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“Mrs Blue” is a 70-year-old Caucasian woman with a 45-year history of schizophrenia. She also has posttraumatic stress disorder (PTSD) stemming from a sexual assault in early adulthood and occasionally smokes marijuana. Her current psychotropic regimen includes aripiprazole (Abilify), valproic acid (Depakote), and citalopram (Celexa), and she is overall stable with no psychiatric hospitalizations in the past 6 years. Prior to the schizophrenia diagnosis, she underwent a hysterectomy at age 20 for ovarian cancer. She has comorbid obesity, hypertension, hyperlipidemia, and osteoporosis. Three years ago, she received a diagnosis of chronic renal failure. Her most recent blood urea nitrogen to creatinine ratio is 51:2.15, with a glomerular filtration rate of 26.

 affects more than 3 million individuals in the United States and is associated with substantial psychiatric, substance-related, and medical 

, patterns of comorbidity in schizophrenia have not been systematically described using real-word data.

 To address this gap, Lu and colleagues leveraged a nationwide health insurance claims data set from Aetna to assess population-level phenotypes associated with schizophrenia.

The investigators conducted data-driven analyses on patient phenotypes before and after the index diagnosis of schizophrenia and compared data on phenotypes with those of matched controls without schizophrenia. The Aetna data set contained 86 million participants from all 50 states, the District of Columbia, 5 populated territories, and Armed Forces Europe, with claims data from January 2008 to December 2019. 

International Classification of Diseases, Ninth Revision

 codes formed the basis of corresponding phenotype codes or phecodes. Schizophrenia was defined as at least 3 occurrences of phecodes 295 and 295.1. 

Inclusion criteria were documented birth year, biological sex, and zip code information. Participants also had to have been on the insurance plan for at least 12 months prior to their first schizophrenia diagnosis. Patients younger than 15 years old were excluded. Patients in the schizophrenia cohort were matched to controls without schizophrenia based on birth year, biological sex, and the first 3 digits of the zip code.

The authors analyzed 1890 phenotypes based on phecodes (requiring at least 3 occurrences) before diagnosis for patients with a first documentation of schizophrenia between ages 15 and 29 years. Data for all participants were analyzed using the Fisher exact test. Data on phenotypes occurring after the onset of schizophrenia were analyzed using Cox proportional hazards models. Patients were removed from these analyses if the phecode was within 1 year of the first schizophrenia diagnosis. The Bonferroni correction was applied to P-values for multiple comparisons.

The authors identified 61,453 patients with schizophrenia (prevalence, 0.7%; 47% were male); average length of patient records was 6 years. The investigators noted 144 phecodes were significantly enriched in patients who later received a schizophrenia diagnosis. Some of the top phecodes were suicidal ideation (odds ratio [OR], 51.2), bipolar (OR, 36.1), antisocial/borderline personality (OR, 18.4), substance addiction and disorders (OR, 17.6), and PTSD (OR, 16.2). Women who later developed schizophrenia were more likely to have type 2 diabetes, obstructive sleep apnea, and eating disorders; men were more likely to have acute renal failure, developmental delay, and rhabdomyolysis (

The authors also noted that 402 phecodes were significantly enriched after the diagnosis of schizophrenia. Some of the top phecodes were coma/stupor/brain damage (HR, 87.3), altered mental status (HR, 86.2), alcoholism (HR, 47.3), and septicemia (HR, 30.4). Women were more likely to develop encephalopathy, epilepsy, and adverse drug events or allergies; men were more likely to develop impulse control disorder, esophageal bleeding, and acute osteomyelitis.

Thus, the authors concluded there was a broad range of comorbidities enhanced in schizophrenia both before and after diagnosis, including PTSD, other anxiety disorders, and alcohol and other substance use disorders. In addition, patient sex significantly influenced associated comorbidities.

Study strengths included the large sample size and comprehensive data, consideration of comorbidities before and after the diagnosis of schizophrenia, and statistical correction for multiple comparisons. Study limitations included the potential lack of generalizability to other schizophrenia populations (ie, the investigation leveraged an employer-sponsored insurance claims data set), the relatively short follow-up time, and the inherent nature of phecodes that represent coarse categories of clinical phenotypes.

This study demonstrates the utility of large-scale, real-world data analyses to elucidate patterns of disease comorbidity, which can provide clinically useful information to treating clinicians.

How often do you see comorbidities in patients with schizophrenia? Which comorbidities are the most troublesome to treatment? Email us at 

is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Georgia. He is on the Editorial Board and serves as the Schizophrenia & Psychosis section editor for

The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and Stanley Medical Research Institute.

1. Patel KR, Cherian J, Gohil K, Atkinson D. 

Schizophrenia: overview and treatment options

Large-scale real-world data analysis identifies comorbidity patterns in schizophrenia

A recent study demonstrates how large-scale, real-world data analyses can elucidate patterns of disease comorbidity.

Comorbidity Complexities: Patterns and Implications

Tales From the Clinic: The Art of Psychiatry

, we delve into a very common neuropsychiatry comorbidity: headaches. Headaches are a common comorbidity among a variety of psychiatric diagnoses. This neuropsychiatric condition can be challenging to manage due to a strong overlap with somatization.

“Mr Wright” is a 37-year-old man with no medical comorbidities who has been in the United States for more than 10 years. Mr Wright presented to primary care with a 4-month history of headaches that were unresponsive to over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs). He is started on amitriptyline 25 mg at bedtime daily and is referred to psychiatry for “anxiety” without any further notes on symptoms of 

. The patient is worried he will be labeled “crazy” and is upset that his suffering is not being taken seriously.

He appears to be in good physical health with good grooming, although he is somewhat reluctant during the 

. He reports that he has been living with his wife and child, and he works at a restaurant. He has teenage kids who do not live with him, but reportedly has a good relationship with them.

, Mr Wright relays that they persist all day long and encompass areas around his bilateral temples and occipital area, although the pain may migrate between these areas. He has tried to lay down to rest, but the relief in pain is temporary. He is unable to focus on driving and has missed several workdays because he did not feel like he could pay attention while driving. He stretches his neck in a variety of different angles during our interaction to help relieve the pain, along with some excess eye blinking that he seems unaware of. He denies a premonitory sensation occurring prior to his movements.

After repeated queries into his stressors around the time his headaches started, Mr Wright is able to verbalize an incident that occurred a week before their onset: He was accommodating his sister at his home after an interpersonal conflict with her husband. The brother-in-law had held him at gunpoint outside his home. He had run inside to safety, and the brother-in-law had eventually left. His sister has since left, and the patient feels that the turmoil of an abusive relationship in his sister’s life is persistent and acceptable to his sister and the rest of the family. He recalls a similar event over 20 years ago when he was chased by a different family member in his home country. At that time, Mr Wright also felt his life was in danger and had to run to safety, and since then, he has been an anxious person in general. He has never received any mental health treatment (including psychotherapy) before.

 (PTSD) including nightmares, flashbacks, and avoidance of increased arousal.

A chart review shows that Mr Wright was seen in the ER twice since he met with his primary care provider. On 1 occasion, he had acute chest pain; negative EKG and cardiac enzymes led to a discharge. On the second occasion, he was evaluated for unprotected sexual contact with an unknown individual. Mr Wright had chosen not to mention any of these instances of his interaction with the medical system, and the psychiatrist chose not to discuss them either.

He was started on amitriptyline 25 mg by his primary care physician 2 weeks ago, and he has been using it as needed on nights he is unable to sleep. He finds it useful, but he is unable to get relief from headaches. He is unable to verbalize any correlation between a life-threatening event and the onset of his headaches.

At the conclusion of the visit, patient and physician agree to continue amitriptyline, but agree that the patient should take it more regularly for best therapeutic results.

As per a systematic review of a global burden of disease across the United States, in 2017, the 5 highest incidence rates of neurological diseases included 

 Migraines have consistently been among the top 3 neurological diseases in terms of disability adjusted life years.

 As a testament to how frequently psychiatrists and neurologists see patients with headaches and psychiatric diagnosis, in 2019, the most frequent psychiatric comorbidities in individuals with primary headaches in the United States were anxiety and depression, followed by posttraumatic/stressor and trauma-related stress disorder. These comorbidities are found in 25%, 23%, and 15% of the general population, respectively.

It is inevitable then that one is likely to come across patients with both primary and secondary headaches in psychiatric practice. Recognizing headaches can be a powerful tool in evaluating the quality of life of our patients. Headaches can be triggering and perpetuating factors for psychiatric conditions in addition to being an important consideration in identifying the best pharmacological options for treatment.

In primary headaches such as migraine and tension headaches, there is no source for nociceptive activity such as a hemorrhage or 

. Many theories have tried to explain connections between distress and primary headaches. Existing studies on connections among distress and primary headaches clearly show that the most important triggering events for primary headaches are distress and sleep issues.

 Stress has also been linked with the transformation of episodic migraines to chronic migraines that carry a greater burden of disease.

 Interestingly, repeated exposure to trauma, even without a formal PTSD diagnosis, is prominent in chronic migraine headaches as compared to healthy adults without migraines.

Biopsychosocial factors are believed to be involved in headache perception. Transactional models propose that the mismatch between threat perception and capability to deal with the threat can be applied to the subjective sense of pain in migraines, as well as to any other pain syndrome.

 Among personality traits, locus of control being perceived as internal versus external predicts better headache outcomes.

During the current COVID-19 pandemic, the role of sudden change in psychosocial environment due to shutdowns among those with preexisting migraines has been investigated. Contrary to the impression that headaches would worsen, at least 1 study has recorded improvement. The study documents reduction in migraine intensity and frequency in adolescents during COVID-19 shut down in Italy in 2020.

 It is reasonable to speculate the reduction in academic and social pressures as being helpful in this improvement and underscore the role of psychosocial intervention on patients with migraines. Moreover, it would be interesting to see if there is an uptick in migraine presentation to neurologists and psychiatrists due to the chronic stress induced by the pandemic, over and above migraine in individuals caused by 

Migraine headaches have a bidirectional relationship with a spectrum of psychiatric illnesses, the strongest correlation being with depression, anxiety, and bipolar disorder. There is evidence of shared genetic predisposition, as well as functional and structural alterations in pain-modulating brain areas, including the amygdala, anterior cingulate cortex, and periaqueductal gray in both migraine and affective disorders. Moreover, they share similar abnormalities in the HPA axis as well as common mechanisms of action of treatment modalities.

The concept of central sensitization is often used to explain pain-related conditions, including migraine. Patients with chronic migraines (as compared to episodic migraines) have more somatic complaints. The role of pain sensitization in episodic migraines has also been investigated in episodic migraines. A recent study suggested that slowly repeated evoked pain sensitization could in fact be useful as a clinical predictor for episodic migraines.

Serotonin, norepinephrine, and the GABAergic system have all been implicated in the etiology of psychiatric as well as primary headaches at the level of neurotransmitters. As such, the evidence for using serotonin and norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs) that target these receptors for preventative treatment for migraines remains strong.

Managing psychiatric symptoms in patients presenting for treatment with headaches may present a unique advantage in overcoming barriers to talking about optimizing mental health. When establishing goals for treatment, it may be useful to educate the patient about the benefit of SNRIs and TCAs in managing headaches as well as mood and anxiety disorders. This may help patients verbalize their mental health needs in the face of 

. At times, presenting an SNRI or TCA as a headache medicine only may help with adherence to treatment in patients who have difficulty expressing their distress.

One of the many challenging difficulties in managing headaches is that initiating SNRIs or TCAs for headache management can itself carry a risk for inducing headaches. A careful consideration of the timeline for medication-induced headache may aid in separating the superimposed symptoms. Clinicians may benefit from considering medication withdrawal as a reason for headache exacerbation when treating psychiatric patients with comorbid headaches and a history of noncompliance. Venlafaxine is notable in this regard for its withdrawal syndrome.

Several studies have been unable to establish the benefit of using selective serotonin reuptake inhibitors (SSRIs) in preventing migraine relapses. Among the most studied SSRIs is fluoxetine, which, to date, has conflicting evidence for its use in primary headaches.

 Other clinical trials of sertraline and citalopram did not show benefit over TCA or placebo. Hence, when a patient with previously established treatment with SSRI is placed on TCAs for headaches, one has to carefully weigh the risks and benefits of switching to monotherapy with TCA or continuing with both medications. If the patient is reporting clinical benefit, they could be managed with low doses of both medication categories while monitoring carefully for 

. Patients can be educated regarding early symptoms of serotonin syndrome when managed in the outpatient setting.

Additionally, many clinicians are concerned about the possibility of inducing serotonin syndrome in patients using antidepressants and are prescribed triptans for aborting episodes of migraines. While there was a Blackbox warning for this interaction, an electronic health record-based study in 2018 did not find any correlation of serotonin syndrome with co-use of SSRIs and SNRIs and triptans.

In patients with medication overuse headaches, the prevalence of psychiatric comorbidities is even higher.

 Some point to the similarities between compulsive medication intake for episodes of migraine and obsessive-compulsive disorder. As such, adding behavioral interventions for this subset of patients may be highly impactful in improving headache outcomes.

It may be prudent for neurologists to prescribe psychotherapy regularly for managing patients with chronic migraines. Behavioral interventions and forecasting models, including stress variables, seem to be useful in managing migraine. Behavioral treatments with evidence for migraine prevention include stress management, relaxation therapy, 

, biofeedback, mindfulness-based therapies, and acceptance and commitment therapy. Some studies point out that although headache frequency or intensity improves, there is no change in physiological markers of headaches such as muscle tension. In a landmark study of electromyographic biofeedback training, participants viewed their headaches as having a more internal locus of control and themselves as more self-efficacious (ie, as capable of influencing their headaches) following treatment.


Finally, when addressing this complex patient population, it is essential to avoid labeling and stigmatization. Patients are usually concerned about physical complaints being dismissed and being told “the symptoms are in your head.” Establishing careful therapeutic rapport goes a long way in open discussions of treatment options and paving the way to productive illness management.


is assistant professor at Baylor College of Medicine, Menninger Department of psychiatry. She specializes in cooccurring psychiatric and neurological disorders.

1. GBD 2017 US Neurological Disorders Collaborators; Feigin VL, Vos T, Alahdab F, et al. 

Burden of neurological disorders across the US from 1990-2017: a global burden of disease study.

2. GBD 2019 Diseases and Injuries Collaborators. 

Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

3. Caponnetto V, Deodato M, Robotti M, et al; European Headache Federation School of Advanced Studies (EHF-SAS). 

Comorbidities of primary headache disorders: a literature review with meta-analysis.

4. Yokoyama M, Yokoyama T, Funazu K, et al. 

Association between headache and stress, alcohol drinking, exercise, sleep, and comorbid health conditions in a Japanese population.

Predictors of episodic migraine transformation to chronic migraine: a systematic review and meta-analysis of observational cohort studies.

7. Dallavalle G, Pezzotti E, Provenzi L, et al. 

Migraine symptoms improvement during the COVID-19 lockdown in a cohort of children and adolescents.

8. De la Coba P, Bruehl S, del Paso GAR. 

Slowly repeated evoked pain (SREP) as a central sensitization marker in episodic migraine patients.

9. Silberstein SD, Holland S, Freitag F, et al; Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. 

Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society.

Association of coprescription of triptan antimigraine drugs and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants with serotonin syndrome.

11. Kristoffersen ES, Straand J, Russell MB, Lundqvist C. 

Disability, anxiety and depression in patients with medication-overuse headache in primary care - the BIMOH study.

12. Holroyd KA, Penzien DB, Hursey KG, et al. 

Change mechanisms in EMG biofeedback training: cognitive changes underlying improvements in tension headache.

Headaches are a common comorbidity among a variety of psychiatric diagnoses. 

Headaches and Psychiatric Illness 


Although the lack of mental health services available to all youth has been exposed as a result of COVID-19, this is particularly problematic for LGBTQ+ youth.

 Specifically, transgender and gender-diverse (TGD) youth experience higher rates of depression, suicidal behaviors, and self-injury than their cisgender peers (see 

A recent survey of adolescents across the United States indicated that about 2% of middle and high school students identify as transgender or gender diverse,

 a number that has been increasing over time.

 Importantly, although many TGD individuals feel a strong discomfort with their body and change their gender expression and roles and/or physical characteristics to align with their identity, not everyone experiences the distress related to the clinical diagnosis of 

With increased research looking at the experiences of TGD individuals separately from their sexual minority peers, we have begun to better understand cooccurring issues for this distinct population. Specifically, depression, self-injurious behaviors, 

, disordered eating, and anxiety have been reported, as have high suicide attempt rates: These rates are at least 3 times higher than those of cisgender peers.

Why are we now seeing such increased rates of comorbidities with TGD individuals? Proposed by Hendricks and colleagues,

 the Gender Minority Stress and Resilience Model (GMSRM) is a framework through which we can understand the unique internal and external stressors that impact TGD individuals, as well as factors that contribute to resilience. The authors posit that external experiences of discrimination, victimization, rejection, and nonaffirmation of gender identity combine with internalized transphobia, negative expectations of the world and others, and concealment; these leave TGD individuals at risk for the development of negative mental health symptoms such as 

, suicidality, and self-injurious behavior.

Therefore, when working with TGD individuals, we need to assess for the internal mechanisms related to any psychiatric diagnosis, but also the external/environmental factors that are contributing to and maintaining the symptoms. For example, numerous studies have looked at the relationship between invalidation and victimization in schools, hospitals, and therapy that led to individuals dropping out of school, not accessing care, or ending treatment.

 In addition, we must continuously use an intersectional lens to be able to understand how additional identities that have been marginalized (eg, race, ethnicity, sexual orientation, ability, religion) may also be impacting the individual’s functioning, as well as the level of gender dysphoria the individual is experiencing. Attention to all these contributing/maintaining factors—both internal and external—is necessary for the best treatment.

Consider this metaphor: If you have to put out a fire, it is important to understand what caused the fire in the first place. Putting water on a grease fire will not only not help—it can make it worse. Similarly, trying to use typical interventions for depression for dysphoria not only will not help, but may also invalidate the patient and make them feel worse about not being seen or heard.

“Max” is an affirmed male (assigned female at birth), aged 14 years, who presented to our program to discuss gender-affirming care. Max reported that he had always known he was a boy and had preferred stereotypical masculine clothing, mannerisms, and activities for as long as he could remember. Max was raised by his maternal aunt “Linda,” who was his sole custodian. Both of Max’s parents had struggled with substances since he was a young child, and they did not have secure housing. None of Max’s family consistently used his chosen name or pronouns, although teachers and peers regularly used them in school. Linda was convinced that Max’s identity was “just a phase” and that the real presenting problem was that he had an eating disorder and was depressed. Linda wanted Max to be admitted to an inpatient unit, as she believed he needed “to get more meds.” She was very upset that the school was “reinforcing ‘her’ issues.”

Upon further discussion alone with the patient, he reported he was restricting food intake because he wanted to stop his menses, as it was very distressing, and he wanted to prevent his chest from growing, as he did not have access to a binder to compress his chest area. He experienced a lot of gender dysphoria when thinking about or discussing his body/bodily functions. Max also reported that he felt like his family would never understand him, use his name or pronouns, or allow him to proceed with any medications to stop his menses, let alone masculinize his body. To “let out” some of his pain, Max would use pencil sharpeners to cut his arms and thighs. Although he felt supported by friends and teachers at school, he felt his family would never accept him, would always make fun of him, and would never support who he is.

In this case example, we see issues such cooccurring gender dysphoria (eg, discomfort with body, effects of estrogen-based pubertal development), symptoms of depression, and restrictive eating. Max’s discomfort with his body and attempts to align his body with his gender identity appear to be directly impacting his eating. Therefore, traditional treatment for an 

 would not work with Max, and it could potentially lead to more gender dysphoria, depressive symptoms, and self-injurious behavior.

Relatedly, Max’s nonaffirmation at home, negative expectations about his future ability to identify as male in the eyes of his family, and negative expectations about treatment appear to be directly related to some of his depressive symptoms and self-injurious behaviors. In addition to a traditional 

, dialectical therapy, or assertive community therapy approach, understanding the GMSRM and educating the family members on the importance of using chosen name/pronouns to decrease depression and suicidal ideation would be imperative to share, as would the general importance of family and peer support.

To conceptualize the presenting problem as well as understand any maintaining factors, clinicians should consider exploring the following issues:

 What has their journey exploring their gender identity looked like? Who has been supportive of this exploration? How has society impacted their views on gender?

 What are their experiences of discrimination, rejection, victimization, and/or nonaffirmation in school? At home? With peers? With immediate as well as extended family members?

 Who is supportive of the youth, their gender journey, and the way they choose to express themselves? Are there differences by domain (eg, family, peers, school, online)?

 Is the youth experiencing negative mood, anger, or thoughts of suicide? How are these feelings related to their gender identity, internalized transphobia, or the felt need to conceal who they are for fear of repercussions or other fears of victimization/nonaffirmation?

 Have they experienced any traumatic events related to their gender identity or expression that may be impacting their sleep, eating, or ability or concentrate?

 Have they been controlling their eating to change their body shape or functions to be more congruent with their gender identity (eg, restricting food to stop menses or decrease curves or eating more to increase curves)?

 How does the youth experience gender joy? How does this impact mood? Can the youth experience gender joy in a safe manner?

TGD youth experience numerous environmental stressors (eg, victimization, invalidation, rejection) as well as gender dysphoria that can contribute and add to preexisting conditions (eg, depression, suicidality, self-injurious behavior, etc).

As clinicians, it is our duty to assess these various contributing factors and ensure the best treatment options for our patients by utilizing the most up-to-date data and protocols. We also have the unique opportunity to potentially be the first person who says to a trans young person, “I see you,” “You are valid,” and most importantly, “There is a future in which you can exist as the person you know you are.”

The advocacy work necessary in providing support for TGD youth allows us to show our patients that they matter and deserve rights. It also shows them that they are not alone on their gender journey.

is associate professor of psychiatry at Yale School of Medicine, and director and cofounder of the Yale Pediatric Gender Program. She is also a Public Voices fellow of the OpEd Project.

is a predoctoral fellow at Yale School of Medicine.

Supporting youth mental health during the COVID-19 pandemic.

2. National survey on LGBTQ youth mental health. The Trevor Project. 2021. Accessed January 3, 2022. 

https://www.thetrevorproject.org/survey-2021/

Substance abuse prevention, assessment, and treatment for lesbian, gay, bisexual, and transgender youth.

Exploring cross-sectional predictors of suicide ideation, attempt, and risk in a large online sample of transgender and gender nonconforming youth and young adults.

6. Marshall E, Claes L, Bouman WP, et al. 

Non-suicidal self-injury and suicidality in trans people: a systematic review of the literature.

7. Johns MM, Lowry R, Andrzejewski J, et al. 

Transgender identity and experiences of violence victimization, substance use, suicide risk, and sexual risk behaviors among high school students – 19 states and large urban school districts, 2017.

Transgender population size in the United States: a meta-regression of population-based probability samples.

9. Thoma BC, Salk RH, Choukas-Bradley S, et al. 

Suicidality disparities between transgender and cisgender adolescents.

Suicide attempts among a cohort of transgender and gender diverse people.

11. Hendricks ML, Testa RJ. A conceptual framework for clinical work with transgender and gender nonconforming clients: an adaptation of the Minority Stress Model. 

Professional Psychology: Research and Practice. 

12. Austin A, Craig SL, D’Souza S, McInroy LB.

 Suicidality among transgender youth: elucidating the role of interpersonal risk factors

13. James S, Herman J, Rankin S, et al. The report of the 2015 US transgender survey. National Center for Transgender Equality. 2016. Accessed January 3, 2022. 

https://transequality.org/sites/default/files/docs/usts/USTS-Full-Report-Dec17.pdf

14. Kosciw JG, Clark CM, Truong NL, Zongrone AD. The 2019 National School Climate Survey: The Experiences of Lesbian, Gay, Bisexual, Transgender, and Queer Youth in Our Nation’s Schools. A report from GLSEN. 2020. Accessed January 3, 2022. 

https://www.glsen.org/sites/default/files/2020-10/NSCS-2019-Full-Report_0.pdf

15. Austin A, Craig SL. Transgender affirmative cognitive behavioral therapy: clinical considerations and applications. 

Professional Psychology: Research and Practice.

16. Russell ST, Pollitt AM, Li G, Grossman AH. 

Chosen name use is linked to reduced depressive symptoms, suicidal ideation, and suicidal behavior among transgender youth.

17. Bochicchio L, Reeder K, Aronson L, et al. 

Understanding factors associated with suicidality among transgender and gender-diverse identified youth.

18. Price MN, Green AE. Association of gender identity acceptance with fewer suicide attempts among transgender and nonbinary youth. 

19. Price MA, Hollinsaid NL, Bokhour EJ, et al. Transgender and gender diverse youth’s experiences of gender-related adversity. 

Transgender and gender-diverse youth experience higher rates of depression, suicidal behaviors, and self-injury than their cisgender peers. Here's what you need to know.  

Disentangling the Web: Comorbidity Issues in Gender-Diverse Youth

Psychiatric and medical comorbidities can complicate the differential diagnosis and hamper treatment success. Thus, investigators around the globe continue to examine how these comorbidities interact with each other. In this Research Roundup, 

 looks at clinical issues and implications of comorbidities associated with depression, eating disorders, COVID-19, and more.

Depression, Bipolar Disorder, and Sleep in Children and Adolescents

Recently, investigators conducted a narrative literature review of affective disorders and sleep difficulties in children and young people, seeking to understand the relationship between sleep and both depression and bipolar disorder.

Monica Comsa, FRACP, of the Child and Adolescent Mental Health Service at Cumbria Northumberland, Tyne and Wear NHS Foundation Trust in the United Kingdom, and colleagues found that parasomnias, narcolepsy, and sleep-related movement disorders are associated with depression in children and adolescents. Additionally, children and adolescents with depression can present with a number of sleep difficulties, which are also associated with several other issues such as more severe depression, greater fatigue, suicidal ideation, physical complaints, pain, and decreased concentration.

, obstructive sleep apnea, and circadian rhythm disorders are associated with both depression and bipolar disorder in children and adolescents. Sleep difficulties can occur before, during, and after an episode of depression or bipolar disorder.

“Sleep disturbances among adolescents with 

 can affect the severity of depressive and manic symptoms, are a poor prognostic indicator, and have been associated with social and academic impairment,” said Comsa and colleagues.

These sleep difficulties may be the result of medication. According to the investigators, antidepressants and antipsychotics can directly affect sleep architecture, and clinicians should be cognizant of this problem when prescribing and might instead consider nonpharmacological interventions. These interventions for sleep problems might minimize the risk of relapse in affective disorders.

Investigators suggested that a multimodal approach to target both the affective and specific sleep disorders is the ideal treatment plan. “Psychoeducation, consistent sleep-wake schedules, and tailored interventions for addressing sleep problems should play an important role in the prevention and treatment of mental health difficulties, at any age,” they wrote. “Concomitantly addressing sleep problems can lead to an increased remission rate of depression.”

More research is required to understand the impact of combined interventions on clinical outcomes, concluded investigators.

“Of most importance is the impact of specific treatment for sleep disorders on the long-term outcome of affective disorders. Clinicians need to know if better nights reliably lead to better days.”

1. Comsa M, Anderson KN, Sharma A, et al. 

The relationship between sleep and depression and bipolar disorder in children and young people.

Impulse Control Disorders and Behavioral Addictions in Patients With Eating Disorders

There is a moderate prevalence of impulse control disorder (ICD) and behavioral addiction (BA) comorbidities in individuals with 

 (EDs), investigators have found in a first-of-its-kind meta- analysis.

Because the prevalence has never been systematically examined, Daniel J. Devoe, PhD, MSc, and colleagues performed a series of random effects meta-analyses of peer-reviewed literature reporting prevalence of ICDs or BAs in individuals with EDs. The investigators included 35 studies with a total of 9646 individuals who had an ED and analyzed the prevalence of different behavioral addictions among these individuals. The mean age of participants was 25.5 years (range, 16.7-43.9), and 97.7% were female.

Results showed that stealing/shoplifting behaviors were the most common form of behavioral addictions in individuals with EDs, with a prevalence of 30%. Devoe et al also noted prevalence of pathological/compulsive buying at 19%, kleptomania at 18%, and pathological internet use at 12%. Intermittent explosive disorder, trichotillomania, and gambling had prevalence rates of 5%, 3%, and 2%, respectively.

ICDs are more closely associated with bulimia nervosa and binge-purge subtype than other ED diagnoses and behaviors, the investigators noted. This finding supports previous research indicating that individuals with binge-purge subtypes are more likely to have ICDs, partly due to impulse control difficulties and greater emotion regulation. The investigators also noted that certain personality traits (eg, perfectionism, impulsivity), psychiatric comorbidity, age of onset (eg, early age of onset may worsen prognoses), and concurrent substance use disorders may also play a role in deteriorating ED prognoses. They suggested that future research explore common underlying pathomechanisms.

“Although causal inferences cannot be drawn, the numbers strongly suggest that clinical screening/monitoring of ICDs/BAs should be part of the clinical routine in cohorts with EDs,” Devoe et al concluded.

1. Devoe DJ, Anderson A, Bahji A, et al. 

The prevalence of impulse control disorders and behavioral addictions in eating disorders: a systematic review and meta-analysis.

First-of-Its-Kind Study of Antidepressant Use in Patients With Depression and Type 2 Diabetes

Although treatment guidelines do not provide specific prescribing recommendations for antidepressants in individuals with 

, effective treatment of depression in patients with comorbid depression and type 2 diabetes is important for both conditions.

In a first-of-its-kind study looking at the prevalence of antidepressant prescribing and associated patient characteristics, Jeffrey et al

 searched 7 databases using terms related to depression, type 2 diabetes, and antidepressant medication. From the 9 utilized reports, the investigators determined that the prevalence of antidepressant prescribing varied considerably between studies—from 18% to 87%.

“This review has highlighted the gap in our knowledge about which antidepressant agents are being used in adults with comorbid depression and [type 2 diabetes], and alongside which concurrent medications and comorbidities. Thus, we are unaware of the extent to which such individuals are at risk from the risks associated with polypharmacy and other 

Investigators also found that women with type 2 diabetes are more likely to be prescribed antidepressants versus men; however, the difference is less than in the general population. Additionally, individuals with more advanced type 2 diabetes mellitus who use insulin were as likely to be prescribed antidepressants as those who did not use insulin.

“This is the first systematic review to our knowledge that investigates the prevalence and characteristics of 

 prescribing in adults with comorbid depression and [type 2 diabetes],” the study authors wrote. They added that, “There is an urgent need for longitudinal studies to inform guidelines on the long-term safety and effectiveness of antidepressant prescription in persons with comorbid depression and [type 2 diabetes].”

With a lack of evidence to support the long-term use of antidepressants in individuals with type 2 diabetes, special care should be taken when prescribing antidepressants—especially in more complex patients who have higher risks of potential adverse events.

1. Jeffrey A, Maconick L, Francis E, et al. 

Prevalence and characteristics of antidepressant prescribing in adults with comorbid depression and type 2 diabetes mellitus: a systematic review and meta-analysis.


COVID-19 Mortality Risk in Patients With Psychiatric Disorders

Patients with psychiatric disorders who were hospitalized for 

experienced higher mortality rates, but not due to their underlying psychiatric disorders, study results show.

The study, led by Nicolas Hoertel, MD, PhD, MPH, of Paris University and Corentin-Celton Hospital in Issy-les-Moulineaux, France, explored previous research indicating a connection between psychiatric disorders and increased mortality in patients with COVID-19. Hoertel et al conducted an observational multicenter respective cohort study of patients who had received a laboratory-confirmed diagnosis of COVID-19. The study included 15,168 patients who were hospitalized with COVID-19, of whom 857 also had received a diagnosis of a psychiatric disorder. Of this population, 59.6% had a substance- or illness-induced psychiatric disorder; 46.4% had a primary psychiatric disorder; and 6.1% had both types of disorders.

The investigators found that across a mean follow-up period of 14.6 days (SD = 17.9 days) 38% of patients with a psychiatric disorder died, compared with 8.9% of patients without a psychiatric disorder (odds ratio [OR] = 6.27; 95% CI; 5.40-7.28; P < 0.01). Individuals with a psychiatric disorder had a 6-fold higher risk of mortality than those without a psychiatric disorder, and this risk remained higher when adjusting for factors such as sex, age, and current smoking status in individual psychiatric diagnoses (adjusted OR [AOR] = 3.27; 95% CI; 2.78-3.85; P < 0.01). However, when adjusting for obesity and other medical comorbidities, the investigators found no statistically significant association with increased mortality in individuals with psychiatric disorders compared with individuals without psychiatric disorders (AOR = 1.02; 95% CI; 0.84-1.23; P = 0.86). Notably, diagnosis of a mood disorder was associated with reduced mortality, which the investigators suggested could be related to use of certain antidepressants such as fluvoxamine and fluoxetine, which may have anti-inflammatory or antiviral effects.

The investigators concluded that the risk of COVID-19–related mortality may be higher in individuals with psychiatric disorders due to the overall higher prevalence of obesity and medical conditions in this population—which also increases the risk of developing severe cases of COVID-19—rather than factors related to the psychiatric disorders themselves.

“Future studies including data on outpatients and inpatients with and without 

 and taking into account main medical risk factors of severe COVID-19 (ie, age, medical comorbidities, and obesity) will be important to determine whether the risk of hospitalization and mortality due to SARS-CoV-2 infection is similar or different across psychiatric diagnoses and psychotropic medications prescribed,” Hoertel et al concluded.

1. Hoertel N, Sánchez-Rico M, Muela P, et al. 

Risk of death in individuals hospitalized for COVID-19 with and without psychiatric disorders: an observational multicenter study in France


Psychiatric Comorbidities Affect Psychotic Depression Outcomes

Results of a recent study on gender and psychiatric comorbidities in individuals with psychotic depression (PD) found that comorbidities have significant implications for PD age of onset and outcomes.

Using the Northern Finland Birth Cohort 1966 and other national registers, Miika Nietola of the Department of Psychiatry at the University of Turku and colleagues analyzed 12,058 individuals who had been followed since they were in utero for lifetime psychiatric diagnoses, age of illness onset, hospitalizations, disability pension rate, and mortality. Fifty-eight individuals in the sample had received a lifetime diagnosis of PD (male, n = 23; female, n = 35); the lifetime prevalence of PD in the participants was 0.5%; and the median age of PD onset for participants was 40.2 years.

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