Acne and its association with internalizing problems

Acne vulgaris or “acne” is a prevalent and burdensome cutaneous condition that has been linked with unique mental health implications. Clinical (i.e., general and social anxiety, and major depression) and subclinical indicators (e.g., excessive worry, social self‐consciousness, and low self‐esteem) of internalizing disorders have been associated with acne across demographics (e.g., age groups and cultures). Considering the persistent burden of disease associated with these mental health outcomes, our primary aim was to concretely synthesize the relation between acne and internalizing symptoms. A secondary aim was to address the role that combined oral contraceptives and isotretinoin (e.g., Accutane), widely prescribed medical treatments for acne, may play in this relation as both have been linked to depression and anxiety. We discuss practical implications that may strengthen the effective biopsychosocial management of acne for suffering individuals. This review actively upholds and amplifies the call for longitudinal research that integrates the developmental psychology and dermatology literature to effectively treat acne in its entirety, including mental health.


| INTRODUCTION
The skin is the body's largest 1 and most visible organ that communicates meaningful, biological, and social information (e.g., facial expressions, attractiveness, ethnicity, health) 2,3 central to our identities.Past research has shown that people living with skin conditions that alter or disfigure the appearance of skin such as acne vulgaris, dermatitis, psoriasis, or vitiligo carry a considerable burden of disease 4 and often endure poor mental health (e.g., depression, anxiety, suicidality, poor body image), 5,6 social, emotional, and vocational challenges (e.g., romantic, sexual, and employment difficulties), 7,8 and diminished quality of life. 9Of such conditions, acne vulgaris, hereafter referred to as "acne," is a skin disorder involving clogged pilosebaceous units that can present as inflammatory (i.e., pustules and papules or "whiteheads") or noninflammatory (i.e., open comedone or "blackhead") facial or body lesions. 10,113][14] Though acne is widely prevalent, 80%-85% of its sufferers are between the ages of 12 and 25, 13 making this often-upsetting condition, and its problematic psychosocial side effects, a defining feature of adolescence and young adulthood.Concerningly, acne takes a significant psychosocial toll on its sufferers by impacting physical appearance. 15,16][21][22][23][24][25] Teens with acne have reported lower attachment to friends, 20 poor self-esteem, 23 decreased dedication to school, 21 reduced intention to participate in extracurricular activities, 21 and anger. 24,25kewise, studies of adults report problematic subclinical indicators such as feelings of immaturity, 26 self-consciousness, 27 and insecurity because acne is typically viewed as a "teenage problem." 28,29These difficult emotions have been shown to impede critical life facets such as employment security, 8 romantic relations, and sexual satisfaction, 7 extending the negative impact of acne far beyond just that of physical appearance.
Some researchers have noted that adolescents may be vulnerable to psychosocial morbidity because acne typically arrives during puberty, [30][31][32] a period of substantial physical, social, and psychological change.During puberty, hormones such as androgens increase in production which can increase the size of the body's oil glands and oil production to result in clogged pores or acne. 10,33Throughout this period of remarkable change, acne can act as an additional stressor to an already perplexing stage of development that is characterized by a heightened concern with physical appearance, 34 emphasis on peer acceptance, 34,35 sensitivity to social evaluation, and emerging selfimage. 36As adolescents mature into young adults, acne may exacerbate core symptoms (e.g., a negative self-view, excessive worrying, fear of social evaluation) of internalizing disorders such as major depressive, general, and social anxiety disorder (SAD), that surge in incidence during this developmental period (i.e., 18-29 years of age). 37,38Acne can also be judged as a developmental rarity in young and middle adulthood, leading to heightened feelings of stigmatization for this age group. 28,39In addition, persistent acne that carries into adulthood may be accompanied by negative psychosocial consequences related to prolonged battles with effortful and expensive remedies. 27,28,40,41nsequently, cumulative research demonstrates that acne is distressing for a broad range of ages and cultures. 42The most recent meta-analysis of 42 cross-sectional studies conducted by Samuels et al. 42 showed that clinical depression was more prevalent in youth (i.e., 12-19 years old) and adults (+19 years) with acne compared to their non-acne counterparts (r = 0.22, p < 0.00001).This finding was true for both community and clinical samples, with the strongest association between acne and depression appearing in the clinical adult sample, though the authors cautioned against overrepresentation of adults in the clinical acne samples. 42The results were similar for anxiety such that it was more prevalent in youth and adults with acne (r = 0.25, p < 0.00001), though significant associations were only found in the clinical acne samples (r = 0.32, p < 0.00001) and not the community samples (r = 0.08, p > 0.05). 42In general, adults reported higher rates of depression and anxiety than youth, which aligns with the societal and developmental norms described above whereby acne is commonly viewed as a teen issue. 42This review included studies from the UK, the Middle East, Central, South and East Asia, New Zealand, and Nigeria indicating that the mental health burden associated with acne is a globat concern. 42Notably, there was only one study conducted in the United States in this review and no Canadian studies. 42Although little is known about the impact of acne on mental health in young Canadians, acne likely thwarts psychosocial adjustment of its sufferers irrespective of culture. 22,42 2019, depressive and anxiety disorders affected approximately 3.75% and 4% of the global population, respectively, and continue to carry one of the largest burdens of disease. 43,44Of note, some researchers have reported increased prevalence rates for both depression and anxiety as the COVID-19 pandemic has persisted, 45,46 though the literature awaits longitudinal studies to corroborate this trend.Nonetheless, identifying people at risk for depression and anxiety is a top priority given their onerous impact on social and emotional well-being. 47,48jor depressive disorder (MDD) is the most common mood disorder and is characterized by persistent low mood, altered sleep and eating patterns, low enjoyment in pleasurable activities, and social withdrawal. 37In younger populations, the DSM-5 criteria of low mood can be replaced with persistent irritability. 37e of onset for major depression can vary, though young adults aged 18-29-year-old often exhibit the highest prevalence 37 with disorder reoccurrence linked to greater impairment. 49,50For young adults, MDD can derail academic and vocational success, 51 impede socialization and friendships, 52 and is a primary risk factor for suicide, 53 which is a top cause of death in this age group. 54MDD is often comorbid with GAD, 55 which is characterized by excessive, recurrent, and uncontrollable worry for a period of at least 6 months and is accompanied by physical symptoms such as feeling on edge, muscle tension, or fatigue. 37Like MDD, diagnosis of GAD is associated with future difficulties including disorder reoccurrence, higher risk for comorbidities like substance use, 48 poor physical health, 56 and unemployment in adulthood. 57SAD is also commonly comorbid with MDD and GAD 37,58 and shares unique and similar debilitating outcomes (e.g., social isolation 58 and substance use 48 ).SAD is characterized by marked fear of evaluation and scrutiny by others, and excessive fear of social embarrassment. 37,58Feared social situations are avoided altogether or are endured with strong discomfort. 37Most previous studies that have examined acne and internalizing disorders have used measures of MDD, GAD, and SAD symptoms or diagnoses 42,59 and thus, are reviewed here.
In a recent review, Natsuaki and Yates emphasized that acne and its relation to poor mental health has remained in the peripheral of the dermatological and developmental psychology literature, despite descriptive studies (e.g., qualitative, cross-sectional, archival) and meta-analytic findings that demonstrate negative effects on psychosocial well-being for multiple age groups and cultures. 60To extend the work of Natsuaki and Yates, the aim of this narrative review was to further synthesize the literature regarding acne and its relation to mental health with a specific focus on internalizing symptoms and diagnoses of MDD, GAD, and SAD. 60The manifestation of internalizing symptoms was explored using a sociocultural framework that identifies exposure to and internalization of beauty ideals and appearance-based psychosocial judgments as critical stakeholders in the relation between acne and mental health.[63]

| ACNE PREVALENCE AND COURSE
Generally, acne first appears during puberty and impacts approximately 90% of adolescents with most youth likely to have some form of skin breakout. 13,33,64Acne also persists into early adulthood with approximately one-quarter of people likely to struggle with acne at 25 years of age, and for some, it can endure into middle adulthood, impacting 20%-30% of people between the ages of 20 and 40. 13,65ough acne often begins in adolescence, some people experience onset in adulthood. 39Often due to hormone cycles, 75% percent of adult acne sufferers are girls and women. 13,397][68] Unfortunately, acne appears on the face in 99% of cases, making it extremely visible to others and a difficult problem to conceal, especially for boys and men. 13,69,70Acne also affects other areas of the body with 50% of cases appearing on the neck, back, and arms. 13,70One study showed that people with facial acne suffered worse body image disturbance than those with body acne, underlining that psychosocial distress may be exacerbated as acne visibility increases. 71e causes and severity of acne can vary from person to person but are often related to a combination of biological (e.g., hormone levels, genetics, sebum production, medications) 12 and environmental (e.g., sweat, cosmetics, irritation of clothing/gear, stress) factors. 33,71th multiple factors conducive to acne onset, it is difficult for physicians to chart its course and determine how it may change over time for a given individual. 10Despite this complex course, acne severity is generally classified using a three-part system that includes mild (i.e., a few small pustules near skin surface), moderate (i.e., multiple pustules or blackheads with inflammation across larger surface area), and severe (i.e., cysts or nodules and strong inflammation in infected area). 13Severe acne can cause soreness, swelling, and bleeding, making pain and discomfort challenging symptoms of this condition. 10,12,33jective acne severity rated by physicians or objective grading scales does not reliably align with the psychosocial experience of the acne sufferer. 16,72,73Indeed, researchers [74][75][76] have shown that it is often the subjective or self-report rating of acne that correlates with psychosocial difficulty; thus, patient distress is not always easily identified based on acne symptoms. 77This is of concern given that researchers have also reported that nonpsychiatric medical physicians have low accuracy in the identification of mental health problems which may leave disorders such as depression or anxiety unnoticed for physical complaints like acne. 78Qualitative investigations of patients with skin diseases (i.e., acne, psoriasis, and eczema) have also shown that they feel misunderstood by physicians when it comes to their psychological impairment and often think doctors are apathetic to the emotional burden of their experience. 79Although this is not the case for all, it is important to acknowledge the patient-practitioner discrepancies that can leave the psychosocial burden of acne undetected, and thereby unaddressed for its sufferers.One study also showed that use of an acne disability index assisted to identify patients with poor self-image, a potential indicator of psychosocial difficulty. 80Combining such measures with mental health assessments may facilitate quicker identification of those at risk.Current evidence supports the prompt treatment of acne to reduce its psychosocial burden. 81Acne treatments take several forms due to its complex etiology, though primary interventions for both sexes include combinations of topical retinoids, benzoyl peroxides, and antibiotics. 10In more severe cases, isotretinoin (e.g., Accutane) may be prescribed. 82For adolescent girls and women, combined HC are also effective in treating low to moderate acne. 83Nonetheless, acne is a common 12 and often prolonged skin condition 13 characterized by high variability in its etiology, 10 presentation, and disease course, 10 making it a nuanced physical condition that unfolds dynamically over time and is associated with subclinical features 84 and clinical diagnoses of taxing disorders like depression and anxiety. 42

| SOCIOCULTURAL APPEARANCE IDEALS
To best contextualize why acne may be so distressing to young adults, it is important to understand the broader sociocultural context in which modern young adults develop in societies.8][89] Sociocultural appearance ideals prescribe social standards for outward appearance and apply societal pressure to conform to narrow definitions of what is considered "attractive," "desirable," and "beautiful." 85,90Consequently, it is not surprising that adolescents and young adults with acne commonly report psychological maladjustment such as selfconsciousness, low self-esteem, depression, and anxiety, because the typical presentation of acne (i.e., redness and inflammation) is a marked departure from the commonly encountered appearance ideal of "clear skin." 3,90tirely clear skin, although non-existent, is a prominent appearance ideal that has been incessantly promoted in the media and beauty industry across the globe.According to the world's leading cosmetic brand, L'Oréal, skincare was the largest business segment in 2021 and comprised nearly 42% of their global beauty market. 913][94] In a qualitative study of 26 Australian people ranging from 10 to 52 years old, Magin et al. 95 found that participants were aware of the discrepancy between themselves and the media's portrayal of clear skin.Moreover, these participants acknowledged that this awareness led them to draw social comparisons that negatively impacted their self-perceptions. 95nversely, those with skin diseases and acne are more often portrayed as malicious, unattractive, or unpopular (e.g., A witch with green skin and a wart on the nose, Leo Balmudo or "Craterface" in the film Grease). 96Interestingly, Ritvo et al. 97 exemplified this appearance narrative in their study when they showed a nationally representative sample of American teens and adults (N = 2008; ages 13-17 and 18+), images of peers with and without facial acne.
Participants consistently assigned lower ratings of several socially valued traits such as intelligence, confidence, popularity, and creativity to images with facial acne compared to the same image without facial acne. 97Importantly, images with facial acne were also more often rated as introverted and shy, boring, lonely, stressed, and unhealthy. 97This is important to note given that teens with acne not only appear to be less likely to receive positive evaluations but also more likely to receive negative evaluations. 97In another study, Jaeger et al. 98 independently assessed the impact of clear versus blemished skin on trait impressions (i.e., trustworthiness, competence, attractiveness) in a sample of 203 college students from the Netherlands.The blemished skin condition consistently had a strong negative effect on trait impressions when compared to baseline images, such that people with just mild acne were rated as less trustworthy, competent, and attractive. 987][98] In turn, this may promote fertile ground for low-selfesteem, social withdrawal, and excessive worry about evaluation, key features of MDD, GAD, and SAD. 37

| ACNE, DEPRESSION, AND ANXIETY
It is well documented that acne sufferers experience a high degree of clinical and subclinical symptoms of depression and anxiety (e.g., anger, suicidality, stress, low-self-esteem, self-consciousness, social withdrawal. 8,21,24,25,71,84,99,100For example, Do et al. 74 surveyed (N = 504) Korean middle school students aged 13-16 years old and found that earlier acne onset was positively associated with selfperceived stress, interpersonal and daily life disturbances, and depression scores, especially for younger girls.As noted previously, this study found these psychosocial impairments were most strongly related to self-reported acne severity rather than objective acne severity, with girls self-reporting more severe acne than boys.Ozturk et al. 101 also reported significant social impairments in their comparison of clinical acne patients (n = 70, ages 16-30) with healthy age and sex matched controls (n = 50); those with acne reported lower scores on subscales of vitality and social functioning and higher scores on emotional difficulty than those without.3][104] For example, Purvis et al. 105 conducted a cross-sectional survey analysis of self-reported acne and subclinical depression and anxiety in a sample of N = 9567 New Zealand youth aged 12-18 years.The authors accounted for age, gender, school ranking, and socioeconomic status in their logistic regression."Problem acne" was reported by 14.1% of their sample and was related to higher odds ratios for depressive and anxiety symptoms, suicidal thoughts, and suicide attempts.The association of acne and suicide attempts remained significant even after controlling for depression and anxiety symptoms. 105Halvorsen et al. 20 also found greater suicidal ideation and impaired social relationships in their cross-sectional survey of Norwegian young adults with acne (i.e., N = 3775, 18-19 years old).
Those with substantial acne reported low attachment to family and friends, not thriving in school, and less romantic and sexual involvement compared to those with little or no acne. 20Without intervention there is high risk for those presenting with subclinical symptoms of depression and anxiety to enter the clinical disorder range, which appears to be the case for some with acne. 104Clinical depression and suicidal ideation are distressing experiences not uncommon to those enduring acne. 19,20,105,106Gupta and Gupta (1998) 19 assessed the prevalence of depression and suicidal ideation in four types of dermatological patients (i.e., mild-moderate noncystic facial acne n = 72, M age = 23.7,alopecia, atopic dermatitis, and psoriasis).Patients with non-cystic facial acne had the second highest depression rating next to psoriasis outpatients, with both groups showing average scores above the clinical cut-off. 19Suicidal ideation showed a similar trend, with 5.6% of acne patients and 7.2% of psoriasis patients endorsing thoughts of suicide. 19However, there were no sex differences in depression or suicidal ideation. 19lvorsen et al. 20 also reported that nearly one-quarter of participants with substantial acne experienced suicidal ideation.Further, in a multivariate model controlling for depression, family income, and ethnicity, Halvorsen et al. 20 found that suicidal ideation remained significant among participants with substantial acne.Suicidal ideation was twice as prevalent in girls with substantial acne compared to girls with little or no acne. 20For boys with substantial acne, suicidal ideation was three-fold compared to boys with little or no acne. 20As acne severity increases, it appears to confer risk for suicidal ideation, a distressing symptom by itself, and a key indicator of MDD. 20,37trospective and archival studies have also illustrated higher prevalence and risk for clinical depression in acne patients. 29,107,108lenhake et al. 107  by a physician for acne were over the age of 18 (61.9%)and were women (65.2%). 108Women with acne also showed double the prevalence of depression than men with acne, with 10.6% and 5.3%, respectively. 108This is in line with traditional depression rates that depict an approximate two to one female to male sex ratio. 37,109Across the world, Yang et al. 29 examined records from the National Health Insurance database in Taiwan (N = 1,000,000) to assess sex differences in acne, major depression, and suicide using International Classification of Diseases-10 criteria.In general, diagnosis of depression was significantly higher in those with acne irrespective of sex, with an overall prevalence of 0.77% and 0.56% in controls.However, the sex analysis revealed that women were at increased risk for major depression compared to men, with acne significantly contributing to this risk. 29Contrary to Halvorsen et al. (2011), suicide was only slightly higher in those with acne but did not reach significance for this study. 20,29Finally, in a large retrospective cohort study, Vallerand et al. 108  obesity, smoking and alcohol use, socioeconomic status, and medical conditions at baseline.Over a 15-year follow-up, their study showed the risk for developing clinical major depression was 18.5% in patients with acne, compared to 12% in the general population. 108This risk was highest within the first year of diagnosis and then decreased.As in other studies, girls and young women carried the greatest depression risk and were more likely to suffer from acne. 108[107][108] Unlike clinical depression and suicidal ideation, fewer studies have assessed the prevalence and relation of clinical anxiety with acne.Most studies include small cross-sectional group comparison methods and assess depression and anxiety concurrently (see Samuels et al. 42 for review).In addition, most of these studies have occurred in Middle Eastern regions such as Turkey and Egypt.In fact, 21 of the 42 studies reviewed in Samuels et al.'s (2020) meta-analysis were from these regions. 42,110,111Nonetheless, most researchers have reported higher odds ratios of clinical anxiety and depression for patients with acne when compared to controls. 101,112,113In one study, Yarpuz et al. 113 compared 83 clinical acne patients between the ages of 15 and 40 years old with 58 age-and sex-matched controls and found that acne patients showed significantly higher average scores on depression and general anxiety than patients without acne.Patients also tended to self-rate their acne as more severe compared to physician grading. 113However, contrary to other studies 73,74 no relation between self-rated acne and psychosocial impairment was reported. 113[36] Using a larger sample, Bez et al. 111  ), but in less than one-quarter of controls (18.4%).Acne patients had significantly higher total avoidance scores on measures of social anxiety and significantly more work and family disability. 111Easures of general anxiety and depression scores showed no significant differences between acne patients and controls. 111This may suggest a stronger relation between acne and social anxiety rather than general anxiety.Comparably, Ozturk et al. 101 also observed the largest group difference between clinically graded acne patients and controls on measures of social anxiety.Further, when looking at the effects of acne severity, those with severe acne (i.e., nodules on face or body) had significantly higher total social anxiety scores compared to those with mild acne (<20 facial lesions), depicting stronger social impairment in this group. 101General depression and anxiety scores were still significantly higher in acne patients than controls, but the strongest difference was observed in social anxiety. 101In another study, Salman et al. 112 compared vitiligo (n = 37) and acne patients (n = 37) to age and sex matched controls (n = 74) in Turkish young adults (>18 years of age).They collected self-reported and physician-rated symptoms and found the acne group reported higher total and subscale scores on social anxiety and depression compared to controls. 112In contrast, in a larger scale Turkish community (n = 615) study, Aktan et al. ( 2000) 110 showed no statistical differences on average scores between acne patients and controls for anxiety or depression.There were also no observed differences based on acne severity or age, though similar to most studies, girls with acne reported higher anxiety scores than boys. 110e only prospective longitudinal study was conducted by Ramrakha et al. 22 and they reported data from the Dunedin Multidisciplinary Health and Development Study in New Zealand.
In their population birth cohort study (n = 1037) that began data collection in 1975 (age 3) with follow-ups every 2 years until the age of 15, then again at ages 18, 21, 26, 32, and 38, participants were evaluated on mental, physical, and psychosocial health, which included measures of depression and anxiety. 22At age 21, participants were asked retrospectively if they had experienced "problem acne" starting at the age of 15 or later; this was continued until the last time point (i.e., age 38). 22Their results showed that acne was consistently and significantly associated with higher odds ratios for anxiety at all time points, and significance persisted when controlling for confounds of sex, socioeconomic status, and previous psychiatric diagnoses. 22MDD diagnosis displayed a similar pattern but did not reach statistical significance. 22Post hoc tests indicated that the relation between acne and depressive symptoms was significant after controlling for the noted confounds, again highlighting the danger that people with acne may linger in the critical subthreshold region of MDD, leaving many problems undetected. 22mpatible trends of anxiety and depression prevalence were reported by Dalgard et al. 6 such that in their large-scale study (N = 4994) of skin diseases, clinical anxiety (15.1%) was more prevalent than depression in patients with acne (5.7%).Ramrakha et al. 22 also reported no interaction effects based on sex or age, suggesting comparable effects across sexes and age groups, which is similar to some studies (see, e.g., Aktan et al. 110 ), though divergent from most (see, e.g., Samuels et al. 42 ).Given that Rhamraka et al. 22 appear to be the only prospective longitudinal study in the literature, there is a need for improved study designs that account for variation in acne presentation and its psychosocial impact across development.
In their meta-analytic review, Samuels et al. 42 summarized that youth and adults with acne exhibit higher risk and rates of depression and anxiety than the general population.Unsurprisingly, this risk is not evenly shared.Girls and young women accrue the highest risk for internalizing symptoms, while boys and men with acne appear more likely to contemplate suicide. 20,29Additionally, suicidality appears most prevalent in those with substantial acne, 20,105 suggesting a relation between mental health symptoms and acne severity.Girls and women are also more likely to seek medical treatment for their acne 107 aligning with research that demonstrates girls and women generally report more appearance anxiety than boys and men. 114rther, due to the visible nature of acne and its relation to negative trait and appearance evaluations by peers, it seems logical that individuals with acne would suffer from social anxiety more than general anxiety symptoms because a core feature of social anxiety is the fear of negative evaluation. 37However, there does appear to be increased general anxiety symptoms in those with acne, though the relation may be less pronounced. 101,110,111Briefly, the studies reviewed here suggest higher prevalence and risk of depressive and anxiety symptoms and disorders in adolescents and adults with acne.However, notable methodological limitations in the aforementioned study designs preclude the determination of causal relations; namely their cross-sectional nature, retrospective assessments of acne and/or mental health problems, and the failure to control for prior mental health symptoms (a known predictor of current mental health). 37,48,58[117][118]

| HORMONAL CONTRACEPTIVES, ISOTRETINOIN, AND ACNE
The rapid and effective treatment of acne is essential to mitigate the damaging subclinical and clinical symptoms of depression and anxiety just reviewed. 81Of note, some treatments for acne have been questioned on their safety when it comes to mental health side effects. 119Isotretinoin is a well-known third-line treatment for severe acne that has been implicated in the development of internalizing symptoms including depression and suicidal ideation and behavior. 119Similarly, combined oral contraceptives (COC; e.g., Ortho Tri Cyclen) are often used to treat acne in women with no medical contraindications and have also been linked with depression and anxiety. 120,121Although isotretinoin and COC remain effective for many in reducing acne, their role in the presentation of internalizing side effects cannot be overlooked if acne treatment is to address all acne symptoms.Broadly, COC are a class of HC that typically contain varying ratios of the exogenous hormones estrogen and progestin. 83COC work to suppress the female body's natural hormone production (e.g., androgens), decrease sebum (i.e., oils), and by extension, diminish acne. 118They are generally prescribed when topical treatments have been exhausted, if acne presentation corresponds with the menstrual cycle or if patients report struggles with oily skin. 121COC may also be prescribed as a precursor to isotretinoin in women. 121To date, there has been no clear link between HC use and internalizing symptoms identified and the literature largely reviews depressive rather than anxiety symptoms. 122vertheless, some subgroups (e.g., adolescent girls and women with previous psychiatric history) have been recognized as at risk of affective disturbance when using HC. 122,123For example, Skovlund et al. 62 assessed adolescents and women aged 15-34 years old at any point during a 14-year period.Depression incidence was measured using "redeemed prescription of antidepressant" and "first diagnosis of depression." 62Categorical cut-offs for depression like these should be interpreted with caution because they fail to capture many people suffering subclinical symptoms of depression and do not reflect the continuous nature of mental health.They reported that users of COC had a risk ratio of first antidepressant use of 1.2 compared to nonusers. 62When analyses were stratified by age, this risk increased to 1.8 for young women aged 15-19 years old, then decreased in women aged 20-34. 62Depression risk among COC users (1.2) was lower compared to other HC methods like the intrauterine system (1.4), vaginal ring (1.6), the patch (2.0), the implant (2.1), and the "depot" injection (2.7). 62It is important to note that depression onset is known to increase markedly after puberty, especially in young women, which may explain some of the variation observed between age groups in Skovlund et al. 37,62 More recently, a large-scale study by Lundin et al. 117 in a sample of (n = 739,585) Swedish women aged 15-25 years old showed lower to equal risk for depression between COC users, non-, and never-users.Marginal increases in depression risk were observed with women who used the patch, vaginal ring, implant, or intrauterine device. 117Again, the use of any HC was associated with increased risk for depression in women aged 15-19 years old when stratified by age.However, when stratified by type of HC, COC specifically showed no increase in depression. 117In another study, Doornweerd et al. 120 assessed general oral contraception (OC) use and internalizing symptom trajectories in a sample of (n = 178 at Wave 1 in 2006) Dutch girls who were followed from age 13-24 years old. 120In this sample, those who reported using OC at some point had stable trajectories of depressive and anxiety symptoms compared to never-users who showed increasing trajectories in late adolescence, indicating possible mediating effects of HC on internalizing symptoms. 120The results remained stable when covariates (e.g., first sexual debut) were added, though this study did not report information on OC type, limiting inferences in this area and about COCs specifically. 120Generally, there appears to be varying risk for depressive symptoms that differ by age or type of HC, with COC use typically showing the least depressive risk. 62olescent girls and young women experienced the highest depressive risk; though, this finding may be partially explained by traditional depression onset known to increase in this age group. 37Physicians Like COC, the relation between isotretinoin and depression has yet to be firmly established and some studies report conflicting results. 119,124The latest meta-analysis of 20 studies reported discrepant results between retrospective studies that assessed depression risk amongst isotretinoin users and prospective studies that assessed depression change (i.e., pre-and post-isotretinoin treatment). 116In the retrospective studies, depression-risk was heightened among isotretinoin users, whereas in depression-change studies, results showed isotretinoin reduced depression symptoms posttreatment. 116Another systematic review and meta-analysis conducted by Huang and Cheng (2016) 124 reported that 25 out of the 31 studies they assessed showed no significant association between low dose (0.5-1 mg/kg) isotretinoin and depression scores.Further, 11 out of those 25 studies reported decreased depression scores and frequency. 124In general, patients with acne had higher baseline depression scores, which suggests an independent link between depression and acne. 124Their study did not assess anxiety symptoms. 124Conversely, another systematic review suggested that while pooled statistical analyses remain hopeful, there are case studies of individuals that experience worsening depressive symptoms and suicidal behavior after beginning treatment with isotretinoin. 61,63,119These reviews have suggested a dose-response relation between isotretinoin and symptoms related to depression (e.g., low libido, weight loss) and stress the need for physicians to uniquely consider each patient's mental health history and biological risk factors before prescription of isotretinoin. 61other review by Oliveira et al. 125 highlights that the studies that suggest this positive association between isotretinoin, depression, and suicide tend to be descriptive in nature (i.e., case reports, database studies, retrospective analyses) and thus are restricted in their power to deduce causal conclusions. 126Nonetheless, Oliveira et al. 125 also advocate for the subset of individuals who may experience worsened internalizing symptoms upon starting isotretinoin treatment.A new large-scale retrospective cohort study compared risk of nine psychiatric outcomes, including depression, MDD, suicidal ideation, and suicide attempt, in acne patients using isotretinoin (n = 75,708) versus oral antibiotics (n = 75, 708).Participants were matched based on sociodemographic and related comorbidities such as smoking.Isotretinoin dosage and psychiatric history were not co-varied.Patients using isotretinoin showed reduced depression risk and similar MDD risk to patients using antibiotics. 127Risk for suicidal ideation was slightly elevated in the isotretinoin group, though suicidal behavior was comparable between both treatment groups. 127Patients using isotretinoin also showed reduced risk for other psychiatric outcomes such as posttraumatic stress disorder, anxiety disorder, bipolar disorder, schizophrenia, and adjustment disorder. 127This study showed similar or reduced mental health risk among two types of acne treatment groups which is consistent with other studies investigating similar outcomes 128 ; however, the absence of a control group does limit comparison to the general population.
The relation between isotretinoin, depression, and suicidal ideation and behavior has yet to be securely established due to a high degree of variation in outcome measurement, and a lack of prospective studies and randomized control trials. 81,124One notable issue with studying demonstrated links is that the temporal ordering has not been assessed.Thus, it is unclear if isotretinoin causes mental health problems or if mental health problems predate the use of isotretinoin.However, based on the most recent cross-sectional, meta-analytic, and large-scale database studies, the relation appears to be mostly neutral or beneficial with isotretinoin treatment ameliorating psychiatric symptoms for most. 116,127As such, swift treatment using COC or isotretinoin is recommended to reduce the psychosocial burden of acne.Despite discrepant opinions, all research urges the extensive baseline screening and on-going monitoring of depression and anxiety symptoms upon administration of these acne treatments. 116,119,124Groups that appear to be most at risk for depressive symptoms and that should be monitored closely include adolescent girls and patients with personal or family history of mental health diagnoses. 116,129

| CONCLUSION
In this narrative review we sought to integrate the literature on acne and mental health with a specific emphasis on three common internalizing disorders and their symptoms, MDD, GAD, and SAD.We used a sociocultural framework to conceptualize how acne may manifest internalizing symptoms for some sufferers and found several trends that may support the effective biopsychosocial treatment of acne.
First, acne is a marked deviation from the sociocultural media narrative that actively promotes clear skin as a beauty norm and expectation for women and men.The vast nature of this narrative may generate an internal overvaluation of the personal and social significance of perfected skin among consumers. 1307][98] Such scrutiny may manifest new or reinforce existing symptoms such as a negative self-view, self-consciousness, depressed mood, suicidal ideations, and marked fear of evaluation.This trend appears to be corroborated in the studies reviewed here.Symptoms of MDD, GAD, and SAD appear to be both more likely and more prevalent among youth and adults who have acne. 22,42cond, the literature reveals important sex differences that may prove useful for physicians monitoring acne treatment.In general, girls and women appear to be at the highest risk for internalizing symptoms if acne is present. 29,107,108,128,131This is consistent with traditionally reported sex differences in internalizing disorders. 37Of note, girls and women may experience more internalizing symptoms than boys and men when acne is perceived as low to moderate. 74,1323][94] As acne severity increases, boys and men seem to accrue more risk especially for symptoms related to MDD such as suicidal ideation. 20Boys and men also have reduced access to primary acne treatments such as COC and are less likely to use makeup to cover blemishes which may exacerbate internalizing symptoms.Thus, boys and men with severe acne should be screened and monitored carefully for depressive symptoms.Boys and men also appear to be less likely to seek treatment for their acne, thus regular discussions about skin hygiene during check-ups may be beneficial to reduce stigma.Importantly, both sexes appear to drift in the subclinical region of MDD, GAD, and SAD when suffering from acne (e.g., low self-esteem, anger, social withdrawal, poor body image). 8,21,24,25,71,84,99,100This is concerning given that a large burden of disease can prevail despite not meeting diagnostic criteria for DSM-5 disorders. 48,102,1034][135][136] Such questionnaires are widely available within the public domain and require little patient time to complete.Despite inconclusive findings on the relation between COC and mental health, internalizing symptoms should be monitored closely to prevent symptom exacerbation when COC are prescribed, especially in adolescent girls with acne.
Third, many studies have focused on GAD symptoms and diagnosis using Hospital Anxiety and Depression Scale or the Beck Anxiety Inventory. 42However, large differences between controls and clinical acne patients were observed in studies that included SAD in their analyses, over and above GAD in some cases. 101,111,112With fear of social pressure and evaluation as probable theoretical forces underlying acne and its relation to internalizing symptoms, longitudinal studies exploring SAD in-depth may shed light on the relation between acne and internalizing disorders. 137nally, as Natsuaki and Yates (2021) 60 noted in their review, developmental approaches are lacking from the acne and mental health literature.This is a notable caveat because acne is known to vary in its incidence and presentation across the life span for women and men and shows a similar developmental course to internalizing symptoms. 12,40,42,69,84Acne increases in prevalence after puberty and into young adulthood, which is similar to MDD, GAD, and SAD, though SAD often emerges slightly earlier in childhood. 10,37Of the studies reviewed here, only one 22 considered the developmental nature of acne, anxiety, and depression using a longitudinal approach.
Prospective statistical methods that account for acne and its relation to mental health across time, and acne and its relation to mental health within the same time point have not yet been conducted.Therefore, longitudinal studies that include at least three time points, explore sex differences, use psychometrically sound assessments for MDD, GAD, and SAD, and control for prior and concurrent mental health symptoms are needed.These methods will provide a clearer picture for physicians by highlighting the individuals who are most vulnerable to psychosocial harm because of acne.That is, when, how, and for whom, is acne likely to adversely impact psychosocial health across development.Such research will reinforce the need for a holistic and encompassing biopsychosocial treatment approach for this widespread and developmentally meaningful condition.
The findings of our review support the rapid provision of available acne treatments to effectively protect against symptoms of depression and anxiety that appear to plague many acne sufferers.
Physicians can take several steps to minimize the psychosocial impact of acne, which include carefully attending to mental health contraindicators such as family or personal history of mental health with detailed intake and screening tools, provide patients with psychoeducation regarding the link between acne and depressive and anxiety symptoms, normalize insecurities related to acne, use measurementbased care to monitor mental health changes throughout acne treatment, especially when COC or isotretinoin are prescribed, schedule appropriate follow-ups, and facilitate patient access to third party practitioners such as dermatologists and mental health clinicians to support the comprehensive and safe management of all acne symptoms, including psychosocial health.
examined medical data in the United States and found that clinical depression was present in 8.8% of individuals with acne.This prevalence nearly doubled for adults, with acne impacting approximately 14% of those aged 36-64 years old.Most patients seen HAMMILL and VAILLANCOURT | 231 compared 140 clinical acne patients aged 15-33 years old (M age = 20.75) with 98 (M = 20.93)controls.Social phobia was diagnosed in almost half of the acne patients (45.7% the mental health contraindications reviewed here to ensure prudent administration of COC for acne, especially for developing young women. examined N = 134,437 individuals with acne and N = 1,731,608 individuals without acne (aged 7-50 years) using a UK primary care database.Vallerand et al. covaried age (young ≦ 19; adult > 19), sex,