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LGBTQ issues are some of the most pressing and difficult topics facing psychiatrists today. In this podcast,

interviews Michael F. Myers about gender and sexuality. Topics of discussion include:

Current subjects in gender and sexuality, including gender dysmorphia

How psychiatry’s understanding of sexuality and gender has changed over time

His own experience as a doctor during the AIDS crisis

Find out more about Dr Myers and his experience treating patients during the AIDS crisis in his new memoir, 

is professor of Clinical Psychiatry and immediate past Vice-Chair of Education and Director of Training in the Department of Psychiatry & Behavioral Sciences at SUNY-Downstate Medical Center in Brooklyn, NY.

Michael F. Myers, MD, discusses issues of gender and sexuality, both today and in recent psychiatric history. 

Psychiatry’s Gender Trouble

Decades of research have investigated inflammation and mental illness, suggesting that there is a robust and complex link. However, the link lacks diagnostic specificity and varies considerably among individuals, and with each stage of illness. Chronic, low-grade 

appears to precede the initial illness episode, at least in some individuals.

 Drugs that modulate the immune system may also affect an individual’s mood and have possible psychiatric adverse effects (AEs). Perhaps the best example is that interferon-α treatment of hepatitis C precipitates depressive episodes.

 is associated with reduction in inflammatory markers.

Statins are best known as competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Statin treatment results in lower low-density lipoprotein cholesterol levels and in benefits to cardiovascular health. Statins also have anti-inflammatory mechanisms of action, including T-cell downregulation, suppression of cytokines, production of chemokines and C-reactive protein, and downregulation of transcription factors.3 In a post hoc, pooled analysis (N = 969) of data collected at baseline and at a 1-year follow-up from a study of patients with acute coronary syndrome, statin treatment was shown to reduce levels of interleukin (IL)-6 and IL-18. Raised levels of these cytokines appeared to predict depression after acute coronary syndrome.

Many epidemiological studies have shown that 

 is associated with a lower risk for depression (

 A population cohort study (N = 4,607,990) using Swedish national registry data investigated the relationship between statin use and the development of depression. The use of any statin was associated with an 8% decrease in risk for depression (odds ratio [OR], 0.92) compared with individuals who did not use statins.

 Elsewhere, in a cohort of individuals 55 years and older (N = 2804), statin use was associated with decreased depression (OR, 0.71).

 However, no association between statin use and depression was determined in an analysis of data from 19,114 individuals, most of whom were 70 years and older, of whom 5987 used statins.

Evidence from clinical trials suggests that, adjuvant to treatment with antidepressants, some statins are associated with better treatment outcomes. A 

 showed that treatment with lovastatin, atorvastatin, and simvastatin, adjunctive to antidepressant treatment, was superior to treatment with a placebo adjunctive to antidepressant treatment for improving depression (indexed by the Hamilton Depression Rating Scale).

 More recently, the results of a trial of rosuvastatin for young individuals with depression indicated that rosuvastatin failed to beat the placebo on the primary outcome, but it was positive on a number of secondary outcome measures, leaving the benefit uncertain.

A trial comparing simvastatin (n = 33) with placebo (n = 33) in participants with schizophrenia treated with risperidone found significantly higher reduction in the first group in negative symptom scores (P = .003) and total score (P = .001). These results measured the time period from baseline to week 8, using the Positive and Negative Syndrome Scale (PANSS).

 Simvastatin did not significantly differ from placebo for treating schizophrenia in an underpowered study (N = 36).

Two meta-analyses of statin add-on therapy in the antipsychotic treatment of schizophrenia have been conducted. 

 identified 5 randomized controlled trials (N = 236) showing improvement of PANSS total score, but not of PANSS subscale scores.

 The meta-analysis included studies of atorvastatin, lovastatin, pravastatin, and simvastatin. Risperidone was used in 3 studies; antipsychotic use was varied or not reported for 2 studies. 

 identified 6 randomized controlled trials (N = 339) showing benefit for improvement of PANSS positive and negative subscales.

 The meta-analysis by Shen et al included all 5 trials from the Nomura et al meta-analysis plus an additional trial of simvastatin versus placebo.

 have been associated with an increased risk for cardiovascular disease (CVD), independent of psychotropic medication use. This comorbidity is bidirectional, since depression is a common outcome after myocardial infarction and is also associated with higher comorbidity and mortality.

 In this context, treatment with statins may have an important dual purpose, with benefits to both mental and cardiovascular health. Evidence from a nested case-control study has shown that exposure to statins and aspirin is associated with a reduced risk of de novo major depression.

Atorvastatin, lovastatin, and simvastatin are lipophilic, while pravastatin, rosuvastatin, pitavastatin, and fluvastatin are hydrophilic. The lipophilic statins readily cross the blood-brain barrier. Hydrophilic statins or their active metabolites may also be detected in the brain, although less readily. Laboratory studies have suggested that statins may be neuroprotective against a range of neurotoxic insults, but statins themselves may be neurotoxic at higher concentrations than those obtained at therapeutic doses.

The best evidence that statins reduce markers of inflammation is derived from the JUPITER study of rosuvastatin.

 It is unclear whether brain penetrance or reduction in peripheral markers of inflammation is the more important mechanism in terms of potential therapeutic efficacy.

There is a potential for drug-drug interactions between statins and psychotropic agents (

). Psychotropic agents with lower cytochrome P450 (CYP450)activity should be considered ahead of those with known strong CYP450 activity to reduce the risk of pharmacokinetic drug-drug interactions.

 Andrade suggests that risks of pharmacokinetic drug-drug interactions between selective serotonin reuptake inhibitors (SSRIs) and statins are negligible at standard therapeutic doses for escitalopram, citalopram, and paroxetine with rosuvastatin, pitavastatin, and pravastatin; there is possible but low risk of interactions for combinations of fluvoxamine with atorvastatin, simvastatin, or lovastatin.

 A study of blood specimens collected from elderly patients (N = 194) investigated the interactions between statins and antiepileptic drugs, including the mood stabilizers lamotrigine and carbamazepine. Carbamazepine, but not lamotrigine, significantly interfered with 

, with lipids reduced for patients taking either drug but significantly greater reduction in lipids for those taking 

 Risks of adverse events may be greater in elderly cohorts compared to nonelderly individuals.

Antipsychotics may upregulate gene expression of lipid metabolism pathways, resulting in metabolic side effects, weight gain, and dyslipidemia. Individuals receiving antipsychotics may have reduced response to treatment with statins for dyslipidemia, with a common gene variant (SREBF1) for a transcription factor in the lipid metabolism pathway.

 Dyslipidemia in individuals treated with antipsychotics may benefit from personalised treatment plans, in which statins may have an important but variable role.

In the clinical setting, medication changes, dose adjustments, and polypharmacy are common in psychiatric practice and are associated with a greater risk of adverse effects. Adding a statin to an existing regimen entails an additional risk that needs to be considered when the statin is first introduced and whenever there are changes to comedications throughout the course of treatment. Case reports on statins and psychotropic comedications have identified rare adverse events of rash,25 QTc interval prolongation,

Preliminary evidence, mainly from small studies, suggests that adjuvant treatment with a statin may be beneficial for individuals taking psychotropic drugs for depression and schizophrenia. People with depression, bipolar disorder, and schizophrenia are substantially more vulnerable to metabolic syndrome and earlier age of mortality than the general population, predominantly from CVD. Such medical comorbidities warrant aggressive prophylactic therapy with available agents, including statins. Thus, there is sufficient evidence to suggest that combining statin therapy with antidepressant or antipsychotic therapy may be sensible for patients with comorbidities when both pharmacotherapies are indicated. However, adjuvant treatment with a statin purely as an augmentation strategy for psychopharmacotherapy is still experimental. Although there is a good theoretical basis and promising preliminary data, further research is required, especially larger, multisite, placebo-controlled randomized clinical trials.

 is a principal fellow in the Department of Psychiatry, University of Melbourne, a clinical associate professor at the Centre for Youth Mental Health, University of Melbourne, and a clinical associate professor in the School of Medicine, Deakin University, Melbourne, Australia. D

is a psychiatrist in the Hospital Clinic de Barcelona in Spain and a researcher at IMPACT, Univer-sity Hospital Geelong, Australia. 

is the Alfred Deakin Professor of Psychiatry and director of IMPACT, the Institute for Mental and Physical Health and Clinical Translation, Deakin University, Melbourne, Australia.

Inflammation and depression: a causal or coincidental link to the pathophysiology?

2. Qato DM, Ozenberger K, Olfson M. Prevalence of prescription medications with depression as a potential adverse effect among adults in the United States. 

3. Kim SW, Kang HJ, Jhon M, et al. Statins and inflammation: new therapeutic opportunities in psychiatry. 

4. Kim SW, Kang HJ, Bae KY, et al. Interactions between pro-inflammatory cytokines and statins on depression in patients with acute coronary syndrome. 

Prog Neuropsychopharmacol Biol Psychiatry. 

5. Köhler O, Benros ME, Nordentoft M, et al. 

Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials

6. Redlich C, Berk M, Williams LJ, . Statin use and risk of depression: a Swedish national cohort study. 

7. Feng L, Tan CH, Merchant RA, Ng TP. Association between depressive symptoms and use of HMG-CoA reductase inhibitors (statins), corticosteroids and histamine H(2) receptor antagonists in community-dwelling older persons: cross-sectional analysis of a population-based cohort. 

8. Agustini B, Mohebbi M, Woods RL, et al; ASPREE Investigator Group. Association between statin use and depressive symptoms in a large community-dwelling older population living in Australia and the USA: a cross-sectional study. 

9. Salagre E, Fernandes BS, Dodd S, Brownstein DJ, Berk M. 

Statins for the treatment of depression: a meta-analysis of randomized, double-blind, placebo-controlled trials

10. Quinn AL, Dean OM, Davey CG, et al. Youth Depression Alleviation-Augmentation with an anti-inflammatory agent (YoDA-A): protocol and rationale for a placebo-controlled randomized trial of rosuvastatin and aspirin. 

11. Tajik-Esmaeeli S, Moazen-Zadeh E, Abbasi N, et al. Simvastatin adjunct therapy for negative symptoms of schizophrenia: a randomized double-blind placebo-controlled trial. 

12. Chaudhry IB, Husain N, Drake R, et al. Add-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: pilot study.

13. Nomura I, Kishi T, Ikuta T, Iwata N. 

Statin add-on therapy in the antipsychotic treatment of schizophrenia: a meta-analysis

Adjunctive therapy with statins in schizophrenia patients: a meta-analysis and implications

15. Van der Kooy K, van Hout H, Marwijk H, et al. Depression and the risk for cardiovascular diseases: systematic review and meta analysis. 

16. Batelaan NM, Seldenrijk A, Bot M, et al. Anxiety and new onset of cardiovascular disease: critical review and meta-analysis. 

17. Berkman LF, Blumenthal J, Burg M, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) randomized trial. 

18. Williams LJ, Pasco JA, Mohebbi M, et al. Statin and aspirin use and the risk of mood disorders among men. 

19. Wood WG, Eckert GP, Igbavboa U, Müller WE. Statins and neuroprotection: a prescription to move the field forward. 

20. Ridker PM, Danielson E, Fonseca FA, et al; JUPITER Trial Study Group. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. 

21. Palleria C, Roberti R, Iannone LF, et al. 

Clinically relevant drug interactions between statins and antidepressants

22. Andrade C. Selective serotonin reuptake inhibitor drug interactions in patients receiving statins. 

23. Mintzer S, Trinka E, Kraemer G, et al. 

Impact of carbamazepine, lamotrigine, and levetiracetam on vascular risk markers and lipid-lowering agents in the elderly

24. Vassas TJ, Burghardt KJ, Ellingrod VL. Pharmacogenomics of sterol synthesis and statin use in schizophrenia subjects treated with antipsychotics. 

25. Walder A, Baumann P. Mood stabilizer therapy and pravastatin: higher risk for adverse skin reactions? 

26. Furst BA, Champion KM, Pierre JM, et al. Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin. 

27. Golomb BA, Evans MA. Statin adverse effects: a review of the literature and evidence for a mitochondrial mechanism. 

Preliminary studies suggest that adjuvant treatment with a statin may be beneficial for patients who are also prescribed psychotropic drugs for depression and schizophrenia.

The Psychiatric Potential of Statins 

Somatic symptom and related disorders (SSRDs) are a set of psychiatric conditions characterized by physical symptoms that are inconsistent with physical disease and influenced by psychological factors. They are common in pediatric medicine, with prevalence rates ranging from 13% to 50% depending on the setting. Across all ages, SSRDs account for nearly 

 There is also a small subset of patients who have multiple somatic complaints and tend to access crisis and emergency services, hospital services at higher rates. They also have high 

Despite the impact of SSRDs on pediatric health care, there is a high level of clinician and patient/familial frustration associated with the evaluation and management of these conditions.

 Without early incorporation of a broader biopsychosocial conceptualization, there can be an undue focus on disability, impairment, and somatic complaints. This leads to low-yield diagnostic testing and increased polypharmacy interventions that do not address the rehabilitative needs of the 

 In the absence of an explanatory model for symptoms, patients and families may feel they are being dismissed, creating a dynamic of mistrust between patients/families and the medical system. Ultimately, without a clear roadmap for evaluation and management, care can be inconsistent and there may be misuse of health care resources, ultimately leading to poor outcomes.

As SSRDs most often present in non-psychiatric settings, a patient’s first contact with a mental health care provider may be through psychiatric consultation in the emergency department or a hospital setting. Therefore, psychiatric consultation should be considered as early as possible in order to foster the perception that consultation-liaison psychiatrists are an integral part of the multispecialty team.

SSRDs account for approximately 15% to 20% of psychiatric consults in the pediatric hospital setting and have been reported as the second most common reason for consultation after 

 As such, there is growing effort to standardize the evaluation and management of pediatric SSRDs. Most recently, the American Academy of Child and Adolescent Psychiatry (AACAP) published a Clinical Consensus Pathway for SSRD Evaluation and Management.

“Julie,” a previously physically healthy 12-year-old female, presented with 6 months of abdominal pain, weight loss, and emesis that began shortly after her parents divorced. As a result, she missed several weeks of schooling.

Workup included a complete blood count, comprehensive metabolic profile, thyroid studies, C-reactive protein, erythrocyte sedimentation rate, abdominal X-ray, abdominal ultrasound, upper and lower endoscopy, and stool culture, all of which were unremarkable. Elimination of gluten from her diet was not helpful. The patient had no previous physical health concerns, including no previous gastrointestinal pathology. There was no history of substance use, sexual activity, psychological trauma, or abuse.

Julie was admitted for her fourth medical admission within 4 months. Child and adolescent psychiatry was consulted for evaluation of anxiety. Julie and her parents were skeptical about any psychological factors influencing her presentation and were hesitant to agree to psychiatric consultation. The parents were advocating for the use of opioids for her pain and an expanded workup.

The patient received concurrent evaluation by the pediatric hospitalist service, gastroenterology, psychology, and psychiatry. No further diagnostic testing was pursued. The team found Julie had comorbid learning difficulties, nonspecific anxiety, maladaptive coping, and increased familial expressed emotion contributing to her presentation in the context of the recent divorce. A multidisciplinary meeting was held with Julie and her parents to discuss the diagnosis of somatic symptom disorder (DSM-5 300.82). The family was presented with a conceptual framework for symptom development by the multidisciplinary care team, in addition to biopsychosocial contributors to her presentation and a future management plan.

Julie was referred for outpatient cognitive behavioral therapy and mirtazapine 7.5 mg at bedtime as initiated for anxiety and sleep difficulties. Her symptoms improved by discharge, and she was minimally symptomatic upon follow up with her primary care provider.

Most SSRDs are seen in non-psychiatric settings, with roughly 6% of hospitalized children relaying symptoms consistent with an SSRD.

 The most common complaints include neurologic symptoms, pain, gastrointestinal distress, and fatigue.

 SSRDs can present at any age, but are more common and less problematic in pre-pubertal youth with increasing impairment and pathology in adolescents.

 Prevalence rates are equal across genders prior to puberty; after puberty, higher prevalence is seen in females.

 Although psychological trauma, particularly sexual trauma, is a well-associated risk factor for SSRDs in adults, it is not necessarily associated with SSRDs in youth.

 However, if present, trauma in youth with SSRDs often results in a more complicated treatment course, more severe symptoms, and increased risk for need of higher levels of psychiatric care.

The evaluation and management of youth experiencing an SSRD is predicated on early recognition of risk factors (

). The foundation of an SSRD evaluation is built on concurrent mental health and physical health evaluation, unified evidence-based language that is consistent across disciplines, and direct communication with the family regarding the multifactorial nature of SSRD presentation. Care of youth with SSRDs requires close interprofessional team support. This includes collaboration among the primary care physician (PCP), emergency physician, hospitalist physician, nursing, social work, child life, rehabilitative staff, subspecialty pediatricians, and consultation-liaison (CL) psychiatrist/psychologist. Roles should be delineated early in the management course.

CL psychology and psychiatry should be consulted at the earliest suspicion of an SSRD to normalize psychiatric involvement in comprehensive care. Beyond assessment, CL psychology and psychiatry can aid with framing conversations with the patient and family, provision of evidence-based interventions, as well as addressing psychiatric comorbidities. Although SSRDs do not necessarily present with other discrete psychiatric conditions, anxiety disorders and mood disorders may be present in up to 50% of youth presenting with SSRDs. These comorbidities should be incorporated in the case formulation for proper management of these conditions.

 Ultimately, this process is dynamic, highly interactive, and should adapt to the needs of the patient and family.

Discussion of symptom development and diagnostic conceptualization should be paired with management strategies, highlighting the multifactorial contributors to symptom development. Pairing the multiple biopsychosocial factors allows for a coherent, systematic approach to rehabilitative care, psychotherapeutic management, and judicious use of targeted psychopharmacology. Joint communication by all involved physicians and other clinicians using consistent DSM-5 language and clear discussions of a conceptual framework for symptom development, highlighting mind-body interactions, is crucial.

Once the evaluation is complete and the diagnosis of SSRD is confirmed, it is helpful to have an interprofessional care meeting with the patient family to share the diagnosis. Explaining a conceptualization of how symptoms formed, progressed, and continue to present along with the related biopsychosocial factors influencing presentation is the most critical part of this conversation. This is accomplished via joint physical health and mental health providers using consistent DSM language with the relationship of physical, environmental, psychological, social, and cognitive factors to symptom development. For the patient and family to invest in the diagnoses and partner in the ongoing management of SSRD, it is crucial they understand this conceptualization.

Importantly, clinicians should gauge the patient’s and family’s readiness to accept the information. As such, communication must be geared to each individual’s understanding, values, and readiness. It is often valuable to pair discussions with the use of motivational interviewing to enhance engagement and understand the patient’s or family member’s experience. Discussions may start with a more biological conceptualization, emphasizing concepts such as somatosensory amplification and visceral hypersensitivity; analogies may be used to highlight mind-body interactions. Some families may be able to appreciate and incorporate psychological constructs earlier in the discussion of this conceptual framework. It is important to validate emotions while shifting discussions to functionality. Patients may want to focus on their impairment; it is, therefore, important to pivot conversation to highlight strengths, abilities, and incremental improvements.

Management an SSRD in youth is an iterative process that begins with setting clear goals and expectations. Misalignment of expectations is often a point of conflict. Patients and families may expect complete resolution of symptoms following initial encounters. Here, psychoeducation is key to the initial framing of the concept of somatization, discussing mind-body interactions, and describing joint medical and psychiatric management. Cognitive behavioral therapy (CBT) has a strong evidence base in addressing psychological factors underpinning pediatric SSRD.

 CBT aids in greater awareness of how cognition, emotions, and other psychological processes impact physical sensations, and it empowers the patient with strategies to dampen somatic complaints. It focuses on improving functioning in small, achievable steps, while shifting the focus away from impairment.

CBT psychotherapy can occur in tandem with delivery of rehabilitative services. As many as 50% of youth with an SSRD will have a comorbid depressive or anxiety disorder, making treatment of psychiatric comorbidities an important component of SSRD management.

 Close involvement with the PCP is necessary, including proactive, regularly scheduled brief visits. These visits should be used to coordinate services, address questions, monitor progress, provide reassurance, and promote functioning. PCPS should conduct judicious evaluations of new concerns, collaborating with psychiatry, psychology, and subspecialty pediatrics as needed. In this way, the propensity to seek care in crisis and pursue care in a disjointed fashion can be extinguished over time.

Care should be provided in the setting that best matches the patient’s needs and severity of illness. For youth with severe worsening of function without a clear diagnostic understanding, medical admission may be warranted for further evaluation and management. Youth with significant psychiatric comorbidity may benefit from inpatient or partial psychiatric hospitalization. Those patients with significant rehabilitative needs will benefit from intensive outpatient or inpatient rehabilitation. Most youth, however, can be successfully managed in the outpatient setting with regular PCP evaluations, ongoing psychotherapy, and psychiatric care, as well as additional rehabilitative and pediatric subspecialty follow-up.

 This approach, which aligns with national consensus, provides the best framework for youth to regain functioning, improve symptomatically, and succeed in the care of SSRD.

Role of the Consultation-Liaison Psychiatrist

Care of youth with SSRDs highlights the important liaison role of CL psychiatry. CL psychiatrists aid in the dissemination of information and develop a shared understanding with the patient and family; they also support appropriate language use and incorporate psychological, social, psychiatric, familial, and cognitive factors in the overall assessment with the larger care team. This should include clearly defining care team roles, as well as setting expectations with patients and their families (

The CL psychiatrist should describe mind-body interactions using analogies that simplify understanding for the patient and family. For example, a computer analogy helps explain SSRDs, in which physical disease is more akin to a hardware problem and a psychosocial and environmental factors are more akin to software issue. Similarly, it can be helpful to describe SSRDs as the body’s alarm system being overactive or hypersensitive to somatosensory interactions, which can lead to identification of factors that can heighten or dampen normative reactions to bodily sensations. The goal is to aid patients and families in understanding the interplay of physiologic, psychological, social, and emotional factors that influence somatic symptoms.

Given the diverse and wide-ranging issues and team members involved in effective SSRD care, the CL psychiatrist should also be at the forefront in aiding standardization of multidisciplinary, evidence-based interventions. This should be informed by existing consensus guidelines, such as those published by the American Academy of Child and Adolescent Psychiatry in 2020, and local resources, systems of care, and practice experiences.

CL psychiatrists may be asked about the use of psychopharmacology in managing SSRDs. There is no evidence to demonstrate that psychopharmacology can directly ameliorate the symptoms of SSRDs, and this should be expressed clearly to patients and families as well as the larger care team.

 At times, youth and families may become frustrated that psychopharmacology has not resulted in resolution of symptoms. Therefore, it is important to reiterate, early on, that management of SSRDs is predicated on a multidisciplinary approach that targets the factors fostering symptom-development and persistence. Here the focus is shifted to improvement in functioning and incremental rehabilitation of cognitive, emotional, and physical health factors.

Psychopharmacology can be helpful in addressing psychiatric comorbidities, and they may provide more immediate relief for other psychiatric factors that are resulting in acute distress. When provided, psychopharmacology should have clear targets for management with clear expectations within the greater context of treatment. It is important to explore familial expectations and continue to set realistic expectations, emphasizing the importance of ongoing engagement with other teams including psychology and rehabilitative services.

CL psychiatry can also have an important role in informing longitudinal management of SSRDs, which may be accomplished through collaborative clinical models. Such models often have psychiatry and psychology providing integrated care in a primary care or subspecialty pediatric practice. Inpatient psychiatric care may be needed for youth with severe psychiatric comorbidities, safety concerns related to suicidal ideation or behavior, or severe psychological trauma. Ultimately, disposition planning must account for the level of training, experience, resources, and standardization of practice that exists within different settings in a given health system.

is a child and adolescent psychiatry fellow at the University of Michigan

is clinical assistant professor in the Department of Psychiatry at the University of Michigan

is a clinical instructor and associate medical director, Nyman Family Unit, Department of Psychiatry, University of Michigan

is associate professor in the Departments of Psychiatry and Pediatrics at the University of Michigan.

1. Malas N, Donohue L, Cook RJ, et al. Pediatric somatic symptom and related disorders: primary care provider perspectives. 

2. Kullgren KA, Shefler A, Malas N, et al. Taking the pain out of somatization: development and implementation of a hospital-based clinical practice guideline to address pediatric somatic symptom and related disorders. 

3. Ibeziako P, Brahmbhatt K, Chapman A, et al S. Developing a clinical pathway for somatic symptom and related disorders in pediatric hospital settings. 

4. Shaw RJ, Pao M, Holland JE, DeMaso DR. Practice patterns revisited in pediatric psychosomatic medicine. 

5. Bujoreanu S, White MT, Gerber B, Ibeziako P. Effect of timing of psychiatry consultation on length of pediatric hospitalization and hospital charges. 

7. Ibeziako P, Bujoreanu S. Approach to psychosomatic illness in adolescents. 

7. Rask CU. Functional somatic symptoms in 5-7 year old children: assessment, prevalence and co-occurrence. 

8. Jones GT, Silman AJ, Power C, Macfarlane GJ. Are common symptoms in childhood associated with chronic widespread body pain in adulthood? Results from the 1958 British Birth Cohort Study. 

9. Malas N, Ortiz-Aguayo R, Giles L, Ibeziako P. Pediatric somatic symptom disorders. 

10. Plioplys S, Doss J, Siddarth P, et al. Risk factors for comorbid psychopathology in youth with psychogenic nonepileptic seizures. 

11. Thomson K, Randall E, Ibeziako P, Bujoreanu IS. Somatoform disorders and trauma in medically-admitted children, adolescents, and young adults: prevalence rates and psychosocial characteristics. 

12. Liu J, Gill NS, Teodorczuk A, et al. The efficacy of cognitive behavioral therapy in somatoform disorders and medically unexplained physical symptoms: A meta-analysis of randomized controlled trials. 

13. Ibeziako P, Randall E, Vassilopoulos A, et al. Prevalence, patterns, and correlates of pain in medically hospitalized pediatric patients with somatic symptom and related disorders. 

14. Kleinstäuber M, Witthöft M, Steffanowski A, et al. Pharmacological interventions for somatoform disorders in adults. 

Clinicians, families, and patients all report frustration with SSRD treatment in hospitals. It’s time to improve it. 

New Best Practices for Treating Youth With Somatic Symptom and Related Disorders 

People suffering from depression die, on average, 10 years earlier than non-depressed individuals.” You must have heard this while attending a conference, reading a journal, or simply in a discussion with a colleague. It has little to do with the risk of suicide: we are mainly talking about death due to physical causes and, in particular, cardiovascular causes. Any mental health professional, upon learning of this fact, may have felt uneasy, even inadequately prepared to address such a complicated issue. After all, until a few years ago, we thought that colleagues from other branches of medicine would take care of those aspects, right? Well, no. A million times, no.

The clinical perspective of the individual practicing physician may not always align with epidemiological data. The excess mortality in depressed populations is an apt example. Without delving into a detailed analysis of the literature, there has been a wave of studies showing an alarming phenomenon: given a certain period of observation, a higher rate of people with depression die than those without depression—this appears to be the case for both genders, but especially for males, and for healthy as well as physically ill individuals.

Clearly, it is difficult to account for all factors that may underlie this phenomenon, and this association does not necessarily mean that depression causes death, even if we consider longitudinal studies.

 Nonetheless, depression is consistently associated with conditions that are known to increase the risk of cardiovascular diseases (

). More importantly, and arguably more likely to be causally related, individuals with depression tend to engage in unhealthy lifestyles, which are potentially modifiable: unbalanced diet, alcohol use, cigarette smoking, lower adherence to medications, and physical inactivity.

In particular, individuals who are depressed not only spend less time engaging in physical activity, but they also 

 sedentary behaviors more commonly than their non-depressed counterparts.

 Ultimately, individuals with depression have low levels of physical fitness, which may not be surprising, but should raise concerns among clinicians because of the implications for mortality. Both muscular strength and cardiorespiratory fitness are meaningful predictors of all-cause mortality and cardiovascular events in men and women.

The epidemiological and experimental evidence showing the wide-ranging beneficial effects of physical activity and 

 for health has proliferated over the past 70 years. Physical activity and exercise are now recognized as fundamental tools for reducing the impact of chronic diseases, especially cardiovascular mortality, as well as improving their course.

1. Exercise directly improves cardiorespiratory fitness. 

Randomized trials show that even short bouts of exercise can improve cardiovascular function, in younger as well as older individuals.

The most effective intervention to lose weight remains caloric restriction. Nonetheless, regular exercise can prevent obesity and excess weight and can buffer some of their negative effects.

 This effect seems to depend on improved regulation of appetite hormones and increased metabolic rate.

3. Exercise improves the function of homeostatic systems. 

The hormonal response to stress, such as the activity of the HPA axis, get fine-tuned by regular exercise and higher cardiorespiratory fitness, showing a blunted response to mild or familiar stressors, and faster recovery.

 Moreover, exercise reduces inflammatory responses and delays the aging of the immune system.

 It also improves the autonomic control of the heart in addition to other organs.8

Randomized clinical trials have shown that exercise improves glycemic control and reduces insulin resistance. Moreover, it improves the lipid profile, by lowering triglycerides and low-density lipoproteins and increasing high-density lipoproteins.

The antihypertensive effect is greater in individuals who already have hypertension, but it is also observed among healthy people.

Despite some controversies, the antidepressant efficacy of exercise has been established with methodological rigor, and exercise can be prescribed as a treatment for mild-to-moderate depression alone or for severe depression in conjunction with other treatments.

 If depression improves, this may reflect positively on behavioral sequalae, including unhealthy lifestyle.

Currently, only a few lifestyle-related cardiovascular risk factors have not been shown to respond significantly to exercise, namely alcohol consumption and cigarette smoking. Still, early results related to smoking cessation, problem drinking, and substance use among individuals with mental health disorders show promise.

 of randomized controlled trials indicate that exercise may ultimately have a significant effect on delaying mortality in patients with established coronary heart disease, stroke, heart failure, and diabetes, to an extent that is comparable to that of first-line medications.

 Clearly, enthusiasm for these findings must be tempered by the relative scarcity of available direct head-to-head studies (exercise vs medications), and by the so-called file-drawer bias, whereby negative results may not get published as much as positive ones. On the other hand, however, literature on exercise, compared with other types of interventions, may be less prone to distortions due to financial conflicts of interest.

The clinician may wonder if evidence from populations with physical illness could be directly translated to individuals with depression. Studies pertaining specifically to individuals with depression are not abundant, but preliminary evidence suggests that the benefits of exercise may apply to this population as well. Overall, given the lack of studies directly testing this hypothesis in depressed populations, the evidence is speculative. That said, considering the benefits and the low clinical risks associated with exercise, we believe recommending exercise to patients with depression and physical comorbidities should already be the norm, rather than the exception.

Given the emerging evidence, interventions to improve the lifestyle of patients with depression seems a viable strategy that may ultimately help to reduce mortality risk.

 But, how can a clinician achieve this seemingly ambitious goal? How is it possible to promote physical activity in individuals that already suffer from a lack of motivation, low sense of physical energy, and reduced initiative as intrinsic symptoms of their mental health condition?

Currently, various recommendations have been proposed for prescribing exercise to individuals with depression, based on either empirical evidence or clinical experience.

 The optimal exercise prescription for the treatment of depression is not known, insofar as the relation between the “dose” of exercise (ie, intensity, frequency, duration) and therapeutic response remains mostly unknown. Therefore, 

 are essentially derived from guidelines that were not specifically developed for depression.

First, the treating clinician should confront and reassess their own prejudices.

 Physicians are sometimes resistant to the idea of exercise as a possible treatment option, or even as an adjunct intervention. Skepticism may depend on various perceived barriers, including the belief that depressed individuals will not even start to exercise, or that they will soon abandon this activity.

 However, especially if good therapeutic alliances exist, many individuals with subthreshold, mild, or moderate depressive symptoms will opt for exercise and will demonstrate satisfactory adherence.

Second, consider one of the main drivers of any activity: pleasure. Affect-based exercise prescription is an emerging trend in exercise science and may be especially useful for the treatment of depression.

 This method goes beyond the traditional focus of exercise prescriptions, which is maximizing fitness or health gains and minimizing risk, to include the promotion of pleasant affective experiences. The consideration of pleasure as a central element aims to ultimately promote adherence.

, the exercise participant is shown a simple rating scale (eg, ranging from +5 or “I feel very good” to -5 or “I feel very bad”) and is instructed to self-regulate their exercise intensity and duration to maintain a rating of +3 (“I feel good”) or higher. Among adults without depression, the affective responses to exercise are associated with the amount of physical activity individuals subsequently choose to do.

 Even if individuals with depression suffer from symptoms of anhedonia, they may still experience exercise as pleasant and affect-enhancing.

Evidence from studies of individuals with depression shows that the affective responses to exercise may predict improvement of depressive symptoms and exercise adherence.

 This method seems to hold promise for clinical application due to its simplicity, making it appealing to physicians who lack specialized training in exercise and to health care organizations concerned about implementation costs. When recommending exercise to patients, the steps and processes for promoting exercise in individuals without depression may prove useful (

Third, mental health professionals should not rely only on themselves to prescribe exercise. Exercise interventions can be delivered by professionals with a variety of disciplinary backgrounds, including group exercise leaders, personal trainers, clinical exercise physiologists, wellness specialists, and physical therapists. 

 that is supervised by a professional is usually associated with lower dropout rates. Given the challenging cognitive and affective features of depression, exercise for individuals with depression should be delivered by professionals with specific experience in mental health care.

 In other words, a well-integrated, collaborative approach is absolutley essential to achieve the best possible effects.

The premature mortality of individuals with depression is an alarming public health concern. Physical exercise may help address this concern, but it represents an underutilized intervention despite substantial evidence documenting its numerous physical benefits. Exercise can simultaneously tackle several mechanisms that likely lead to premature mortality in this population. Moreover, if it is prescribed, delivered, and supported correctly, exercise can be as effective as other first-line treatments in reducing depressive symptoms, while being mostly free of adverse side-effects.

is assistant professor, Department of Neuroscience, University of Ferrara, Parma, Italy; 

 is professor, Department of Kinesiology, Iowa State University, Ames, IA. The authors report no conflicts of interest concerning the subject matter of this article.

1. Machado MO, Veronese N, Sanches M, et al. The association of depression and all-cause and cause-specific mortality: An umbrella review of systematic reviews and meta-analyses. 

2. Schuch F, Vancampfort D, Firth J, et al. Physical activity and sedentary behavior in people with major depressive disorder: A systematic review and meta-analysis. 

3. Lieberman DE. Is EExercise Really Medicine? An evolutionary perspective. 

4. Magutah K, Thairu K, Patel N. Effect of short moderate intensity exercise bouts on cardiovascular function and maximal oxygen consumption in sedentary older adults. 

5. Ekkekakis P, Vazou S, Bixby WR, Georgiadis E. The mysterious case of the public health guideline that is (almost) entirely ignored: call for a research agenda on the causes of the extreme avoidance of physical activity in obesity. 

6. Chen C, Nakagawa S, An Y, Ito K, Kitaichi Y, Kusumi I. The exercise-glucocorticoid paradox: how exercise is beneficial to cognition, mood, and the brain while increasing glucocorticoid levels. 

7. Campbell JP, Turner JE. Debunking the myth of exercise-induced immune suppression: redefining the impact of exercise on immunological health across the lifespan. 

Physical activity and exercise are recognized as fundamental tools for reducing the impact of chronic diseases, including depression.

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