Psychological predictors of insomnia, anxiety and depression in university students: potential prevention targets.

BACKGROUND: Perfectionism, low self-esteem and external locus of control are psychological constructs linked to insomnia, anxiety and depression. Examining how these constructs impact mental health and serve as risk factors for the development of clinically significant symptoms may help direct psychological support resources and preventative measures for university students. AIMS: To longitudinally examine associations between the aforementioned psychological constructs and symptoms of insomnia, anxiety and depression in a large representative sample of first-year university students. METHOD: Electronic surveys including validated measures of the predictors and outcomes were emailed to all first-year undergraduate students at entry to a major Canadian university, and followed up on at conclusion of the academic year. RESULTS: Compared with healthy sleepers, students screening positive for insomnia had lower self-esteem, higher self-evaluative perfectionism and increased external locus of control (all P < 0.001). Self-evaluative perfectionism (standardised ß = 0.13, P < 0.01), self-esteem (ß = -0.30, P < 0.001) and external locus of control (ß = 0.07, P = 0.02) measured at entry were significantly associated with insomnia symptoms at follow-up. Insomnia symptoms at entry were strong predictors of symptoms of depression (ß = 0.15, P < 0.001) and anxiety (ß = 0.16, P < 0.001) at follow-up, even after controlling for baseline symptoms of those disorders. CONCLUSIONS: Perfectionism, low self-esteem and external locus of control may predispose the development of insomnia symptoms in university students. In turn, insomnia symptoms appear to be robust predictors for depressive and anxiety symptoms. Sleep may be an important prevention target in university students.

Hypnotic and Melatonin/Melatonin-Receptor Agonist Treatment in Bipolar Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Bipolar disorder (BD) is a chronic relapsing-remitting psychiatric disorder. Sleep and circadian rhythm disturbances persist during acute mood episodes of the disorder and during euthymia. However, the treatment potential of hypnotic agents that might be used to manage sleep disturbance in BD is not well understood. Similarly, melatonin and medications with a melatonin-receptor agonist mechanism of action may have chronotherapeutic potential for treating people with the disorder, but the impact of these substances on sleep and circadian rhythms and core symptoms in BD is unclear. OBJECTIVE: Our aim was to conduct a systematic review and meta-analysis evaluating the current evidence for hypnotic and melatonin/melatonin-receptor agonist pharmacotherapy for symptoms of sleep disturbance, mania, and depression in patients with BD. METHODS: AMED, Embase, MEDLINE and PsychINFO databases were searched for studies published in English from the date of inception to 31 October 2021. Studies included in this review were randomised controlled trials (RCTs) and non-controlled/non-randomised studies for BD that examined hypnotic medications selected based on a common pattern of usage for treating insomnia (i.e. chloral, clomethiazole, diphenhydramine, doxepin, doxylamine, promethazine, suvorexant, zaleplon, zolpidem, zopiclone, and eszopiclone) and melatonin and the melatonin-receptor agonist drugs ramelteon and agomelatine. Risk of bias was assessed using the RoB2 and AXIS tools. Pooled effect sizes for RCT outcomes were estimated using random-effects models. RESULTS: A total of eleven studies (six RCTs and five experimental feasibility studies) involving 1279 participants were included. Each study examined melatonin or melatonin-receptor agonists. No studies of hypnotics were found that fulfilled the review inclusion criteria. Pilot feasibility studies suggested beneficial treatment effects for symptoms of sleep disturbance, depression, and mania. However, the pooled effect of the two available RCT studies assessing sleep quality via Pittsburgh Sleep Quality Index scores was not statistically significant (g = - 0.04 [95% CI - 0.81 to 0.73]) and neither was the pooled effect for depressive symptoms (four studies; g = - 0.10 [95% CI - 0.27 to 0.08]). Some RCT evidence suggests ramelteon might prevent relapse into depression in BD. The largest efficacy signal detected was for manic symptoms (four studies; g = - 0.44 [95% CI - 1.03 to 0.14]) but there was substantial heterogeneity between studies and patient characteristics. In the two RCTs assessing manic symptoms during acute mania, adjunctive melatonin demonstrated superior treatment effects versus placebo. CONCLUSIONS: There is a paucity of studies examining pharmacological interventions for sleep and circadian rhythm disturbance in BD. Few studies assessed sleep-related symptoms, and none quantitatively examined endogenous melatonin patterns or other circadian rhythms. Melatonin may be a promising candidate for the adjunctive treatment of bipolar mania. However, dose-finding studies and studies with larger sample sizes are needed to confirm its efficacy. We recommend parallel monitoring of sleep and circadian rhythms in future trials. Chronobiology-informed trial designs are needed to improve the quality of future studies. PROTOCOL REGISTRATION: PROSPERO (CRD42020167528).

Psychological and behavioural interventions in bipolar disorder that target sleep and circadian rhythms: A systematic review of randomised controlled trials.

Sleep and circadian disruptions are prominent symptoms of bipolar disorder (BD) and potential targets for adjunctive interventions. The aim of this review was to appraise the effectiveness of psychological and behavioural interventions in BD that target sleep and circadian rhythms, as reported by randomised controlled trials. Nineteen studies met the inclusion/exclusion criteria. They were summarised via narrative synthesis and meta-analysis wherever appropriate. Six studies delivered bright light therapy, five interpersonal and social rhythm therapy, two blue-light blocking glasses, one cognitive behavioural therapy for insomnia, one total sleep deprivation, and four combination treatments. More than half of the studies (N = 10, 52 %) did not measure sleep or circadian rhythms despite being the principal target of the intervention. Overall, the evidence base for the effectiveness of these interventions was limited. There was a small number of studies for each intervention, and a lack of consistency in protocols and outcomes. Meta-analysis was possible for the effect of bright light therapy on depression, revealing a medium-to-large post-treatment effect (Nc = 6; g=-0.74 [95 % CI=-1.05 to -0.42], p < 0.001).

Sleep and circadian rhythm actigraphy measures, mood instability and impulsivity: A systematic review.

The normal spectrum trait measures of mood instability and impulsivity are implicated in and comprise core symptoms of several psychiatric disorders. A bidirectional relationship between these traits and sleep disturbance and circadian rhythm dysfunction has been hypothesised, although has not been systematically assessed using objective measures in naturalistic settings. We systematically reviewed the literature following PRISMA guidelines, according to a pre-registered protocol (PROSPERO: CRD 42018108213). Peer-reviewed quantitative studies assessing an association between actigraphic variables and any measure of mood instability or impulsivity in participants aged 12-65 years old were included. Studies were critically appraised using the AXIS tool. Twenty-three articles were retained for inclusion. There was significant heterogeneity in the selection and reporting of actigraphic variables and metrics of mood instability and impulsivity. We identified emerging evidence of a positive association between circadian rest-activity pattern disturbance and delayed sleep timing with both mood instability and impulsivity. Evidence for an association with sleep duration, sleep efficiency or sleep quality was inconsistent. Future research should focus on longitudinal intra-individual associations to establish the directionality between these measures and may lead to the development of chronotherapeutic interventions for a number of psychiatric disorders.

A service evaluation of short-term mentalisation based treatment for personality disorder.

BACKGROUND: People with personality disorder experience long waiting times for access to psychological treatments, resulting from a limited availability of long-term psychotherapies and a paucity of evidence-based brief interventions. Mentalisation-based treatment (MBT) is an efficacious therapeutic modality for personality disorder, but little is known about its viability as a short-term treatment. AIMS: We aimed to evaluate mental health, client satisfaction and psychological functioning outcomes before and after a 10-week group MBT programme as part of a stepped-care out-patient personality disorder service. METHOD: We examined routinely collected pre-post treatment outcomes from 176 individuals (73% female) aged 20-63 years, attending a dedicated out-patient personality disorder service, who completed MBT treatment. Participants completed assessments examining mentalising capacity, client satisfaction, emotional reactivity, psychiatric symptom distress and social functioning. RESULTS: Post-MBT outcomes suggested increased mentalising capacity (mean difference 5.1, 95% CI 3.4-6.8, P < 0.001) and increased client satisfaction with care (mean difference 4.3, 95% CI 3.3-5.2, P < 0.001). Post-MBT emotional reactivity (mean difference -6.3, 95% CI -8.4 to -4.3, P < 0.001), psychiatric symptom distress (mean difference -5.2, 95% CI -6.8 to -3.7, P < 0.001) and impaired social functioning (mean difference -0.7, 95% CI -1.2 to -0.3, P = 0.002) were significantly lower than pre-treatment. Improved mentalising capacity predicted improvements in emotional reactivity (ß = -0.56, P < 0.001) and social functioning (ß = -0.35, P < 0.001). CONCLUSIONS: Short-term MBT as a low-intensity treatment for personality disorder was associated with positive pre-post treatment changes in social and psychological functioning. MBT as deployed in this out-patient service expands access to personality disorder treatment.

The Emerging Circadian Phenotype of Borderline Personality Disorder: Mechanisms, Opportunities and Future Directions.

PURPOSE OF REVIEW: We review the recent evidence suggesting that circadian rhythm disturbance is a common unaddressed feature of borderline personality disorder (BPD); amelioration of which may confer substantial clinical benefit. We assess chronobiological BPD studies from a mechanistic and translational perspective and highlight opportunities for the future development of this hypothesis. RECENT FINDINGS: The emerging circadian phenotype of BPD is characterised by a preponderance of comorbid circadian rhythm sleep-wake disorders, phase delayed and misaligned rest-activity patterns and attenuated amplitudes of usually well-characterised circadian rhythms. Such disturbances may exacerbate symptom severity, and specific maladaptive personality dimensions may produce a liability towards extremes in chronotype. Pilot studies suggest intervention may be beneficial, but development is limited. Endogenous and exogenous circadian rhythm disturbances appear to be common in BPD. The interface between psychiatry and chronobiology has led previously to novel efficacious strategies for the treatment of psychiatric disorders. We believe that better characterisation of the circadian phenotype in BPD will lead to a directed biological target for treatment in a condition where there is a regrettable paucity of accessible therapies.

Digital Communication Biomarkers of Mood and Diagnosis in Borderline Personality Disorder, Bipolar Disorder, and Healthy Control Populations.

Background: Remote monitoring and digital phenotyping harbor potential to aid clinical diagnosis, predict episode course and recognize early signs of mental health crises. Digital communication metrics, such as phone call and short message service (SMS) use may represent novel biomarkers of mood and diagnosis in Bipolar Disorder (BD) and Borderline Personality Disorder (BPD). Materials and Methods: BD (n = 17), BPD (n = 17) and Healthy Control (HC, n = 21) participants used a smartphone application which monitored phone calls and SMS messaging, alongside self-reported mood. Linear mixed-effects regression models were used to assess the association between digital communications and mood symptoms, mood state, trait-impulsivity, diagnosis and the interaction effect between mood and diagnosis. Results: Transdiagnostically, self-rated manic symptoms and manic state were positively associated with total and outgoing call frequency and cumulative total, incoming and outgoing call duration. Manic symptoms were also associated with total and outgoing SMS frequency. Transdiagnostic depressive symptoms were associated with increased mean incoming call duration. For the different diagnostic groups, BD was associated with increased total call frequency and BPD with increased total and outgoing SMS frequency and length compared to HC. Depression in BD, but not BPD, was associated with decreased total and outgoing call frequency, mean total and outgoing call duration and total and outgoing SMS frequency. Finally, trait-impulsivity was positively associated with total call frequency, total and outgoing SMS frequency and cumulative total and outgoing SMS length. Conclusion: These results identify a general increase in phone call and SMS communications associated with self-reported manic symptoms and a diagnosis-moderated decrease in communications associated with depression in BD, but not BPD, participants. These findings may inform the development of clinical tools to aid diagnosis and remote symptom monitoring, as well as informing understanding of differential psychopathologies in BD and BPD.

Blood pressure in bipolar disorder: evidence of elevated pulse pressure and associations between mean pressure and mood instability.

BACKGROUND: Bipolar disorder (BD) is associated with excess and premature cardiovascular mortality. Elevated blood pressure (BP) is a leading contributor to cardiovascular risk. However, few studies have examined BP in BD in comparison to other psychiatric disorders. Furthermore, the association between BP and mood instability is not presently clear despite increasing interest in repurposing existing antihypertensive medications as possible novel BD treatments. Thus we examined BP differences between BD and borderline personality disorder (BPD), a disorder with a similar symptom profile through chronic mood instability. METHODS: A total of 106 adults (38 BD, 25 BPD, and 43 healthy controls), evaluated in the Automated Monitoring of Symptom Severity (AMoSS) study, completed a week-long home blood pressure monitoring assessment and ecological momentary assessment of mood. We examined group-wise differences in mean BP and BP variability and their association with mood instability. RESULTS: BD individuals had a significantly wider resting pulse pressure (40.8 ± 7.4, mmHg) compared to BPD (35.7 ± 5.3, mmHg, P = 0.03) and control participants (37.3 ± 6.3, mmHg, P = 0.036). Systolic BP was negatively associated with sad mood instability, and all measures of mean BP (systolic, diastolic, and mean arterial pressure) were negatively associated with positive mood instability. CONCLUSIONS: This study demonstrates BP differences between BD and healthy and clinical controls that are within a normotensive range. Early pulse pressure widening may be a modifiable pathophysiological feature of BD that confers later cardiovascular risk. BP may be an important transdiagnostic predictor of mood instability and a potential explicit treatment target.

The impact of social jetlag and chronotype on attention, inhibition and decision making in healthy adults.

Sleep and circadian clock disruption are associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder, but the impact on neurocognitive performance is unclear. We assessed whether chronotype and everyday circadian misalignment manifested as social jetlag were associated with inter-individual neurocognitive performance across domains of attention, inhibitory control and decision making. One hundred and eighty-eight healthy young adults were assessed for sleep and circadian properties and performed two neurocognitive tasks, the Continuous Performance Test and the Iowa Gambling Task. Social jetlag was associated with significantly faster and less variable reaction times and commission errors on the Continuous Performance Test. Poorer subjective sleep quality was associated with poorer decision making on the Iowa Gambling Task. No effects were present for polymorphisms in the circadian clock genes CLOCK and PER3. We conclude that circadian disruption shaped by everyday environmental factors may impact on attentional/inhibitory performance but not on a measure of risky decision making.

Circadian rest-activity patterns in bipolar disorder and borderline personality disorder.

Bipolar disorder (BD) and borderline personality disorder (BPD) are two psychiatric disorders with overlapping features that can be challenging to separate diagnostically. Growing evidence suggests that circadian rhythm disturbances are associated with psychiatric illness, however circadian patterns of behaviour have not been elucidated in BPD or differentiated from BD. This study compared the circadian structure and timing of rest-activity patterns in BPD with BD and healthy volunteers. Participants with BD (N = 31) and BPD (N = 21) and healthy controls (HC, N = 35) wore an actigraph on their non-dominant wrist for 28 day periods as part of the Automated Monitoring of Symptom Severity (AMoSS) study. Non-parametric circadian rhythm analysis of rest-activity patterns and cosinor analysis of distal temperature rhythms were conducted to elucidate circadian function between groups. Covariates controlled for included employment status, BMI and gender. Compared with HC and BD, individuals with BPD showed significantly delayed phase of night-time rest patterns ("L5 onset") (mean difference = 1:47 h, P < 0.001; mean difference = 1:38 h, P = 0.009, respectively), and relative to HC showed delayed daytime activity onset ("M10 onset") (mean difference = 2:13 h, P = 0.048) and delayed temperature phase (mean difference = 1:22 h, P = 0.034). These findings suggest that delayed circadian function may be a clinically important phenotype in individuals with BPD. Future work should interrogate the causality of this association and examine interventions which target delayed circadian function in the treatment of BPD.

Sleep and circadian rhythm function and trait impulsivity: An actigraphy study.

We report the relationship between daily rest-activity patterns and trait impulsivity in healthy young adults. The Barratt Impulsiveness Scale was used to identify high and low impulsive individuals among a group of 51 volunteers. Participants' sleep behaviour and circadian rhythm function was assessed using week-long actigraphy. High impulsive individuals displayed phase-delayed patterns of sleep, a decreased total sleep time and sleep efficiency, and disrupted circadian function. Such outcomes were also associated with greater self-reported attention deficit hyperactivity disorder symptoms. The results highlight that sleep and circadian rhythm disturbances may be associated with impulsive traits replicating relationships described in psychiatric illnesses in which impulsivity is a core feature.

A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder.

Reports of sleep disturbances in attention deficit hyperactivity disorder (ADHD) are common in both children and adults; however, the aetiology of such disturbances is poorly understood. One potentially important mechanism which may be implicated in disrupted sleep in ADHD is the circadian clock, a known key regulator of the sleep/wake cycle. In this systematic review, we analyse the evidence for circadian rhythm changes associated with ADHD, as well as assessing evidence for therapeutic approaches involving the circadian clock in ADHD. We identify 62 relevant studies involving a total of 4462 ADHD patients. We find consistent evidence indicating that ADHD is associated with more eveningness/later chronotype and with phase delay of circadian phase markers such as dim light melatonin onset and delayed sleep onset. We find that there is evidence that melatonin treatment may be efficacious in addressing ADHD-related sleep problems, although there are few studies to date addressing other chronotherapeutic approaches in ADHD. There are only a small number of genetic association studies which report linkages between polymorphisms in circadian clock genes and ADHD symptoms. In conclusion, we find that there is consistent evidence for circadian rhythm disruption in ADHD and that such disruption may present a therapeutic target that future ADHD research might concentrate explicitly on.

Sleep quality, chronotype and social jetlag differentially associate with symptoms of attention deficit hyperactivity disorder in adults.

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder which has been associated with sleep and circadian rhythm disturbances. Numerous studies have linked evening circadian typology with traits and behaviours associated with the disorder, although a precise reason for this relationship has not been clarified. The current study examines ADHD symptoms, impulsivity, cognitive failures, sleep quality and chronotype in a cohort of healthy young adults (N = 396). Results show significant, small magnitude associations between mid-point of sleep on free days, social jetlag (SJL) and ADHD symptoms and impulsivity, although not with cognitive failures. Similarly, sleep quality is also associated with ADHD symptoms and impulsivity. Group-wise approaches show that higher SJL is associated with significantly more ADHD symptoms and impulsivity, and later mid-sleep on free days is also associated with more ADHD symptoms. Stepwise multiple linear regression reveals that, when controlling for age and sex, SJL but not mid-sleep on free days is a significant predictor of ADHD symptoms and impulsivity. These results indicate that SJL may be an important factor to consider when exploring circadian rhythm associations with ADHD symptoms.

Circadian and behavioural responses to shift work-like schedules of light/dark in the mouse.

BACKGROUND: Disruption of circadian rhythms is associated with several deleterious health consequences and cognitive impairment. It is estimated that as many as one in five workers are exposed to this risk factor due to experiencing some degree of chronodisruption by way of recurring patterns of shift work. It is not presently clear therefore how efficiently the mammalian circadian system entrains to alternative light/dark cycles such as those found in shift work schedules. METHODS: The present study examines male CD-1 mice exposed to three different paradigms of rapidly rotating shift work-like light/dark manipulations compared to control animals maintained on a standard 12:12 h light/dark cycle. RESULTS: Analysis of circadian patterns of behaviour under such conditions reveals that for fast rotating schedules of light/dark there is minimal circadian entrainment. Further, when placed in constant conditions after a period under the "shift work" lighting conditions there were changes to circadian period associated with the shift work schedules. In contrast to previous studies the shift work-like conditions did not produce changes in animal body-weight. Behavioural testing suggests possible anxiogenic and hyperactive outcomes dependent on rotation speed as animals displayed open field thigmotaxis and hyperlocomotion. CONCLUSION: These results indicate that exposure to alternating patterns of light and dark as experienced by millions of shift workers may produce long-lasting changes in both mammalian circadian and neurobehavioural systems.