age in females than in males.

The current study is based on cross-sectional data collected at the first time-point of the Longitudinal Adolescent Brain Study (LABS), a 5-year longitudinal study with testing conducted every 4 months following adolescents as they age from 12 years up to, and including, when they reach 17 years. The Kessler psychological distress scale (K10) (Kessler et al., 1992) is a brief self-report of depression and anxiety symptoms, and it has been shown to be a valid and reliable way of detecting early signs of mental ill health (Sakurai et al., 2011). Hence, the current study utilised the K10 as proxy measure for emerging psychologic distress (including anxiety) in participants aged 12 years who also completed the Pittsburgh Sleep Quality Index (PSQI), and underwent MRI scanning. Thus, our aim was to investigate sex-based differences in self-reported sleep quality and psychological distress, and TBV adjusted volumes of the hippocampus and amygdala, in early adolescents. Based on previous findings demonstrating the relationship between sleep and psychological distress and the earlier onset of the circadian rhythm phase-delay in females we proposed the following hypotheses. During early adolescence: (1) Females will report poorer sleep quality than males, (2) Females will report increased psychological distress compared with males. (3) Females will have larger TBV adjusted volumes of the amygdala and hippocampus. And finally, it is hypothesised that (4) the combination of sleep quality and volumes of the left and right amygdala and hippocampus will predict psychological distress levels in females but not males.

Methods

Participants

All data were collected at the University of the Sunshine Coast - Thompson Institute Inclusion criteria at study entry was that participants were 12 years of age and in grade 7 (first year of high school). Participants were recruited from the Sunshine Coast Region region and had to be proficient in spoken and written English. Participants who reported suffering from a major neurological disorder, intellectual disability, major medical illness or having sustained a head injury that involved loss of consciousness for greater than 30 minutes were excluded. The LABS protocol is broadly divided into two assessment blocks (AB). AB-1 involves a self-report questionnaire, cognitive assessment, neuropsychiatric interview and debriefing procedure while AB-2 involves an electroencephalography (EEG) and magnetic resonance imaging (MRI).

Ethical Approval

Ethics approval has been granted by the University Human Research Ethics Committee (Approval Number: A181064). Informed consent was obtained from all participants and their guardian/s.

Measures

Sleep Quality

Participants undertook the Pittsburgh Sleep Quality Index (PSQI), an 18-item self-report, retrospective (past month) questionnaire (Buysse et al., 1989). The PSQI is designed to measure seven components of sleep: (i) subjective sleep quality, (ii) sleep latency, (iii) sleep duration, (iv) habitual sleep efficiency, (v) sleep disturbance, (vi) use of sleep medication, and (vii) daytime dysfunction. Responses are provided in hours and minutes (for duration and time to sleep/awake) and on a four-point Likert-type scale (not during last month, less than once a week, once or twice a week, and three or more times a week) then tallied to give an overall score. Although the PSQI was initially validated using an adult sample (Buysse et al., 1989) it has since been shown to be a reliable and hence a valid measure of sleep quality and quantity for use in a wide range of populations including adolescents and young adults (Cronbach’s alpha = 0.73, Test-retest reliability = 0.87) (Raniti et al., 2018).

Psychological Distress

Participants also completed the Kessler-10 (K10) a 10-item self-report questionnaire designed to measure psychological distress levels on a five-point Likert scale by asking about their feelings over the past 30 days (Kessler et al., 1992). Individual item scores are then tallied to provide an overall score ranging from 10 to 50, with higher scores indicating increased psychological distress. The K10 has been shown to have good reliability and validity across cultures and clinical populations, and has been widely used as a proxy of anxiety and depression symptoms at various levels of severity (Spies et al., 2009; Thelin et al., 2017).

MRI Acquisition

All participants underwent a multimodal MRI protocol at the Nola Thompson Centre for Advanced Imaging. All scans were acquired on a 3 Tesla Siemens Skyra (Erlangen, Germany) scanner using a 64-channel head and neck coil. Structural MRI was performed using a Magnetization Prepared Rapid Acquisition Gradient Echo (MP-RAGE) T1-weighted sequence with the following parameters: TR = 2200 ms, TE = 1.76 TI = 850 ms, flip angle 7°, resolution= 0.9mm isotropic, FOV 230 mm).

Image Processing

Preprocessing of raw images was carried out using FSL (Smith et al., 2004). Brain extraction was undertaken using FSL BET (Smith, 2002). Visual inspection and cleanup of remaining skull and/or neck tissue was undertaken using the FSLeyes editing tool. The FSL FMRIB’s Automated Segmentation Tool (FAST) was then utilised to create whole brain partial volume estimates (in mm³) and voxel numbers of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) (Zhang et al., 2001). The whole brain GM and WM volumes were then summed to calculate the total brain volume (TBV) for each participant. Finally, FSL FIRST was applied to the brain extracted image to produce bilateral volumetric measures (in mm³) for the amygdala and hippocampus (Patenaude et al., 2011).

Statistical Analysis

Of the initial N = 70 participants, 7 were excluded from the current study due to susceptibility artefacts (mainly due to dental braces) and motion artefacts which negatively impacted brain imaging quality, leaving a final sample of N = 63. Prior to undertaking statistical analysis, hippocampal and amygdala volumes were adjusted for TBV using the proportional approach for each participant which involves dividing the volume of each region of interest by the TBV (O’Brien et al., 2011).

SPSS® Version 26 (SPSS Inc., Chicago, Illinois, USA) was used to perform an independent samples t-test on the variables K10, PSQI total, TBV adjusted hippocampal and amygdala volumes with sex entered as the grouping variable. Whole group correlational analysis was then undertaken using the PSQI and K10 scores and scatterplots were produced to provide a visual representation of this relationship. Multiple regression analysis was then performed with PSQI score, sex, and TBV adjusted volumes of the left and right amygdala and hippocampus entered as the predictor variables and K10 score entered as the DV. This was followed by separate multiple regression analyses for females and males with PSQI score and TBV adjusted volumes of the left and right amygdala and hippocampus entered as the predictor variables and K10 score entered as the DV.

Results

Total group and sex-based comparisons for age, handedness, K10 and PSQI were calculated and are provided in Table 1. Significance test results (p-values) are in relation to sex-based comparisons. Female participants showed significantly poorer sleep quality (higher PSQI) and significantly increased psychological distress (higher K10).

Table 1.

Demographic Characteristics, K10, PSQI Scores Total Sample and Sex Differences.

	Total sample (n = 63)	Females (n = 29)	Males (n = 34)	(p value)	Effect sizeCohen’s d
Age, weeks (SD)	657.90 (15.87)	657.23 (15.43)	658.47 (16.45)	.759	0.07
Handedness	90.5% right	89.7% right	91.2% right	.879
K10*	15.76 (5.20)	17.41 (6.06)	14.35 (3.89)	.019	0.60
PSQI*	5.02 (2.97)	5.97 (3.38)	4.21 (2.33)	.018	0.61

*p-values significant <.05 are provided in bold. Significance test relates to female versus male comparison.

Table 2 provides the uncorrected volumes of the total brain, amygdala and hippocampus as well as the results of an independent samples t-test sex-based comparison on the TBV (uncorrected) along with the TBV adjusted amygdala and hippocampal volumes.

Table 2.

Unadjusted Total Brain, Amygdala and Hippocampus Volumes in mm³ and Sex-Based Independent Samples t-Test.

Variable	Sex (F = 29, M = 34)	Unadjusted volumes in mm³	SD	t	df	p value	Effect sizeCohen’s d
Total brain vol (TBV)*	Female	1,161,161	65,759	−5.246	62	<.001	1.30
Total brain vol (TBV)*	Male	1,274,620	104,083	−5.246	62	<.001	1.30
Amyg_L	Female	843.13	264.21	1.357	62	.180	0.35
Amyg_L	Male	821.57	305.85	1.357	62	.180	0.35
Amyg_R*	Female	1032.64	246.83	3.290	62	.002	0.81
Amyg_R*	Male	914.09	270.74	3.290	62	.002	0.81
Hipp_L	Female	3355.25	622.15	.759	62	.451	0.18
Hipp_L	Male	3573.61	516.91	.759	62	.451	0.18
Hipp_R*	Female	3534.65	316.47	2.499	62	.015	0.64
Hipp_R*	Male	3573.08	586.27	2.499	62	.015	0.64

Note. Equal variance not assumed values reported where Levene’s test was significant.

Female participants had significantly larger corrected volumes of the right amygdala and hippocampus.

Correlational analysis showed a significant correlation between PSQI and K10 scores r = .659, p<.001 (Figure 1). Separate correlations found that while the relationship between sleep and psychological distress was significant independently for both female participants (r = .760, p<.001), and male participants (r = .372, p= .030), the relationship was stronger for females and this is visually depicted in Figure 2.

Figure 1.

Whole group Sleep quality (PSQI total) and Psychological distress (K10) correlations. Note the Y axis starts at 10 as this is the minimum score of the Kessler psychological distress scale.

Figure 2.

Sleep quality (PSQI total) and Psychological distress (K10) correlations with separate fit lines for male and female participants. Note the Y axis starts at 10 as this is the minimum score of the Kessler psychological distress scale.

Unadjusted volumes mm³ are presented. TBV was calculated as the total gray matter and white matter volume. Tests of significant differences for amygdala and hippocampus were undertaken after controlling for TBV.

Results of the whole group multiple regression analysis revealed that the overall model was significant (F(6,56) = 7.68, p < .001) and explained 45% of the variance (Adjusted R² = .39, with sleep quality (t = 5.88, p < .001) the only significant predictor ( $β = 1.09)$ . Follow-up separate multiple regression analyses were conducted for female vs. male participants only. For females, the overall model was significant (F(5,23) = 7.18, p < .001) and explained 61% of the variance (Adjusted R² = .53), with sleep quality (t = 5.61, p < .001) being the only significant predictor ( $β = 1.38)$ . Whereas for males, the regression model was non-significant.

Discussion

The relationship between sleep quality and symptoms synonymous with anxiety disorders such as psychological distress is now well established (Jamieson et al., 2020; Wulff et al., 2010). Activation and volume of the amygdala and hippocampus have also been associated with both sleep and anxiety symptoms, and decreased GM in the amygdala and hippocampus has been linked to increased psychological distress at 12 years old, indicating that neurobiological changes may be present prior to the onset of mental health disorders (Broadhouse et al., 2019; Geuze et al., 2005; Phelps & LeDoux, 2005). Additionally, sex differences have been demonstrated in amygdala and hippocampal activity and volume as well as in sleep measures and symptoms of anxiety (McRae et al., 2008; Neufang et al., 2009). However, these relationships have yet to be studied in a sample comprised entirely of early adolescents. This is an important period for investigating potential early indicators of anxiety disorders such as psychological distress given the well-established decline in sleep quality (Carskadon, 2011) and the increased incidence of symptoms associated with anxiety during early adolescence (Paus et al., 2008). The exploration of sex-based differences in these variables is of particular interest given the observed sex-based heterogeneity in the efficacy of treatments for anxiety symptoms (Grubbs et al., 2015).

Broadly, the current study aimed to uncover sex-based differences in sleep quality, TBV adjusted amygdala volume, TBV adjusted hippocampal volume, and psychological distress in a sample of participants aged 12 years. Based on previous findings it was hypothesised that at age 12: (1) female participants would have poorer sleep quality than males, and (2) female participants would have higher levels of psychological distress. (3) Females will have larger volumes of the amygdala and hippocampus after adjusting for TBV. And finally that (4) the combination of sleep quality and volumes of the left and right amygdala and hippocampus will predict psychological distress levels in females but not males.

In accordance with our first hypothesis, females were found to have significantly poorer sleep quality than male participants. This hypothesis was based on previous findings showing that the puberty aligned circadian rhythm phase-delay occurs around 12 months earlier in females than males and the mean age of our sample suggests this phase-delay is more likely to have impacted females than males (Hagenauer et al., 2009). This finding suggests that females could enter the period of increased mental disorder incidence early than males and may provide guidance for sex-specific timing of preventative interventions such as sleep hygiene education.

In accordance with our second hypothesis females were found to have significantly higher levels of psychological distress than males. This hypothesis was based on previous research linking poor sleep and increased psychological distress (Carskadon, 2011). It has been reported previously that the circadian rhythm phase delay when combined with the need to wake up early for formal activities such as school is likely to negatively impact sleep quality and quantity (Carskadon, 2011). As this circadian rhythm phase delay is believed to be linked to pubertal onset it seems likely that it will impact females at a younger age (Carskadon, 2011; Hagenauer et al., 2009). Our findings depicted in Figure 2 suggest that not only are females more likely to suffer from reduced sleep quality during early adolescence, but they appear to also experience a heightened impact on their psychological distress levels as a result.

With regards to our third hypothesis, the analysis of the sex-based differences in the amygdala and hippocampal volumes showed females had significantly larger TBV corrected hippocampal and amygdala volumes in the right hemisphere than males while no significant sex-based difference was found in the left amygdala or hippocampus (see Table 2). Findings from a previous study of young adults (mean age 23.1 years ±2.3) reported no significant sex-based difference in hippocampal volume after correcting for head size (Perlaki et al., 2014). While Neufang et al. (2009) reported larger volumes for males in the left amygdala and larger bilateral hippocampal volumes for females. Moreover, Broadhouse et al. (2019) found that smaller sub-regions of the hippocampus and amygdala at age 12 were linked to greater psychological distress. Our finding of significantly larger right hippocampal volume in females support the previous finding from Neufang et al. (2009) and suggests that steroid hormones may play a role in brain development in females by 12 years of age.

With regards to our final hypothesis, multiple regression analysis revealed that poorer sleep quality significantly predicted increased psychological distress, while sex and TBV adjusted volumes of the left and right amygdala and hippocampus are held constant. The separate regression models then demonstrated that poor sleep quality predicts increased psychological distress, despite any differences in amygdala and hippocampal volumes, for female but not males participants, which is consistent with our hypothesis.

Studies of hippocampal volume and symptoms associated with psychiatric disorders have reported mixed results. In a study of females aged 9–15 years, Chen et al. (2010) found participants with an increased risk of depression (based on family history) showed reduced bilateral hippocampal volume compared with participants with no family history of depression. However, Vakili et al. (2000) found no significant difference in hippocampal volume in a comparison of adults with and without depression. In a meta-analysis investigating the relationship between hippocampal volume and psychiatric disorders, Geuze et al. (2005) found that smaller hippocampal volume was associated with a number of disorders including PTSD and obsessive-compulsive disorder. Our finding that females, at 12 years of age, had larger right hippocampal volumes and increased levels of psychological distress suggest that this relationship may be more complex.

Previous results regarding the association between anxiety symptoms such as psychological distress and the volume of the amygdala have also reported some mixed results. In a study comparing Autism spectrum disorder participants with and without anxiety symptoms, Herrington et al. (2017) found those with anxiety symptoms had decreased right amygdala volumes. An early study by de Bellis et al. (2000) found that larger amygdala volumes may be associated with generalised anxiety disorder. While Baur et al. (2012) found a positive association between the volume of the left amygdala and trait anxiety. In the current study, we found female participants had larger right amygdala volumes as well as increased levels of psychological distress. The heterogeneity of these findings suggest that further research is required to tease apart the confounding factors.

Limitations and Future Directions

Some limitations of the current study need to be acknowledged. Firstly, the use of a self-report measure of sleep quality has some limitations. The PSQI was chosen due to its demonstrated validity and reliability, as well as its convenience and feasibility given the multi-modal, complex protocols of LABS. The PSQI has been shown to be a reliable and valid measure of sleep quality for studies of adolescents (Raniti et al., 2018) and importantly has demonstrated convergent validity with measures of anxiety in an adolescent sample (Raniti et al., 2018). Future replication of this study would benefit from the inclusion of an objective measure of sleep quality such as polysomnography or actigraphy to provide an objective measure of sleep quality.

Secondly, the use of an automated segmentation tool (FSL FIRST) could be viewed as a limitation. While manual segmentation has previously been described as the “gold standard” for subcortical segmentation (Perlaki et al., 2017), FSL FIRST automated segmentation tool was chosen to avoid the introduction of subjectivity into the segmentation process which can occur when manually tracing subcortical structures and to allow easy replication and comparison of volumes between studies (Quilis-Sancho et al., 2020). Future studies would also benefit from analyses that separate the gray and white matter volumes of these subcortical structures to better understand the role of developmental processes such as synaptic pruning and neurogenesis.

Thirdly, Changes in sleep patterns and psychological distress are also likely to be influenced by a number of psychosocial and/or psychosexual factors. Differences in circadian rhythm timing could indeed be one factor in a model involving a number of influences such as emotional reactivity, hormonal changes, and cognitive factors such as body image that lead to the heightened incidence of depression in females by mid adolescence compared to males (Hyde et al., 2008). The use of smart phones and computer tablets have also been shown to further delay sleep onset and reduce sleep duration in adolescents (Hisler et al., 2020). While the current study did not measure participant’s use of electronic media, it is suggested that future studies could include a measure of bedtime smartphone and computer tablet use allowing correlations to be measured between sleep and electronic device use. Social connectivity has also been shown to be associated with reduced sleep quantity (Simon & Walker, 2018). Future studies would benefit from the inclusion of a measure of social connectivity to allow further explanation of sleep measures.

Finally, the cross-sectional nature of the data limits the ability to draw conclusions from the findings. Future replication using data from multiple time points would allow developmental changes to be tracked across time. This would allow us to investigate sex-specific changes during early adolescence in hippocampal and amygdala volume and how these are related to gender-specific changes in sleep quality and psychological distress. Future longitudinal studies could also investigate the relationship between early adolescent psychological distress and the likelihood of the development of anxiety disorders and affective disorders during mid to late adolescence and adulthood.

Conclusion

Elucidating the early signs of anxiety disorders has the potential to greatly reduce the burden on the individual and society. Early adolescence is an important period to undertake this investigation due to the well-established increase in incidence of anxiety related symptoms during this period. The current study of 12-year-old participants found females had significantly poorer sleep quality, significantly increased psychological distress, and larger volumes of the right amygdala and hippocampus. These findings represent an important step towards understanding the sex specific relationships between these variables and provide a springboard to future longitudinal studies to investigate these variables across early adolescence.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research is supported by the Department of Health, Australian Government (Australian Commonwealth Government’s ‘Prioriti and Research Training Program (RTP) Scholarship and Au).

ORCID iD

Daniel Jamieson

Author Biographies

Jim Lagopoulos – Professor - Director Thompson Institute - University of the Sunshine Coast – Professor Lagopoulos is the Director of the Sunshine Coast Mind and Neuroscience Thompson Institute. He has well over 200 peer reviewed publications investigating topics including sleep and white matter associations, hippocampal volume and sleep, functional connectivity correlates and nocturnal awakening, and Pineal volume and melatonin levels in people with affective disorders.

Daniel F Hermens – Professor Youth Mental Health and Neurobiology - Thompson Institute - University of the Sunshine Coast – Professor Hermens has around 200 peer reviewed journal articles with over 35 publications on sleep-wake. These cover topics such as dim-light melatonin, white matter and sleep, polysomnography, circadian rhythms and core temperature, and sleep-wake’s usefulness in predicting manic episodes.

Dr. Daniel Jamieson - Thompson Institute - University of the Sunshine Coast – The focus of Daniel’s PhD was on the associations between sleep quality and white matter structural integrity. Specifically investigating the role of sleep quality during adolescence on myelination of anterior white matter tracts and how this relates to levels of psychological distress. Peer-reviewed publications at this stage include a review article, sleep quality and psychological distress article and a sleep quality and diffusion derived white matter integrity article. Recently Daniel authored a theoretical review article in Sleep Medicine Reviews which provided a neurobiologically informed model linking sleep quality to the likelihood of developing an anxiety disorder.

Amanda Boyes – PhD candidate holds a Bachelor of Criminology and Criminal Justice (Criminal Justice Major) (First Class Honours) and a Bachelor of Social Science (Psychology) (First Class Honours). She has worked in research roles for over 5 years. Amanda joined the Sunshine Coast Mind and Neuroscience Thompson Institute in 2016 and is a PhD student and Research Assistant on the Longitudinal Adolescent Brain Study (LABS). Her research interests include youth mental health, wellbeing, psychological distress, neuroscience, cognition, and early intervention.

Dr. Zack Shan obtained a PhD in biomedical engineering from the program jointly held by Cleveland Clinic Foundation and Cleveland State University (OH, USA). His research focused on translational neuroimaging, which included i) testing hypotheses and identifying brain changes underlying neurological diseases and ii) developing brain models for disease diagnosis and prediction of clinical outcomes using multivariate brain modelling and multimodal deep learning methods.

Dashiell Sacks holds a Bachelor of Psychology (First Class Honours) acquired at the University of the Sunshine Coast, Queensland, Australia. He is a current PhD candidate and Research Assistant at the Thompson Institute, University of the Sunshine Coast, focusing on the Longitudinal Adolescent Brain Study (LABS). Dash’s research focuses on using neuroimaging to investigate biomarkers of youth mental health and cognition to facilitate better early identification and treatment of mental disorder. He has published papers focusing on both MRI & EEG correlates of youth mental health.

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